Whitley J et al., 2025·American journal of obstetrics and gynecology·
Open Access
Our objective was to determine if oxytocin discontinuation in the active phase of labor impacts the rate of cesarean delivery compared to continuation of oxytocin. This study was a systematic review and meta-analysis of randomized controlled trials. A research librarian performed a database search using a combination of standardized terms and keywords related to oxytocin discontinuation and stages of labor from database inception until February 2024. This protocol was registered in The International Prospective Register of Systematic Reviews (PROSPERO). Randomized controlled trials of pregnant patients who received oxytocin for induction or augmentation of labor, whose outcomes compared discontinuation and continuation of oxytocin in active labor, were included. We defined "active phase of labor" as defined by each trial. Nonrandomized trials, quasi-randomized trials, and animal models were excluded. The primary outcome was the rate of cesarean delivery. Secondary maternal outcomes included postpartum hemorrhage, total blood loss, and infectious outcomes. Secondary neonatal outcomes included Apgar score at 5 minutes <7, umbilical arterial pH <7.10, neonatal therapeutic hypothermia, neonatal intensive care unit admission, neonatal resuscitation at birth, and neonatal death. STUDY APPRAISAL The risk of bias in each study was assessed using the guidelines outlined in the Cochrane Handbook for Systematic Reviews of Interventions. Heterogeneity was measured using Higgins I2. Meta-analysis was performed in Review Manager 5.4.1 and StataSE 16 to determine summary treatment effects in terms of relative risk or mean difference with 95% confidence intervals. The adherence of each included trial to the trustworthiness criteria outlined by the OBGYN Editors' Integrity Group was assessed, and a leave-1-out analysis was performed to evaluate the effect of studies with concerns regarding trustworthiness. Fifteen randomized controlled trials, including 5734 patients, were ultimately included in the meta-analysis. The rate of cesarean delivery, reported in 13 studies, was lower with discontinuation of oxytocin in the active phase of labor (relative risk=0.80; 95% confidence interval, 0.66-0.97; 95% prediction interval, 0.38-1.22). Discontinuation of oxytocin was also associated with a lower risk of uterine tachysystole (relative risk=0.45; 95% confidence interval, 0.34-0.60; I2, 26%), and nonreassuring fetal heart rate tracing (relative risk=0.64; 95% confidence interval, 0.49-0.82; I2, 41%). Discontinuation of oxytocin increased the duration of active labor by an average of 30 minutes and second stage of labor by an average of 6 minutes. Although associated with an extension of labor by half an hour, discontinuation of oxytocin in the active phase of labor was associated with a 20% decreased risk of cesarean delivery and a lower risk of uterine tachysystole and nonreassuring fetal heart rate tracing. While the pooled analysis suggests a beneficial effect, this finding is dependent on the inclusion of studies with concerns regarding trustworthiness.
There is growing interest in the use of microbial-seeding interventions to mitigate the impacts of prenatal antibiotics, C-section, and lack of breastfeeding on mother-child microbe sharing. However, the relative importance of maternal vaginal vs. fecal microbiota in this process is unclear. Analyzing 16S rRNA sequences from five US birth cohorts, we found that maternal vaginal and fecal microbiota became more similar as pregnancy progressed, and both niches influenced the child's fecal microbiota. The relative contribution of maternal vaginal microbiota increased when vaginal sampling occurred later in gestation. As children aged from birth to 5 years, their fecal microbiota increasingly resembled their mother's fecal microbiota as compared to vaginal microbiota. Patterns of sharing appeared to differ by prenatal antibiotic use, birth mode (C-section vs. vaginal), and breastfeeding. Our findings enhance understanding of niche-specific mother-child microbe sharing and may inform microbial-seeding interventions. Metagenomic studies are needed to identify specific shared strains.
Young-Wolff KC et al., 2024·JAMA internal medicine
Many studies have evaluated whether in utero cannabis exposure is associated with fetal and neonatal outcomes, yet little is known about whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. To evaluate whether prenatal cannabis use is associated with maternal health outcomes during pregnancy. DESIGN, SETTING, This population-based retrospective cohort study included pregnancies in Northern California from January 2011 to December 2019 that lasted 20 weeks or longer and were screened for prenatal cannabis use. Prenatal cannabis use was defined as any self-reported use during early pregnancy or a positive toxicology test result based on universal screening at entrance to prenatal care (approximately 8-10 weeks' gestation). Self-reported frequency of use (daily, weekly, monthly or less, never, unknown), use defined only by self-report, and use defined only by toxicology test results were examined. Electronic health record data were used to define the following outcomes: gestational hypertension, preeclampsia, eclampsia, gestational diabetes, gestational weight gain greater and less than guidelines, placenta previa, placental abruption, placenta accreta, and severe maternal morbidity. Adjusted risk ratios (aRRs) were calculated using a modified Poisson regression. The sample (n = 316 722 pregnancies; 250 221 unique individuals) included 84 039 (26.5%) Asian/Pacific Islander, 20 053 (6.3%) Black, 83 145 (26.3%) Hispanic, and 118 333 (37.4%) White individuals; the mean (SD) age was 30.6 (5.4) years. Overall, 20 053 (6.3%) screened positive for prenatal cannabis use; 2.9% were positive by self-report, 5.3% by toxicology testing, and 1.8% by both. The frequency of cannabis use was 1930 (0.6%) daily, 2345 (0.7%) weekly, 4892 (1.5%) monthly or less, and 10 886 (3.4%) unknown. Prenatal cannabis use was associated with greater risk of gestational hypertension (aRR, 1.17; 95% CI, 1.13-1.21), preeclampsia (aRR, 1.08; 95% CI, 1.01-1.15), weight gain less than (aRR, 1.05; 95% CI, 1.01-1.08) and greater than (aRR, 1.09; 95% CI, 1.08-1.10) guidelines, and placental abruption (aRR, 1.19; 95% CI, 1.05-1.36). The pattern of results was similar when defining prenatal cannabis use only by self-report or only by toxicology testing, and associations between the frequency of prenatal cannabis use and outcomes varied with outcome. The results of this cohort study suggest that prenatal cannabis use was associated with several adverse maternal health outcomes during pregnancy. Continued research is needed to understand whether characteristics of prenatal cannabis use (eg, dose, mode, and timing) moderate these associations.
Maternal b-HCG levels fell to undetectable levels one month after birth without treatment. She was doing well and a follow-up six months later revealed no evidence of retained tissue or recurrence.
Pineles BL et al., 2023·AJOG Glob Rep·
Open Access
Cesarean delivery is a major source of maternal morbidity, and repeat cesarean delivery accounts for 40% of cesarean delivery, but recent data on the trial of labor after cesarean and vaginal birth after cesarean are limited. This study aimed to report the national rates of trial of labor after cesarean and vaginal birth after cesarean by number of previous cesarean deliveries and examine the effect of demographic and clinical characteristics on these rates. This was a population-based cohort study using the US natality data files. The study sample was restricted to 4,135,247 nonanomalous singleton, cephalic deliveries between 37 and 42 weeks of gestation, with a history of previous cesarean delivery and delivered in a hospital between 2010 and 2019. Deliveries were grouped by number of previous cesarean deliveries (1, 2, or ≥3). The trial of labor after cesarean (deliveries with labor among deliveries with previous cesarean delivery) and vaginal birth after cesarean (vaginal deliveries among trial of labor after cesarean) rates were computed for each year. The rates were further subgrouped by history of previous vaginal delivery. Year of delivery, number of previous cesarean deliveries, history of previous cesarean delivery, age, race and ethnicity, maternal education, obesity, diabetes mellitus, hypertension, inadequate prenatal care, Medicaid payer, and gestational age were examined concerning the trial of labor after cesarean and vaginal birth after cesarean using multiple logistic regression. SAS software (version 9.4) was used for all analyses. The trial of labor after cesarean rates increased from 14.4% in 2010 to 19.6% in 2019 (P<.001). This trend was seen in all categories of number of previous cesarean deliveries. Moreover, vaginal birth after cesarean rates increased from 68.5% in 2010 to 74.3% in 2019. The trial of labor after cesarean and vaginal birth after cesarean rates were the highest for deliveries with a history of both 1 previous cesarean delivery and a vaginal delivery (28.9% and 79.7%, respectively) and the lowest for those with a history of ≥3 previous cesarean deliveries and no history of vaginal delivery (4.5% and 46.9%, respectively). Factors associated with the trial of labor after cesarean and vaginal birth after cesarean rates are similar, but several factors have different directions of effect, such as non-White race and ethnicity, which is associated with a higher likelihood of trial of labor after cesarean but a lower likelihood of successful vaginal birth after cesarean. More than 80% of patients with a history of previous cesarean delivery deliver by repeat scheduled cesarean delivery. With vaginal birth after cesarean rates increasing among those who attempt a trial of labor after cesarean, emphasis should be put on safely increasing the trial of labor after cesarean rates.
Selective fetal growth restriction (sFGR) complicates 10%-26% of monochorionic twins. Treatment options include cord coagulation, expectant management, and fetoscopic laser photocoagulation. This review compared laser to expectant management for situations when cord coagulation is not an option. The MEDLINE, EMBASE, and Cochrane databases were queried for studies that compared laser to expectant management for sFGR. GRADE was used to assess quality prior to meta-analysis. A random-effects model was used to generate relative risks. Six studies were included, encompassing 299 pregnancies. One study was randomized and the remainder were retrospective cohorts. Laser is associated with more fetal deaths of the FGR twin compared to expectant management (risk ratio [RR] 2.5, 95% confidence interval [CI] 1.43-4.37, p = 0.001, I2 = 48%). Neonatal deaths and gestational age at delivery did not differ. Laser was associated with decreased abnormal neuroimaging in the AGA twin (RR 0.25, 95% CI 0.07-0.97, p = 0.05). Neurodevelopmental outcomes did not differ, although these data are limited. Laser causes more fetal deaths of the FGR twin without altering gestational age at delivery or rates of neonatal death. The literature is heterogeneous and the level of bias is high. Randomized trials that address laser for type II sFGR are needed and should include long-term neurological outcomes.
Buskmiller C et al., 2022·Am J Obstet Gynecol MFM·
Perinatal palliative care is an emerging concept in fetal medicine that offers quality-of-life options and anticipatory grief management for families of fetuses with complex conditions. Few perinatal palliative care outcomes are detailed in peer-reviewed literature. This study aimed to describe outcomes of perinatal palliative care at the Fetal Center of the University of Texas Health Science Center at Houston and Women's Center at Children's Memorial Hermann Hospital. This was a retrospective cohort of families receiving perinatal palliative care for life-limiting fetal diagnosis, such as trisomy 13 or 18 and some major structural anomalies between 2016 and 2020. The primary outcome was whether delivery events matched families' birth plans, including fetal/neonatal clinical course matching expectations described by consultant notes. Secondary outcomes included maternal safety outcomes, use of perinatal interventions, delivery outcomes, and resource utilization outcomes. Of 187 perinatal palliative care consults, delivery events matched families' plans and clinicians' expectations in 89% of cases (165/185); 39% (73/187) of families requested some perinatal interventions, 64% of whom planned postnatal comfort care even while choosing antenatal interventions. Demographics and median income were similar between families who chose some interventions and those who chose comfort care. Patients choosing any interventions had more mismatches between their plans and delivery events (19% vs 2%; P<.001), were more likely to change their plans (24% vs 6%; P=.001), and unsurprisingly used more healthcare resources. They were also more likely to have intraamniotic infection or postpartum hemorrhage (9% vs 22%; P=.02), but this was associated with mode of delivery and not choice of interventions. Most families' perinatal experiences matched birth plans and expectations in this perinatal palliative care program. Families who desired interventions used more healthcare resources, but often did so with plans for postnatal comfort care, demonstrating insight into neonatal prognosis but achieving value-consistent goals, such as meeting a live neonate. Perinatal palliative care was safe for maternal patients and equitable across racial, ethnic, and income groups. Perinatal palliative care and some perinatal interventions are options for care of the whole family in complex fetal medicine cases.
Sklar A et al., 2022·American journal of obstetrics and gynecology
After preterm premature rupture of membranes at <24 weeks' gestation, pregnant women may choose continuation (expectant management) or termination of pregnancy, via either dilation and evacuation or labor induction. Neonatal outcomes after expectant management are well described. In contrast, limited research addresses maternal outcomes associated with expectant management compared to termination of pregnancy. This study aimed to compare maternal morbidity after preterm premature rupture of membranes at <24 weeks' gestation in women who choose either expectant management or termination of pregnancy. This retrospective cohort study included women with preterm premature rupture of membranes between 14 0/7 and 23 6/7 weeks' gestation with singleton or twin pregnancies at 3 institutions from 2011 to 2018. We excluded pregnancies complicated by fetal anomalies, rupture of membranes immediately after obstetrical procedures (chorionic villus sampling, amniocentesis, cerclage placement, fetal reduction), spontaneous delivery <24 hours after membrane rupture, and contraindications to expectant management. Our primary outcome was the difference in composite maternal morbidity between women choosing expectant management and women choosing termination of pregnancy. We defined composite maternal morbidity as at least 1 of the following: chorioamnionitis, endometritis, sepsis, unplanned operative procedure after delivery (dilation and curettage, laparoscopy, or laparotomy), injury requiring repair, unplanned hysterectomy, unplanned hysterotomy (excluding cesarean delivery), uterine rupture, hemorrhage of >1000 mL, transfusion, admission to the maternal intensive care unit, acute renal insufficiency, venous thromboembolism, pulmonary embolism, and readmission to the hospital within 6 weeks. We compared the demographic and antenatal characteristics of women choosing expectant management with that of women choosing termination of pregnancy and used logistic regression to quantify the association between initial management decision and composite maternal morbidity. We identified 350 women with pregnancies complicated by preterm premature rupture of membranes at <24 weeks' gestation, and 208 women were eligible for the study. Of the 208 women, 108 (51.9%) chose expectant management as initial management, and 100 (48.1%) chose termination of pregnancy as initial management. Among women selecting termination of pregnancy, 67.0% underwent labor induction, and 33.0% underwent dilation and evacuation. Compared to women who chose termination of pregnancy, women who chose expectant management had 4.1 times the odds of developing chorioamnionitis (38.0% vs 13.0%; 95% confidence interval, 2.03-8.26) and 2.44 times the odds of postpartum hemorrhage (23.1% vs 11.0%; 95% confidence interval, 1.13-5.26). Admissions to the intensive care unit and unplanned hysterectomy only occurred after expectant management (2.8% vs 0.0% and 0.9% vs 0.0%). Of women who chose expectant management, 36.2% delivered via cesarean delivery with 56.4% non-low transverse uterine incisions. Composite maternal morbidity rates were 60.2% in the expectant management group and 33.0% in the termination of pregnancy group. After adjusting for gestational age at rupture, site, race and ethnicity, gestational age at entry to prenatal care, preterm premature rupture of membranes in a previous pregnancy, twin pregnancy, smoking, cerclage, and cervical examination at the time of presentation, expectant management was associated with 3.47 times the odds of composite maternal morbidity (95% confidence interval, 1.52-7.93), corresponding to an adjusted relative risk of 1.91 (95% confidence interval, 1.35-2.73). Among women who chose expectant management, 15.7% avoided morbidity and had a neonate who survived to discharge. Expectant management for preterm premature rupture of membranes at <24 weeks' gestation was associated with a significantly increased risk of maternal morbidity when compared to termination of pregnancy.
To determine whether discontinuing oxytocin stimulation in the active phase of induced labour is associated with lower caesarean section rates. International multicentre, double blind, randomised controlled trial. Nine hospitals in Denmark and one in the Netherlands between 8 April 2016 and 30 June 2020. 1200 women stimulated with intravenous oxytocin infusion during the latent phase of induced labour. Women were randomly assigned to have their oxytocin stimulation discontinued or continued in the active phase of labour. Delivery by caesarean section. A total of 607 women were assigned to discontinuation and 593 to continuation of the oxytocin infusion. The rates of caesarean section were 16.6% (n=101) in the discontinued group and 14.2% (n=84) in the continued group (relative risk 1.17, 95% confidence interval 0.90 to 1.53). In 94 parous women with no previous caesarean section, the caesarean section rate was 7.5% (11/147) in the discontinued group and 0.6% (1/155)in the continued group (relative risk 11.6, 1.15 to 88.7). Discontinuation was associated with longer duration of labour (median from randomisation to delivery 282 v 201 min; P<0.001), a reduced risk of hyperstimulation (20/546 (3.7%) v 70/541 (12.9%); P<0.001), and a reduced risk of fetal heart rate abnormalities (153/548 (27.9%) v 219/537 (40.8%); P<0.001) but rates of other adverse maternal and neonatal outcomes were similar between groups. In a setting where monitoring of the fetal condition and the uterine contractions can be guaranteed, routine discontinuation of oxytocin stimulation may lead to a small increase in caesarean section rate but a significantly reduced risk of uterine hyperstimulation and abnormal fetal heart rate patterns. ClinicalTrials.gov NCT02553226.
Bowman R et al., 2021·BMC Complement Med Ther·
Open Access
Childbearing women have been using various herbs to assist with pregnancy, labour and birth for centuries. One of the most common is raspberry leaf. The evidence base for the use of raspberry leaf is however under-developed. It is incumbent on midwives and other maternity care providers to provide women with evidence-based information so they can make informed choices. The aim of this study was to review the research literature to identify the evidence base on the biophysical effects, safety and efficacy of raspberry leaf in pregnancy. A systematic, integrative review was undertaken. Six databases were searched to identify empirical research papers published in peer reviewed journals including in vitro, in vivo, human and animal studies. The search included the databases CINAHL, MEDLINE, Cochrane Library, Scopus and Web of Science Core Collection and AMED. Identified studies were appraised independently by two reviewers using the MMAT appraisal instrument. An integrative approach was taken to analysis. Thirteen studies were included. Five were laboratory studies using animal and human tissue, two were experiments using animals, and six were human studies. Included studies were published between 1941 and 2016. Raspberry leaf has been shown to have biophysical effects on animal and human smooth muscle including the uterus. Toxity was demonstrated when high doses were administered intravenously or intaperitoneally in animal studies. Human studies have not shown any harm or benefit though one study demonstrated a clinically meaningful (though non-statistically significant) reduction in length of second stage and augmentation of labour in women taking raspberry leaf. Many women use raspberry leaf in pregnancy to facilitate labour and birth. The evidence base supporting the use of raspeberry leaf in pregnancy is weak and further research is needed to address the question of raspberry leaf’s effectiveness.
The neuropeptide oxytocin acts as a hormone and a neuromodulator, influencing a multitude of human social behaviors, including reproduction. During childbirth and the postpartum period, it plays a key role in regulating and controlling processes that ensure a safe birth and the health of mother and child. Especially the onset of labor, the progress of labor and initial breastfeeding are mediated by oxytocin. In the maternal brain it controls the initiation of the mother-infant bond and the mother's emotional responses towards her child. In this review we summarize the current state of knowledge about the role of oxytocin during the different aspects and mechanisms of human childbirth, combining research from human and animal studies. Physiological and psychological stress during childbirth and lactation can have negative effects on the progress of labor, breastfeeding and bonding. We discuss how maternity caregivers can support the positive effects of oxytocin and minimize the effects of stress. Furthermore, we highlight aspects of the basic neurobiological principles and connections where further research is needed to improve our understanding of the regulation and the effects of oxytocin to support maternal and infant health.
Stafford IA et al., 2020·Am J Obstet Gynecol MFM·
Open Access
Incidence, risk factors, and perinatal morbidity and mortality rates related to amniotic fluid embolism remain a challenge to evaluate, given the presence of differing international diagnostic criteria, the lack of a gold standard diagnostic test, and a significant overlap with other causes of obstetric morbidity and mortality. The aims of this study were (1) to analyze the clinical features and outcomes of women using the largest United States-based contemporary international amniotic fluid embolism registry, and (2) to investigate differences in demographic and obstetric variables, clinical presentation, and outcomes between women with typical versus atypical amniotic fluid embolism, using previously published and validated criteria for the research reporting of amniotic fluid embolism. The AFE Registry is an international database established at Baylor College of Medicine (Houston, TX) in partnership with the Amniotic Fluid Embolism Foundation (Vista, CA) and the Perinatology Research Branch of the Division of Intramural Research of the NICHD/NIH/DHHS (Detroit, MI). Charts submitted to the registry between August 2013 and September 2017 were reviewed, and cases were categorized into typical, atypical, non-amniotic fluid embolism, and indeterminate, using the previously published and validated criteria for the research reporting of AFE. Demographic and clinical variables, as well as outcomes for patients with typical and atypical AFE, were recorded and compared. Student t tests, χ(2) tests, and analysis of variance tables were used to compare the groups, as appropriate, using SAS/STAT software, version 9.4. A total of 129 charts were available for review. Of these, 46% (59/129) represented typical amniotic fluid embolism and 12% (15/129) atypical amniotic fluid embolism, 21% (27/129) were non-amniotic fluid embolism cases with a clear alternative diagnosis, and 22% (28/129) had an uncertain diagnosis. Of the 27 women misclassified as an amniotic fluid embolism with an alternative diagnosis, the most common actual diagnosis was hypovolemic shock secondary to postpartum hemorrhage. Ten percent (6/59) of the women with typical amniotic fluid embolism had a pregnancy complicated by placenta previa, and 8% (5/61) had undergone in vitro fertilization to achieve pregnancy. In all, 66% (49/74) of the women with amniotic fluid embolism reported a history of atopy or latex, medication, or food allergy, compared to 34% of the obstetric population delivered at our hospital over the study period (P < .05). Our data represent a series of women with amniotic fluid embolism whose diagnosis has been validated by detailed chart review, using recently published and validated criteria for research reporting of amniotic fluid embolism. Although no definitive risk factors were identified, a high rate of placenta previa, reported allergy, and conceptions achieved through in vitro fertilization was observed.
Dahlke JD et al., 2020·Obstet Gynecol·
Open Access
In this Commentary, we explain the case for a standardized cesarean delivery surgical technique. There are three strong arguments for a standardized approach to cesarean delivery, the most common major abdominal surgery performed in the world. First, standardization within institutions improves safety, efficiency, and effectiveness in health care delivery. Second, surgical training among obstetrics and gynecology residents would become more consistent across hospitals and regions, and proficiency in performing cesarean delivery measurable. Finally, standardization would strengthen future trials of cesarean delivery technique by minimizing the potential for aspects of the surgery which are not being studied to bias results. Before 2013, more than 155 randomized controlled trials, meta-analyses or systematic reviews were published comparing various aspects of cesarean delivery surgical technique. Since 2013, an additional 216 similar studies have strengthened those recommendations and offered evidence to recommend additional cesarean delivery techniques. However, this amount of cesarean delivery technique data creates a forest for the trees problem, making it difficult for a clinician to synthesize this volume of data. In response to this difficulty, we propose a comprehensive, evidence-based and standardized approach to cesarean delivery technique.
This study describes hospital-based obstetric service losses in rural US counties between 2014 and 2018 overall and by county population and urban adjacency.
Claramonte Nieto M et al., 2019·BMC pregnancy and childbirth
Women of advanced maternal age (AMA) are a growing population, with higher obstetric risks. The Mediterranean population has specific characteristics different from other areas. Thus, the objective of this study was to establish a cut-off to define AMA in a selected mediterranean population coming from a tertiary referral private/mutual health hospital in Barcelona. Retrospective cohort of euploid singleton pregnancies delivered from January 2007 to June 2017. Main maternal outcomes were: gestational diabetes, preeclampsia, placenta previa, c-section and prolonged hospitalization (≥ 7 days). Main adverse perinatal outcomes were: stillbirth, prematurity, preterm prelabor rupture of membranes, low birth weight, need of admission at a neonatal intensive care unit and perinatal mortality. Adjustment for confounding factors (smoking, previous comorbilities, parity, assisted reproductive techniques (ART) and obesity) was performed. A total of 25054 pregnancies were included. Mean maternal age was 34.7 ± 4.2 years, with 2807 patients in the group of age between 40 and 44 years (11.2%) and 280 patients ≥45 years (1.1%). Women at AMA had higher incidence of previous comorbilities (compared to the reference group of women < 30 years): prior c-section, chronic hypertension and obesity. In addition, they were more likely to use ART. After adjusting for confounding factors, maternal age was an independent and statistically significant risk factor for gestational diabetes (OR 1.66/2.80/3.14) for ages 30-39, 40-44 and ≥ 45 years respectively, c-section (OR 1.28/2.41/7.27) and placenta previa (OR 2.56/4.83) for ages 40-44 and ≥ 45 years respectively, but not for preeclampsia (neither early-onset nor late-onset). Risk of emergency c-section was only increased in women ≥45 years (OR, 2.03 (95% CI, 1.50-2.74). In the other groups of age, the increase in c-section rate was because of elective indications. Age ≥ 45 years was associated with iatrogenic prematurity < 37 weeks (OR 2.62, 95% CI 1.30-5.27). No other relevant associations between AMA and maternal or neonatal outcomes were found. Maternal age is an independent risk factor for adverse obstetric outcomes. Age ≥ 40 years was associated to relevant increased risks and reveals to be an adequate cut-off to define AMA in our population.
Jauniaux E et al., 2019·American Journal of Obstetrics and Gynecology·
Open Access
The objective of this study was to evaluate the prevalence of placenta accreta spectrum in general population studies and the main maternal outcomes at delivery. We searched PubMed, Google Scholar, clinicalTrials.gov, and MEDLINE between 1982 and 2018. Articles that provided data on the number of cases of placenta accreta spectrum per pregnancies, births, or deliveries in a defined population were used. STUDY APPRAISAL Study characteristics were evaluated by 2 independent reviewers who used a predesigned protocol. Primary outcomes were the prevalence of placenta accreta spectrum and clinical diagnostic data at birth; the pathologic criteria were used to confirm the diagnosis. Secondary outcomes included cases that required transfusion, incidence of peripartum hysterectomy, and maternal mortality rates. Heterogeneity between studies was analyzed with the Cochran's Q-test and the I2 statistics. Of the 98 full-text studies that were identified, 29 articles met the defined criteria and included 22 retrospective and 7 prospective studies comprising 7001 cases of placenta accreta spectrum of 5,719,992 births. Prevalence rates ranged from 0.01-1.1% with an overall pooled prevalence of 0.17% (95% confidence interval, 0.14-0.19). Only 10 studies provided detailed histopathologic data. The pool prevalence for the adherent vs the invasive grades was 0.5 (95% confidence interval, 0.3-0.36) and 0.3 (95% confidence interval, 0.2-0.4) per 1000 births, respectively. The pooled incidence for peripartum hysterectomy was 52.2% (95% confidence interval, 38.3-66.4; I2=99.8%) and 46.9% (95 % confidence interval, 34-59.9; I2=98.8%) for hemorrhage that required transfusion. The pooled estimate of maternal death was 0.05% (95% confidence interval, 0.06-0.69; I2=73%). We found large amounts of heterogeneity between studies for all parameters and further quantification was limited because of methodologic inconsistencies between studies with regards to clinical criteria that were used for the diagnosis of the condition at birth and the histopathologic confirmation of the diagnosis and differential diagnosis between adherent and invasive accreta placentation. This meta-analysis indicated wide variation between studies for the prevalence rate of placenta accreta spectrum and for the different grades of accreta placentation that highlighted the need for consistency in definitions that are used to describe placenta accreta spectrum at birth and in the reporting of this increasing common obstetric complication.
Birth by cesarean delivery is increasing globally, particularly cesarean deliveries without medical indication. Children born via cesarean delivery may have an increased risk of negative health outcomes, but the evidence for psychiatric disorders is incomplete. To evaluate the association between cesarean delivery and risk of neurodevelopmental and psychiatric disorders in the offspring. Ovid MEDLINE, Embase, Web of Science, and PsycINFO were searched from inception to December 19, 2018. Search terms included all main mental disorders in the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition). Two researchers independently selected observational studies that examined the association between cesarean delivery and neurodevelopmental and psychiatric disorders in the offspring. Two researchers independently extracted data according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) reporting guidelines and assessed study quality using the Newcastle-Ottawa Scale. Random-effects meta-analyses were used to pool odds ratios (ORs) with 95% CIs for each outcome. Sensitivity and influence analyses tested the robustness of the results. The ORs for the offspring with any neurodevelopmental or psychiatric disorder who were born via cesarean delivery compared with those were born via vaginal delivery. A total of 6953 articles were identified, of which 61 studies comprising 67 independent samples were included, totaling 20 607 935 deliveries. Compared with offspring born by vaginal delivery, offspring born via cesarean delivery had increased odds of autism spectrum disorders (OR, 1.33; 95% CI, 1.25-1.41; I2 = 69.5%) and attention-deficit/hyperactivity disorder (OR, 1.17; 95% CI, 1.07-1.26; I2 = 79.2%). Estimates were less precise for intellectual disabilities (OR, 1.83; 95% CI, 0.90-3.70; I2 = 88.2%), obsessive-compulsive disorder (OR, 1.49; 95% CI, 0.87-2.56; I2 = 67.3%), tic disorders (OR, 1.31; 95% CI, 0.98-1.76; I2 = 75.6%), and eating disorders (OR, 1.18; 95% CI, 0.96-1.47; I2 = 92.7%). No significant associations were found with depression/affective psychoses or nonaffective psychoses. Estimates were comparable for emergency and elective cesarean delivery. Study quality was high for 82% of the cohort studies and 50% of the case-control studies. The findings suggest that cesarean delivery births are associated with an increased risk of autism spectrum disorder and attention-deficit/hyperactivity disorder, irrespective of cesarean delivery modality, compared with vaginal delivery. Future studies on the mechanisms behind these associations appear to be warranted.
Recently WHO researchers described seven dimensions of mistreatment in maternity care that have adverse impacts on quality and safety. Applying the
WHO framework for quality care, service users partnered with NGOs, clinicians, and researchers, to design and conduct the Giving Voice to Mothers (GVtM)-US study.
Our multi-stakeholder team distributed an online cross-sectional survey to capture lived experiences of maternity care in diverse populations.
Patient-designed items included indicators of verbal and physical abuse, autonomy, discrimination, failure to meet professional standards of care, poor rapport with providers, and poor conditions in the health system. We quantified the prevalence of mistreatment by race, socio-demographics, mode of birth, place of birth, and context of care, and describe the intersectional relationships between these variables.
Of eligible participants (n = 2700), 2138 completed all sections of the survey. One in six women (17.3%) reported experiencing one or more types of mistreatment such as: loss of autonomy; being shouted at, scolded, or threatened; and being ignored, refused, or receiving no response to requests for help. Context of care (e.g. mode of birth; transfer; difference of opinion) correlated with increased reports of mistreatment. Experiences of mistreatment differed significantly by place of birth: 5.1% of women who gave birth at home versus 28.1% of women who gave birth at the hospital. Factors associated with a lower likelihood of mistreatment included having a vaginal birth, a community birth, a midwife, and being white, multiparous, and older than 30 years. Rates of mistreatment for women of colour were consistently higher even when examining interactions between race and other maternal characteristics. For example, 27.2% of women of colour with low SES reported any mistreatment versus 18.7% of white women with low SES. Regardless of maternal race, having a partner who was Black also increased reported mistreatment.
This is the first study to use indicators developed by service users to describe mistreatment in childbirth in the US. Our findings suggest that mistreatment is experienced more frequently by women of colour, when birth occurs in hospitals, and among those with social, economic or health challenges.
Mistreatment is exacerbated by unexpected obstetric interventions, and by patient-provider disagreements.
Tanos V et al., 2019·Best Pract Res Clin Obstet Gynaecol·
The increasing rate of elective and indicated caesarean sections worldwide has led to new pathologies and management challenges. The number of patients undergoing trial of labor after caesarean section (TOLAC) is also increasing. Three professional societies provide detailed guidelines based on scientific evidence for the management of patients attempting vaginal birth after caesarean section (VBAC). However, they do not provide any recommendations for the actual surgical steps to be followed to minimize the risks of uterine rupture (UR) during TOLAC. Uterine scar condition, intrapartum management and maternal health status correlate to uterine scar rupture risk and provide guidance for parturient TOLAC eligibility. TOLAC and vaginal delivery success rate as reported by the largest studies is between 60% and 77%. Uterine rupture is more prevalent in VBAC-2 patients (1.59%) in contrast to VBAC-1 (0.72%). Additionally, VBAC-2 patients have higher incidence of caesarean hysterectomy 0.56% vs. 0.19% for VBAC-1. The chances of successful VBAC increase when the interpregnancy/interdelivery interval is less than 6.3 years and less than 24 months, respectively. No difference was detected between the techniques of uterine incision closure of the previous CS and TOLAC results, although closure of the CS uterine incision in 2 layers seems to be practiced more widely. Niche or isthmocele presents another complication of CS. Secondary infertility due to niche, will eventually direct to hysteroscopic or laparoscopic repair, depending on the residual myometrial thickness (RMT) as measured by US scan. When RMT is below 3 mm or 2.5 mm surgery can be performed, to prevent any spontaneous UR in case of pregnancy. Monitoring by US scanning of hysterotomy scar after myomectomy can detect hematoma. In patients with severe postoperative pain but hemodynamically stable follow up by US scan examination can direct the management decision. In those patients with active bleeding and deterioration of hysterotomy scar edema will be an indication to surgery. There is no firm evidence regarding which type of thread, knotting or sequence of suturing is more favorable to reduce the risk of UR after VBAC or hysterotomy after myomectomy.
Comment in
JAMA. 2018 Mar 27;319(12):1203-1204. doi: 10.1001/jama.2018.1646. Hospital-based obstetric services have decreased in rural US counties, but whether this has been associated with changes in birth location and outcomes is unknown.
To examine the relationship between loss of hospital-based obstetric services and location of childbirth and birth outcomes in rural counties.
DESIGN, SETTING, A retrospective cohort study, using county-level regression models in an annual interrupted time series approach.
Births occurring from 2004 to 2014 in rural US counties were identified using birth certificates linked to American Hospital Association Annual Surveys.
Participants included 4 941 387 births in all 1086 rural counties with hospital-based obstetric services in 2004.
Loss of hospital-based obstetric services in the county of maternal residence, stratified by adjacency to urban areas.
Primary outcomes were county rates of (1) out-of-hospital births; (2) births in hospitals without obstetric units; and (3) preterm births (<37 weeks' gestation).
Between 2004 and 2014, 179 rural counties lost hospital-based obstetric services. Of the 4 941 387 births studied, the mean (SD) maternal age was 26.2 (5.8) years. A mean (SD) of 75.9% (23.2%) of women who gave birth were non-Hispanic white, and 49.7% (15.6%) were college graduates. Rural counties not adjacent to urban areas that lost hospital-based obstetric services had significant increases in out-of-hospital births (0.70 percentage points [95% CI, 0.30 to 1.10]); births in a hospital without an obstetric unit (3.06 percentage points [95% CI, 2.66 to 3.46]); and preterm births (0.67 percentage points [95%
CI, 0.02 to 1.33]), in the year after loss of services, compared with those with continual obstetric services. Rural counties adjacent to urban areas that lost hospital-based obstetric services also had significant increases in births in a hospital without obstetric services (1.80 percentage points [95% CI, 1.55 to 2.05]) in the year after loss of services, compared with those with continual obstetric services, and this was followed by a decreasing trend (-0.19 percentage points per year [95% CI, -0.25 to -0.14]).
In rural US counties not adjacent to urban areas, loss of hospital-based obstetric services, compared with counties with continual services, was associated with increases in out-of-hospital and preterm births and births in hospitals without obstetric units in the following year; the latter also occurred in urban-adjacent counties. These findings may inform planning and policy regarding rural obstetric services.
To evaluate the utilization rate of salpingectomy for cesarean deliveries and postpartum and interval tubal sterilization procedures. This is a retrospective cohort study using the electronic medical record to identify women older than 18 years of age undergoing surgical sterilization from June 2011 to May 2016 in an integrated health care system. The primary objective is to describe the change in utilization rate of salpingectomy for tubal sterilization procedures over time and after a systemwide practice recommendation was issued in 2013. Rates of salpingectomy and tubal occlusion were calculated for each of the five 1-year intervals in the study. Secondary outcomes included blood loss, operating time, length of stay, readmission, and emergency department visits. A total of 10,741 tubal sterilization procedures were identified. There was an increase in salpingectomies from 0.4% (8/1,938; 95% CI 0.2-0.8) to 35.5% (902/2,538; 95% CI 33.7-37.4) of tubal sterilization procedures performed over the study period (test for trend, P<.001). Salpingectomy instead of tubal occlusion increased at cesarean delivery from 0.1% (1/1,141; 95% CI 0.0-0.5) to 9.2% (125/1,354; 95% CI 7.8-10.9) (test for trend, P<.001); postpartum from 0% (0/124; 95% CI 0.0-3.0) to 4.5% (9/201; 95% CI 2.4-8.3) (test for trend, P=.003); and as an interval (nonpartum) tubal sterilization procedure from 1% (7/673; 95% CI 0.5-2.1) to 78% (768/983; 95% CI 75.4-80.6) (test for trend, P<.001). Median operative minutes was increased from 52 (95% CI 51-52) to 61.5 (95% CI 57-64), from 33 (95% CI 32-34) to 50 (95% CI 35-64), and from 30 (95% CI 29-30) to 33 (95% CI 32-33), respectively, for salpingectomy compared with tubal occlusion at cesarean delivery and postpartum and interval sterilization. Median blood loss was similar for salpingectomy and tubal occlusion at cesarean delivery (660 mL; 95% CI 600-700 mL compared with 700 mL; 95% CI 680-700 mL) and interval sterilization (both 5 mL; 95% CI 5-5 mL) but was more for salpingectomy postpartum (250 mL; 95% CI 200-500 mL compared with 200 mL; 95% CI 200-200 mL). There was a significant increase in salpingectomy for sterilization from June 2011 to May 2016. In the final year of the study, salpingectomy accounted for 78% of interval laparoscopic tubal sterilization procedures and 9% of intrapartum and postpartum procedures.
The US cesarean delivery rate remains 30%-32%. Increases in maternal age, obesity, and diabetes put upward pressure on this rate. Alternatives to cesarean delivery, vaginal birth after cesarean (VBAC), and operative vaginal delivery, are underutilized and there are substantial challenges to their resurgence. Practice guidelines offer promise, but demonstrate only minor reductions in cesarean delivery. We estimate that the overall rate in the US will remain 27%-30% for the immediate future. As more states move to recognize the independent practice of midwifery and more payers seek lower cost options for childbirth, we anticipate the overall rate will drop to 20% or 25%, but not for another 15 years or more.
Dotters-Katz SK et al., 2017·Obstetrics and gynecology·
Open Access
To identify risk factors for maternal morbidity after previable prelabor rupture of membranes (PROM). We conducted a case-control study of singleton and twin pregnancies complicated by previable PROM (14.0-22.9 weeks of gestation) at a single tertiary care referral institution, 2000-2015. Pregnancies complicated by fetal anomalies, previable PROM within 2 weeks of chorionic villus sampling or amniocentesis, and those with contraindications to expectant management (eg, chorioamnionitis) were excluded. Cases were women with the primary outcome of composite maternal morbidity (defined as having at one or more of the following: sepsis, intensive care unit admission, acute renal insufficiency, uterine curettage, hysterectomy, deep vein thrombosis, pulmonary embolus, blood transfusion, readmission, or maternal death). Controls were women without the primary composite morbidity. Bivariate analysis compared demographic, clinical, and management characteristics of women in the case group and those in the control group. Multivariable logistic regression models were developed to quantify the association between maternal characteristics and composite severe maternal morbidity. During the study period, 174 women presented with by previable PROM and were candidates for expectant management. Sixty-five (37%) women opted for immediate delivery; 109 (63%) elected expectant management. Twenty-five of 174 (14%) experienced one or more components of the composite maternal morbidity (cases) and were compared with 149 (86%) women in the control group. Women in the case group were more not more likely to elect expectant management (68% compared with 59%, P=.40), but were more likely to be aged 35 years or older (40% compared with 14%, P=.002) or to be carrying twins (52% compared with 16%, P<.01). In the regression model, twin gestation and age 35 years or older were both significantly associated with increased odds of composite maternal morbidity (odds ratio [OR] 5.62, 95% confidence interval [CI] 2.21-14.3 and OR 4.00, 95% CI 1.48-10.8, respectively). Antenatal counseling of women with previable PROM should include that one in seven women experience significant morbidity. Although expectant management was not associated with increased risk in this cohort, women with twins or those aged 35 years or older were at substantially increased risk.
Vettori D et al., 2015·Journal of Neonatal-Perinatal Medicine
Aplasia cutis congenita (ACC) is rare skin disorder of newborns that has been linked to both assisted reproductive technology (ART) and feto-reduction procedures. ACC is characterized by well-demarcated lesions that are devoid of all skin layers. Group-V ACC presents with a distinctive and symmetrical distribution pattern. It is thought to result from an insult to the fetus after concomitant twin demise and is almost exclusively reported in monochorionic gestations.A 41-year-old female with an in vitro fertilization (IVF) assisted tri-chorionic gestation subsequently underwent selective feto-reduction of Fetus C. The patient delivered two pre-term neonates secondary to pre-eclampsia. The initial exam of Twin B showed extensive, well-demarcated, symmetrical areas devoid of any skin over the anterior and lateral trunk, extending up the lateral thoracic walls. Chest and abdominal viscera were visible through a thin fibrous membrane. The skin defects were managed conservatively with twice-daily dressings of Aquaphor, and Vaseline gauze. The areas of aplasia slowly contracted, though residual scarring was noted. After four weeks in the NICU, most of the areas were healed.ACC in multi-fetal pregnancies is a rare, but well-described complication. This is, to our knowledge, the first reported case in a tri-chorionic IVF gestation after feto-reduction. With increased incidence of ART-associated pregnancies and the use of feto-reduction for higher order gestations, this may become more common. Neonates often require specialized intensive care. Conservative management usually will suffice, although surgical grafting may be required. Physicians should be aware of this condition and counsel their feto-reduction patients of the risk.
Buckley SJ, 2015·The Journal of perinatal education·
Open Access
This report synthesizes evidence about innate hormonally mediated physiologic processes in women and fetuses/newborns during childbearing, and possible impacts of common maternity care practices and interventions on these processes, focusing on four hormone systems that are consequential for childbearing. Core hormonal physiology principles reveal profound interconnections between mothers and babies, among hormone systems, and from pregnancy through to the postpartum and newborn periods. Overall, consistent and coherent evidence from physiologic understandings and human and animal studies finds that the innate hormonal physiology of childbearing has significant benefits for mothers and babies. Such hormonally-mediated benefits may extend into the future through optimization of breastfeeding and maternal-infant attachment. A growing body of research finds that common maternity care interventions may disturb hormonal processes, reduce their benefits, and create new challenges. Developmental and epigenetic effects are biologically plausible but poorly studied. The perspective of hormonal physiology adds new considerations for benefit-harm assessments in maternity care, and suggests new research priorities, including consistently measuring crucial hormonally mediated outcomes that are frequently overlooked. Current understanding suggests that safely avoiding unneeded maternity care interventions would be wise, as supported by the Precautionary Principle. Promoting, supporting, and protecting physiologic childbearing, as far as safely possible in each situation, is a low-technology health and wellness approach to the care of childbearing women and their fetuses/newborns that is applicable in almost all maternity care settings.
Marshall NE et al., 2011·American Journal of Obstetrics and Gynecology
The purpose of this study was to determine the impact of increasing numbers of cesarean deliveries on maternal morbidity. This study was performed for the 2010 National Institutes of Health Consensus Development Conference on Vaginal Birth After Cesarean: New Insights. We conducted a systematic review and metaanalysis of observational studies. Twenty-one studies (2,282,922 deliveries) were included. The rate of hysterectomy, blood transfusions, adhesions, and surgical injury all increased with increasing number of cesarean deliveries. The incidence of placenta previa increased from 10/1000 deliveries with 1 previous cesarean delivery to 28/1000 with ≥3 cesarean deliveries. Compared with women with previa and no previous cesarean delivery, women with previa and ≥3 cesarean deliveries had a statistically significant increased risk of accreta (3.3-4% vs 50-67%), hysterectomy (0.7-4% vs 50-67%), and composite maternal morbidity (15% vs 83%; odds ratio, 33.6; 95% confidence interval, 14.6-77.4). Serious maternal morbidity progressively increased as the number of previous cesarean deliveries increased.
An obstetric hemorrhage may occur before or after delivery, but more than 80% of cases occur postpartum. Worldwide, a massive obstetric hemorrhage, resulting from the failure of normal obstetrical, surgical and/or systemic hemostasis, is responsible for 25% of the estimated 358,000 maternal deaths each year. Most women will not have identifiable risk factors. Nonetheless, primary prevention of a postpartum hemorrhage (PPH) begins with an assessment of identifiable risk factors. Women identified as being at high risk of a PPH should be delivered in a center with access to adequately trained staff and an onsite blood bank. A critical feature of a massive hemorrhage in obstetrics is the development of disseminated intravascular coagulation (DIC), which, in contrast to DIC that develops with hemorrhage from surgery or trauma, is frequently an early feature. Data from clinical trials to guide management of transfusion in PPH are lacking. There are likely to be similarities in the management of transfusion in severe PPH to that of major bleeding in other clinical situations, but the pathophysiological processes that contribute to a massive PPH may necessitate different transfusion strategies such as the ratio of red blood cells to plasma components, in particular fibrinogen. Caution should be exercised when considering the appropriate place for recombinant activated factor VII (rFVIIa) in the management of a major PPH. An early hysterectomy is recommended for severe bleeding as a result of placenta accreta or uterine rupture. However, in women with uterine atony who have ongoing bleeding in spite of an adequate transfusion, it may be reasonable to consider a trial of rFVIIa before a hysterectomy.
Yogev Y et al., 2010·American journal of obstetrics and gynecology
The purpose of this study was to evaluate pregnancy outcome in women at extremely advanced maternal age (≥ 45 years). We compared the condition of women aged ≥ 45 years (n = 177) in a 10:1 ratio (20-29, 30-39, and 40-44 years.). Subgroup analysis compared the condition of women aged 45-49 years with those women aged ≥ 50 years. The rates of gestational diabetes mellitus and hypertensive complications were higher for the study group, compared with the whole group (17.0% vs 5.6% and 19.7% vs 4.5%, respectively; P < .001), as was the rate of preterm delivery at <37 and <34 weeks of gestation (odds ratio [OR], 2.1; 95% confidence interval [CI], 1.2-3.6 and OR, 3.5; 95% CI, 1.4-9.0, respectively). The rates of cesarean delivery (OR, 31.8; 95% CI, 18.0-56.1), placenta previa, postpartum hemorrhage, and adverse neonatal outcome were significantly higher among the study group. The risk for gestational diabetes mellitus, preeclampsia toxemia, preterm delivery, and neonatal intensive care unit admission was increased for women aged ≥ 50 years. Pregnancy at extreme advanced maternal age is associated with increased maternal and fetal risk.
To systematically review the evidence about maternal and neonatal outcomes relating to vaginal birth after cesarean (VBAC). Relevant studies were identified from multiple searches of MEDLINE, DARE, and the Cochrane databases (1980 to September 2009) and from recent systematic reviews, reference lists, reviews, editorials, Web sites, and experts. Inclusion criteria limited studies to the English-language and human studies conducted in the United States and developed countries specifically evaluating birth after previous cesarean delivery. Studies focusing on high-risk maternal or neonatal conditions, including breech vaginal delivery, or fewer than 10 patients were excluded. Poor-quality studies were not included in analyses. TABULATION, INTEGRATION, We identified 3,134 citations and reviewed 963 articles for inclusion; 203 articles met the inclusion criteria and were quality rated. Overall rates of maternal harms were low for both trial of labor and elective repeat cesarean delivery. Although rare in both elective repeat cesarean delivery and trial of labor, maternal mortality was significantly increased for elective repeat cesarean delivery at 0.013% compared with 0.004% for trial of labor. The rates of maternal hysterectomy, hemorrhage, and transfusions did not differ significantly between trial of labor and elective repeat cesarean delivery. The rate of uterine rupture for all women with prior cesarean was 0.30%, and the risk was significantly increased for trial of labor (0.47% compared with 0.03% for elective repeat cesarean delivery). Perinatal mortality was also significantly increased for trial of labor (0.13% compared with 0.05% for elective repeat cesarean delivery). Overall the best evidence suggests that VBAC is a reasonable choice for the majority of women. Adverse outcomes were rare for both elective repeat cesarean delivery and trial of labor. Definitive studies are lacking to identify patients who are at greatest risk for adverse outcomes.
To study the relationship between suboptimal maternal thyroid function during gestation and breech presentation at term. Prospective follow-up study during three trimesters of gestation. A total of 1058 Dutch Caucasian healthy pregnant women were prospectively followed from 12 weeks gestation until term (>or=37 weeks) delivery. Maternal thyroid parameters [TSH, free T4 (FT4) and auto-antibodies to thyroid peroxidase] were assessed at 12, 24 and 36 weeks gestation as well as foetal presentation at term. At term, 58 women (5.5%) presented in breech. Compared with women with foetuses in the cephalic position, those women who presented in breech at term had significantly higher TSH concentrations, but only at 36 weeks gestation (P = 0.007). No between group differences were obtained for FT4 level at any assessment. The prevalence of breech presentation in the subgroup of women with TSH >or= 2.5 mIU/l (90th percentile) at 36 weeks gestation was 11%, compared with 4.8% in the women with TSH < 2.50 mIU/l (P = 0.006). Women with TSH below the 5th percentile had no breech presentations. Breech position was significantly and independently related to high maternal TSH concentration (>or=2.5 mIU/l) at 36 weeks gestation (O.R.: 2.23, 95% CI: 1.14-4.39), but not at 12 and 24 weeks gestation. Women with TSH levels above 2.5 mIU/l during end gestation are at risk for breech presentation, and as such for obstetric complications.
Fitzsimons KJ et al., 2009·Obstetric medicine·
Open Access
Maternal obesity is now considered one of the most commonly occurring risk factors seen in obstetric practice. Compared with women with a healthy pre-pregnancy weight, women with obesity are at increased risk of miscarriage, gestational diabetes, preeclampsia, venous thromboembolism, induced labour, caesarean section, anaesthetic complications and wound infections, and they are less likely to initiate or maintain breastfeeding. Babies of obese mothers are at increased risk of stillbirth, congenital anomalies, prematurity, macrosomia and neonatal death. Intrauterine exposure to obesity is also associated with an increased risk of developing obesity and metabolic disorders in childhood. This article reviews the prevalence of obesity in pregnancy and the associated maternal and fetal complications. Recommendations and suggestions for pre-conception, antenatal and postnatal care of women with obesity are presented, and current research in the UK and future research priorities are considered.
Laberge PY, 2008·Journal de gynecologie, obstetrique et biologie de la reproduction
Endometrial ablation (EA) has been performed for the past two decades as an alternative to hysterectomy in women with dysfunctional-uterine bleeding unresponsive to medical treatment. However, unlike hysterectomy, this minimally invasive procedure is not an effective means of contraception. Pregnancy following EA has been reported, but the risks and complications related have not been emphasized. This is a report on two such cases and review of the literature, with a closer look at the frequent negative outcome. A 25-year-old woman underwent EA for dysfunctional-uterine bleeding unresponsive to medical treatment. She had no previous surgery, specifically she had no past myomectomy or caesarean section. She declined concomitant tubal ligation. She became pregnant five years later in early spring 2007 and sustained a large uterine rupture at 24 weeks and died in June 2007 secondary to massive internal bleeding at age 29. A 34-year-old woman with previous hysteroscopic EA became pregnant less than one year after surgery. At that time, she had refused concomitant tubal sterilization since her husband had a vasectomy. Unfortunately, the relationship ended soon after surgery and she had unprotected sexual intercourse with a new partner. Pregnancy termination was complicated by placenta increta, which required immediate abdominal hysterectomy. Pregnancy after EA is not a rare occurrence, regardless of which technique is used. Whether women choose to go on or terminate their pregnancy, this clinical situation can be associated with serious complications and even maternal death. Counselling about contraceptive options at the time of EA is paramount.
Yeung PP Jr et al., 2008·J Matern Fetal Neonatal Med·
This is the first known case of extended somatic support beyond viability for a pregnant woman with brain death resulting from metastatic malignant melanoma, resulting in a live birth.
Luke B et al., 2007·Fertility and sterility·
Open Access
To evaluate the risks of pregnancy complications and adverse outcomes associated with increasing maternal age and higher plurality. Population-based, historic cohort study. US birth certificates and infant death certificates. PATIENT(S): Live births of > or =20 weeks gestation between 1995-2000: 22,991,306 singleton, 316,696 twin, and 12,193 triplet pregnancies. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy-associated hypertension, incompetent cervix, tocolysis, premature rupture of membranes, excessive bleeding at delivery, delivery <29 weeks, and infant death. RESULT(S): Compared to singletons, the risks for all adverse outcomes among multiple pregnancies were significantly elevated, and were highest for tocolysis, delivery <29 weeks, and infant mortality. Within pluralities, increasing maternal age was associated with significantly higher risks of pregnancy-associated hypertension, excessive bleeding, and incompetent cervix, but for twin and triplet pregnancies, significantly lower risks for tocolysis (ages > or =40, singleton adjusted odds ratio [AOR] 0.97, twin AOR 0.67, triplet AOR 0.72), delivery <29 weeks (ages > or =40, singleton AOR 1.55, twin AOR 0.72, triplet AOR 0.52), and infant mortality (ages > or =40, singleton AOR 1.34, twin AOR 0.71, triplet AOR 0.42). CONCLUSION(S): Older maternal age and higher plurality are each associated with increasing risks for many pregnancy complications, but with significantly lower risks of tocolysis, early preterm birth, and infant mortality.
Although repeat cesarean deliveries often are associated with serious morbidity, they account for only a portion of abdominal deliveries and are overlooked when evaluating morbidity. Our objective was to estimate the magnitude of increased maternal morbidity associated with increasing number of cesarean deliveries. Prospective observational cohort of 30,132 women who had cesarean delivery without labor in 19 academic centers over 4 years (1999-2002). There were 6,201 first (primary), 15,808 second, 6,324 third, 1,452 fourth, 258 fifth, and 89 sixth or more cesarean deliveries. The risks of placenta accreta, cystotomy, bowel injury, ureteral injury, and ileus, the need for postoperative ventilation, intensive care unit admission, hysterectomy, and blood transfusion requiring 4 or more units, and the duration of operative time and hospital stay significantly increased with increasing number of cesarean deliveries. Placenta accreta was present in 15 (0.24%), 49 (0.31%), 36 (0.57%), 31 (2.13%), 6 (2.33%), and 6 (6.74%) women undergoing their first, second, third, fourth, fifth, and sixth or more cesarean deliveries, respectively. Hysterectomy was required in 40 (0.65%) first, 67 (0.42%) second, 57 (0.90%) third, 35 (2.41%) fourth, 9 (3.49%) fifth, and 8 (8.99%) sixth or more cesarean deliveries. In the 723 women with previa, the risk for placenta accreta was 3%, 11%, 40%, 61%, and 67% for first, second, third, fourth, and fifth or more repeat cesarean deliveries, respectively. Because serious maternal morbidity increases progressively with increasing number of cesarean deliveries, the number of intended pregnancies should be considered during counseling regarding elective repeat cesarean operation versus a trial of labor and when debating the merits of elective primary cesarean delivery. II-2.
Landon MB et al., 2004·New England Journal of Medicine
The proportion of women who attempt vaginal delivery after prior cesarean delivery has decreased largely because of concern about safety. The absolute and relative risks associated with a trial of labor in women with a history of cesarean delivery, as compared with elective repeated cesarean delivery without labor, are uncertain. We conducted a prospective four-year observational study of all women with a singleton gestation and a prior cesarean delivery at 19 academic medical centers. Maternal and perinatal outcomes were compared between women who underwent a trial of labor and women who had an elective repeated cesarean delivery without labor. Vaginal delivery was attempted by 17,898 women, and 15,801 women underwent elective repeated cesarean delivery without labor. Symptomatic uterine rupture occurred in 124 women who underwent a trial of labor (0.7 percent). Hypoxic-ischemic encephalopathy occurred in no infants whose mothers underwent elective repeated cesarean delivery and in 12 infants born at term whose mothers underwent a trial of labor (P<0.001). Seven of these cases of hypoxic-ischemic encephalopathy followed uterine rupture (absolute risk, 0.46 per 1000 women at term undergoing a trial of labor), including two neonatal deaths. The rate of endometritis was higher in women undergoing a trial of labor than in women undergoing repeated elective cesarean delivery (2.9 percent vs. 1.8 percent), as was the rate of blood transfusion (1.7 percent vs. 1.0 percent). The frequency of hysterectomy and of maternal death did not differ significantly between groups (0.2 percent vs. 0.3 percent, and 0.02 percent vs. 0.04 percent, respectively). A trial of labor after prior cesarean delivery is associated with a greater perinatal risk than is elective repeated cesarean delivery without labor, although absolute risks are low. This information is relevant for counseling women about their choices after a cesarean section.
Copyright 2004 Massachusetts Medical Society.
Weiss JL et al., 2004·American journal of obstetrics and gynecology
This study was undertaken to determine whether obesity is associated with obstetric complications and cesarean delivery. A large prospective multicenter database was studied. Subjects were divided into 3 groups: body mass index (BMI) less than 30 (control), 30 to 34.9 (obese), and 35 or greater (morbidly obese). Groups were compared by using univariate and multivariable logistic regression analyses. The study included 16,102 3,752 control, 1,473 obese, and 877 morbidly obese patients. Obesity and morbid obesity had a statistically significant association with gestational hypertension (odds ratios [ORs] 2.5 and 3.2), preeclampsia (ORs 1.6 and 3.3), gestational diabetes (ORs 2.6 and 4.0), and fetal birth weight greater than 4000 g (ORs 1.7 and 1.9) and greater than 4500 g (ORs 2.0 and 2.4). For nulliparous patients, the cesarean delivery rate was 20.7% for the control group, 33.8% for obese, and 47.4% for morbidly obese patients. Obesity is an independent risk factor for adverse obstetric outcome and is significantly associated with an increased cesarean delivery rate.
This report presents 2001 data on U.S. births according to a wide variety of characteristics. Data are presented for maternal demographic characteristics including age, live-birth order, race, Hispanic origin, marital status, and educational attainment; maternal characteristics (medical risk factors, weight gain, tobacco, and alcohol use); medical care utilization by pregnant women (prenatal care, obstetric procedures, complications of labor and/or delivery, attendant at birth, and method of delivery); and infant characteristics (period of gestation, birthweight, Apgar score, abnormal conditions, congenital anomalies, and multiple births). Also presented are birth and fertility rates by age, live-birth order, race, Hispanic origin, and marital status. Selected data by mother's State of residence are shown, as well as data on month and day of birth, sex ratio, and age of father. Trends in fertility patterns and maternal and infant characteristics are described and interpreted. Descriptive tabulations of data reported on the birth certificates of the 4.026 million births that occurred in 2001 are presented. Denominators for population-based rates are derived from the 1990 U.S. census. As a result, rates are generally larger than would be the case if 2000-based estimates were used. The magnitude of the overestimate will vary by population subgroup; overestimates are likely greatest for those of Hispanic origin. The number of births, the birth rate, fertility rate, and total fertility rates all declined 1 percent in 2001. The teenage birth rate reached another historic low. Birth rates for women in their twenties declined slightly, whereas rates for women aged 30 to 44 years continued to rise. Births to unmarried women changed very little. Smoking by pregnant women was down again. Women were more likely to begin care in the first trimester of pregnancy (83.4 percent). The cesarean delivery rate rose for the fifth consecutive year to 24.4 percent; the primary cesarean rate was up 5 percent and the rate of vaginal births after a previous cesarean fell 20 percent. Preterm and low birthweight levels both rose for 2001. The twin birth rate continued to climb, and following 2 years of decline, the rate of triplet/+ births also increased.
As a result of oocyte donation, women in their sixth decade of life are now able to conceive and carry pregnancies to term. However, little is known about pregnancy outcomes in this population. To describe pregnancy outcomes in women aged 50 years or older who conceived after in vitro fertilization with donor oocytes. Retrospective analysis of cycles conducted at a US university assisted reproduction program during calendar years 1991-2001. Seventy-seven postmenopausal women with no chronic medical conditions (mean [SD] age, 52.8 [2.9] years; range, 50-63 years) who underwent 121 embryo transfer procedures (89 fresh and 32 frozen). Pregnancy outcomes were ascertained by chart review and telephone follow-up. Maternal and neonatal outcomes. There were 55 clinical pregnancies for a total pregnancy rate of 45.5%. The live birth rate was 37.2%. Of the 45 live births, 31 were singletons, 12 were twins, and 2 were triplets, for which the mean (SD) gestational ages at delivery were 38.4 (2.1) weeks, 35.8 (2.8) weeks, and 32.2 weeks, respectively. Mean (SD) birth weights were 3039 g (703 g), 2254 g (581 g), and 1913 g, respectively. Apgar scores at 1 and 5 minutes were 8.2 (0.9) and 9.1 (0.5), respectively. Of singletons, 68% were delivered by cesarean, and all multiples were delivered by cesarean. Mild preeclampsia was noted in 25% of patients and severe preeclampsia in 10%. Gestational diabetes required diet modification in 17.5%, and 2.5% required insulin. Appropriately screened women aged 50 years or older can successfully conceive via oocyte donation and experience similar pregnancy rates, multiple gestation rates, and spontaneous abortion rates as younger recipients. During pregnancy, they appear at increased risk of preeclampsia and gestational diabetes. A majority can expect to deliver via cesarean. However, there does not appear to be any definitive medical reason for excluding these women from attempting pregnancy on the basis of age alone.
To investigate whether women's experiences of their first birth affects future reproduction.
Prospective cohort study.
South Hospital, Stockholm, Sweden.
Six hundred and seventeen women who gave birth to their first child 1989-1992.
A global measure of women's experiences of their first birth, assessed two months postpartum, was available from a birth centre trial, together with information on a range of background variables. This information was linked to the Swedish Medical Birth Register, which included information on the number of subsequent births during the following 8-10 years.
Number of births (0 or > or =1) following the first birth.
Women with a negative experience of their first birth had fewer subsequent children and a longer interval to the second baby (RR 1.7, 95% CI 1.3-2.3). Being 35 years and older (RR 2.6, 95% CI 1.6-3.7), or single (RR 2.6, 95% CI 1.7-3.9) was also associated with subsequent infertility.
A negative birth experience was associated with subsequent infertility, and women's experiences should therefore be considered seriously in the provision of maternity care.
Mattison DR et al., 2001·Paediatr Perinat Epidemiol·
And his daughter‐in‐law, the wife of Phinehas, was pregnant near to giving birth, and got to hear the report that the ark of the true God was captured and that her father‐in‐law and her husband had died. At that she bowed herself and began giving birth, because her pangs came unexpectedly upon her.
The role of human chorionic gonadatropin (hCG) in the maintenance of early pregnancy is well known. Recent data suggests that hCG may play a role in the maintenance of the later stages of pregnancy as well, by directly and indirectly promoting uterine quiescence. If hCG acts as an endogenous tocolytic in normal pregnancy, then it may be an ideal candidate for therapy of preterm labor as well. We present compelling in vitro as well as in vivo data, which support the role of hCG in the maintenance of normal uterine quiescence. Additionally, we will present in vivo and in vitro data that confirms the ability of hCG to directly promote relaxation of uterine contractions. This review provides a basis for future study of the use of hCG in clinical obstetrics. Given the limited effectiveness of tocolytic therapies available at the time, hCG may provide a promising pharmacological approach to the pervasive problem of preterm labor in human pregnancy. While further work is needed, initial data strongly support this novel use of hCG in clinical obstetrics.
To compare the incidence of pregnancy-induced hypertension in patients with and without polycystic ovary disease (PCOD). We conducted a retrospective, case-control analysis of patients who achieved singleton pregnancies with human menopausal gonadotropin (hMG) therapy. Twenty-two PCOD patients were compared to 27 infertility patients without PCOD who were pregnant after hMG therapy. Non-PCOD patients received hMG for superovulation as part of superovulation/intrauterine insemination or in vitro fertilization/embryo transfer. PCOD patients were receiving hMG for simple ovulation induction. Pregnancy-induced hypertension was defined as late pregnancy blood pressure > 140/90 mm Hg on two readings six hours apart and return to normal blood pressure by four to six weeks postpartum. There were no differences between PCOD and non-PCOD patients with reference to age, body mass index, parity or other pregnancy-induced hypertension risk factors (i.e., chronic hypertension, diabetes or chronic renal disease). Pregnant PCOD patients had a much higher incidence of pregnancy-induced hypertension, 31.8% (7/22), versus non-PCOD patients, who only had a pregnancy-induced hypertension incidence of 3.7% (1/27) (P = .016, OR = 12.1, 95% CI = 1.3-566.8). PCOD patients are at very high risk of pregnancy-induced hypertension when pregnant after ovulation induction.
The number of births, the crude birth rate (14.5 in 2001), and the fertility rate (67.2 in 2001) all declined slightly (by 1% or less) from 2000 to 2001. Fertility rates were highest for Hispanic women (107.4), followed by Native American (70.7), Asian or Pacific Islander (69.4), black (69.3), and non-Hispanic white women (58.0). During the early to mid 1990s, fertility declined for non-Hispanic white, black, and American Indian women. Rates for these population groups have changed relatively little since 1995; however, fertility has increased for Asian or Pacific Islander and Hispanic women. The birth rate for teen mothers continued to fall, dropping 5% from 2000 to 2001 to 45.9 births per 1000 females aged 15 to 19 years, another record low. The teen birth rate has fallen 26% since 1991; declines were more rapid (35%) for younger teens aged 15 to 17 years than for older teens aged 18 to 19 years (20%). The proportion of all births to unmarried women remained about the same at one-third. Smoking during pregnancy continued to decline; smoking rates were highest among teen mothers. The use of timely prenatal care increased slightly to 83.4% in 2001. From 1990 to 2001, the use of timely prenatal care increased by 6% (to 88.5%) for non-Hispanic white women, by 23% (to 74.5%) for black women, and by 26% (to 75.7%) for Hispanic women. The number and rate of twin births continued to rise, but the triplet/+ birth rate declined for the second year in a row. For the first year in almost a decade, the preterm birth rate declined (to 11.6%); however, the low birth weight rate was unchanged at 7.6%. The total cesarean delivery rate jumped 7% from 2000 to 2001 to 24.4% of all births, the highest level reported since these data became available on birth certificates (1989). The primary cesarean rate rose 5%, whereas the rate of vaginal birth after a previous cesarean delivery tumbled 20%. In 2001, the provisional infant mortality rate was 6.9 per 1000 live births, the same as in 2000. Racial differences in infant mortality remain a major public health concern, with the rate for infants of black mothers 2.5 times those for infants of non-Hispanic white or Hispanic mothers. In 2000, 66% of all infant deaths occurred among the 7.6% of infants born low birth weight. Among all states, Maine and Massachusetts had the lowest infant mortality rates. The United States continues to rank poorly in international comparisons of infant mortality. The provisional death rate in 2001 was 8.7 deaths per 1000 population, the same as the 2000 final rate. In 2000, unintentional injuries and homicide remained the leading and second-leading causes of death for children 1 to 19 years of age, although the death rate for homicide decreased by 10% from 1999 to 2000. Among unintentional injuries to children, two-thirds were motor vehicle-related; among homicides, two-thirds were firearm-related.
Previous studies have demonstrated that human myometrium contains receptors for human chorionic gonadotropin (hCG) and that hCG can inhibit myometrial contractions in vitro. To use for the first time hCG as a tocolytic agent in the treatment of preterm labor. The study group included 100 women with preterm labor; 50 were assigned to receive HCC and 50 placebo. Assignment was made with stratification according to four categories of gestational age between 20–35 weeks. One half of the surviving infants were followed-up at 18 months. The protocol of the dosage consisted of one single dose of hCG 5,000 IV and 10,000 units of hCG in 500 dextrose as a drip of 20 drops per minute. The mean length of time from randomization to delivery differs significantly for the two groups: 28.8 days for the hCG group and 15 days for the placebo treatment group (highly statistically significant, P <0.001). There was statistically significant difference (P <0.05) between the two groups regarding the induction of delivery before 37 weeks and the proportion of infants weighing less than 2,500 g. Human chorionic gonadotropin treatment was associated with an improvement score on the Bayley psychomotor development index. Human chorionic gonadotropin exhibits potent tocolysis with no fetal side effects. This preliminary study suggests that HCG may be a candidate for tocolytic therapy of preterm labor.
To compare the efficacy of intravaginal and intrarectal plus oral indomethacin for the treatment of preterm labor. Between December 1996 and November 1998, 46 eligible gravidas admitted with singleton pregnancies and idiopathic preterm labor before 33 gestational weeks were randomized to receive 200 mg of intravaginal or intrarectal plus oral indomethacin. Twenty-three subjects were allocated to each study group. The interval from initiation of treatment to delivery was significantly longer in the intravaginal indomethacin group (26.5 +/- 5.7 versus 12.6 +/- 3.7 days; P =.007). Delivery was delayed by more than 7 days in 18 of 23 subjects (78%) in the intravaginal indomethacin group compared with ten (43%) in the intrarectal plus oral indomethacin group (P =.03). Birth weights were significantly higher (2306 +/- 436 versus 1862 +/- 232 g; P =.002) and hospitalization in a neonatal intensive care unit (NICU) (3.1 +/- 0.8 versus 9.3 +/- 3. 7 days; P =.001) and mechanical ventilation (1.4 +/- 0.2 versus 5.3 +/- 1.6 days; P =.001) were significantly shorter in the intravaginal indomethacin group. Intravaginal indomethacin is more effective than intrarectal plus oral application in delaying preterm labor and is associated with higher birth weights, shorter NICU stays, and shorter intervals of mechanical ventilation.
To examine whether induced abortion influences subsequent pregnancy duration. Women who had their first pregnancies during 1980, 1981, and 1982 were identified in three Danish national registries. A total of 15,727 women whose pregnancies were terminated by first-trimester induced abortions were compared with 46,026 whose pregnancies were not terminated by induced abortions. All subsequent pregnancies until 1994 were identified by register linkage. Preterm and post-term singleton live births were more frequent in women with one, two, or more previous induced abortions. After adjusting for potential confounders and stratifying by gravidity, the odds ratios of preterm singleton live births in women with one, two, or more previous induced abortions were 1.89 (95% confidence interval [CI] 1.70, 2.11), 2.66 (95% CI 2.09, 3.37), and 2.03 (95% CI 1.29, 3.19), respectively. Odds ratios of post-term singleton live births in women with one, two, or more previous induced abortions were 1.34 (95% CI 1.24, 1.44), 1.50 (95% CI 1.26, 1.78), and 1.58 (95% CI 1.09, 2.28), respectively. The study showed an increase in preterm and post-term pregnancies after induced abortions. The risk of post-term delivery was high regardless of the interpregnancy interval, whereas increased risk of preterm delivery was seen mainly when interpregnancy intervals were longer than 12 months.
The number of teenage pregnancies has increased throughout the world and these pregnancies are reported in association with a higher rate of maternal and fetal complications. To evaluate the social surroundings; the results of ante-, intrapartum surveillance and perinatal outcome in adolescent pregnancies where mothers were below the age of 18. Between 1st January, 1991 and 31st December, 1996 there were 13,131 births at our department. During this period, 209 newborns were born of 207 adolescent mothers. We compared the data of adolescent mothers with the data of all mothers who delivered in Hungary during the study period. 39 (18.6%) from 209 newborns were delivered before 37th week of gestation, and 34 (16.3%) newborns showed signs of intrauterine growth retardation (IUGR). The rate of primiparous adolescent mothers was 72.0%, 131 (63.3%) were primigravidae, and 136 (65.7%) received adequate prenatal care. Maternal complications (pregnancy induced hypertension, threatened preterm delivery, gestational diabetes and pre-eclampsia) and adverse perinatal outcome (higher rate of IUGR and perinatal mortality) were found more frequently in adolescent pregnancies. As young maternal age is associated with an increased risk of unfavourable fetal outcome, teenage mothers need improved prenatal care and increased observation during labour. In addition, improvement of the social environment of adolescents and the prevention of teenage pregnancies should be recommended.
This article reviews the arguments for the use of multifetal pregnancy reduction (MFPR) for the prevention of preterm deliveries in triplet and higher order multiple pregnancies and evaluates its effectiveness based on data from published studies. The arguments in favour of pregnancy reduction are based on the substantial mortality and morbidity associated with these pregnancies. Triplets and higher order multiples have increased rates of preterm delivery and intrauterine growth retardation, both of which are independent risk factors for death and handicap. Even controlling for gestational age, rates of mortality and handicap are higher for multiples than for singletons. Moreover, the family's risk of losing a child or having a handicapped child is greater because there are more infants at risk. MFPR effectively lowers these risk by reducing the frequency of preterm delivery. However, its effectiveness may be limited. In some studies, the proportion of preterm deliveries in reduced pregnancies remains above levels found in spontaneous twin or singleton pregnancies and MFPR does not appear to reduce the prevalence of low birth weight. Furthermore, the procedure itself has unwanted side effects: it increases the risk of miscarriage, premature rupture of the membranes and causes adverse psychological effects such as grief or depression for many patients. The authors note that a majority of the higher order multiple pregnancies result from a medical intervention in the first place, either through IVF techniques or the use of ovulation stimulation drugs. Although MFPR is an effective measure for reducing the substantial morbidity and mortality associated with higher order multiple pregnancies, preventive methods, such as limiting to 2 the number of embryos transferred for IVF and better control of the use of ovulation induction drugs, remain more effective and less intrusive.
To determine whether singleton IVF pregnancies carry adverse maternal or fetal outcome when compared with naturally conceived gestations. An analysis of the obstetric outcome of singleton IVF pregnancies in comparison with matched, naturally conceived singleton controls. In vitro fertilization unit and obstetric service at a tertiary medical center. PATIENT(S): Two hundred sixty consecutive singleton IVF pregnancies and 260 naturally conceived singleton controls matched 1:1 for maternal age, parity, ethnic origin, and location and date of delivery. INTERVENTION(S): In vitro fertilization-ET. MAIN OUTCOME MEASURE(S): The rate of antenatal obstetric complications, nonvertex presentation, cesarean section, preterm labor, low birth weight, small and very small for gestational age, neonatal intensive care unit admissions, and perinatal mortality. RESULT(S): The rates of most antenatal complications were similar in both groups. Urinary tract infection was the only complication diagnosed significantly more frequently after IVF (7.3% versus 1.2%); however, the rates of severe urinary tract infection necessitating hospitalization were similar. The incidence of nonvertex presentation was also similar. The cesarean section rate was significantly higher among IVF patients (41.9% versus 15.5%). The rates of preterm labor, low birth weight, small and very small for gestational age, neonatal intensive care unit admissions, and perinatal mortality were comparable. CONCLUSION(S): When controlling for maternal age, parity, ethnic origin, and location and date of delivery, singleton IVF pregnancies do not carry an increased risk for prematurity, low birth weight, or maternal or fetal complications. Still, these pregnancies are associated with a high rate of cesarean sections.
To characterize the continuum between normal and preterm labor to prevent spontaneous preterm birth and low birth weight. Between August 1, 1992, and November 30, 1993, obstetric patients from a large managed care medical group were assigned in rotation to five private practice offices for pregnancy care. In the study office (374 births), a systematic approach of visit-by-visit screening, patient education, selective office evaluation of cervical change by transvaginal ultrasound examination, outpatient modification of activity, and graded oral or subcutaneous tocolysis was used; inpatient tocolysis was used only when outpatient management failed. In the comparison offices (1391 births), transvaginal ultrasound was not used and conventional methods were used at the discretion of the attending physicians. Birth weights below 1500 g (P = .008; odds ratio [OR] 0.08, 95% confidence interval [CI] 0.05-1.32), 2000 g (P = .21; OR 0.21, 95% CI 0.05-0.88), and 2500 g (P = .008; OR 0.44, 95% CI 0.23-0.83) occurred significantly less often in the study group than in the comparison group. The difference in spontaneous preterm births under 2500 g was also significant (P < .001; OR 0.08, 95% CI 0.01-0.58). By emphasizing transvaginal ultrasound and graded outpatient tocolysis, the diagnosis and management of preterm prelabor was associated with a reduction in the rate of spontaneous preterm birth and low birth weight infants.
Silent intrauterine infection as cause of preterm labour should be recognised early by measuring C-reactive protein (CRP) levels in the maternal serum. Ensuing antibiotic therapy may not only cause gestational prolongation, but also has a positive effect on pathology during the puerperal period. Consequently, we examined the rate of infectious puerperal complications of 181 patients who suffered from so-called idiopathic preterm labour. 84 patients showed normal CRP-levels at the onset of tocolysis (< 5 mg/l); an elevated level was found in 97 patients (> 5 mg/l). Patients with elevated CRP-levels and supplemented antibiotic therapy during pregnancy (n = 51) showed significantly fewer symptoms of postpartal endometritis than women with similarly elevated CRP-levels but without antibiotics (n = 46). This effect was not produced when preterm labour was associated with normal CRP-levels. Patients with premature contractions and elevated CRP-values at the onset of tocolysis seem to benefit from the antibiotic therapy during pregnancy because they show reduced infectious complications throughout the puerperal period.
To determine prospectively the incidence of several pulmonary diagnoses among infants born through clear or meconium-stained amniotic fluid (AF) managed by a selective approach to tracheal intubation. All live births greater than 36 weeks' gestation occurring between January 1990 and December 1992 were included. Diagnostic criteria for several respiratory disorders were determined prospectively and monitored. Infants with light meconium and vigorous infants with moderate to thick meconium were selectively not suctioned. A control group of infants with clear AF matched for gestational age and year of birth was randomly selected for comparison. The incidence and severity of respiratory disease were compared between the groups. Of 4938 live births, 799 (16%) had meconium-stained AF (light, 334; moderate to thick, 465). Compared to 211 infants with moderate to thick meconium selectively not suctioned, 196 suctioned infants had significantly greater rates of abnormal fetal heart rate (FHR) patterns, fetal acidosis, low Apgar scores at 5 minutes, need for resuscitation, and neonatal intensive care unit admission. Meconium aspiration syndrome was significantly more common in suctioned infants as compared to those selectively not suctioned, those with light meconium, and those with clear fluid (11 versus 3 versus 0 versus 0%; P < .01). The need for ventilator or oxygen support was similar between infants with clear fluid, lightly stained fluid, and moderate to thick fluid who were selectively not suctioned, but was significantly greater among suctioned infants (P < .01). We conclude that a selective approach to tracheal intubation and suction of infants with meconium-stained AF was not associated with increased pulmonary morbidity or mortality. Postnatal management of neonates at greatest risk of meconium aspiration syndrome does not necessarily prevent adverse pulmonary outcome.
The clinician is often held responsible for obstetric events that are suspected of being related to cerebral palsy. To review the incidence of cerebral palsy and to aid the clinician in this situation, a search of published studies was conducted. Composite rates of cerebral palsy in different birth weight infants and cerebral palsy with and without serious mental retardation were calculated. The cumulative incidence rate at the age of 5 to 7 years was 2.7 cases of cerebral palsy for 1000 birth cohorts. Approximately 36% of all cerebral palsy occurred in the infant less than 2500 gm. Serious mental retardation (intelligence quotient less than 50) accompanied cerebral palsy approximately 30% of the time for the term infant and 18% of the time when the infant was less than 2500 gm. On the basis of a past estimation that 70% of cerebral palsy is of antepartum or unknown origin, the term infant at risk for intrapartum-attributed cerebral palsy may be about 1 in 2000 term births.
Bhalla AK et al., 1992·Aust N Z J Obstet Gynaecol·
Pregnancies of 112 patients who had conceived after a history of a minimum of 2 years of infertility were compared to an equal number of matching controls without prior infertility to find out any risk of increased pregnancy complications. These patients were at a significantly higher risk of developing first trimester bleeding, antepartum haemorrhage and intrauterine fetal death. Also there were higher rates of preterm delivery and Caesarean section. The patients in the study group had a significantly higher number of stillborn babies. The incidence of other complications such as ectopic pregnancy, multiple pregnancy, and medical complications was also higher in these patients but the difference was not statistically significant.
A pregnant woman may become anxious if she has not delivered by the date given to her by her physician. Much anxiety would be alleviated if a range of dates (38-42 weeks) was substituted for a specific date of delivery.
Maternal serum C-reactive protein (CRP) has been studied extensively as an adjunct in the diagnosis of subclinical infection among pregnant women with preterm labor or preterm rupture of membranes. However, before the utility of CRP can be studied in pregnancies with these complications, the effects of normal pregnancy and labor on maternal serum CRP levels must be established. We determined CRP levels serially from 22 weeks' gestation until delivery in healthy pregnant women without antepartum complications. Median CRP values for women not in labor ranged from 0.7-0.9 mg/dL, depending on gestational age; 95% of the values were 1.5 mg/dL or lower. No consistent change in CRP levels with gestational age was found among serially sampled women not in labor. The median CRP value for women in labor at term was 1.3 mg/dL, and 32% of values were over 1.5 mg/dL. Median CRP values in normal pregnancies appear to be higher than standardized values for nonpregnant individuals, and CRP values are further elevated in labor. Understanding the physiology and temporal course of the increase in CRP in normal pregnancy and labor may help to clarify the appropriate use of CRP in complicated pregnancies.
The relative contribution of uterine activity obtained by home monitoring with a guard ring tocodynamometer compared with seven specific signs and symptoms reported during patient/nurse contact as an aid in detecting preterm labor has not been studied. In this prospective, multicenter study, patients at risk for developing early labor who were randomized to receive home uterine activity monitoring and perinatal nursing support were assessed. The initiator of provider contact (uterine activity detected on routine transmission, patient-perceived signs and symptoms of preterm labor during perinatal nurse contact, or both) resulting in a diagnosis of preterm labor was recorded. Contraction data were then analyzed for an association with preterm labor. There was a strong association of increased uterine activity (four or more contractions per hour) on a repeat monitoring strip with preterm labor (P less than .001). Among patients diagnosed with preterm labor, 31% had increased uterine activity detected on a routine transmission without patient-reported signs and symptoms, compared with 24% who were diagnosed as the result of patient-reported symptoms without increased uterine activity. Daily objective uterine activity data alone have greater incremental value over and above other signs and symptoms as an aid to the physician in diagnosing preterm labor.
The early detection of preterm labor and the prevention of preterm birth require special attention to early subtle signs and symptoms of preterm labor. The concept of "Braxton Hicks contractions" may negate these early signs and symptoms by falsely reassuring patients, thus encouraging them not to seek medical care promptly.
To assess uterine activity before labor in patients delivering preterm, at term, and postterm, the maximum spontaneous contraction frequency per 10-minute window during the initial portion of antepartum fetal heart rate monitoring was analyzed. Patients with multiple gestation, third trimester bleeding, polyhydramnios, or premature rupture of membranes and those already diagnosed with preterm labor were eliminated from the study. Of the 2446 remaining patients (7247 antepartum fetal heart rate tests) who went into spontaneous labor, 237 did so before 37 completed weeks of gestation, 1077 entered labor at term (38 to 42 completed weeks), and 1132 did so after 42 weeks. There was a significant increase in maximum uterine activity per 10-minute window from 30 to 44 weeks of gestation (average 4.7% per week; r = 0.97, p less than 0.0001). When compared with patients delivering spontaneously at term, average maximum uterine activity per 10-minute window was greatest in the preterm labor group (p less than 0.05) and least in the postterm labor group (p less than 0.05). These differences were present for several weeks preceding the onset of spontaneous labor. All three groups showed a surge of uterine activity during the 3 days before the onset of spontaneous labor.
Cervical cerclage as a temporizing measure for the treatment of patients with placenta previa was evaluated in 25 patients admitted to the hospital for vaginal bleeding between 24-30 weeks' gestation and sonographic evidence of a placenta previa. The patients were randomly assigned to either cerclage (13) or conventional management (12). Cerclage patients had significantly better perinatal outcome, as indicated by more advanced gestational age at the time of delivery (34.9 +/- 3.0 versus 31.6 +/- 2.9 weeks; P = .02), larger birth weight (2709 +/- 511 versus 1812 +/- 506 g; P = .002), and fewer neonatal complications (two of 13 versus ten of 12 infants; P = .001). Maternal bleeding was more frequent and severe for patients in the control group. The total hospital cost was less for cerclage patients than for those receiving conventional expectant management ($9898 +/- 3943 versus $27,271 +/- 9901; P = .02). These results support the use of cervical cerclage for the treatment of patients with symptomatic placenta previa early in gestation.
C-reactive protein has been used to identify patients at high risk for infectious morbidity with preterm labor or preterm rupture of membranes. In this article we report on 104 patients with preterm labor symptoms (n = 45) or preterm rupture of the membranes (n = 59) and serial evaluations of C-reactive protein measured by latex agglutination and laser nephelometry. The simple, inexpensive latex method appears comparable to the laser method in predicting infectious morbidity and can be used clinically. Elevated C-reactive protein values before delivery predict infectious morbidity in only 8% to 29% of patients, and up to 18% of patients with serious infections may be misdiagnosed as having normal C-reactive protein values before delivery.
Effective tocolytic therapy depends on the ability to make an early diagnosis of preterm labor. This study was designed to assess whether daily ambulatory home monitoring of uterine activity could facilitate early diagnosis of preterm labor. Of 76 patients at high risk for preterm labor who used daily ambulatory tocodynamometry, approximately half developed preterm labor. Evaluation when the diagnosis of preterm labor was first established has shown that in 8% of the patients the cervix was dilated more than 2 cm, shortened to less than 0.5 cm in 23%, and the fetal membranes were intact in all subjects. The same evaluation in 76 nonrandom contemporary controls matched for risk factors, maternal age, and parity has shown that more than 50% had a cervix dilated more than 2 cm, 38% had a cervix shorter than 0.5 cm, and 24% had rupture of the fetal membranes. Ultimately, 88% of the monitored patients and 59% of controls delivered at term. Comparisons between these groups indicate that intermittent home tocodynamometry may indeed be useful in making the early diagnosis of preterm labor.
We investigated the effects of using intrapartum electronic fetal monitoring in all pregnancies, as compared with using it only in cases in which the fetus is judged to be at high risk. Predominant risk factors included oxytocin stimulation of labor, dysfunctional labor, abnormal fetal heart rate, or meconium-stained amniotic fluid. This prospective alternate-month clinical trial took place over a 36-month period during which 34,995 women gave birth. In alternate months, either 7 (for "selective monitoring") or 19 (for "universal monitoring") fetal monitors were made available in the labor and delivery unit. During the "selective" months, 6420 of 17,409 women (37 percent) were electronically monitored, as compared with 13,956 of 17,586 women (79 percent) during the "universal months." Universal monitoring was associated with a small but significant increase in the incidence of delivery by cesarean section because of fetal distress, but perinatal outcomes as assessed by intrapartum stillbirths, low Apgar scores, a need for assisted ventilation of the newborn, admission to the intensive care nursery, or neonatal seizures were not significantly different. We conclude that not all pregnancies, and particularly not those considered at low risk of perinatal complications, need continuous electronic fetal monitoring during labor.
Cervical examination between 26 and 30 weeks' gestation is described as a method for identifying women at risk for delivery before 34 weeks. Blinded cervical examinations were performed in 185 consecutive women, and 15 (8%) were found to have cervixes dilated 2 or 3 cm. The incidence of delivery before 34 weeks' gestation was 27% in such women compared with 2% in those whose cervixes were undilated or 1 cm. Other factors linked to cervical dilatation included parity and prior preterm delivery. However, parous women with cervical dilatation remained at increased risk for delivery before 34 weeks' gestation. We conclude that early third-trimester cervical examination may be an important adjunct in identifying women at risk for preterm delivery.
A group of 8303 women was studied to determine the timing of cervical ripening. It was confirmed that these signs of cervical change can be observed several weeks before preterm births. The precocious signs of external ripening can be recognized during a vaginal examination and may be useful in predicting preterm labor.
The likelihood of repetition of preterm birth after spontaneous onset of labour has been studied in 6572 reproductive careers after excluding stillbirths, multiple births, all careers in which any labour had been induced, and all careers in which the gestation length in any pregnancy was not certain. The analysis was controlled not only for pregnancy number, but for the nature of the reproductive outcomes. In most reproductive sequences there was a weak correlation between the gestation in one pregnancy and subsequent ones. The risk of preterm birth was tripled after one previous preterm birth with or without a preceding abortion, and increased six-fold after two previous preterm births. However, the attributable risk was low, and most multiparae with preterm births did not have a previous history.
The results of combined ritodrine and indomethacine treatment (RI) in premature labor contractions were compared with ritodrine alone (R). One hundred and twenty patients with threatened premature labor in weeks 26-34 were studied. Sixty RI women received 100 mg ritodrine in infusion followed by 60 mg daily orally until 35 weeks and indomethacine 200 mg on the first day of treatment only. The R group included 60 women with identical tocolysis indices, age of pregnancy and anamnestic parameters who received ritodrine only. The mean prolongation index (PI) was 18.2 in the RI group, against 11.5 in the R patients (P less than 0.05). The mean prolongation of pregnancy was 5.6 weeks in the first and 3.6 in the control group (P less than 0.05). Birthweight and Apgar scores were similar in the two groups. In order to examine the possible early closure of the ductus arteriosus due to the indomethacin therapy, echocardiograms were done on all newborn in the RI group: the pre-ejection period and right ventricular ejection time ratio was 0.19-0.26 after delivery and 0.17-0.22 1 month later, which excludes pulmonary diastolic hypertension due to premature closure of the duct. The combined RI treatment is more effective that R alone and does not give rise to any complications in the mother or the fetus.
All forms of birth control require some motivation, and motivation calls for understanding. If a woman learns to interpret her own cycles, her understanding of her body will be enhanced, and this could have benefits in all aspects of her fertility control. Professional nurses and health visitors are frequently expected to explain the intrigues of the menstrual cycle whether it be in family planning clinics, on gynecology wards, or in a client's home. When information about the monthly cycle is linked with the signs women observe in their own bodies, knowledge will result. With accurate knowledge about the span of the fertile phase, it should be within most women's grasp to control their own fertility, whether they use this knowledge alone or together with some mechanical contraceptive method. The endocrine hormones which control each menstrual cycle come from the pituitary gland and the ovaries, and they work in a feedback system, triggering each other. The start of the cycle is day 1 of the period when the pituitary gland starts the production of follicle stimulating hormone (FSH). This is taken in the bloodstream to the ovary where, as its name implies, it stimulates the ripening of follicles, each of which contains an egg cell. Operating in a feedback system, estrogen is carried back to the pituitary gland where it then causes a lessening in the production of FSH and stimulates the release of the luteinizing hormone (LH). LH proceeds back to the ovary and together with estrogen suppresses the growth of all the follicles except one, which then matures to release an egg at ovulation. If the egg is not fertilized, the pituitary gland detects the high level of progesterone and ceases production of LH, which causes the corpus luteum to die away. The 1st phase of the cycle leading up to ovulation is known as the follicular phase, and its length can vary considerably from month to month. The 2nd phase, leading up to menstruation, is the luteal phase, and its length does not vary more than 12-16 days, normally 14. There are 3 main observations that women can make each month: daily temperature; the cervical mucus; and a "calendar" assessment, and after a few months the likely course of the cycle is evident. Each of these 3 ways of interpreting cycles are reviewed in detail. If the motivation and understanding is there, most women can become adept at reading the signs each month. While still learning, it is important to seek advice from those who understand the methods and can ensure accurate interpretation. Encouraging women to discover how their bodies work is not aimed at discouraging the use of mechanical or chemical contraceptive methods. It is simply a way to enhance a woman's understanding of her body which could bring her positive physical and emotional benefits. Practically, if more women could read their body cycles, there would most likely be an increase in motivation to use contraception and an associated reduction in unwanted pregnancies.
The management of patients with premature rupture of membranes (PROM) poses one of the most serious dilemmas in obstetrics since PROM significantly increases the likelihood of prematurity and serious perinatal infection. Early infection is not reliably predicted nor detected by standard laboratory parameters. Serum C-reactive protein (CRP) levels were assayed along with white blood cell count, differential, and temperature course in patients with PROM and controls. Elevated CRP very accurately divided patients with evidence of infectious morbidity from those without such evidence (p < 0.001). In 109 patients there were 11 false negatives and no false positives. In 14 of 20 patients followed with serial comparisons who developed morbidity, CRP became elevated at least 12 hours prior to any other parameter measured. Changes in the other six patients were concurrent. The results suggest that CRP may be a reliable, early predictor of infectious morbidity and thus may be of benefit in the selective management of patients with PROM.
Now that principles of NFP have been established specific programs are necessary to disperse information and to teach techniques. The hospital-based NFP program offers the community a needed service and benefits the hospital.
Bujold E et al., 2026·American Journal of Obstetrics and Gynecology·
Open Access
Normal uterine function depends on cyclical regeneration and the capacity to sustain pregnancy. A cesarean incision represents an injury to this remarkable organ. Although the uterus possesses exceptional healing potential, cesarean delivery increases the risk of secondary infertility, pelvic pain, uterine rupture, and abnormal placentation in subsequent pregnancies. The two most important determinants of successful hysterotomy healing after cesarean delivery are the location of the incision and the surgical technique used for closure. The anatomic site of entry-whether the corpus, lower uterine segment, or cervix-defines the tissue composition, vascularity, and contractility at the wound margins, which in turn influence how the scar remodels and withstands subsequent pregnancies. Surgical technique is also important. A robust body of experimental and clinical evidence demonstrates that restoring anatomic integrity by reapproximating uterine layers while excluding the endometrium produces stronger scars and reduces late complications. The rationale for excluding the endometrium is to prevent displacement of endometrial tissue into the myometrium and to avoid mucosal tearing against a foreign body (i.e. suture material), both of which predispose to defective healing. When the endometrium is incorporated, healing is often impaired, leading to niches or isthmoceles, adenomyosis, and endometriosis at the scar site. Over time, these defects have been recognized as contributors to abnormal bleeding, pelvic pain, infertility, uterine rupture, and placenta accreta spectrum disorders. Despite this evidence, single-layer closures that incorporate endometrium became widely adopted because of their speed and simplicity, while their long-term sequels were initially underappreciated. This has prompted renewed scrutiny of closure techniques, including comparisons of single-layer vs double-layer closure, locking vs nonlocking sutures, type of sutures, and the direction of suture. Collectively, the data show that optimal closure respects uterine anatomy, restores the natural alignment of tissues, and achieves hemostasis without compromising perfusion or strangulating tissues. Building on these principles, we herein describe a refined 3-layer closure. The first layer approximates decidua and junctional myometrium while excluding surface endometrium to prevent tissue entrapment and bacterial contamination. The second layer restores anatomic wall integrity by reapproximating the bulk of the myometrium, thereby reinforcing strength and distributing tension across the scar. The third layer reapproximates superficial myometrium and serosa, smoothing the uterine surface and reducing adhesions. This technique is not simply a return to traditional double-layer methods or an extension of single-layer practice, but rather a refinement that integrates lessons from visceral surgery and contemporary obstetric data. Its rationale is to restore anatomy, secure hemostasis without ischemia, and preserve long-term uterine function. While short-term safety appears comparable across closure methods, evidence increasingly indicates that long-term reproductive outcomes depend on how closure respects tissue biology. We argue that appropriate repair is more important than a fast repair: meticulous restoration of uterine anatomy should take precedence over operative speed. The enduring success of a hysterotomy repair depends on the surgical technique employed, as it directly affects women's future reproductive health.
Pregnancy Complications · Premature Rupture of Membranes
Hsu JZ et al., 2025·Eur J Obstet Gynecol Reprod Biol·
Endometriosis is a chronic gynaecological condition affecting reproductive-aged women. It has been associated with infertility and potential risks for adverse pregnancy outcomes, although population-level evidence remains limited. This retrospective cohort study, including 147,950 pregnant women aged 20-45 years, used nationwide population-based data to compare the outcomes between women with (n = 11,400) and without (n = 136,550) endometriosis between 2000 and 2021. Baseline characteristics, comorbidities and pregnancy outcomes were compared between the groups. Multivariable regression analyses were performed to calculate adjusted relative risks (aRR) and 95 % confidence intervals (CI) for various pregnancy outcomes, and subgroup analyses were conducted by maternal age and infertility status. Among 147,950 pregnancies, women with endometriosis [mean ± standard deviation (SD) age 32.38 ± 4.51 years] had higher socio-economic status, more comorbidities, and more surgical history compared with women without endometriosis (mean ± SD age 30.06 ± 4.96 years). Women with endometriosis had increased risk of miscarriage (aRR 1.13, 95 % CI 1.03-1.24), preterm birth (aRR 1.31, 95 % CI 1.26-1.37), premature rupture of membranes (aRR 1.11, 95 % CI 1.06-1.16), placenta previa (aRR 1.63, 95 % CI 1.45-1.84), urinary tract infection (aRR 1.44, 95 % CI 1.31-1.59), and caesarean section (aRR 1.13, 95 % CI 1.11-1.16). Subgroup analysis revealed that risk of miscarriage was only higher in women aged 35-45 years and women without infertility. Risks of preterm birth, placenta previa and caesarean section were elevated across all subgroups, suggesting that endometriosis contributes independently to adverse pregnancy outcomes. Endometriosis is an independent risk factor for several pregnancy complications, supporting the need for tailored prenatal care and closer monitoring of affected women to improve maternal outcomes.
Plain Language This study quantifies losses and gains of obstetric care services at US rural and urban short-term acute care hospitals between 2010 and 2022.
Solmonovich R et al., 2025·Fertility and sterility
To determine whether an association exists between in vitro fertilization (IVF) and severe maternal morbidity among low-risk pregnant patients. Retrospective cohort study. Low-risk pregnant patients who delivered between January 2019 and December 2022. Low-risk was defined as having an obstetric comorbidity index score of 0. In vitro fertilization. MAIN OUTCOME MEASURE(S): The primary outcome (dependent variable) was any severe maternal morbidity. The secondary outcome was the need for a cesarean delivery. A modified Poisson regression with robust error variance was used to model the probability of severe maternal morbidity as a function of IVF. Risk ratios and their associated 95% confidence intervals (CIs) were computed. An α value of 0.05 was considered statistically significant. RESULT(S): A total of 39,668 pregnancies were included for analysis, and 454 (1.1%) were conceived by IVF. The overall severe maternal morbidity rate was 2.4% (n = 949), with the most common indicator being blood transfusion. The overall cesarean delivery rate was 18.8% (n = 7,459). On modified Poisson regression, IVF-conceived pregnancies were associated with 2.56 times the risk of severe maternal morbidity (95% CI, 1.73-3.79) and 1.54 times the risk of having a cesarean delivery (95% CI, 1.37-1.74) compared with non-IVF pregnancies. CONCLUSION(S): In vitro fertilization is associated with higher rates of severe maternal morbidity, primarily the need for a blood transfusion, and cesarean delivery in low-risk pregnancies without major comorbidities. Recognizing this association allows healthcare providers to implement proactive measures for better monitoring and tailored postpartum care.
Zakherah M et al., 2024·Middle East Fertil Soc J·
Open Access
The increasing prevalence of cesarean section (CS) deliveries globally has sparked apprehension regarding potential long-term complications, notably the emergence of uterine niches. CS results in a scar that in certain patients, inadequate healing of that scar results in the development of a uterine niche. While most small niches show no symptoms, large cesarean scar niches in nonpregnant women can give rise to cesarean scar disorder syndrome. This syndrome is characterized by abnormal uterine bleeding, dysmenorrhea, and secondary infertility. In pregnant women, the presence of substantial niches may be linked to potentially life-threatening complications, including cesarean scar dehiscence, uterine rupture, placenta accreta spectrum disorders, placenta previa, and cesarean scar ectopic pregnancy.
Main body
Given the potential dangers associated with uterine niche occurrence, numerous studies in recent years have delved into the concept of cesarean scar niche, exploring its risk factors, diagnostic approaches, and treatment options. Various diagnostic modalities, such as twoor three-dimensional transvaginal ultrasonography, twoand three-dimensional sono-hysterography, hysterosalpingography, hysteroscopy, or magnetic resonance imaging, can be employed to detect uterine niches. However, none of these diagnostic methods is universally accepted as the “gold standard,” and there remains a lack of unequivocal guidelines on certain aspects related to the diagnosis of cesarean scar niche. These niches, characterized by hypoechoic regions within the myometrium at the site of a previous CS scar, pose diagnostic complexities and provoke inquiries into their prevalence, factors influencing their development, clinical presentations, and appropriate therapeutic approaches.
As CS rates rise, this review aims to understand and address uterine niches and mitigate their impact on maternal health and reproductive outcomes.
Preston M et al., 2024·European journal of obstetrics, gynecology, and reproductive biology·
Open Access
Preterm Birth (delivery before 37 weeks of gestation) is the leading cause of childhood mortality and is also associated with significant morbidity both in the neonatal period and beyond. The aetiology of spontaneous preterm birth is unclear and likely multifactorial incorporating factors such as infection/inflammation and cervical injury. Placental insufficiency is emerging as an additional contributor to spontaneous preterm delivery; however, the mechanisms by which this occurs are not fully understood. Serum biomarkers and imaging techniques have been investigated as potential predictors of placental insufficiency, however none have yet been found to have a sufficient predictive value. This review examines the evidence for the role of the placenta in preterm birth, preterm prelabour rupture of the membranes and abruption as well as highlighting areas where further research is required.
Treatment with vaginal progesterone reduces the risk of miscarriage and preterm birth in selected high-risk women. The hypothesis that vaginal progesterone can reduce the risk of hypertensive disorders of pregnancy (HDP) is unexplored. To summarise the evidence on the effectiveness of vaginal progesterone to reduce the risk of HDP.
Search Strategy: We searched Embase (OVID), MEDLINE (OVID), PubMed, CENTRAL and clinicaltrials.gov from inception until 20 June 2023.
Selection Criteria: We included placebo-controlled randomised trials (RCTs) of vaginal progesterone for the prevention or treatment of any pregnancy complications.
Data Collection and Analysis: We extracted absolute event numbers for HDP and pre-eclampsia in women receiving vaginal progesterone or placebo, and meta-analysed the data with a random effects model. We appraised the certainty of the evidence using GRADE methodology. MAIN The quantitative synthesis included 11 RCTs, of which three initiated vaginal progesterone in the first trimester, and eight in the second or third trimesters. Vaginal progesterone started in the first trimester of pregnancy lowered the risk of any HDP (risk ratio [RR] 0.71, 95% confidence interval [CI] 0.53-0.93, 2 RCTs, n = 4431 women, I(2) = 0%; moderate-certainty evidence) and pre-eclampsia (RR 0.61, 95% CI 0.41-0.92, 3 RCTs, n = 5267 women, I(2) = 0%; moderate-certainty evidence) when compared with placebo. Vaginal progesterone started in the second or third trimesters was not associated with a reduction in HDP (RR 1.19, 95% CI 0.67-2.12, 3 RCTs, n = 1602 women, I(2) = 9%; low-certainty evidence) or pre-eclampsia (RR 0.97, 95% CI 0.71-1.31, 5 RCTs, n = 4274 women, I(2) = 0%; low-certainty evidence). Our systematic review found first-trimester initiated vaginal micronised progesterone may reduce the risk of HDP and pre-eclampsia.
Qin XD et al., 2023·Environmental health perspectives
Estrogens play a critical role in parturition, and poly- and perfluoroalkyl substances (PFAS), which have estrogenic effects, have been associated with preterm birth. However, the impact of estrogens on the association between PFAS and preterm birth is unknown. The objective of this study is to investigate if estrogens modified the association between PFAS and preterm birth, using a nested case-control study design. A total of 371 preterm births and 508 controls were selected from a birth cohort study in China between 2016 and 2018. Perfluorobutanoic acid (PFBA), perfluorohexanesulfonic acid (PFHxS) and its branched isomer, perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS) and its branched isomer, and perfluorononanoic acid (PFNA) were quantified in maternal serum (mean gestational age of 32 wk). Estradiol and estriol were quantified in cord serum. Preterm birth was defined as live delivery at <37 gestational weeks. Causal mediation analysis was used to estimate the mediation and interaction effects of estrogen on the association between PFAS and preterm birth. Latent profile analysis was used to identify important estrogen profiles. Multiple linear regression was used to estimate associations between PFAS and preterm birth and interactions between PFAS and estrogens on preterm birth. Overall, higher odds ratios (ORs) of preterm birth were associated with each 1 ln-unit PFAS increase: PFBA [1.20, 95% confidence interval (CI): 1.14, 1.26], PFNA (1.30, 95% CI: 1.21, 1.39), PFOA (1.98, 95% CI: 1.54, 2.55), and PFOS (1.91, 95% CI: 1.76, 2.07) and its branched isomer (1.91, 95% CI: 1.90, 1.92). We detected statistically significant interactions between cord estradiol and PFAS on preterm birth, while no mediation effects of cord estrogen were observed. The ORs of PFOS (4.29, 95% CI: 1.31, 8.25), its branched isomer (6.71, 95% CI: 1.06, 11.91), and preterm birth were greater for participants with high cord estrogen levels than for participants with low cord estrogen levels. Our findings suggest that estrogen modified the association between maternal PFAS exposure and preterm birth. Further studies on maternal PFAS exposure and preterm birth, taking interaction effects of cord estrogens into account, are warranted. https://doi.org/10.1289/EHP11377.
Spontaneous preterm birth significantly increases the risk for a recurrent preterm birth. Only a few identifiable clinical risk factors can be referenced in counseling for recurrent preterm birth. Furthermore, treatment using progesterone supplementation has not consistently prevented preterm birth among high-risk patients, but it may be effective in a subset of those patients. Placental pathology from a previous pregnancy may be used to predict which patients will experience a recurrent preterm birth or to identify a subset of patients more likely to respond to treatment with antenatal progesterone. This study aimed to determine if histologic patterns are associated with recurrent preterm birth among patients with an index spontaneous preterm birth. A secondary objective was to determine if placental histologic types and/or progesterone receptor density in the decidua are associated with the response to progesterone supplementation with intramuscular 17-hydroxyprogesterone caproate. This was a retrospective cohort study at a single institution of women with singleton pregnancies with an index spontaneous preterm birth and a subsequent birth within the same hospital system between 2009 and 2019. Patients were included if placental pathology was available for the index spontaneous preterm birth. A logistic regression was used to determine if there were independent associations between 4 histologic types (acute inflammation, maternal vascular malperfusion, fetal vascular malperfusion, chronic inflammation) and recurrent preterm birth. For the secondary endpoint, 17-hydroxyprogesterone caproate response was defined as prolonging gestation by >3 weeks beyond the gestational age at delivery in the index pregnancy. Patients who delivered <3 weeks beyond the gestational age in the index pregnancy but at ≥39 weeks' gestation were excluded. A logistic regression was used to assess the independent association between placental histology and 17-hydroxyprogesterone caproate response. Sensitivity analyses were completed using only patients with an index birth <36 weeks' gestation, and then excluding those with medically indicated preterm birth in a subsequent pregnancy. A nested case-control immunohistochemical study was done among 20 patients with a subsequent term birth and 20 patients with a subsequent spontaneous preterm birth. The percentage of cells in the maternal decidua positive for progesterone receptors was correlated with the subsequent pregnancy outcome. A total of 352 patients were included. Acute inflammation was the most common histologic type seen among patients with spontaneous preterm birth (44.1%), followed by chronic inflammation (40.9%) and maternal vascular malperfusion (31.3%). No histologic type was independently associated with recurrent preterm birth. A total of 155 patients received 17-hydroxyprogesterone caproate in a second pregnancy. Low-grade acute inflammation was significantly associated with a decreased likelihood of 17-hydroxyprogesterone caproate response. Low-grade maternal vascular malperfusion among those with an index pregnancy delivered at <36 weeks' gestation was significantly associated with a more than 4 times increased likelihood of 17-hydroxyprogesterone caproate response when excluding those with a subsequent iatrogenic preterm birth. Progesterone receptor staining was not associated with recurrent preterm birth. Although acute inflammation was prevalent among spontaneous preterm births, more than half of the spontaneous preterm births were not associated with acute inflammation. Low-grade acute inflammation was associated with a significantly decreased response to 17-hydroxyprogesterone caproate supplementation. Low-grade maternal vascular malperfusion was associated with a 4-fold increased likelihood of 17-hydroxyprogesterone caproate response among those with index deliveries <36 weeks' gestation. Further work is needed to determine if placental pathologic examination can be used to target treatment in subsequent pregnancies to prevent recurrent preterm birth.
H Petersen S et al., 2023·Hypertension (Dallas, Tex. : 1979)
Frozen embryo transfer (frozen-ET) is increasingly common because of improved cryopreservation methods and elective freezing of all embryos. Frozen-ET is associated with higher risk of hypertensive disorders in pregnancy than both natural conception and fresh embryo transfer (fresh-ET), but whether this is attributable to parental factors or treatment is unknown. Using the Medical Birth Registries of Denmark (1994-2014), Norway, and Sweden (1988-2015), linked to data from national quality registries and databases on assisted reproduction, we designed a population-based cohort study with within-sibship comparison. We included 4 426 691 naturally conceived, 78 300 fresh-ET, and 18 037 frozen-ET singleton pregnancies, of which 33 209 sibships were conceived using different conception methods. Adjusted odds ratios (aOR) of hypertensive disorders in pregnancy for fresh-ET and frozen-ET versus natural conception with 95% CI were estimated using multilevel logistic regression, where random effects provided conventional population-level estimates and fixed effects gave within-sibship estimates. Main models included adjustment for birth year, maternal age, parity, and country. Risk of hypertensive disorders in pregnancy was higher after frozen-ET compared to natural conception, both at population-level (7.4% versus 4.3%, aOR, 1.74 [95% CI, 1.61-1.89]) and within sibships (aOR, 2.02 [95% CI, 1.72-2.39]). For fresh-ET, risk was similar to natural conception, both at population-level (aOR, 1.02 [95% CI, 0.98-1.07]) and within sibships (aOR, 0.99 [95% CI, 0.89-1.09]). Frozen-ET was associated with substantially higher risk of hypertensive disorders in pregnancy, even after accounting for shared parental factors within sibships.
The Mediterranean diet pattern is inversely associated with the leading causes of morbidity and mortality, including metabolic diseases and cardiovascular disease, but there are limited data on its association with adverse pregnancy outcomes (APOs) among US women. To evaluate whether concordance to a Mediterranean diet pattern around the time of conception is associated with lower risk of developing any APO and individual APOs. DESIGN, SETTING, This prospective, multicenter, cohort study, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, enrolled 10 038 women between October 1, 2010, and September 30, 2013, with a final analytic sample of 7798 racially, ethnically, and geographically diverse women with singleton pregnancies who had complete diet data. Data analyses were completed between June 3, 2021, and April 7, 2022. An Alternate Mediterranean Diet (aMed) score (range, 0-9; low, 0-3; moderate, 4-5; and high, 6-9) was computed from data on habitual diet in the 3 months around conception, assessed using a semiquantitative food frequency questionnaire. Adverse pregnancy outcomes were prospectively ascertained and defined as developing 1 or more of the following: preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, delivery of a small-for-gestational-age infant, or stillbirth. Of 7798 participants (mean [SD] age, 27.4 [5.5] years), 754 (9.7%) were aged 35 years or older, 816 (10.5%) were non-Hispanic Black, 1294 (16.6%) were Hispanic, and 1522 (19.5%) had obesity at baseline. The mean (SD) aMed score was 4.3 (2.1), and the prevalence of high, moderate, and low concordance to a Mediterranean diet pattern around the time of conception was 30.6% (n=2388), 31.2% (n=2430), and 38.2% (n=2980), respectively. In multivariable models, a high vs low aMed score was associated with 21% lower odds of any APO (adjusted odds ratio [aOR], 0.79 [95% CI, 0.68-0.92]), 28% lower odds of preeclampsia or eclampsia (aOR, 0.72 [95% CI, 0.55-0.93]), and 37% lower odds of gestational diabetes (aOR, 0.63 [95% CI, 0.44-0.90]). There were no differences by race, ethnicity, and prepregnancy body mass index, but associations were stronger among women aged 35 years or older (aOR, 0.54 [95% CI, 0.34-0.84]; P = .02 for interaction). When aMed score quintiles were evaluated, similar associations were observed, with higher scores being inversely associated with the incidence of any APO. This cohort study suggests that greater adherence to a Mediterranean diet pattern is associated with lower risk of APOs, with evidence of a dose-response association. Intervention studies are needed to assess whether dietary modification around the time of conception can reduce risk of APOs and their downstream associations with future development of cardiovascular disease risk factors and overt disease.
To estimate the cost of maternal morbidity for all 2019 pregnancies and births in the United States.
Using data from 2010 to 2020, we developed a cost analysis model that calculated the excess cases of outcomes attributed to nine maternal morbidity conditions with evidence of outcomes in the literature. We then modeled the associated medical and nonmedical costs of each outcome incurred by birthing people and their children in 2019, projected through five years postpartum.
We estimated that the total cost of nine maternal morbidity conditions for all pregnancies and births in 2019 was $32.3 billion from conception to five years postpartum, amounting to $8,624 in societal costs per birthing person.
We found only nine maternal morbidity conditions with sufficient supporting evidence of linkages to outcomes and costs. The lack of comprehensive data for other conditions suggests that maternal morbidity exacts a higher toll on society than we found.
Although this study likely provides lower bound cost estimates, it establishes the substantial adverse societal impact of maternal morbidity and suggests further opportunities to invest in maternal health.
To evaluate the effect of birth ball abdominal core training on fatigue, waist pain, and delivery outcomes in middle and late pregnancy. A prospective study of 209 primipara in total with 24–27 weeks of gestation were recruited and divided into the training group (109 cases) and the control group (100 cases). The control group received routine prenatal exercise. On the basis of routine prenatal exercise, pregnant women in the training group were given birth ball exercises based on abdominal core training. The difference in pregnancy fatigue, waist discomfort, and delivery outcomes between the two groups were compared. The waist pain and fatigue ratings of women were significantly lower and the vaginal delivery rate (74.3%) was significantly higher (62%) (P < 0.001) in the training group. There were no significant differences in the total stage of labor, postpartum hemorrhage, neonatal weight and 1‐min neonatal Apgar score between the two groups. The rate of episiotomy in the training group (14.7%) was significantly lower than that in the control group (25.0%) (P < 0.05). Birth ball exercises can relieve fatigue and waist pain in middle and late 2021 pregnancy, reduce the rate of episiotomy, and promote spontaneous vaginal delivery.
Welch BM et al., 2022·JAMA pediatrics·
Open Access
Phthalate exposure is widespread among pregnant women and may be a risk factor for preterm birth. To investigate the prospective association between urinary biomarkers of phthalates in pregnancy and preterm birth among individuals living in the US. DESIGN, SETTING, Individual-level data were pooled from 16 preconception and pregnancy studies conducted in the US. Pregnant individuals who delivered between 1983 and 2018 and provided 1 or more urine samples during pregnancy were included. Urinary phthalate metabolites were quantified as biomarkers of phthalate exposure. Concentrations of 11 phthalate metabolites were standardized for urine dilution and mean repeated measurements across pregnancy were calculated. Logistic regression models were used to examine the association between each phthalate metabolite with the odds of preterm birth, defined as less than 37 weeks of gestation at delivery (n = 539). Models pooled data using fixed effects and adjusted for maternal age, race and ethnicity, education, and prepregnancy body mass index. The association between the overall mixture of phthalate metabolites and preterm birth was also examined with logistic regression. G-computation, which requires certain assumptions to be considered causal, was used to estimate the association with hypothetical interventions to reduce the mixture concentrations on preterm birth. The final analytic sample included 6045 participants (mean [SD] age, 29.1 [6.1] years). Overall, 802 individuals (13.3%) were Black, 2323 (38.4%) were Hispanic/Latina, 2576 (42.6%) were White, and 328 (5.4%) had other race and ethnicity (including American Indian/Alaskan Native, Native Hawaiian, >1 racial identity, or reported as other). Most phthalate metabolites were detected in more than 96% of participants. Higher odds of preterm birth, ranging from 12% to 16%, were observed in association with an interquartile range increase in urinary concentrations of mono-n-butyl phthalate (odds ratio [OR], 1.12 [95% CI, 0.98-1.27]), mono-isobutyl phthalate (OR, 1.16 [95% CI, 1.00-1.34]), mono(2-ethyl-5-carboxypentyl) phthalate (OR, 1.16 [95% CI, 1.00-1.34]), and mono(3-carboxypropyl) phthalate (OR, 1.14 [95% CI, 1.01-1.29]). Among approximately 90 preterm births per 1000 live births in this study population, hypothetical interventions to reduce the mixture of phthalate metabolite levels by 10%, 30%, and 50% were estimated to prevent 1.8 (95% CI, 0.5-3.1), 5.9 (95% CI, 1.7-9.9), and 11.1 (95% CI, 3.6-18.3) preterm births, respectively. Results from this large US study population suggest that phthalate exposure during pregnancy may be a preventable risk factor for preterm delivery.
Fertility and Outcomes · Conception After Excision
Schliep KC et al., 2022·Paediatr Perinat Epidemiol·
Women with endometriosis may have an increased risk of adverse pregnancy outcomes. Research has focused on infertility clinic populations limiting generalisability. Few studies report differences by endometriosis severity. We investigated the relationships between endometriosis diagnosis, staging and typology and pregnancy outcomes among an operative and population-based sample of women. Menstruating women ages 18-44 years enrolled in the ENDO Study (2007-2009), including the operative cohort: 316 gravid women undergoing laparoscopy/laparotomy at surgical centres in Utah and California; and the population cohort: 76 gravid women from the surgical centres' geographic catchment areas. Pregnancy outcomes were ascertained by questionnaire and included all pregnancies prior to study enrolment. Endometriosis was diagnosed via surgical visualisation in the operative cohort and pelvic magnetic resonance imaging in the population cohort. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were estimated using generalised linear mixed models for pregnancy outcomes, adjusting for women's age at study enrolment and at pregnancy, surgical site, body mass index and lifestyle factors. Women in the operative cohort with visualised endometriosis (n = 109, 34%) had a lower prevalence of live births, aPR 0.94 (95% CI 0.85, 1.03) and a higher prevalence of miscarriages, aPR 1.48 (95% CI 1.23, 1.77) compared with women without endometriosis. The direction and magnitude of estimates were similar in the population cohort. Women with deep endometriosis were 2.98-fold more likely (95% CI 1.12, 7.95) to report a miscarriage compared with women without endometriosis after adjusting for women's age at study enrolment and at pregnancy, surgical site and body mass index. No differences were seen between endometriosis staging and pregnancy outcomes. While there was no difference in number of pregnancies among women with and without endometriosis in a population-based sample, pregnancy loss was more common among women with endometriosis, notably among those with deep endometriosis.
Sanders JN et al., 2022·Reprod Health·
Open Access
In vitro fertilization (IVF) births contribute to a considerable proportion of preterm birth (PTB) each year. However, there is no formal surveillance of adverse perinatal outcomes for less invasive fertility treatments. The study objective was to describe associations between fertility treatment (in vitro fertilization, intrauterine insemination, usually with ovulation drugs (IUI), or ovulation drugs alone) and preterm birth, compared to no treatment in subfertile women. The Fertility Experiences Study (FES) is a retrospective cohort study conducted at the University of Utah between April 2010 and September 2012. Women with a history of primary subfertility self-reported treatment data via survey and interviews. Participant data were linked to birth certificates and fetal death records to asses for perinatal outcomes, particularly preterm birth. A total 487 birth certificates and 3 fetal death records were linked as first births for study participants who completed questionnaires. Among linked births, 19% had a PTB. After adjustment for maternal age, paternal age, maternal education, annual income, religious affiliation, female or male fertility diagnosis, and duration of subfertility, the odds ratios and 95% confidence intervals (CI) for PTB were 2.17 (CI 0.99, 4.75) for births conceived using ovulation drugs, 3.17 (CI 1.4, 7.19) for neonates conceived using IUI and 4.24 (CI 2.05, 8.77) for neonates conceived by IVF, compared to women with subfertility who used no treatment during the month of conception. A reported diagnosis of female factor infertility increased the adjusted odds of having a PTB 2.99 (CI 1.5, 5.97). Duration of pregnancy attempt was not independently associated with PTB. In restricting analyses to singleton gestation, odds ratios were not significant for any type of treatment. IVF, IUI, and ovulation drugs were all associated with a higher incidence of preterm birth and low birth weight, predominantly related to multiple gestation births.
Lee YL et al., 2022·Scientific Reports·
Open Access
Preterm delivery of low-birth weight infants is considered a leading cause of morbidity and mortality among neonates. Various studies have reported a positive correlation between periodontal disease (PD) and premature birth (PB) and yet no population-based study has assessed the impact of PD severity and treatments on premature birth. This cohort study used Taiwan's national medical records (1999-2012, included 1,757,774 pregnant women) to investigate the association between PD severity and PB. Women with PD during the 2-year period prior for giving birth were more likely to have PB (11.38%) than those without PD (10.56%; p < 0.001). After variables adjustment, the advanced PD group had OR of 1.09 (95% CI 1.07-1.11) for PB, the mild PD group had OR of 1.05 (95% CI 1.04-1.06), while no-PD group had OR of 1. Increased PD severity was related to higher risk of PB. When stratified by age, the highest ORs for PB were those aged from 31 to 35 years in both mild PD group (OR = 1.09, 95% CI 1.07-1.11) and advanced PD group (OR = 1.13, 95% CI 1.09-1.17). Improving periodontal health before or during pregnancy may prevent or reduce the occurrence of adverse pregnancy outcomes and therefore maternal and perinatal morbidity and mortality.
Sunderam S et al., 2022·MMWR Surveillance Summaries
Since the first US infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to have multiple births because multiple embryos might be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth, and low birthweight. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2018 and compares birth outcomes that occurred in 2018 (resulting from ART procedures performed in 2017 and 2018) with outcomes for all infants born in the United States in 2018. 2018. In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from the 50 US states, the District of Columbia, and Puerto Rico. In 2018, a total of 203,119 ART procedures (range: 196 in Alaska to 26,028 in California) were performed in 456 US fertility clinics and reported to CDC. These procedures resulted in 73,831 live-birth deliveries (range: 76 in Puerto Rico and Wyoming to 9,666 in California) and 81,478 infants born (range: 84 in Wyoming to 10,620 in California). Nationally, among women aged 15-44 years, the rate of ART procedures performed was 3,135 per 1 million women.
Preterm birth is the leading cause of neonatal morbidity and mortality. The recurrence rate of spontaneous preterm birth is high, and additional preventive measures are required. Our objective was to assess the effectiveness of low-dose aspirin compared to placebo in the prevention of preterm birth in women with a previous spontaneous preterm birth. Findings: We performed a parallel multicentre, randomised, double-blinded, placebo-controlled trial (the APRIL study). The study was performed in 8 tertiary and 26 secondary care hospitals in the Netherlands. We included women with a singleton pregnancy and a history of spontaneous preterm birth of a singleton between 22 and 37 weeks. Participants were randomly assigned to aspirin 80 mg daily or placebo initiated between 8 and 16 weeks of gestation and continued until 36 weeks or delivery. Randomisation was computer generated, with allocation concealment by using sequentially numbered medication containers. Participants, their healthcare providers, and researchers were blinded for treatment allocation. The primary outcome was preterm birth <37 weeks of gestation. Secondary outcomes included a composite of poor neonatal outcome (bronchopulmonary dysplasia, periventricular leukomalacia > grade 1, intraventricular hemorrhage > grade 2, necrotising enterocolitis > stage 1, retinopathy of prematurity, culture proven sepsis, or perinatal death). Analyses were performed by intention to treat. From May 31, 2016 to June 13, 2019, 406 women were randomised to aspirin (n = 204) or placebo (n = 202). A total of 387 women (81.1% of white ethnic origin, mean age 32.5 ± SD 3.8) were included in the final analysis: 194 women were allocated to aspirin and 193 to placebo. Preterm birth <37 weeks occurred in 41 (21.2%) women in the aspirin group and 49 (25.4%) in the placebo group (relative risk (RR) 0.83, 95% confidence interval (CI) 0.58 to 1.20, p = 0.32). In women with ≥80% medication adherence, preterm birth occurred in 24 (19.2%) versus 30 (24.8%) women (RR 0.77, 95% CI 0.48 to 1.25, p = 0.29). The rate of the composite of poor neonatal outcome was 4.6% (n = 9) versus 2.6% (n = 5) (RR 1.79, 95% CI 0.61 to 5.25, p = 0.29). Among all randomised women, serious adverse events occurred in 11 out of 204 (5.4%) women allocated to aspirin and 11 out of 202 (5.4%) women allocated to placebo. None of these serious adverse events was considered to be associated with treatment allocation. The main study limitation is the underpowered sample size due to the lower than expected preterm birth rates. In this study, we observed that low-dose aspirin did not significantly reduce the preterm birth rate in women with a previous spontaneous preterm birth. However, a modest reduction of preterm birth with aspirin cannot be ruled out. Further research is required to determine a possible beneficial effect of low-dose aspirin for women with a previous spontaneous preterm birth. Dutch Trial Register (NL5553, NTR5675) https://www.trialregister.nl/trial/5553.
While some studies have found an association between marijuana use and adverse neonatal outcomes, results have not been consistent across all trials. To assess available data on neonatal outcomes in marijuana-exposed pregnancies. PubMed, Medline, ClinicalTrials.gov, Cochrane, Scopus, and Web of Science were searched from each database's inception until August 16, 2021. All interventional and observational studies that included pregnant women who were exposed to marijuana compared with pregnant women who were not exposed to marijuana and that reported neonatal outcomes were included. Reporting followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses guideline. Data were extracted by 2 authors for all outcomes, which were pooled using a random-effects model as mean difference or risk ratio (RR) and 95% CI. Data were analyzed from August through September 2021. All outcomes were formulated prior to data collection. Outcomes included incidence of birth weight less than 2500 g, small for gestational age (defined as less than the fifth percentile fetal weight for gestational age), rate of preterm delivery (defined as before 37 weeks' gestation), gestational age at time of delivery, birth weight, incidence of neonatal intensive care unit (NICU) admission, Apgar score at 1 minute, Apgar score at 5 minutes, incidence of an Apgar score less than 7 at 5 minutes, fetal head circumference, and fetal length. Among 16 studies including 59 138 patients, there were significant increases in 7 adverse neonatal outcomes among women who were exposed to marijuana during pregnancy vs those who were not exposed during pregnancy. These included increased risk of birth weight less than 2500 g (RR, 2.06 [95% CI, 1.25 to 3.42]; P = .005), small for gestational age (RR, 1.61 [95% CI, 1.44 to 1.79]; P < .001), preterm delivery (RR, 1.28 [95% CI, 1.16 to 1.42]; P < .001), and NICU admission (RR, 1.38 [95% CI, 1.18 to 1.62]; P < .001), along with decreased mean birth weight (mean difference, -112.30 [95% CI, -167.19 to -57.41] g; P < .001), Apgar score at 1 minute (mean difference, -0.26 [95% CI, -0.43 to -0.09]; P = .002), and infant head circumference (mean difference, -0.34 [95% CI, -0.63 to -0.06] cm; P = .02). This study found that women exposed to marijuana in pregnancy were at a significantly increased risk of some adverse neonatal outcomes. These findings suggest that increasing awareness about these risks may be associated with improved outcomes.
Guidelines by Clinical Area · Obstetric Guidelines
This is the second edition of this guideline; the first edition was published in 2011 under the same name. It supplements NICE guideline NG25 Preterm labour and birth. Cerclage remains one of the standard options for prophylactic intervention in the care of women at risk of preterm birth and second trimester fetal loss and is used by most obstetricians, despite difficulties in identifying the population of women who would most benefit. The procedure, a stitch inserted into the cervix, was first performed in 1902 in women with a history of second trimester loss or spontaneous preterm birth suggestive of cervical insufficiency, with the aim of preventing recurrent loss. Cervical insufficiency is an imprecise clinical diagnosis frequently applied to women with such a history, where it is assumed that the cervix is ‘weak’ and unable to remain closed during the pregnancy. Recent evidence suggests that, rather than being a dichotomous variable, cervical integrity is likely to be a continuum influenced by factors related not solely to the intrinsic structure of the cervix but also to processes driving premature effacement and dilatation. While cerclage may provide a degree of structural support to a ‘weak’ cervix, its role in maintaining the cervical length and the endocervical mucus plug as a mechanical barrier to ascending infection may be more important. There is lack of consensus on the optimal cerclage technique, timing of suture placement, the role of amniocentesis before emergency cerclage insertion and optimal care following insertion. Complications are not well documented and often difficult to separate from risks inherent to the underlying condition. The purpose of this guideline is to review the literature and provide evidence-based guidance on the use of cerclage in women at risk of preterm birth and second trimester loss. This guideline supplements NICE guideline [NG25] Preterm labour and birth.1 Within this document we use the terms woman and women’s health. However, it is important to acknowledge that it is not only people who identify as women for whom it is necessary to access women’s health and reproductive services in order to maintain their gynaecological health and reproductive wellbeing. Gynaecological and obstetric services and delivery of care must therefore be appropriate, inclusive and sensitive to the needs of those individuals whose gender identity does not align with the sex they were assigned at birth. This Royal College of Obstetricians and Gynaecologists (RCOG) guideline was developed in accordance with the standard methodology for producing RCOG Green-top Guidelines.2 The Cochrane Library (including the Cochrane Database of Systematic Reviews), DARE, EMBASE, TRIP, Medline and PubMed (electronic databases) were searched for relevant randomized control trials, systematic reviews and meta-analyses. The search was restricted to articles published between 2011 and April 2020. The databases were searched using the relevant MeSH terms, including all subheadings and this was combined with a keyword search. Search words included ‘cervical cerclage’, ‘cervical suture’, ‘cervical stitch’, ‘midtrimester miscarriage’, ‘McDonald cerclage’, ‘Shirodkar cerclage’, ‘infection and cerclage’, ‘tocolytics and cerclage’ and ‘inflammatory mediators and cerclage’; the search was limited to humans and the English language. The National Library for Health and National Guidelines Clearing House were also searched for relevant guidelines and reviews. The full search strategy is available to view online as supporting information (Appendices S1 and S2). Previous terminology (prophylactic, as a planned procedure, emergency, urgent, rescue) of cervical sutures/cerclage can be ambiguous. More appropriate nomenclature based on indication for cervical suture is recommended. The terms below are increasingly used in the scientific literature. History-indicated cerclage Insertion of a cerclage as a result of factors in a woman’s obstetric or gynaecological history, which increase the risk of spontaneous second trimester loss or preterm birth.3 A history-indicated suture is performed as a prophylactic measure in asymptomatic women and usually inserted as a planned procedure at 11–14 weeks of gestation. Preterm Birth Birth before to 37+0 weeks’ gestation. Ultrasound-indicated cerclage Insertion of a cerclage as a therapeutic measure in cases of cervical length shortening seen on transvaginal ultrasound.3 Ultrasound-indicated cerclage is performed on asymptomatic women who do not have exposed fetal membranes in the vagina. Sonographic assessment of the cervix is usually performed between 14 and 24 weeks of gestation by transvaginal scan and with an empty maternal bladder. Emergency cerclage (also known as physical exam-indicated or emergency cerclage) Insertion of cerclage as a salvage measure in the case of premature cervical dilatation with exposed fetal membranes in the vagina.3 This may be discovered by ultrasound examination of the cervix or as a result of a speculum/physical examination performed for symptoms such as vaginal discharge, bleeding or ‘sensation of pressure’. It can be considered up to 27+6 weeks gestation.1 Transvaginal cerclage (McDonald) A transvaginal purse-string suture placed at the cervical isthmus junction, without bladder mobilization.4 High transvaginal cerclage requiring bladder mobilization (including Shirodkar) A transvaginal purse-string suture placed following bladder mobilization, to allow insertion above the level of the cardinal ligaments.5 Transabdominal cerclage A suture performed via a laparotomy or laparoscopy, placing the suture at the cervicoisthmic junction.6 Occlusion cerclage Occlusion of the external os by placement of a continuous non-absorbable suture. The theory behind the potential benefit of occlusion cerclage is retention of the mucus plug.7 Routine surveillance of women at low risk is not currently recommended by the National Screening Committee. Ultrasound surveillance of cervical length is advocated in women at high and intermediate risk in Element 5 of the Saving Babies Lives Care Bundle,21 the timing of which is dependent on the women’s history. These women are recommended to be reviewed by a preterm prevention specialist by 12 weeks where possible, or with the dating scan whichever is sooner, and offered transvaginal cervix scanning as a secondary screening test every 2–4 weeks between 16 and 24 weeks. There is, however, uncertainty as to how to care for these women if a short cervix is identified in women who have had serial screening but do not have a history of a previous preterm birth; an ultrasound indicated cerclage may be considered. STOPPIT-2 is a randomised trial of the Arabin pessary to prevent preterm birth in twin pregnancies with a short cervix. Data collection is now complete and the results are currently being analysed.26 Carers should be aware of the potential psychological sequelae associated with fetal death and miscarriage, and women and their families supported by debriefing services and the offer of counselling. Families should also be signposted to the relevant patient support groups. There is no clear evidence that the gestation at which the cerclage is inserted affects the magnitude of prolongation of the pregnancy; however, consideration should be given to the fact that, in cases presenting before 20 weeks of gestation, insertion of a emergency cerclage is highly likely to result in a preterm birth before 28 weeks of gestation. Furthermore, emergency cerclage can rarely be justified beyond 24 weeks’ gestation due to the potential risk of iatrogenic membrane rupture and subsequent preterm birth. Prior to cerclage insertion, women should be given appropriate verbal and written information; patient information can be found on the RCOG website.50 The interval between presentation and suture insertion varies between studies. Any delay must balance the risk of inserting a suture in a cervix that is inevitably going to continue dilating against the increased risk of ascending infection. There are no studies evaluating the effect of sexual intercourse on the risk of second trimester loss or preterm birth in women with cervical cerclage. Although other tests are commercially available for the prediction of preterm birth, such as Partosure and Actim Partus no studies to date have evaluted their use following cervical cerclage insertion. Multiple studies have compared different agents (cerclage, progesterone and pessaries) for the prevention of preterm birth, however these often do not control for clinician preference and many of the studies are retrospective in nature. Conde-Agudelo et al.87 also compared the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth and short cervix undertaking a meta-analysis of RCTs comparing vaginal progesterone to placebo/no treatment or cerclage to no cerclage in women with a singleton gestation, previous spontaneous preterm birth and a sonographic cervical length less than 25 mm. Five trials comparing vaginal progesterone versus placebo and five comparing cerclage versus no cerclage were included. Both progesterone and cerclage were equally effective for preventing preterm birth and improving perinatal outcomes. However, cerclage and progesterone were not compared directly. A number of randomized controlled trials are planned comparing the efficacy of cerclage versus pessary versus progesterone.83, 88 There are no studies comparing elective removal of transvaginal cerclage with removal in labour. However, in the absence of preterm labour, elective removal at 36–37 weeks of gestation is advisable owing to the potential risk of cervical injury in labour and the minimal risk to a neonate born at this gestation. There are no studies regarding the use of anaesthesia in the removal of a cerclage inserted with bladder mobilization but, given that the technique involves burial of the suture, an anaesthetic is likely to be necessary for removal. Decisions regarding use of anaesthetic should be taken jointly with the woman. There are no published studies on long-term outcome comparing a policy of removing a transabdominal cerclage to it remaining in place. However, if further pregnancies are contemplated, it is reasonable to recommend leaving the cerclage in place. There have been anecdotal reports of suture ‘pulling through’ prior to labour, and a vaginal birth can occur safely if this is identified. The developers would like to acknowledge Miss Meekai To for their work as co-developer of the previous edition of this guideline. AHS has declared no conflicts of interest. LS has declared no conflicts of interest. Full disclosure of interests are available to view online as supporting information. All those involved in the development of the Green-top Guidelines, including the Guidelines Committee, Guidelines Committee co-chairs, guideline developers, peer reviewers and other reviewers, are unpaid volunteers and receive no direct funding for their work in producing the guideline. The exception to this are the RCOG staff involved who are salaried employees of the College and GC members who receive reimbursement for expenses for attending GC meetings. Please see more information on travel expense rules on the RCOG website. Appendix S1. Cervical cerclage literature search strategy. Appendix S2. Cervical cerclage search strategy top up. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. This guideline was produced on behalf of the Royal College of Obstetricians and Gynaecologists by: Professor Andrew H Shennan FRCOG, London; Dr Lisa Story MRCOG, London. and peer reviewed by: Miss A Gorry MRCOG, London; Dr G Kumar FRCOG, Wrexham; Mr D Fraser FRCOG, Norwich; Dr P Maouris FRCOG, Perth, Western Australia; Mr B Kumar FRCOG, Wrexham; Dr KC Dundas FRCOG, Edinburgh; Miss M To MRCOG, London; Professor JE Norman FRCOG, Bristol; RCOG Women’s Network; Imperial College Academic Health Science Centre. Committee lead reviewers were: Dr A Macleod FRCOG,1 Edinburgh, Dr B Magowan FRCOG, Melrose2 and Mr A McKelvey MRCOG, Norfolk.3 1until December 2020; 2until May 2021; 3from December 2021. The chair of the Guidelines Committee was: Dr MA Ledingham MRCOG, Glasgow; Dr B Magowan FRCOG, Melrose. All RCOG guidance developers are asked to declare any conflicts of interest. A statement summarising any conflicts of interest for this guideline is available from: https://www.rcog.org.uk/en/guidelines-research-services/guidelines/gtg75. The final version is the responsibility of the Guidelines Committee of the RCOG. The guideline will be considered for update 3 years after publication, with an intermediate assessment of the need to update 2 years after publication. The Royal College of Obstetricians and Gynaecologists produces guidelines as an educational aid to good clinical practice. They present recognised methods and techniques of clinical practice, based on published evidence, for consideration by obstetricians and gynaecologists and other relevant health professionals. The ultimate judgement regarding a particular clinical procedure or treatment plan must be made by the doctor or other attendant in the light of clinical data presented by the patient and the diagnostic and treatment options available. This means that RCOG Guidelines are unlike protocols or guidelines issued by employers, as they are not intended to be prescriptive directions defining a single course of management. Departure from the local prescriptive protocols or guidelines should be fully documented in the patient’s case notes at the time the relevant decision is taken.
α-Lipoic acid (ALA) is a natural molecule that is inconsistently synthesized by the human body and must be provided from exogenous sources, such as food and dietary supplements. Once absorbed, the oxidized form of ALA is transformed into its reduced form, dihydrolipoic acid (DHLA). ALA/DHLA exert direct and indirect antioxidant, anti-inflammatory and fine immunomodulatory effects. ALA/DHLA reduce the levels of pro-inflammatory cytokines (IL-1β, IL-6, IL-8 and IL-17), while increasing the secretion of anti-inflammatory cytokines (IL-10). They also inhibit cyclooxygenase 2, thereby decreasing the secretion of prostaglandin E2 and nitrogen oxide, and reducing the risk of miscarriage in the first trimester of pregnancy. In patients at risk of abortion, administration of ALA from the first trimester has shown efficacy by accelerating subchorionic hematoma resorption, with a significant decrease in the accompanying abdominal pain. ALA has been proven to be efficient in maintaining the length of the cervix and keeping it closed following one episode of premature labor. Preeclampsia is a dysfunction caused by abnormal placentation and an excessive maternal inflammatory response, leading to extreme hypoxia in the placental bed and exaggerated oxidative stress, with release of oxygen free radicals. Oxidative stress plays a key role in the development of preeclampsia and intrauterine growth restriction. The hypothesis of antioxidant supplementation may play an essential part in disease prevention and fetal neuroprotection.
Hypertensive disorders of pregnancy (HDP) is one of the most common pregnancy complications and causes of maternal morbidity and mortality. Assisted reproductive technology (ART) has been associated with adverse pregnancy outcomes, including HDP. However, the impact of multiple pregnancies, oocyte donation, as well as fresh and frozen embryo transfer needs to be further studied. We conducted a systematic review and meta-analyses to evaluate the association between ART and HDP or preeclampsia relative to spontaneous conception (SC).
We identified studies from EMBASE, MEDLINE, and Cochrane Library (up to April 8, 2020) and manually using structured search strategies. Cohort studies that included pregnancies after in vitro fertilization (IVF) with or without intracytoplasmic sperm fertilization (ICSI) relative to SC with HDP or preeclampsia as the outcome of interest were included. The control group was women who conceived spontaneously without ART or fertility medications. The pooled results were reported in odds ratios (OR) with 95% confidence intervals based on random effects models. Numbers needed to harm (NNH) were calculated based on absolute risk differences between exposure and control groups.
Eighty-five studies were included after a screening of 1879 abstracts and 283 full text articles. Compared to SC, IVF/ICSI singleton pregnancies (OR 1.70; 95% CI 1.60-1.80; I2 = 80%) and multiple pregnancies (OR 1.34; 95% CI 1.20-1.50; I2 = 76%) were both associated with higher odds of HDP. Singleton pregnancies with oocyte donation had the highest odds of HDP out of all groups analyzed (OR 4.42; 95% CI 3.00-6.51; I2 = 83%). Frozen embryo transfer resulted in higher odds of HDP (OR 1.74; 95% CI 1.58-1.92; I2 = 55%) than fresh embryo transfer (OR 1.43; 95% CI 1.33-1.53; I2 = 72%). The associations between IVF/ICSI pregnancies and SC were similar for preeclampsia. Most interventions had an NNH of 40 to 100, while singleton and multiple oocyte donation pregnancies had particularly low NNH for HDP (16 and 10, respectively).
Our meta-analysis confirmed that IVF/ICSI pregnancies are at higher odds of HDP and preeclampsia than SC, irrespective of the plurality. The odds were especially high in frozen embryo transfer and oocyte donation pregnancies.
Buskmiller C et al., 2021·Ultrasound Obstet Gynecol·
Preoperative short cervical length (CL) remains a major risk factor for preterm birth after laser surgery for twin-twin transfusion syndrome (TTTS), but the optimal intervention to prolong pregnancy remains elusive. The objective of this study was to compare secondary methods for the prevention of preterm birth in twin pregnancies with TTTS undergoing fetoscopic laser photocoagulation (FLP), in the setting of a short cervix at the time of FLP, in five North American Fetal Treatment Network (NAFTNet) centers. This was a secondary analysis of data collected prospectively at five NAFTNet centers, conducted from January 2013 to March 2020. Inclusion criteria were a monochorionic diamniotic twin pregnancy complicated by TTTS, undergoing FLP, with preoperative CL < 30 mm. Management options for a short cervix included expectant management, vaginal progesterone, pessary (Arabin, incontinence or Bioteque cup), cervical cerclage or a combination of two or more treatments. Patients were not included if the intervention was initiated solely on the basis of having a twin gestation rather than at the diagnosis of a short cervix. Demographics, ultrasound characteristics, operative data and outcomes were compared. The primary outcome was FLP-to-delivery interval. Propensity-score matching was performed, with each treatment group matched (1:1) to the expectant-management group for CL, in order to estimate the effect of each treatment on the FLP-to-delivery interval. A total of 255 women with a twin pregnancy complicated by TTTS and a short cervix undergoing FLP were included in the study. Of these, 151 (59%) were managed expectantly, 32 (13%) had vaginal progesterone only, 21 (8%) had pessary only, 21 (8%) had cervical cerclage only and 30 (12%) had a combination of treatments. A greater proportion of patients in the combined-treatment group had had a prior preterm birth compared with those in the expectant-management group (33% vs 9%; P = 0.01). Mean preoperative CL was shorter in the pessary, cervical-cerclage and combined-treatment groups (14-16 mm) than in the expectant-management and vaginal-progesterone groups (22 mm for both) (P < 0.001). There was no significant difference in FLP-to-delivery interval between the groups, nor in gestational age at delivery or the rate of live birth or neonatal survival. Vaginal progesterone was associated with a decrease in the risk of delivery before 28 weeks' gestation compared with cervical cerclage and combined treatment (P = 0.03). Using propensity-score matching for CL, cervical cerclage was associated with a reduction in FLP-to-delivery interval of 13 days, as compared with expectant management. A large proportion of pregnancies with TTTS and a short maternal cervix undergoing FLP were managed expectantly for a short cervix, establishing a high (62%) risk of delivery before 32 weeks in this condition. No treatment that significantly improved outcome was identified; however, there were significant differences in potential confounders and there were also likely to be unmeasured confounders. Cervical cerclage should not be offered as a secondary prevention for preterm birth in twin pregnancies with TTTS and a short cervix undergoing FLP. A large randomized controlled trial is urgently needed to determine the effects of treatments for the prevention of preterm birth in these pregnancies.
Most evidence for interpregnancy interval (IPI) and adverse birth outcomes come from studies that are prone to incomplete control for confounders that vary between women. Comparing pregnancies to the same women can address this issue. We conducted an international longitudinal cohort study of 5,521,211 births to 3,849,193 women from Australia (1980-2016), Finland (1987-2017), Norway (1980-2016) and the United States (California) (1991-2012). IPI was calculated based on the time difference between two dates-the date of birth of the first pregnancy and the date of conception of the next (index) pregnancy. We estimated associations between IPI and preterm birth (PTB), spontaneous PTB, and small-for-gestational age births (SGA) using logistic regression (between-women analyses). We also used conditional logistic regression comparing IPIs and birth outcomes in the same women (within-women analyses). Random effects meta-analysis was used to calculate pooled adjusted odds ratios (aOR). Compared to an IPI of 18-23 months, there was insufficient evidence for an association between IPI <6 months and overall PTB (aOR 1.08, 95% CI 0.99-1.18) and SGA (aOR 0.99, 95% CI 0.81-1.19), but increased odds of spontaneous PTB (aOR 1.38, 95% CI 1.21-1.57) in the within-women analysis. We observed elevated odds of all birth outcomes associated with IPI ≥60 months. In comparison, between-women analyses showed elevated odds of adverse birth outcomes for <12 month and >24 month IPIs. We found consistently elevated odds of adverse birth outcomes following long IPIs. IPI shorter than 6 months were associated with elevated risk of spontaneous PTB, but there was insufficient evidence for increased risk of other adverse birth outcomes. Current recommendations of waiting at least 24 months to conceive after a previous pregnancy, may be unnecessarily long in high-income countries.
To assess whether paternal health is associated with maternal peripartum and neonatal outcomes. Retrospective cohort study. University research departments. PATIENT(S): Analytic sample of children born to paired fathers and mothers covering live births within the United States between 2009-2016. INTERVENTION(S): Paternal health status (e.g., metabolic syndrome diagnoses, individual chronic disease diagnoses). MAIN OUTCOME MEASURE(S): Primary outcome of preterm birth (i.e., live birth before 37 weeks), and secondary outcomes of low birth weight, neonatal intensive care unit (NICU) stay, gestational diabetes, preeclampsia, eclampsia, and length of maternal stay. RESULT(S): The IBM Marketscan Research database covers reimbursed health care claims data on inpatient and outpatient encounters who are privately insured through employment-sponsored health insurance. We assessed 785,809 singleton live births, with 6.6% born preterm. The presence of paternal comorbidities was associated with higher odds of preterm birth, low birth weight (LBW), and NICU stay. After adjusting for maternal factors, fathers with most or all components of the metabolic syndrome had 19% higher odds of having a child born preterm (95% CI 1.11-1.28), 23% higher odds of LBW (95% CI 1.01-1.51), and 28% higher odds of NICU stay (95% CI 1.08-1.52). Maternal morbidity (e.g., gestational diabetes or preeclampsia) was also positively associated with preconception paternal health. CONCLUSION(S): Increased preconception paternal comorbidity may be associated with negative infant and maternal outcomes. Although the paternal effect remains modest, these findings highlight the importance of the health of both parents, particularly the mother, on healthy pregnancy.
Waterfield G et al., 2020·Environmental health : a global access science source
Per- and polyfluoroalkyl substances (PFASs) have been detected in drinking water supplies around the world and are the subject of intense regulatory debate. While they have been associated with several illnesses, their effects on reproductive outcomes remains uncertain. We analyzed birth outcomes in the east Minneapolis-St. Paul metropolitan area from 2002 to 2011, where a portion of the population faced elevated exposure to PFASs due to long-term contamination of drinking water supplies from industrial waste disposal. Installation of a water filtration facility in the highly contaminated city of Oakdale, MN at the end of 2006 resulted in a sharp decrease in exposure to PFASs, creating a "natural experiment". Using a difference-in-differences approach, we compare the changes in birth outcomes before and after water filtration in Oakdale to the changes over the same period in neighboring communities where the treatment of municipal water remained constant. Average birth weight and average gestational age were statistically significantly lower in the highly exposed population than in the control area prior to filtration of municipal water supply. The highly exposed population faced increased odds of low birth weight (adjusted odds ratio 1.36, 95% CI 1.25-1.48) and pre-term birth (adjusted odds ratio 1.14, 95% CI 1.09-1.19) relative to the control before filtration, and these differences moderated after filtration. The general fertility rate was also significantly lower in the exposed population (incidence rate ratio 0.73, 95% CI 0.69-0.77) prior to filtration and appeared to be rebounding post-2006. Our findings provide evidence of a causal relationship between filtration of drinking water containing high levels of exposure to PFASs and improved reproductive outcomes.
Liew Z et al., 2020·Environmental health perspectives
Per- and polyfluoroalkyl substances (PFAS) are widespread persistent organic pollutants and endocrine disruptors. High doses of perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) exposure can cause pregnancy loss and infant deaths in animals, but the associations between PFAS exposures and risk of miscarriage in humans are not well studied. Using a case-control study nested within the Danish National Birth Cohort (DNBC, 1996-2002), we compared 220 pregnancies ending in miscarriage during weeks 12-22 of gestation, with 218 pregnancies resulting in live births. Levels of seven types of PFAS [PFOS, PFOA, perfluorohexane sulfonate (PFHxS), perfluoroheptane sulfonate (PFHpS), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluorooctanesulfonic acid (PFOSA)] were measured in maternal plasma collected in early gestation (mean gestational week 8). We estimated the odds ratios (ORs) and 95% confidence intervals (CIs) for miscarriage and each PFAS as a continuous variable or in quartiles, controlling for maternal age, parity, socio-occupational status, smoking and alcohol intake, gestational week of blood sampling, and maternal history of miscarriage. Stratification by parity and PFAS mixture analyses using weighted quantile sum (WQS) regression were also conducted. We observed a monotonic increase in odds for miscarriage associated with increasing PFOA and PFHpS levels. The ORs comparing the highest PFOA or PFHpS quartile to the lowest were 2.2 (95% CI: 1.2, 3.9) and 1.8 (95% CI: 1.0, 3.2). The ORs were also elevated for the second or third quartile of PFHxS or PFOS, but no consistent exposure-outcome pattern emerged. An interquartile range (IQR) increment in the WQS index of seven PFAS was associated with 64% higher odds for miscarriage (95% CI: 1.15, 2.34). The associations were stronger in parous women, while findings were inconsistent among nulliparous women. Maternal exposures to higher levels of PFOA, PFHpS, and PFAS mixtures were associated with the risk of miscarriage and particularly among parous women. Larger replication studies among nulliparous women are needed to allay concerns about confounding by reproductive history. https://doi.org/10.1289/EHP6202.
Sunderam S et al., 2020·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2017. Sunderam S, Kissin DM, Zhang Y, Jewett A, Boulet SL, Warner L, Kroelinger CD, Barfield WD. Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to have multiple-birth infants because multiple embryos may be transferred. Multiple births can pose substantial risks for both mothers and infants, including obstetric complications, preterm birth (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2017 and compares birth outcomes that occurred in 2017 (resulting from ART procedures performed in 2016 and 2017) with outcomes for all infants born in the United States in 2017. 2017. In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from the 50 states, the District of Columbia, and Puerto Rico. In 2017, a total of 196,454 ART procedures (range: 162 in Alaska to 24,179 in California) with at least one embryo transferred were performed in 448 U.S. fertility clinics and reported to CDC. These procedures resulted in 68,908 live-birth deliveries (range: 67 in Puerto Rico to 8,852 in California) and 78,052 infants born (range: 85 in Puerto Rico to 9,926 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years) was 3,040. ART use rates exceeded the national rate in 14 states (Connecticut, Delaware, District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Utah, Vermont, and Virginia). ART use exceeded 1.5 times the national rate in seven states (Connecticut, the District of Columbia, Illinois, Maryland, Massachusetts, New Jersey, and New York). Nationally, among all ART transfer procedures, the average number of embryos transferred increased slightly with increasing age (1.3 among women aged <35 years, 1.4 among women aged 35-37 years, and 1.5 among women aged >37 years). This year, single-embryo transfer (SET) rates among all embryo-transfer procedures are presented instead of elective single-embryo transfer procedures previously reported. Nationally, SET rates were 67.3% (range: 38.9% in South Dakota to 90.4% in Delaware), 65.0% (range: 23.6% in Puerto Rico to 89.4% in Delaware), and 60.0% (range: 28.6% in Puerto Rico to 83.1% in Delaware) among women aged <35 years, aged 35-37 years, and aged >37 years, respectively. In 2017, ART contributed to 1.9% of all infants born in the United States (range: 0.4% in Puerto Rico to 5.0% in Massachusetts). Approximately 73.6% of ART-conceived infants were singleton infants. Overall, ART contributed to 14.7% of all multiple births, including 14.7% of all twin infants and 17.3% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (18,890 of 19,570) of all ART-conceived infants born in multiple deliveries. The percentage of multiple births was higher among infants conceived with ART (26.4%) than among all infants born in the total birth population (3.4%). Approximately 25.5% of ART-conceived infants were twins, and 0.9% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 4.5% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 20.2% had low birthweight, compared with 8.3% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (27.8%) than among all infants born in the total birth population (9.9%). The percentage of low birthweight among singletons was 8.1% among ART-conceived infants and 6.6% among all infants born. The percentage of preterm births among ART-conceived singleton infants was 14.0%, compared with 8.1% among all singleton infants. The percentages of small for gestational age infants was 7.6% among ART-conceived infants, compared with 9.9% among all infants. Although singleton infants accounted for the majority of ART-conceived infants, multi
Farland LV et al., 2019·Obstetrics & Gynecology·
Open Access
To investigate the relationship between endometriosis and adverse pregnancy outcomes. Women between ages 25 and 42 years in 1989 (n=116,429) reported detailed information on pregnancies and reproductive health at baseline and every 2 years thereafter in the Nurses' Health Study II, a cohort study. In 2009, they completed a detailed, pregnancy-focused questionnaire. A total of 196,722 pregnancies were reported. Adverse pregnancy outcomes included spontaneous abortion, ectopic pregnancy, stillbirth, gestational diabetes mellitus (GDM), hypertensive disorders of pregnancy (preeclampsia or gestational hypertension), preterm birth, and low birth weight. We estimated the relative risks (RRs) and 95% CIs of adverse pregnancy outcomes comparing pregnancies in women with and without a history of laparoscopically confirmed endometriosis using multivariable log-binomial regression, with generalized estimating equations to account for multiple pregnancies per woman. Endometriosis was associated with a greater risk of pregnancy loss (spontaneous abortion: RR 1.40, 95% CI 1.31–1.49; ectopic pregnancy: RR 1.46, 95% CI 1.19–1.80). Endometriosis was also associated with a greater risk of GDM (RR 1.35, 95% CI 1.11–1.63) and hypertensive disorders of pregnancy (RR 1.30, 95% CI 1.16–1.45). We observed an association between laparoscopically confirmed endometriosis and several adverse pregnancy outcomes. Future research should focus on the potential biological pathways underlying these relationships to inform screening or preventive interventions.
Almasi-Hashiani A et al., 2019·BMC Pregnancy Childbirth·
Open Access
The objective of this systematic review and meta-analyses was to assess the risk of preeclampsia among women who conceived with assisted reproductive technology (ART). We searched the ISI Web of Knowledge, Medline/PubMed, Scopus, and Embase (from inception to May 2017) for English language articles using a list of key words. In addition, reference lists from identified studies and relevant review articles were also searched. Data extraction was performed by two authors, and the study quality was assessed using the Newcastle-Ottawa Scale. Random-effects model meta-analysis was applied to pool the relative risks (RR) across studies. A total of 48 studies (5 case-control studies and 43 cohort studies) were included in this meta-analysis. The Cochran Q test and I(2) statistics revealed substantial heterogeneity (Q = 26,313.92, d.f. = 47, p < 0.001 and I(2) = 99.8%). Meta-analysis showed a significant increase in preeclampsia in women who conceived by ART compared with those who conceived spontaneously (RR = 1.71, 95% CI = 1.11-2.62, p = 0.015). The findings of this systematic review indicate that the use of ART treatment is associated with a 1.71-fold increase in preeclampsia.
Prescribing Safety · Medication Safety in Pregnancy
Presentation examining the safety and potential benefits of low-dose naltrexone (LDN) use during pregnancy. Reports on a patient survey of 237 successful pregnancies comparing outcomes between LDN users and non-users. Addresses three key questions: safety of LDN in pregnancy, additional benefits to mother and baby, and optimal duration of treatment. Findings suggest LDN is safe during pregnancy with trends toward improved outcomes (reduced prematurity, fewer SCBU admissions, fewer complications) for those continuing LDN beyond 26 weeks, though results did not achieve statistical significance. Also discusses potential epigenetic benefits of LDN for reducing endometriosis expression in the next generation and possible reduction of autism risk through immune modification.
Bay B et al., 2019·BJOG : an international journal of obstetrics and gynaecology
To assess the risk of stillbirth in low-risk in vitro fertilisation (IVF) pregnancies. Register-based national cohort study. Denmark 2003-2013. Cohort of 425 732 singleton pregnancies including 10 235 conceived following IVF/intracytoplasmic sperm injection (ICSI), 4521 conceived following intrauterine insemination (IUI), and 410 976 spontaneously conceived. Information on pregnancy, obstetrical risk factors, stillbirth, and fertility treatment was obtained from the Danish national health registers for all pregnancies after gestational week 21+6 . We estimated the overall and gestational age-specific risk of stillbirth in low-risk term pregnancies following IVF, ICSI, and IUI. Further, we estimated the association between stillbirth and IVF and ICSI respectively as well as fresh or frozen-thawed embryo transfer. Risk of stillbirth. The number of stillbirths in spontaneously conceived and IVF/ICSI low-risk term pregnancies was 525 (0.1%) and 35 (0.3%), respectively. In multivariate analysis, the risk of stillbirth in pregnancies following IVF/ICSI was increased (odds ratio 2.1, 95% CI 1.4-3.1). The risk of stillbirth was correspondingly increased in time-to-event analyses taking risk time for each fetus into account from gestational week 37 and onwards (hazard ratio 2.4, 95% CI 1.6-3.6). In sub-analyses, the risk of stillbirth was increased for pregnancies following ICSI (odds ratio 2.2, 95% CI 1.2-3.1), but not IVF (odds ratio 1.7, 95% CI 0.9-3.1). We found a systematically increased risk of stillbirth in low-risk term pregnancies following IVF/ICSI. Whether the risk was related to the treatment or to underlying subfertility is uncertain. The results may indicate a need for obstetrical surveillance for these pregnancies when reaching term. Increased risk of stillbirth in low-risk term pregnancies following fresh cycle IVF/ICSI.
Sunderam S et al., 2019·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2016. Sunderam S(1), Kissin DM(1), Zhang Y(1), Folger SG(1), Boulet SL(2), Warner L(1), Callaghan WM(1), Barfield WD(1). (1)Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. (2)Emory University School of Medicine, Atlanta, Georgia. Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g). This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2016 and compares birth outcomes that occurred in 2016 (resulting from ART procedures performed in 2015 and 2016) with outcomes for all infants born in the United States in 2016. 2016. In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). In 2016, a total of 197,706 ART procedures (range: 162 in Wyoming to 24,030 in California) with the intent to transfer at least one embryo were performed in 463 U.S. fertility clinics and reported to CDC. These procedures resulted in 65,964 live-birth deliveries (range: 57 in Puerto Rico to 8,638 in California) and 76,892 infants born (range: 74 in Alaska to 9,885 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART use rate, was 3,075. ART use rates exceeded the national rate in 14 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, Utah, and Virginia). ART use exceeded 1.5 times the national rate in nine states, including three (Illinois, Massachusetts, and New Jersey) that also had comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four oocyte retrievals). Nationally, among ART transfer procedures for patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age (1.5 among women aged <35 years, 1.7 among women aged 35-37 years, and 2.2 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 42.7% (range: 8.3% in North Dakota to 83.9% in Delaware). In 2016, ART contributed to 1.8% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.7% in Massachusetts). ART also contributed to 16.4% of all multiple-birth infants, including 16.2% of all twin infants and 19.4% of all triplets and higher-order infants. ART-conceived twins accounted for approximately 96.5% (21,455 of 22,233) of all ART-conceived infants born in multiple deliveries. The percentage of multiple-birth infants was higher among infants conceived with ART (31.5%) than among all infants born in the total birth population (3.4%). Approximately 30.4% of ART-conceived infants were twins and 1.1% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.0% of all low birthweight (<2,500 g) infants. Among ART-conceived infants, 23.6% had low birthweight compared with 8.2% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (29.9%) than among all infants born in the total birth population (9.9%). The percentage of ART-conceived infants who had low birthweight was 8.7% among singletons, 54.9% among twins, and 94.9% among triplets and higher-order multiples; the corresponding percentages among all infants born were 6.2% among singletons, 55.4% among twins, and 94.6% among triplets and higher-order multiples. The percentage of ART-conceived infants who were born preterm was 13.7% among singletons, 64.2% among twins, and 97.0% among triplets and higher-order infants; t
Guidelines by Clinical Area · Obstetric Guidelines
American College of Obstetricians and Gynecologists et al., 2018·Obstetrics & Gynecology
Placenta accreta spectrum, formerly known as morbidly adherent placenta, refers to the range of pathologic adherence of the placenta, including placenta increta, placenta percreta, and placenta accreta. The most favored hypothesis regarding the etiology of placenta accreta spectrum is that a defect of the endometrial-myometrial interface leads to a failure of normal decidualization in the area of a uterine scar, which allows abnormally deep placental anchoring villi and trophoblast infiltration. Maternal morbidity and mortality can occur because of severe and sometimes life-threatening hemorrhage, which often requires blood transfusion. Although ultrasound evaluation is important, the absence of ultrasound findings does not preclude a diagnosis of placenta accreta spectrum; thus, clinical risk factors remain equally important as predictors of placenta accreta spectrum by ultrasound findings. There are several risk factors for placenta accreta spectrum. The most common is a previous cesarean delivery, with the incidence of placenta accreta spectrum increasing with the number of prior cesarean deliveries. Antenatal diagnosis of placenta accreta spectrum is highly desirable because outcomes are optimized when delivery occurs at a level III or IV maternal care facility before the onset of labor or bleeding and with avoidance of placental disruption. The most generally accepted approach to placenta accreta spectrum is cesarean hysterectomy with the placenta left in situ after delivery of the fetus (attempts at placental removal are associated with significant risk of hemorrhage). Optimal management involves a standardized approach with a comprehensive multidisciplinary care team accustomed to management of placenta accreta spectrum. In addition, established infrastructure and strong nursing leadership accustomed to managing high-level postpartum hemorrhage should be in place, and access to a blood bank capable of employing massive transfusion protocols should help guide decisions about delivery location.
Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Although the majority of infants conceived through ART are singletons, women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks for both mothers and infants, including obstetric complications, preterm delivery (<37 weeks), and low birthweight (<2,500 g) infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2015 and compares birth outcomes that occurred in 2015 (resulting from ART procedures performed in 2014 and 2015) with outcomes for all infants born in the United States in 2015. Period Covered: 2015. Description of System: In 1995, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493 [October 24, 1992]). Data are collected through the National ART Surveillance System, a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico).
In 2015, a total of 182,111 ART procedures (range: 135 in Alaska to 23,198 in California) with the intent to transfer at least one embryo were performed in 464 U.S. fertility clinics and reported to CDC. These procedures resulted in 59,334 live-birth deliveries (range: 55 in Wyoming to 7,802 in California) and 71,152 infants born (range: 68 in Wyoming to 9,176 in California). Nationally, the number of ART procedures performed per 1 million women of reproductive age (15-44 years), a proxy measure of the ART utilization rate, was 2,832. ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, and Virginia). Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.6 among women aged <35 years, 1.8 among women aged 35-37 years, and 2.3 among women aged >37 years). Among women aged <35 years, the national elective single-embryo transfer (eSET) rate was 34.7% (range: 11.3% in Puerto Rico to 88.1% in Delaware). In 2015, ART contributed to 1.7% of all infants born in the United States (range: 0.3% in Puerto Rico to 4.5% in Massachusetts). ART also contributed to 17.0% of all multiple-birth infants, 16.8% of all twin infants, and 22.2% of all triplets and higher-order infants. The percentage of multiple-birth infants was higher among infants conceived with ART (35.3%) than among all infants born in the total birth population (3.4%). Approximately 34.0% of ART-conceived infants were twins and 1.0% were triplets and higher-order infants. Nationally, infants conceived with ART contributed to 5.1% of all low birthweight infants. Among ART-conceived infants, 25.5% had low birthweight, compared with 8.1% among all infants. ART-conceived infants contributed to 5.3% of all preterm (gestational age <37 weeks) infants. The percentage of preterm births was higher among infants conceived with ART (31.2%) than among all infants born in the total birth population (9.7%). Among singletons, the percentage of ART-conceived infants who had low birthweight was 8.7% compared with 6.4% among all infants born. The percentage of ART-conceived infants who were born preterm was 13.4% among singletons compared with 7.9% among all infants. Interpretation: Multiple births from ART contributed to a substantial proportion of all twins, triplets, and higher-order infants born in the United States. For women aged <35 years, who are typically considered good candidates for eSET, the national average of 1.6 embryos was transferred per ART procedure. Of the four states (Illinois, Massachusetts, New Jersey, and Rhode Island) with comprehensive mandated health insurance coverage for ART procedures (i.e., coverage for at least four cycles of IVF), three (Illinois, Massachusetts, and New Jersey) had rates of ART use exceeding 1.5 times the national rate. This type of mandated insurance coverage has been associated with greater use of ART and likely accounts for some of the difference in per capita ART use observed among states. Public Health Action: Twins account for the majority of ART-conceived multiple births. Reducing the number of embryos transferred and increasing use of eSET when clinically appropriate could help reduce multiple births and related adverse health consequences for both mothers and infants. State-based surveillance of ART might be useful for monitoring and evaluating maternal and infant health outcomes of ART in states with high ART use.
Gonzales SK et al., 2018·Journal of minimally invasive gynecology
The objective of this study is to report our center's series of robotic-assisted laparoscopic abdominal cerclage (RALAC) placement during pregnancy. Descriptive study (Canadian Task Force classification III). Single academic institution. Patients undergoing RALAC placement during pregnancy. Eleven patients underwent RALAC. Nine out of 11 (81.8%) primary RALAC procedures resulted in a viable live-born neonate; 8 (72.7%) were born at >34 weeks of gestation. Three patients (27.3%) had preterm premature rupture of membranes on postoperative day one, 2 of whom subsequently underwent a dilation and curettage, and 1 patient carried the pregnancy to 29 weeks and delivered a live-born neonate. Four patients had subsequent pregnancies after placement of a RALAC in the antepartum period, all of whom carried successfully beyond 36 weeks, for a total of 16 pregnancies. Fourteen pregnancies (87.5%) resulted in a live birth, and 13 pregnancies (81.3%) were delivered beyond 34 weeks. RALAC is a minimally invasive procedure with an acceptable risk profile and comparable efficacy to traditional open abdominal cerclage. RALAC may be considered an acceptable alternative to open abdominal cerclage in pregnancy, and may be a particularly favorable option in certain settings.
To study the perinatal outcomes between singleton live births achieved with the use of commissioned versus spontaneously conceived embryos carried by the same gestational surrogate. Retrospective cohort study. Academic in vitro fertilization center. PATIENT(S): Gestational surrogate. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Pregnancy outcome, gestational age at birth, birth weight, perinatal complications. RESULT(S): We identified 124 gestational surrogates who achieved a total of 494 pregnancies. Pregnancy outcomes for surrogate and spontaneous pregnancies were significantly different (P<.001), with surrogate pregnancies more likely to result in twin pregnancies: 33% vs. 1%. Miscarriage and ectopic rates were similar. Of these pregnancies, there were 352 singleton live births: 103 achieved from commissioned embryos and 249 conceived spontaneously. Surrogate births had lower mean gestational age at delivery (38.8 ± 2.1 vs. 39.7 ± 1.4), higher rates of preterm birth (10.7% vs. 3.1%), and higher rates of low birth weight (7.8% vs. 2.4%). Neonates from surrogacy had birth weights that were, on average, 105 g lower. Surrogate births had significantly higher obstetrical complications, including gestational diabetes, hypertension, use of amniocentesis, placenta previa, antibiotic requirement during labor, and cesarean section. CONCLUSION(S): Neonates born from commissioned embryos and carried by gestational surrogates have increased adverse perinatal outcomes, including preterm birth, low birth weight, hypertension, maternal gestational diabetes, and placenta previa, compared with singletons conceived spontaneously and carried by the same woman. Our data suggest that assisted reproductive procedures may potentially affect embryo quality and that its negative impact can not be overcome even with a proven healthy uterine environment.
To evaluate the effect of endometriosis on pregnancy outcomes. Systematic review and meta-analysis. Not applicable. PATIENT(S): Women with or without endometriosis. INTERVENTION(S): Electronic databases searched from their inception until February 2017 with no limit for language and with all cohort studies reporting the incidence of obstetric complications in women with a diagnosis of endometriosis compared with a control group (women without a diagnosis of endometriosis) included. MEAN OUTCOME MEASURE(S): Primary outcome of incidence of preterm birth at <37 weeks with meta-analysis performed using the random effects model of DerSimonian and Laird to produce an odds ratio (OR) with 95% confidence interval (CI). RESULT(S): Twenty-four studies were analyzed comprising 1,924,114 women. In most of them, the diagnosis of endometriosis was made histologically after surgery. Women with endometriosis had a statistically significantly higher risk of preterm birth (OR 1.63; 95% CI, 1.32-2.01), miscarriage (OR 1.75; 95% CI, 1.29-2.37), placenta previa (OR 3.03; 95% CI, 1.50-6.13), small for gestational age (OR 1.27; 95% CI, 1.03-1.57), and cesarean delivery (OR 1.57; 95% CI, 1.39-1.78) compared with the healthy controls. No differences were found in the incidence of gestational hypertension and preeclampsia. CONCLUSION(S): Women with endometriosis have a statistically significantly higher risk of preterm birth, miscarriage, placenta previa, small for gestational age infants, and cesarean delivery.
Anti-Infective and Anti-Inflammatory Agents · Nonsteroidal Anti-Inflammatory Drugs
Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia. In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle. A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events. Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).
Kroll-Desrosiers AR et al., 2017·Depression and anxiety
Due to its potent effects on social behavior, including maternal behavior, oxytocin has been identified as a potential mediator of postpartum depression and anxiety. The objective of this study was to examine the relationship between peripartum synthetic oxytocin administration and the development of depressive and anxiety disorders within the first year postpartum. We hypothesized that women exposed to peripartum synthetic oxytocin would have a reduced risk of postpartum depressive and anxiety disorders compared with those without any exposure. Population-based data available through the Massachusetts Integrated Clinical Academic Research Database (MiCARD) were used to retrospectively (2005-2014) examine this relationship and calculate the relative risk of peripartum synthetic oxytocin for the development of postpartum depressive and anxiety disorders in exposed (n = 9,684) compared to unexposed (n = 37,048) deliveries. Among deliveries to women with a history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 36% (relative risk (RR): 1.36; 95% confidence interval (95% CI): 1.20-1.55). In deliveries to women with no history of prepregnancy depressive or anxiety disorder, exposure to peripartum oxytocin increased the risk of postpartum depressive or anxiety disorder by 32% compared to those not exposed (RR: 1.32; 95% CI: 1.23-1.42). Contrary to our hypothesis, results indicate that women with peripartum exposure to synthetic oxytocin had a higher relative risk of receiving a documented depressive or anxiety disorder diagnosis or antidepressant/anxiolytic prescription within the first year postpartum than women without synthetic oxytocin exposure.
This population-based cohort study examined preconception TSH levels and their association with pregnancy outcomes in 184,611 Chinese women planning to conceive. Women were classified into reference (0.48-2.49 mIU/L), upper limit (2.5-4.28 mIU/L), and high TSH (4.29-10 mIU/L) groups. The high normal TSH group showed higher rates of spontaneous abortion, preterm birth, and operative vaginal delivery compared to reference. The high TSH group had higher rates of spontaneous abortion, stillbirth, and preterm births.
Sunderam S et al., 2017·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2014. Sunderam S(1), Kissin DM(1), Crawford SB(1), Folger SG(1), Jamieson DJ(1), Warner L(1), Barfield WD(1). (1)Division of Reproductive Health, National Center for Chronic Disease Prevention and Health Promotion, CDC. Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks to both mothers and infants, including obstetric complications, preterm delivery, and low birthweight infants. This report provides state-specific information for the United States (including the District of Columbia and Puerto Rico) on ART procedures performed in 2014 and compares birth outcomes that occurred in 2014 (resulting from ART procedures performed in 2013 and 2014) with outcomes for all infants born in the United States in 2014. 2014. In 1996, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia, and Puerto Rico). In 2014, a total of 169,568 ART procedures (range: 124 in Wyoming to 21,018 in California) with the intent to transfer at least one embryo were performed in 458 U.S. fertility clinics and reported to CDC. These procedures resulted in 56,028 live-birth deliveries (range: 52 in Wyoming to 7,230 in California) and 68,782 infants born (range: 64 in Wyoming to 8,793 in California). Nationally, the total number of ART procedures performed per million women of reproductive age (15-44 years), a proxy measure of the ART usage rate, was 2,647 (range: 364 in Puerto Rico to 6,726 in Massachusetts). ART use exceeded the national average in 13 reporting areas (Connecticut, Delaware, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Pennsylvania, Rhode Island, and Virginia). Eight reporting areas (Connecticut, the District of Columbia, Hawaii, Illinois, Maryland, Massachusetts, New Jersey, and New York) had rates of ART use exceeding 1.5 times the national average. Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.7 among women aged <35 years, 1.9 among women aged 35-37 years, and 2.3 among women aged >37 years). Among women aged <35 years, who typically are considered to be good candidates for elective single embryo transfer (eSET) procedures, the national eSET rate was 28.5% (range: 4.3% in Puerto Rico to 67.9% in Delaware). In 2014, ART contributed to 1.6% of all infants born in the United States (range: 0.4% in Puerto Rico to 4.7% in Massachusetts) and 18.3% of all multiple-birth infants (range: 5.5% in Alaska and West Virginia to 37.3% in Hawaii), including 18.0% of all twin infants (range: 5.2% in some states to 36.2% in Hawaii) and 26.4% of all triplets and higher-order infants (range: 0% in some states to 65.2% in Hawaii). Percentages of live births that were multiple-birth deliveries were higher among infants conceived with ART (39.4%; range: 11.5% in Delaware to 55.6% in Puerto Rico) than among all infants born in the total birth population (3.5%; range: 2.2% in Puerto Rico to 4.4% in New Jersey). Approximately 38.0% of ART-conceived infants were twin infants, and 2.0% were triplets and higher-order infants. ART-conceived twins accounted for approximately 95.3% of all ART-conceived infants born in multiple deliveries. Nationally, infants conceived with ART contributed to 5.5% of all low birthweight (<2,500 g) infants (range: 1.2% in West Virginia to 14.2% in Massachusetts). Among ART-conceived infants, 27.8% were low birthweight (range: 10.6% in Delaware to 44.4% in Puerto Rico), compared with 8.0% among all infants (range: 5.9% in Alaska to 11.3% in Mississippi). ART-conceived infants contributed to 4.7% of all preterm (<37 weeks) infants (range: 1.2% in Puerto Rico to 13.4% in Massachusetts). Percentages of preterm births were higher among infants conceived with ART (33.2%; range: 18.9% in the District of Columbia to 45.9% in Puerto Rico) than among all infants born in the total birth population (11.3%; range: 8.5% in California to 16.0% in Mississippi). The percentage of ART-c
Kathpalia SK et al., 2016·Medical journal, Armed Forces India·
Open Access
Many infertile couples need treatment in different forms including Assisted Reproductive Techniques. In Vitro Fertilization and Embryo Transfer is the most advanced method of infertility treatment. Management of these pregnancies is difficult as the couples and treating doctors have undue concern and apprehension and worry about outcome of such pregnancies. This study was undertaken to find out the complications and mode of delivery and if there is a need to manage them at tertiary care centers. 130 cases were included in the study after pregnancy was confirmed in this prospective study. These cases were followed throughout pregnancy and labour. Pregnancy, labour, and neonatal complications were noted. Incidence of primary infertility was more common. Mean age of patient was more. All the cases were provided standard routine antenatal care. Multiple pregnancies and preterm labour were more frequent in the study group. A large number of cases delivered vaginally. A large number of pregnancies terminated in vaginal delivery, thereby indicating that these pregnancies though high risk can have vaginal delivery. They can be managed at any hospital once clinical pregnancy is confirmed.
There is evidence that 3.17% of women report post-traumatic stress disorder (PTSD) after childbirth. This meta-analysis synthesizes research on vulnerability and risk factors for birth-related PTSD and refines a diathesis-stress model of its aetiology. Systematic searches were carried out on
PsycINFO, PubMed, Scopus and Web of Science using PTSD terms crossed with childbirth terms. Studies were included if they reported primary research that examined factors associated with birth-related PTSD measured at least 1 month after birth. In all, 50 studies (n = 21 429) from 15 countries fulfilled inclusion criteria. Pre-birth vulnerability factors most strongly associated with PTSD were depression in pregnancy (r = 0.51), fear of childbirth (r = 0.41), poor health or complications in pregnancy (r = 0.38), and a history of
PTSD (r = 0.39) and counselling for pregnancy or birth (r = 0.32). Risk factors in birth most strongly associated with PTSD were negative subjective birth experiences (r = 0.59), having an operative birth (assisted vaginal or caesarean, r = 0.48), lack of support (r = -0.38) and dissociation (r = 0.32).
After birth, PTSD was associated with poor coping and stress (r = 0.30), and was highly co-morbid with depression (r = 0.60). Moderator analyses showed that the effect of poor health or complications in pregnancy was more apparent in high-risk samples. The results of this meta-analysis are used to update a diathesis-stress model of the aetiology of postpartum PTSD and can be used to inform screening, prevention and intervention in maternity care.
Vissenberg R et al., 2016·Eur J Obstet Gynecol Reprod Biol·
Thyroid dysfunction has been described as a possible risk factor for having an abnormal fetal position at birth. In this study we aim to determine the association between thyroid function in early pregnancy and breech presentation at term. We used data from the Amsterdam Born Children and their Development (ABCD) cohort. 3347 pregnant women were included between January 2003 and March 2004 in Amsterdam, the Netherlands. Thyroid function tests were performed between 5 and 37 weeks gestational age (median 12.9 weeks). The main outcome measure was the association between thyroid function in early pregnancy and breech presentation at term. Univariate and multivariate analysis were performed to determine the association between thyroid function and breech presentation. Increased TSH in pregnancy, defined as thyroid stimulating hormone (TSH) >97.5th percentile (>3.53mIU/L), was associated with a higher risk for breech presentation at term (aOR 2.32, CI 1.1-4.8, p=0.02) compared to euthyroidism (TSH between 2.5th and 97.5th percentile). After exclusion of overt hypothyroidism and hyperthyroidism the aOR was 2.34 (CI 1.1-5.0, p=0.03). Trimester specific analysis showed a significant association of increased TSH levels (>3.68mIU/L) in the second trimester with breech presentation (aOR 3.7, CI 1.7-7.8, p=0.001). In the second trimester low free thyroxine (FT4) <2.5th percentile (<6.7pmol/L) was also associated with breech presentation (aOR 2.5, CI 1.0-6.3, p=0.04). Increased TSH and decreased FT4 in the second trimester of pregnancy are associated with an increased risk for breech presentation at term. The association of abnormal thyroid parameters in the first of third trimester is still unclear.
Masoudian P et al., 2016·American journal of obstetrics and gynecology
The purpose of this study was to determine whether pregnancies that were achieved via oocyte donation, compared with pregnancies achieved via other assisted reproductive technology methods or natural conception, demonstrate increased risk of preeclampsia or gestational hypertension. Comparative studies of pregnancies that were achieved with oocyte donation vs other methods of assisted reproductive technology or natural conception with preeclampsia or gestational hypertension were included as 1 of the measured outcomes. Abstracts and unpublished studies were excluded. Two reviewers independently selected studies, which were assessed for quality with the use of methodological index for non-randomized studies, and extracted the data. Statistical analysis was conducted. Of the 523 studies that were reviewed initially, 19 comparative studies met the predefined inclusion and exclusion criteria and were included in the metaanalysis, which allowed for analysis of a total of 86,515 pregnancies. Our pooled data demonstrated that the risk of preeclampsia is higher in oocyte-donation pregnancies compared with other methods of assisted reproductive technology (odds ratio, 2.54; 95% confidence interval, 1.98-3.24; P < .0001) or natural conception (odds ratio, 4.34; 95% confidence interval, 3.10-6.06; P < .0001). The risk of gestational hypertension was also increased significantly in oocyte donation pregnancies in comparison with other methods of assisted reproductive technology (odds ratio, 3.00; 95% confidence interval, 2.44-3.70; P < .0001) or natural conception (odds ratio, 7.94; 95% confidence interval, 1.73-36.36; P = .008). Subgroup analysis that was conducted for singleton and multiple gestations demonstrated a similar risk for preeclampsia and gestational hypertension in both singleton and multiple gestations. This metaanalysis provides further evidence that supports that egg donation increases the risk of preeclampsia and gestational hypertension compared with other assisted reproductive technology methods or natural conception.
To determine whether there are any increases in pregnancy-related complications and adverse pregnancy outcomes in singleton pregnancies after assisted reproductive technology (ART) compared with those conceived naturally. Meta-analysis. University-affiliated teaching hospital. PATIENT(S): Singleton pregnancies conceived with ART and naturally. INTERVENTION(S): PubMed, Google Scholar, Cochrane Libraries and Chinese database were searched through March 2015 to identify studies that met pre-stated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators. MAIN OUTCOME MEASURE(S): Pregnancy-related complications and adverse pregnancy outcomes. RESULT(S): Fifty cohort studies comprising 161,370 ART and 2,280,241 spontaneously conceived singleton pregnancies were identified. The ART singleton pregnancies had a significantly increased risk of pregnancy-induced hypertension (relative risk [RR] 1.30, 95% confidence interval [CI] 1.04-1.62; I(2) = 79%), gestational diabetes mellitus (RR 1.31, 95% CI 1.13-1.53; I(2) = 6%), placenta previa (RR 3.71, 95% CI 2.67-5.16; I(2) = 72%), placental abruption (RR 1.83, 95% CI 1.49-2.24; I(2) = 22%), antepartum hemorrhage (RR 2.11, 95% CI 1.86-2.38; I(2) = 47%), postpartum hemorrhage (RR 1.29, 95% CI 1.06-1.57; I(2) = 65%), polyhydramnios (RR 1.74, 95% CI 1.24-2.45; I(2) = 0%), oligohydramnios (RR 2.14, 95% CI 1.53-3.01; I(2) = 0%), cesarean sections (RR 1.58, 95% CI 1.48-1.70; I(2) = 92%), preterm birth (RR 1.71, 95% CI 1.59-1.83; I(2)=80%), very preterm birth (RR 2.12, 95% CI 1.73-2.59; I(2) = 90%), low birth weight (RR 1.61, 95% CI 1.49-1.75; I(2) = 80%), very low birth weight (RR 2.12, 95% CI 1.84-2.43; I(2) = 67%), small for gestational age (RR 1.35, 95% CI 1.20-1.52; I(2) = 82%), perinatal mortality (RR 1.64, 95% CI 1.41-1.90; I(2)=45%), and congenital malformation (RR 1.37, 95% CI 1.29-1.45; I(2)=41%). Relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded consistent results. No evidence of publication bias was observed. CONCLUSION(S): The ART singleton pregnancies are associated with higher risks of adverse obstetric outcomes. Obstetricians should manage these pregnancies as high risk.
Bonnesen B et al., 2015·Acta Obstet Gynecol Scand·
Very few studies describe the obstetric and neonatal outcome of spontaneous pregnancies in women with irregular menstrual cycles. However, menstrual cycle irregularities are common and may be associated with increased risk, and women who develop pregnancy complications more frequently recollect irregular menstrual cycles before the time of conception in case-control studies. MATERIAL AND This retrospective cohort study compares obstetric and neonatal outcomes in spontaneous singleton pregnancies in 3440 primiparous Danish women stratified according to menstrual cycle regularity. All pregnancies delivered after 22 weeks of gestation and had a nuchal translucency examination at Copenhagen University Hospital Hvidovre between 1 January 2009 and 31 December 2010. Menstrual cycle irregularity was defined as more than 7 days' deviation between self-reported and ultrasound examination-based gestational age. Outcome measures were gestational diabetes, hypertension, preeclampsia, preterm premature rupture of membranes, preterm birth, prolonged pregnancy, birthweight, umbilical artery pH <7.1, APGAR <7 after 5 min, admission to neonatal intensive care unit and stillbirth. Women with more than 7 days' deviation between self-reported and ultrasound examination-based gestational age were compared with women with a deviation of 7 days or less. Irregular menstrual cycle before conception increases the risk of preeclampsia (7.9% vs. 5.2%, p < 0.05) and low birthweight (6.0% vs. 3.6%, p < 0.05) in spontaneous pregnancies, but reduces the risk of prolonged pregnancy (1.4% vs. 4.7%, p < 0.001). Irregular menstrual cycle before conception is associated with increased risk of adverse obstetric and neonatal outcome.
To provide an up-to-date comparison of pregnancy-related complications and adverse pregnancy outcomes of multiple pregnancies generated with assisted reproductive technology (ART) vs. spontaneous conception. Meta-analysis. University-affiliated teaching hospital.Patient(s)Multiple pregnancies conceived by ART or naturally.Intervention(s)Searches through October 2014 were conducted on PubMed, Google Scholar, Cochrane Libraries, China Biology Medicine disc, Chinese Scientific Journals Fulltext Database, China National Knowledge Infrastructure, and Wanfang Data, to identify studies that met prestated inclusion criteria. Either a fixed- or a random-effects model was used to calculate the overall combined risk estimates. Subgroup analysis was performed to explore potential heterogeneity moderators.Main outcome measure(s)Pregnancy-related complications and adverse pregnancy outcomes.Result(s)Thirty-nine cohort studies involving 146,008 multiple births were included in the meta-analysis. Multiple pregnancies from ART were associated with a higher risk of premature rupture of membranes (relative risk [RR] = 1.20, 95% confidence interval [CI]: 1.05-1.37; I(2) = 15%); pregnancy-induced hypertension (RR = 1.11, 95% CI: 1.04-1.19; I(2) = 6%); gestational diabetes mellitus (RR = 1.78, 95% CI: 1.25-2.55; I(2) = 42%); preterm birth (RR = 1.08, 95% CI: 1.03-1.14; I(2) = 83%); very preterm birth (RR = 1.18, 95% CI: 1.04-1.34; I(2) = 79%); low birth weight (RR = 1.04, 95% CI: 1.01-1.07; I(2) = 47%); very low birth weight (RR = 1.13, 95% CI: 1.01-1.25; I(2) = 62%); and congenital malformation (RR = 1.11, 95% CI: 1.02-1.22; I(2) = 30%). The relevant heterogeneity moderators have been identified by subgroup analysis. Sensitivity analysis yielded similar results. No evidence of publication bias was observed.Conclusion(s)Although the role of potential bias and evidence of heterogeneity should be carefully evaluated, the present study suggests that multiple pregnancies generated via ART, vs. spontaneous conception, are associated with higher risks of pregnancy-related complications and adverse pregnancy outcomes. Further research is needed to determine which aspect of ART poses the most risk and how this risk can be minimized.
Sunderam S et al., 2015·Morbidity and mortality weekly report. Surveillance summaries (Washington, D.C. : 2002)
Assisted Reproductive Technology Surveillance - United States, 2013. Sunderam S, Kissin DM, Crawford SB, Folger SG, Jamieson DJ, Warner L, Barfield WD; Centers for Disease Control and Prevention (CDC). Since the first U.S. infant conceived with assisted reproductive technology (ART) was born in 1981, both the use of ART and the number of fertility clinics providing ART services have increased steadily in the United States. ART includes fertility treatments in which eggs or embryos are handled in the laboratory (i.e., in vitro fertilization [IVF] and related procedures). Women who undergo ART procedures are more likely than women who conceive naturally to deliver multiple-birth infants. Multiple births pose substantial risks to both mothers and infants, including obstetric complications, preterm delivery, and low birthweight infants. This report provides state-specific information for the United States (including Puerto Rico) on ART procedures performed in 2013 and compares infant outcomes that occurred in 2013 (resulting from ART procedures performed in 2012 and 2013) with outcomes for all infants born in the United States in 2013. 2013. In 1996, CDC began collecting data on ART procedures performed in fertility clinics in the United States as mandated by the Fertility Clinic Success Rate and Certification Act of 1992 (FCSRCA) (Public Law 102-493). Data are collected through the National ART Surveillance System (NASS), a web-based data collection system developed by CDC. This report includes data from 52 reporting areas (the 50 states, the District of Columbia [DC], and Puerto Rico). In 2013, a total of 160,521 ART procedures (range: 109 in Wyoming to 20,299 in California) with the intent to transfer at least one embryo were performed in 467 U.S. fertility clinics and were reported to CDC. These procedures resulted in 53,252 live-birth deliveries (range: 47 in Alaska to 6,979 in California) and 66,691 infants (range: 61 in Alaska to 8,649 in California). Nationally, the total number of ART procedures performed per million women of reproductive age (15-44 years), a proxy measure of the ART usage rate, was 2,521 (range: 352 in Puerto Rico to 7,688 in DC). ART use exceeded the national rate in 13 reporting areas (California, Connecticut, Delaware, Hawaii, Illinois, Maryland, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Virginia, and DC). Nationally, among ART transfer procedures in patients using fresh embryos from their own eggs, the average number of embryos transferred increased with increasing age of the woman (1.8 among women aged <35 years, 2.0 among women aged 35-37 years, and 2.5 among women aged >37 years). Among women aged <35 years, who typically are considered to be good candidates for elective single embryo transfer (eSET) procedures, the national eSET rate was 21.4% (range: 4.0% in Idaho to 77.5% in Delaware). In 2013, ART contributed to 1.6% of all infants born in the United States (range: 0.2% in Puerto Rico to 4.8% in Massachusetts) and 18.7% of all multiple-birth infants (range: 4.5% in Puerto Rico to 35.7% in Massachusetts), including 18.5% of all twin infants (range: 4.5% in Mississippi to 35.3% in Massachusetts) and 25.2% of all triplet and higher-order infants (range: 0% in several reporting areas to 51.5% in New Jersey). Multiple-birth deliveries were higher among infants conceived with ART (41.1%; range: 20.4% in Delaware to 61.6% in Wyoming) than among all infants born in the total birth population (only 3.5%; range: 1.8% in Puerto Rico to 4.5% in Massachusetts and New Jersey). Approximately 39% of ART-conceived infants were twin infants, and 2% were triplet and higher-order infants. ART-conceived twins accounted for approximately 95.4% of all ART-conceived infants born in multiple deliveries. Nationally, infants conceived with ART contributed to 5.8% of all low birthweight (<2,500 grams) infants (range: 0.9% in Puerto Rico to 15.1% in Massachusetts). Among ART-conceived infants, 29.1% were low birthweight (range: 18.3% in Delaware to 42.6% in Louisiana), compared with 8.0% among all infants (range: 5.8% in Alaska to 11.5% in Mississippi). ART-conceived infants contributed to 4.6% of all preterm (<37 weeks) infants (range: 0.6% in Puerto Rico to 13.3% in Massachusetts). Preterm birth rates were higher among infants conceived with ART (33.6%; range: 22.3% in DC to 50.7% in Louisiana) than among all infants born in the total birth population (11.4%; range: 8.8% in California to 16.6% in Mississippi). The percentage of ART-conceived infants who were low birthweight was 9.0% (range: 5.1% in Mississippi to 19.7% in Puerto Rico) among singletons and 56.3% (range: 48.3% in Maine to 72.4% in Puerto Rico) among twins; the corresponding percentages among all infants born were 6.3% for singletons (range: 4.6% in Alaska to 9.6% in Mississippi and Puerto Rico) and 55.3% for twins (range: 43.6% in Alas
We reviewed the occurrence of prematurity, low birth weight, multiple gestations, frequency of stillbirths and maternity care-associated variables including hospital stay and hospital charges of women conceiving using assisted reproductive technology (ART) or artificial insemination (AI) compared with women with a history of infertility who conceived naturally, and all other naturally conceived pregnancies in California at non-federal hospitals between 2009 and 2011. At a single center, infants born after ART/AI were compared with infants provided care in the normal nursery. Publically available inpatient data sets from the California Office of Statewide Health Planning and Development for years 2009-2011 using data from all California non-federal hospitals were used to determine the impact of ART on a variety of pregnancy-related outcomes and infant characteristics. Infant data from a single center was used to determine hospital charges for infants delivered over an 18-month period to compare the hospital and physician charges indexed to similar charges for infants admitted to the 'normal' newborn nursery. Among ART/AI pregnancies, there was a 4-5-fold increase in stillbirths, compared with a 2-3-fold increase among women with infertility compared with other naturally conceiving women. ART/AI pregnancies underwent more cesarean sections (fourfold), and a near fourfold increase in the rate of preterm deliveries. Multiple gestations were increased 24-27-fold compared with naturally conceived pregnancies. Maternal hospital stay and hospital charges were increased among those undergoing ART/AI. Infant charges were increased multi-fold for singletons, twins and triplets delivered after ART/AI compared with naturally conceived infants. Multiple births, preterm births and a higher overall rate of fetal anomalies were found in California after ART/AI for 2009-2011. Cesarean section rates, longer length of maternal stay and hospital charges among women receiving ART/AI could be lowered if emphasis on elective single embryo transfers was a higher priority among providers. Charges for the care of infants delivered after ART/AI are substantially higher than among naturally conceived infants born late preterm or at term. Families seeking ART/AI need to be informed of the impact of these adverse pregnancy outcomes, including neonatal outcomes and charges for medical care for their infant(s), when considering ART/AI.
Bell AF et al., 2014·Journal of midwifery & women's health
Emerging research raises questions that synthetic oxytocin during childbirth may alter the endogenous oxytocin system and influence maternal stress, mood, and behavior. Endogenous oxytocin is a key component in the transition to motherhood, affecting molecular pathways that buffer stress reactivity, support positive mood, and regulate healthy mothering behaviors (including lactation). Synthetic oxytocin is widely used throughout labor and postpartum care in modern birth. Yet research on the implications beyond labor of maternal exposure to perinatal synthetic oxytocin is rare. In this article, we review oxytocin-related biologic pathways and behaviors associated with the transition to motherhood and evidence supporting the need for further research on potential effects of intrapartum oxytocin beyond labor. We include a primer on oxytocin at the molecular level.
Anti-Infective and Anti-Inflammatory Agents · Nonsteroidal Anti-Inflammatory Drugs
Schisterman EF et al., 2013·Paediatr Perinat Epidemiol·
Open Access
Low-dose aspirin (LDA) has been proposed to improve pregnancy outcomes in couples experiencing recurrent pregnancy loss. However, results from studies of LDA on pregnancy outcomes have been inconsistent, perhaps because most studies evaluated LDA-initiated post-conception. The purpose of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial was to determine whether preconception-initiated LDA improves livebirth rates in women with one to two prior losses. We performed a multicentre, block randomised, double-blind, placebo-controlled trial. Study participants were recruited using community-based advertisements and physician referral to four university medical centres in the US (2006-12). Eligible women were aged 18-40 years actively trying to conceive, with one to two prior losses. Participants were randomised to receive daily LDA (81 mg/day) or a matching placebo, and all were provided with daily 400-mcg folic acid. Follow-up continued for ≤6 menstrual cycles while attempting to conceive. For those who conceived, treatment was continued until 36 weeks gestation. The primary outcome was the cumulative livebirth rate over the trial period. There were 1228 women randomised (615 LDA, 613 placebo). Participants had a mean age of 28.7, were mostly white (95%), well educated (86% more than high school education), and employed (75%) with a household income >$100 000 annually (40%). The characteristics of those in the treatment and placebo arms were well balanced. We describe the study design, recruitment, data collection, and baseline characteristics of participants enrolled in EAGeR, which aimed to determine the effect of LDA on livebirth and other pregnancy outcomes in these women.
Novak C et al., 2013·Seminars in Reproductive Medicine
Health disparities are observed in all fields of medicine and reproductive health is not immune to this phenomenon. The incidence of women using infertility treatments to conceive is increasing. Women undergoing assisted reproduction appear to be at increased risk of adverse outcomes, and minority women tend to be at even greater risk. This article examines several adverse obstetrical outcomes including preterm birth, congenital malformations, and preeclampsia among women receiving infertility treatments compared with those who conceive spontaneously. It will further examine societal costs associated with these procedures.
Barnhart KT, 2013·Fertility and Sterility·
Open Access
Interrogating the association between assisted reproductive technologies (ART) and perinatal outcome is complicated but very important. This is an introduction to a series of articles that review this potential association with an eye toward etiology of risk, and what aspects of in vitro fertilization (IVF) can be modified to reduce this risk. When an association is not due to chance (i.e., statistically significant), one must also consider how the association may be affected due to bias or confounding. Despite lack of the perfect study, perinatal consequences of ART are apparent, even though the vast majority of children conceived with ART are healthy. Pregnancy after IVF is altered as evidenced by risk of preterm delivery, low birth weight among infants, and an alerted prevalence of preeclampsia. The long-term clinical implications of ART, such as childhood development and metabolism, have not been established and ongoing study is proceeding. The risk attributed to multiple births is iatrogenic and needs to be minimized. Optimizing the environment at the time a woman conceives will likely have an effect on gestation as well as the health of children. Reproduction effects health and health effects reproduction.
Metabolic and Endocrine Agents · Insulin Sensitizing Agents
Kumar P et al., 2012·J Hum Reprod Sci·
Open Access
Use of metformin throughout pregnancy in women with polycystic ovary syndrome (PCOS) has shown to reduce the rates of early pregnancy loss, preterm labor, and prevention of fetal growth restriction. Metformin has been shown to have encouraging effects on several metabolic aspects of polycystic ovarian syndrome, such as insulin sensitivity, plasma glucose concentration and lipid profile and since women with PCOS are more likely than healthy women to suffer from pregnancy-related problems like early pregnancy loss, gestational diabetes mellitus and hypertensive states in pregnancy, the use of metformin therapy in these patients throughout pregnancy may have beneficial effects on early pregnancy loss and development of gestational diabetes.
To compare the risk of preterm delivery, low birth weight, and admission of the newborn to a neonatal intensive care unit (NICU) in women pregnant after fertility treatment and subfertile women with the risk in fertile women. Prospective follow-up study. Aarhus University Hospital, Skejby, Denmark, 1989-2006. PATIENT(S): A total of 20,080 liveborn singletons. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Preterm delivery, low birth weight, and admission of the newborn to a NICU. RESULT(S): After adjustment we found a statistically significantly increased risk of preterm delivery and very preterm delivery in women who conceived after in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) compared with fertile women. Compared with fertile women, the risk of preterm delivery and very preterm delivery was not statistically significantly different in women pregnant after non-IVF assisted reproductive treatment (non-IVF ART) or subfertile women. We found no association between IVF/ICSI and the risk of low birth weight at term or admittance to the NICU. CONCLUSION(S): The increased risk of preterm delivery after IVF/ICSI may be due to the fertility treatment or unknown characteristics in the couples who undergo IVF/ICSI.
The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter. The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter. The present study is a component of a recently published large-scale prospective trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter. The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter. Women were divided into two groups based on their initial group A, TSH level below 2.5 mIU/liter, excluding hyperthyroid women defined as an undetectable TSH with an elevated free T(4), and group B, TSH level between 2.5 and 5.0 mIU/liter. The study was conducted at two ambulatory clinics of community hospitals in southern Italy. A total of 4123 women were evaluated. There was no intervention. The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured. The rate of pregnancy loss was significantly higher in group B as compared with group A (6.1 vs. 3.6% respectively, P = 0.006). There was no difference in the rate of preterm delivery between the two groups. The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter.
Wisborg K et al., 2010·Human reproduction (Oxford, England)
Previous studies have indicated that the risk of stillbirth is increased in singleton pregnancies achieved after assisted reproduction technology (ART). However, no previous study fully accounted for factors with potential influence on the risk of stillbirth. Further, whether fertility treatment, the possible reproductive pathology of the infertile couples or other characteristics related to being subfertile may explain a possible association with stillbirth remains unclear. This study compares the risk of stillbirth in women pregnant after fertility treatment (IVF/ICSI and non-IVF ART) and subfertile women with that in fertile women. We used prospectively collected data from the Aarhus Birth Cohort, Denmark and included information about 20 166 singleton pregnancies (1989-2006). Outcome measure was stillbirth. The risk of stillbirth in women who conceived after IVF/ICSI was 16.2 per thousand ( per thousand) and in women who conceived after non-IVF ART 2.3 per thousand. In fertile and subfertile women, the risk of stillbirth was 3.7 per thousand and 5.4 per thousand, respectively. Compared with fertile women, women who conceived after IVF/ICSI had more than four times the risk of stillbirth [odds ratio (OR): 4.44, 95% confidence interval (CI): 2.38-8.28], and adjustments for maternal age, BMI, education, smoking habits and alcohol and coffee intake during pregnancy had only minor impact on the findings (OR: 4.08; 95% CI: 2.11-7.93). The risk of stillbirth in women who conceived after non-IVF ART and in women who conceived spontaneously with a waiting time to pregnancy of a year or more was not significantly different from the risk in women with a shorter time to pregnancy. Compared with fertile women, women who conceived by IVF/ICSI had an increased risk of stillbirth that was not explained by confounding. Our results indicate that the increased risk of stillbirth seen after fertility treatment is a result of the fertility treatment or unknown factors pertaining to couples who undergo IVF/ICSI.
Shah PS et al., 2009·BJOG : an international journal of obstetrics and gynaecology
History of induced termination of pregnancy (I-TOP) is suggested as a precursor for infant being born low birthweight (LBW), preterm (PT) or small for gestational age (SGA). Infection, mechanical trauma to the cervix leading to cervical incompetence and scarred tissue following curettage are suspected mechanisms. To systematically review the risk of an infant being born LBW/PT/SGA among women with history of I-TOP. Medline, Embase, CINAHL and bibliographies of identified articles were searched for English language studies. Studies reporting birth outcomes to mothers with or without history of induced abortion were included. and analyses Two reviewers independently collected data and assessed the quality of the studies for biases in sample selection, exposure assessment, confounder adjustment, analytical, outcome assessments and attrition. Meta-analyses were performed using random effect model and odds ratio (OR), weighted mean difference and 95% confidence interval (CI) were calculated. Thirty-seven studies of low-moderate risk of bias were included. A history of one I-TOP was associated with increased unadjusted odds of LBW (OR 1.35, 95% CI 1.20-1.52) and PT (OR 1.36, 95% CI 1.24-1.50), but not SGA (OR 0.87, 95% CI 0.69-1.09). A history of more than one I-TOP was associated with LBW (OR 1.72, 95% CI 1.45-2.04) and PT (OR 1.93, 95% CI 1.28-2.71). Meta-analyses of adjusted risk estimates confirmed these findings. A previous I-TOP is associated with a significantly increased risk of LBW and PT but not SGA. The risk increased as the number of I-TOP increased.
Jonas W et al., 2009·Breastfeeding medicine : the official journal of the Academy of Breastfeeding Medicine
Oxytocin and prolactin stimulate milk ejection and milk production during breastfeeding. The aim of the present study was to make a detailed analysis of maternal release of oxytocin and prolactin in response to breastfeeding during the second day postpartum in mothers who had received oxytocin either intravenously for stimulation of labor or intramuscularly for prevention of postpartum hemorrhage and/or epidural analgesia or those who had received no such treatment in connection with birth. In a descriptive comparative study plasma oxytocin and prolactin concentrations were measured in response to suckling during the second day postpartum in women who had received intravenous intrapartum oxytocin (n = 8), intramuscular postpartum oxytocin (n = 13), or epidural analgesia, either with (n = 14) or without (n = 6) intrapartum oxytocin infusion, and women who received none of these interventions (n = 20). Hormone levels were analyzed by enzyme immunoassay. All mothers showed a pulsatile oxytocin pattern during the first 10 minutes of breastfeeding. Women who had received epidural analgesia with oxytocin infusion had the lowest endogenous median oxytocin levels. The more oxytocin infusion the mothers had received during labor, the lower their endogenous oxytocin levels were during a breastfeeding during the second day postpartum. A significant rise of prolactin was observed after 20 minutes in all women, but after 10 minutes in mothers having received oxytocin infusion during labor. In all women, oxytocin variability and the rise of prolactin levels between 0 and 20 minutes correlated significantly with median oxytocin and prolactin levels. Oxytocin, released in a pulsatile way, and prolactin were released by breastfeeding during the second day postpartum. Oxytocin infusion decreased endogenous oxytocin levels dose-dependently. Furthermore, oxytocin infusion facilitated the release of prolactin. Epidural analgesia in combination with oxytocin infusion influenced endogenous oxytocin levels negatively.
We postulated that impaired endometrial differentiation in women with pelvic endometriosis predisposes for pre-eclampsia. A retrospective case-control study set at the University of Ghent IVF centre. The incidence of pre-eclampsia and pregnancy-induced hypertension (PIH) following the clinical and/or laparoscopic diagnosis of endometriosis-associated infertility (case group; n = 245 pregnancies) was compared with the incidence of these obstetric complications in pregnancies following treatment for male-factor infertility (control group; n = 274 pregnancies). Pregnancy data were obtained by searching electronic databases and postal questionnaires. The case and control groups were matched for age, parity and multiple pregnancies. The incidence of pre-eclampsia was significantly lower in the case group (0.8%) when compared with control group (5.8%) (P = 0.002; odds ratio (OR) = 7.5, 95% confidence interval (CI): 1.7-33.3). Analysis of obstetric outcome in the subgroup of patients with laparoscopic data confirmed the lower risk of pre-eclampsia in the case (1.2%) versus control (7.4%) groups (P = 0.032; OR = 6.6, 95% CI: 1.2-37). PIH occurred in 3.5% and 8.7% of case and control pregnancies, respectively (P = 0.018; OR = 2.6, 95% CI: 1.2-6.0). The odds of developing pre-eclampsia were 5.67 times higher in the control group than in pregnancies following endometriosis-associated infertility. In multiple pregnancies, the odds of developing pre-eclampsia increased 1.93 times per additional child, with or without endometriosis. We found no evidence that endometriosis predisposes for pre-eclampsia. Instead, the risk of hypertensive disorder in pregnancy is significantly reduced in women with endometriosis-associated infertility.
To evaluate whether the use of 17alpha-hydroxyprogesterone caproate for the prevention of recurrent preterm deliveries is cost-effective. Using decision-analysis modeling, we compared the cost-effectiveness of using 17alpha-hydroxyprogesterone caproate in four subgroups: 1) Prior preterm deliveries less than 32 weeks; 2) prior preterm deliveries 32-37 weeks; 3) prior term delivery; and 4) no prior delivery. Each subgroup was compared with a "no treatment" group. Costs included those for 17alpha-hydroxyprogesterone caproate, hospital admissions, and complications from preterm deliveries. The main outcome measures include cost per quality-adjusted life-year gained and the number of preterm deliveries prevented. Secondary outcomes include neonatal complications prevented. One-way and multiway sensitivity analyses were performed. The use of 17alpha-hydroxyprogesterone caproate for the prevention of preterm deliveries result in cost-savings in women with prior preterm deliveries less than 32 weeks and 32-37 weeks. The sensitivity analyses revealed the model to be robust over a wide range of values for evaluated variables. Within our baseline assumptions, 17alpha-hydroxyprogesterone caproate was associated with cost-savings when used for the prevention of preterm deliveries in women with prior preterm deliveries.
Metabolic and Endocrine Agents · Thyroid Replacement
Euthyroid women with autoimmune thyroid disease show impairment of thyroid function during gestation and seem to suffer from a higher rate of obstetrical complications. We sought to determine whether these women suffer from a higher rate of obstetrical complications and whether levothyroxine (LT(4)) treatment exerts beneficial effects. This was a prospective study. The study was conducted in the Department of Obstetrics and Gynecology. A total of 984 pregnant women were studied from November 2002 to October 2004; 11.7% were thyroid peroxidase antibody positive (TPOAb(+)). TPOAb(+) patients were divided into two groups: group A (n = 57) was treated with LT(4), and group B (n = 58) was not treated. The 869 TPOAb(-) patients (group C) served as a normal population control group. Rates of obstetrical complications in treated and untreated groups were measured. At baseline, TPOAb(+) had higher TSH compared with TPOAb(-); TSH remained higher in group B compared with groups A and C throughout gestation. Free T(4) values were lower in group B than groups A and C after 30 wk and after parturition. Groups A and C showed a similar miscarriage rate (3.5 and 2.4%, respectively), which was lower than group B (13.8%) [P < 0.05; relative risk (RR), 1.72; 95% confidence interval (CI), 1.13-2.25; and P < 0.01; RR = 4.95; 95% CI = 2.59-9.48, respectively]. Group B displayed a 22.4% rate of premature deliveries, which was higher than group A (7%) (P < 0.05; RR = 1.66; 95% CI = 1.18-2.34) and group C (8.2%) (P < 0.01; RR = 12.18; 95% CI = 7.93-18.7). Euthyroid pregnant women who are positive for TPOAb develop impaired thyroid function, which is associated with an increased risk of miscarriage and premature deliveries. Substitutive treatment with LT(4) is able to lower the chance of miscarriage and premature delivery.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY·
Preterm birth remains a leading cause of perinatal mortality, with rates in the United States rising significantly over the latter half of the twentieth century despite decades of awareness. NaProTechnology's integrated prevention approach, developed at the Pope Paul VI Institute, addresses this problem through systematic risk stratification, hormonal support, infection surveillance, and cervical monitoring across the full course of pregnancy.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY·
Management of pregnancies complicated by lethal fetal anomalies is addressed within an ethical framework that provides perinatal palliative care, parental support, and medical management without recourse to induced abortion. The chapter outlines clinical protocols for continuing care that respect fetal life while attending to maternal physical and psychological wellbeing through delivery and bereavement.
Preterm birth affects 12% of all births in the United States. Recent studies support the hypothesis that progesterone supplementation reduces preterm birth in a select group of women (ie, those with a prior spontaneous birth at <37 weeks of gestation). Despite the apparent benefits of progesterone in this high-risk population, the ideal progesterone formulation is unknown. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice believes that further studies are needed to evaluate the use of progesterone in patients with other high-risk obstetric factors, such as multiple gestations, short cervical length, or positive test results for cervicovaginal fetal fibronectin. When progesterone is used, it is important to restrict its use to only women with a documented history of a previous spontaneous birth at less than 37 weeks of gestation because unresolved issues remain, such as optimal route of drug delivery and long-term safety of the drug.
This review addresses questions related to medicosocial concerns surrounding the care of women with multiple births and their infants. Relevant articles and texts on twin and triplet pregnancies were reviewed. Population-based data were selected for inclusion whenever possible. Relevant tables were simplified from original sources. The review clarifies obstetric and perinatal questions in a manner that is helpful to clinicians and their patients.
To review the evidence of effectiveness of prenatal care for preventing low birth weight (LBW). We reviewed original research, systematic reviews, meta-analyses and commentaries for evidence of effectiveness of the three core components of prenatal care--risk assessment, health promotion and medical and psychosocial interventions--for preventing the two constituents of preterm birth and intrauterine growth restriction (IUGR). Clinical risk assessment will fail to identify the majority of pregnancies at risk for preterm delivery or IUGR. While biophysical and biochemical modalities appear promising, their cost-effectiveness has not been demonstrated, nor can their routine use be recommended in the absence of effective interventions. Smoking cessation programs appear to be modestly effective. There is insufficient evidence to conclude a benefit for nutrition interventions, work counseling or preterm birth education. Only antenatal corticosteroid therapy has demonstrated a clear benefit in the tertiary prevention of preterm delivery. Interventions for which there is insufficient evidence to conclude a benefit include bed rest, hydration, sedation, cerclage, progesterone supplementation, antibiotic treatment, tocolysis without concomitant use of corticosteroids, thyrotropin-releasing hormone, psychosocial support and home visitation. Additionally, there is a paucity of evidence supporting the effectiveness of prenatal interventions, such as low-dose aspirin, bed rest, maternal hyperoxygenation, plasma volume expansion and antenatal fetal assessment, in preventing IUGR or its associated morbidity and mortality. Neither preterm birth nor IUGR can be effectively prevented by prenatal care in its present form. Preventing LBW will require reconceptualization of prenatal care as part of a longitudinally and contextually integrated strategy to promote optimal development of women's reproductive health not only during pregnancy, but over the life course.
Women who have had a spontaneous preterm delivery are at greatly increased risk for preterm delivery in subsequent pregnancies. The results of several small trials have suggested that 17 alpha-hydroxyprogesterone caproate (17P) may reduce the risk of preterm delivery. We conducted a double-blind, placebo-controlled trial involving pregnant women with a documented history of spontaneous preterm delivery. Women were enrolled at 19 clinical centers at 16 to 20 weeks of gestation and randomly assigned by a central data center, in a 2:1 ratio, to receive either weekly injections of 250 mg of 17P or weekly injections of an inert oil placebo; injections were continued until delivery or to 36 weeks of gestation. The primary outcome was preterm delivery before 37 weeks of gestation. Analysis was performed according to the intention-to-treat principle. Base-line characteristics of the 310 women in the progesterone group and the 153 women in the placebo group were similar. Treatment with 17P significantly reduced the risk of delivery at less than 37 weeks of gestation (incidence, 36.3 percent in the progesterone group vs. 54.9 percent in the placebo group; relative risk, 0.66 [95 percent confidence interval, 0.54 to 0.81]), delivery at less than 35 weeks of gestation (incidence, 20.6 percent vs. 30.7 percent; relative risk, 0.67 [95 percent confidence interval, 0.48 to 0.93]), and delivery at less than 32 weeks of gestation (11.4 percent vs. 19.6 percent; relative risk, 0.58 [95 percent confidence interval, 0.37 to 0.91]). Infants of women treated with 17P had significantly lower rates of necrotizing enterocolitis, intraventricular hemorrhage, and need for supplemental oxygen. Weekly injections of 17P resulted in a substantial reduction in the rate of recurrent preterm delivery among women who were at particularly high risk for preterm delivery and reduced the likelihood of several complications in their infants.
It has become almost a platitude to lament the complexity and intractability of the problem of preterm delivery, the poor predictive value of screening tests for its occurrence, its resistance to attempted interventions, and its increasing rate.1 Preterm delivery is more common among blacks, the poor, the unmarried, cigarette smokers, underweight women, women with multiple gestations, women with uterine anomalies, women with a history of previous preterm delivery, and women without prenatal care. Although the perinatal mortality rate due to prematurity has decreased dramatically during the past three decades, this reduction has resulted from improvements in perinatal and pediatric care . . .
Guidelines by Clinical Area · Obstetric Guidelines
The purpose of this study was to evaluate the effect of prophylactic vaginal progesterone in decreasing preterm birth rate in a high-risk population. A randomized, double-blind, placebo-controlled study included 142 high-risk singleton pregnancies. Progesterone (100 mg) or placebo was administered daily by vaginal suppository and all patients underwent uterine contraction monitoring with an external tocodynamometer once a week for 60 minutes, between 24 and 34 weeks of gestation. Progesterone (n = 72) and placebo (n = 70) groups were compared for epidemiologic characteristics, uterine contraction frequency, and incidence of preterm birth. Data were compared by chi(2) analysis and Fisher exact test. The preterm birth rate was 21.1% (30/142). Differences in uterine activity were found between the progesterone and placebo groups (23.6% vs 54.3%, respectively; P <.05) and in preterm birth between progesterone and placebo (13.8% vs 28.5%, respectively; P <.05). More women were delivered before 34 weeks in the placebo group (18.5%) than in the progesterone group (2.7%) (P <.05). Prophylactic vaginal progesterone reduced the frequency of uterine contractions and the rate of preterm delivery in women at high risk for prematurity.
To estimate the relationship of assisted reproductive technologies and ovulation-inducing drugs with preeclampsia in multiple gestations. This historical cohort study was conducted on 528 multiple gestations from a Colorado health maintenance organization. Using univariate and logistic regression analysis, we determined if women who conceived a multiple gestation as a result of assisted conception were at a greater risk of preeclampsia than those who conceived spontaneously. Between January 1994 and November 2000, there were 330 unassisted and 198 assisted multiple gestations. Sixty-nine multiple gestations followed assisted reproductive technologies (in vitro fertilization and gamete intrafallopian transfer). Human menopausal gonadotropins and clomiphene citrate were associated with 38 and 91 of the multiple gestations, respectively. Compared with unassisted multiple gestations, the relative risk of mild or severe preeclampsia among mothers who received assisted reproductive technologies was 2.7 (95% confidence interval [CI] 1.7, 4.7) and 4.8 (CI 1.9, 11.6), respectively. Adjusted for maternal age and parity, women who received assisted reproductive technologies were two times more likely to develop preeclampsia (odds ratio 2.1, CI 1.1, 4.1) compared with those who conceived spontaneously. The adjusted odds ratios of nulliparity and maternal age for preeclampsia were 2.1 (CI 1.3, 3.4) and 1.1 (CI 1, 1.1), respectively. Although the incidence of preeclampsia was greater in mothers who received clomiphene citrate and human menopausal gonadotropins, this association did not reach statistical significance at the P <.05 level. Women who conceive multiple gestations through assisted reproductive technologies have a 2.1-fold higher risk of preeclampsia than those who conceive spontaneously.
We examined the hypothesis that amniotic fluid (AF) infection and elevated cytokine concentrations may cause neonatal injury beyond that expected solely from prematurity. The effects of exposure to AF infection and elevated cytokine concentrations were measured in 151 infants born to afebrile women in preterm labor with intact membranes at less than or equal to 34 weeks' gestation. Amniotic fluid was collected by amniocentesis for culture and determination of tumor necrosis factor-alpha and interleukin-6. Cytokine concentrations, stratified by AF infection, were compared for three gestational age groups. We then examined the associations between a positive AF culture or elevated AF tumor necrosis factor-alpha concentration and adverse neonatal outcomes, adjusted for birth weight. Amniotic fluid from 45 (30%) of 151 pregnancies had microorganisms, an elevated tumor necrosis factor-alpha concentration, or both. Amniotic fluid cytokine concentrations were significantly higher among women in preterm labor at less than or equal to 30 weeks, compared with 31-34 weeks. Nine of 11 infants who died at less than or equal to 24 hours of age had AF infection or elevated AF tumor necrosis factor-alpha. For the 140 surviving infants, AF infection and/or an elevated AF tumor necrosis factor-alpha was associated with respiratory distress syndrome (adjusted odds ratio [OR] 1.7), grade 3-4 intraventricular hemorrhage (adjusted OR 2.2), necrotizing enterocolitis (adjusted OR 1.8), and multiple organ dysfunction (adjusted OR 3.0). Among infants born at less than or equal to 34 weeks to women who have intact membranes and are initially afebrile, those exposed to AF bacteria or cytokines have more adverse neonatal outcomes than unexposed infants of similar birth weight.
Although shortened cervical length has been consistently associated with spontaneous preterm birth, it is not known when in gestation this risk factor becomes apparent. To determine whether sonographic cervical findings between 16 weeks' and 18 weeks 6 days' gestation predict spontaneous preterm birth and whether serial evaluations up to 23 weeks 6 days' gestation improve prediction in high-risk women. DESIGN, SETTING, Blinded observational study performed between March 1997 and November 1999 at 9 university-affiliated medical centers in the United States in 183 women with singleton gestations who previously had experienced a spontaneous birth before 32 weeks' gestation. Certified sonologists performed 590 endovaginal sonographic examinations at 2-week intervals. Cervical length was measured from the external os to the functional internal os along a closed endocervical canal. Funneling and dynamic cervical shortening were also recorded. Spontaneous preterm birth before 35 weeks' gestation, analyzed by selected cutoff values of cervical length. Forty-eight women (26%) experienced spontaneous preterm birth before 35 weeks' gestation. A cervical length of less than 25 mm at the initial sonographic examination was associated with a relative risk (RR) for spontaneous preterm birth of 3.3 (95% confidence interval [CI], 2.1-5.0; sensitivity = 19%; specificity = 98%; positive predictive value = 75%). After controlling for cervical length, neither funneling (P =.24) nor dynamic shortening (P =.054) were significant independent predictors of spontaneous preterm birth. However, using the shortest ever observed cervical length on serial evaluations, after any dynamic shortening, the RR of a cervical length of less than 25 mm for spontaneous preterm birth increased to 4.5 (95% CI, 2.7-7.6; sensitivity = 69%; specificity = 80%; positive predictive value = 55%). Compared with a single cervical measurement at 16 weeks' to 18 weeks 6 days' gestation, serial measurements at up to 23 weeks 6 days significantly improved the prediction of spontaneous preterm birth in a receiver operating characteristic curve analysis (P =.03). Cervical length assessed by endovaginal sonography between 16 weeks' and 18 weeks 6 days' gestation, augmented by serial evaluations, predicts spontaneous preterm birth before 35 weeks' gestation in high-risk women.
To examine prenatal, maternal, and infant outcomes and costs through 1 year after delivery using a model of prenatal care for women at high risk of delivering low-birth-weight infants in which half of the prenatal care was provided in women's homes by nurse specialists with master's degrees. Randomized clinical trial. A sample of 173 women (and 194 infants) with high-risk pregnancies (gestational or pregestational diabetes mellitus, chronic hypertension, preterm labor, or high risk of preterm labor) were randomly assigned to the intervention group (85 women and 94 infants) or the control group (88 women and 100 infants). Control women received usual prenatal care. Intervention women received half of their prenatal care in their homes, with teaching, counseling, telephone outreach, daily telephone availability, and a postpartum home visit by nurse specialists with physician backup. For the full sample, mean maternal age was 27 years; 85.5% of women were single mothers, 36.4% had less than a high school education, 93.6% were African American, and 93.6% had public health insurance, with no differences between groups on these variables. The intervention group had lower fetal/infant mortality vs the control group (2 vs 9), 11 fewer preterm infants, more twin pregnancies carried to term (77.7% vs 33.3%), fewer prenatal hospitalizations (41 vs 49), fewer infant rehospitalizations (18 vs 24), and a savings of more than 750 total hospital days and $2,496,145 [corrected]. This model of care provides a reasoned solution to improving pregnancy and infant outcomes while reducing healthcare costs.
To determine the association between indomethacin tocolysis and neonatal intraventricular hemorrhage. Fifty-six preterm neonates with intraventricular hemorrhage were matched by gestational age with neonates (n = 224) without this morbidity. Maternal and neonatal charts were reviewed to ascertain the type of tocolytic exposure experienced by the neonate. Other maternal and neonatal demographic and outcome data were also abstracted. Results were analyzed using the Student t test, chi(2) analysis, and multivariable logistic regression. The number of studied subjects provided 80% power to determine if antenatal exposure to indomethacin was twice as likely among infants with intraventricular hemorrhage. Univariate analysis revealed that there were no significant differences between the study and control groups with respect to maternal age, parity, or betamethasone exposure. Infants with intraventricular hemorrhage were significantly more likely to be born at an earlier gestational age, a lower birth weight, after maternal chorioamnionitis, after vaginal delivery, and after exposure to either indomethacin alone or a combination of indomethacin and magnesium. Additionally, their neonatal course was significantly more likely to be complicated by sepsis and respiratory distress syndrome. In a multivariable logistic model, only gestational age, chorioamnionitis, vaginal delivery, and respiratory distress syndrome continued to be significantly associated with intraventricular hemorrhage. Indomethacin exposure, either as single-agent (adjusted odds ratio 1.3, 95% confidence interval 0.5, 3.3) or combination tocolytic therapy (adjusted odds ratio 2.0, 95% confidence interval 0.8, 4.8), was not significantly associated with intraventricular hemorrhage. Indomethacin tocolysis is not associated with an increased risk of intraventricular hemorrhage.
To evaluate maternal serum tumor necrosis factor-alpha (TNF alpha) levels in patients with preterm labor without clinical signs of chorioamnionitis and to compare these with levels in nonlaboring controls. The study group consisted of 44 patients with a singleton pregnancy admitted to our department with the diagnosis of preterm labor between 26 and 36 weeks' gestation. The control group consisted of 25 healthy consecutive patients with a singleton pregnancy without preterm contractions who were seen for routine antenatal visits. Maternal serum TNF alpha was measured using a solid-phase, two-site chemiluminescent enzyme immunometric assay method, and levels were compared in patients with preterm labor and nonlaboring controls. The median maternal serum TNF alpha level for patients with preterm labor was 29.4 pg/mL (range, 12.3-173) as compared with 23 pg/mL (range, 11.9-62.7) in the control group (P = .031). Among 44 patients with preterm labor, 14 (32%) delivered within one week of admission. The median maternal serum TNF alpha level was significantly higher in patients who delivered within one week than in those who delivered after one week and controls (71.3 pg/mL [range, 28-173]) versus 22 pg/mL (range, 12.3-86) versus 23 pg/mL (range, 11.9-62.7) (P < .0001). TNF alpha was elevated in patients with preterm labor, suggesting a role for maternal serum TNF alpha in its initiation.
To evaluate serial measurements of salivary estriol (E3) to detect increased risk of spontaneous preterm labor and preterm birth. A masked, prospective, multicenter trial of 956 women with singleton pregnancies was completed at eight United States medical centers. Saliva was collected weekly, beginning at the 22nd week of gestation until birth, and tested for unconjugated E3 by enzyme-linked immunosorbent assay. Women were separated into high-risk and low-risk groups using the Creasy scoring system. A single, positive (at or above 2.1 ng/mL) salivary E3 test predicted an increased risk of spontaneous preterm labor and delivery in the total population (relative risk [RR] 4.0, P <.005), in the low-risk population (RR 4.0, P < or =.05), and in the high-risk population (RR 3.4, P =.05). Two consecutive positive tests significantly increased the RR in all study groups, with a dramatic improvement in test specificity and positive predictive value but only a modest decrease in sensitivity. In women who presented with symptomatic preterm labor, salivary E3 identified 61% of those who delivered within 2 weeks, using a threshold of 1.4 ng/mL. Elevated salivary E3 is associated with increased risk of preterm birth in asymptomatic women and symptomatic women who present for evaluation of preterm labor.
To determine whether the degree of cervical lengthening after cerclage and whether serial follow-up measurements of cervical length after cerclage are predictive of pregnancy outcome. Eighty women whose primary physician determined that a prophylactic (n = 50) or urgent cerclage (n = 30) was indicated had transvaginal ultrasonographic evaluation before and after cerclage. Thereafter, most women had three additional transvaginal ultrasound examinations until 32 weeks' gestation. At each examination, the mean of three measurements was calculated. Statistical analyses were done by t test, analysis of variance, and logistic regression, with significance set at P <.05. The mean +/- standard deviation precerclage cervical length was 27.2 +/- 10.3 mm and after cerclage was 34.1 +/- 9.9 mm (n = 80, P <.001, paired t test). No significant association was found (r = -0.26) between the difference in cervical length (postcerclage - precerclage lengths) and pregnancy outcome. Patients with a prophylactic cerclage had a mean cervical length that was consistently longer in patients delivering at term compared with those who delivered preterm at 20 to 32 weeks' gestation. In the urgent cerclage group a significant difference in cervical length between those who delivered at term compared with preterm was evident only at 28 to 32 weeks. The increase in cervical length after cerclage is not predictive of term delivery. Serial cervical length measurements in the late second or early third trimester predict preterm birth but could provide earlier warning in patients with a prophylactic cerclage than in patients with urgent cerclage.
To evaluate the potential role of amniotic fluid (AF) interleukin (IL)-6 as a predictor of preterm delivery and to consider possible explanations for the proportion of women with elevated AF IL-6 who deliver preterm yet lack microbiologically detectable intra-amniotic infection. We searched the English language human literature in MEDLINE, 1966 through September 1999, using the keywords "labor/infant," "premature," "cytokines/interleukin-6," and "AF." We also examined abstracts from the 1999 meetings of the Society for Maternal-Fetal Medicine and the Society for Epidemiologic Research. We identified other studies by reviewing the reference lists of published articles. The MEDLINE search yielded 55 citations. We focused on studies that reported on the association between AF IL-6 and preterm delivery. TABULATION, INTEGRATION, There is consensus in the literature that elevated AF IL-6 is a stronger predictor of preterm delivery than intra-amniotic infection detected by either microbiologic culture or polymerase chain reaction (PCR). Among women with elevated AF IL-6, PCR could detect a higher proportion of intra-amniotic infection than culture. A number of women with elevated AF IL-6 (33-70%) deliver preterm and do not have evidence of intra-amniotic infection by either culture or PCR. Possible explanations for this observation are considered. Elevated AF IL-6 is strongly associated with preterm delivery and merits future consideration in clinical settings to predict preterm delivery and guide patient care. Development of improved polymerase chain reaction-based clinical methods to detect intra-amniotic infection is necessary to better understand the relationship between elevated AF IL-6, intra-amniotic infection, and preterm delivery.
To quantify the contribution of in vitro fertilization (IVF) on changes in the rates of low birth weight (LBW), preterm delivery, very low birth weight, and multiple births during the past 3 years. Data on IVF pregnancies from 1994 to 1996 within Alberta were reviewed. Population data were obtained from the Provincial notice of a live or stillbirth. The IVF component of increased LBW rate in the province was 17.8% for infants <2500 g and 43.5% for those born <1500 g. IVF accounted for 10.5% of the provincial rate increase in deliveries <37 weeks' gestation and 66.2% of those <30 weeks' gestation. IVF accounted for 21.4% of the twins and all of the sets of triplets in the province. During a 3-year period IVF has affected the incidence of LBW, preterm delivery, and multiple birth. IVF is a substantial contributor to changes in very low birth weight and delivery before 30 weeks, which is partly related to multiple births.
To assess maternal morbidity, and neonatal outcome and especially long term sequelae in infants born preterm due to maternal or fetal indications.
Analysis of retrospective cohort.
Oulu University Central Hospital, Finland. Population: One hundred and three women, who were between the 24th and the 33rd week of pregnancy, delivered by caesarean delivery because of maternal or fetal indications. They were matched with 103 women who had spontaneous preterm delivery at corresponding gestational weeks between 1990-1997. Maternal morbidity, reasons for caesarean delivery, neonatal mortality and morbidity rates, and later development of the infants. Pre-eclampsia was diagnosed in 57% of the women in the indicated group and only in one woman in the control group. All infants in the indicated group and almost a third in the control group were born by caesarean birth; the main indication was threatening fetal asphyxia. There was a significant difference in neonatal mortality rates between the groups (175 vs 78 per thousand live births in the indicated vs control infants; RR 2.3, 95% CI 1.02, 4.9) and the main cause of death was respiratory insufficiency: 64% in the indicated group and 22% in the controls; RR 2.9, 95% CI 0.8, 10. Respiratory distress syndrome occurred more often (73% vs 53%, RR 1.4, 95% CI 1.1, 1.7) and it was more severe and more complicated in infants in the indicated group, compared with those in the control group. Symptomatic chronic lung disease at one year of age was more common in infants in the indicated group than in the control group (15% vs 3%; RR 4.6, 95% CI 1.4, 15.9). Not only the risks of neonatal mortality and morbidity but also long term pulmonary consequences, appear to be greater in infants born preterm by indicated delivery than in preterm infants born spontaneously at corresponding weeks.
We compared nifedipine and ritodrine for treatment of preterm labor with respect to neonatal outcome. We conducted an open randomized multicenter study of neonatal outcome in 185 women who received either oral nifedipine (n = 95) or intravenous (IV) ritodrine (n = 90) for treatment of preterm labor. Secondary outcome measures included neonatal mortality and morbidity, especially neonatal intensive care unit (NICU) admission, respiratory distress syndrome (RDS), and intracranial bleeding. There were no significant differences in umbilical artery pH values and Apgar scores between groups. Nifedipine was associated with lower admission rates to the NICU (49% versus 66%; odds ratio 0. 51, confidence interval 0.28, 0.93) compared with ritodrine, and lower incidences of RDS (21% versus 37%; 0.46, 0.24, 0.89), intracranial bleeding (18% versus 31%; 0.48, 0.24, 0.96), and neonatal jaundice (52% versus 67%; 0.53, 0.29, 0.97). Logistic regression analysis showed that even after correction for gestational age at birth, newborn risk of RDS, intracranial bleeding, or neonatal jaundice was significantly lower in the nifedipine group than the ritodrine group. Nifedipine for treatment of preterm labor was associated with a lower incidence of neonatal morbidity than ritodrine. That difference appeared to be partly because of the higher tocolytic efficacy of nifedipine and partly because of an intrinsic beneficial effect of nifedipine, or the lack of harmful effects when compared with ritodrine.
Prescribing Safety · Medication Safety in Pregnancy
To examine the effectiveness of any tocolytic compared with a placebo or no tocolytic for preterm labor. We checked MEDLINE (1966-1998) and the Cochrane Controlled Trials Register for articles, using the search terms "randomized controlled trial" (RCT), "preterm labor," "tocolysis," "betamimetics," "ritodrine," "terbutaline," "hexaprenaline," "isoxuprine," "prostaglandin synthetase inhibitors," "indomethacin," "sulindac," "calcium channel blockers," "nifedipine," "oxytocin receptor blockers," "atosiban," "nitroglceride," and "magnesium sulfate." We included all RCTs that compared effect of a tocolytic with a placebo or no tocolytic in women in preterm labor, and reported perinatal, neonatal, or maternal outcomes. Studies were excluded if loss to follow-up exceeded 20% of those originally enrolled, or if data were not reported on a per-patient-treated basis. Eighteen of 76 articles retrieved met the inclusion criteria. TABULATION, INTEGRATION, Two authors independently reviewed the articles and abstracted the data. Discrepancies were resolved by consensus. Meta-analyses (odds ratio [OR] and 95% confidence interval [CI]) were done for each outcome for all trials and for specific types of tocolytic therapy when possible. Tocolytics decreased the risk of delivery within 7 days (OR 0.60, 95% CI 0.38, 0.95). Betamimetics, indomethacin, atosiban, and ethanol, but not magnesium sulfate, were associated with significant prolongations in pregnancy. Tocolytics were not associated with improved perinatal outcomes. Maternal side effects significantly associated with tocolytic use were palpitations, nausea, tremor, chorioamnionitis, hyperglycemia, hypokalemia, and need to discontinue treatment. Although tocolytics prolong pregnancy, they have not been shown to improve perinatal or neonatal outcomes and have adverse effects on women in preterm labor.
We sought to determine the predictive accuracy for preterm delivery of transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation in high-risk patients and to determine whether cerclage prevents preterm delivery in patients with ultrasonographic cervical changes. Patients with asymptomatic singleton pregnancies at high risk for preterm delivery were followed prospectively from 14 weeks' to 23 weeks 6 days' gestation with transvaginal ultrasonography of the cervix. The subgroup of patients with either a cervical length of <25 mm or funneling of >25% or both was offered McDonald salvage cerclage, which was performed at the discretion of the patient and the obstetrician. The 2 groups (with and without cerclage) were compared for the primary outcome of preterm delivery at <35 weeks' gestation. One hundred sixty-eight women were followed, including 97 (58%) with >/=1 prior 14- to 34-week preterm deliveries. Of 63 (37. 5%) patients identified as having cervical changes, 23 (37%) had preterm delivery; of 105 patients with no cervical changes, 8 (8%) had preterm delivery (relative risk, 4.8; 95% confidence interval, 2. 3-10.1). The sensitivity, specificity, and positive and negative predictive values of either a short cervix of <25 mm or funneling of >25% or both were 74%, 70%, 37%, and 92%, respectively. Of 63 pregnancies in which there were cervical changes, 39 underwent cerclage and 24 did not. These 2 groups were similar for demographic characteristics, risk factors, and transvaginal ultrasonographic cervical length and funneling but dissimilar for gestational age at identification of cervical changes (18.3 vs 21.2 weeks' gestation in the groups with and without cerclage, respectively; P <.001). Multivariate logistic regression analysis after adjustment for gestational age at cervical changes showed no difference in the rate of preterm delivery between the groups with and without cerclage (odds ratio, 1.1; 95% confidence interval, 0.3-4.6). Stratified analysis of patients identified between 18 and 24 weeks revealed 22 pregnancies with cerclage and 22 pregnancies without cerclage, which was similar for all characteristics studied. The incidence of preterm delivery remained similar (27% vs 23%, respectively; P =.7), as did days from cervical changes to delivery (111 vs 96, respectively; P =.2). Transvaginal ultrasonography of the cervix between 14 and 24 weeks' gestation is a good predictor of preterm delivery in high-risk pregnancies. Cerclage may not prevent preterm delivery in patients identified to be at high risk for this outcome by transvaginal ultrasonography.
To determine the accuracy of amniotic fluid (AF) matrix metalloproteinase-9 measurements for diagnosing intra-amniotic infection in women with preterm labor. We performed amniocenteses in 44 women between 22 and 35 weeks' gestation who presented to our center with preterm labor and clinical suspicion of intra-amniotic infection. Each sample was analyzed by glucose measurement, Gram stain, and culture for aerobes, anaerobes, and mycoplasmas. We tested the AF for matrix metalloproteinase-9 using gelatin zymography and a commercial enzyme-linked immunosorbent assay (ELISA) system. We calculated accuracy and confidence intervals (CIs) for AF matrix metalloproteinase-9, glucose, and Gram stain for diagnosing intra-amniotic infection, using culture as the criterion standard. All patients who had matrix metalloproteinase-9 detectable by ELISA also demonstrated matrix metalloproteinase-9 by zymography. Six cases of intra-amniotic infection were confirmed by culture (prevalence 14%). The performance statistics of AF matrix metalloproteinase-9 for diagnosing intra-amniotic infection were: sensitivity 83% (95% CI 53, 99), specificity 95% (95% CI 88, 99), positive predictive value 71% (95% CI 37, 99), and negative predictive value 97% (95% CI 92, 99). Two women had false-positive results; one had gram-negative rods on the AF Gram stain and developed clinical signs and symptoms of chorioamnionitis several hours after amniocentesis and the other had a purulent vaginal discharge and an AF glucose level less than 15 mg/dL. Both delivered within 24 hours of amniocentesis. Measuring matrix metalloproteinase-9 in the AF appeared to be reliable for diagnosing intra-amniotic infection. An elevated matrix metalloproteinase-9 concentration in the AF at a preterm gestational age may portend imminent delivery regardless of microbiologic confirmation of intra-amniotic infection.
To determine changes in length of incompetent cervices after cerclage, using transvaginal ultrasound. Patients were enrolled in a prospective, observational study under an Institutional Review Board-approved protocol. McDonald or Shirodkar sutures were placed according to physician preference. Pre- and postcerclage cervical lengths were measured within 72 hours of the procedure. At each examination, the first measurement was discarded, and a mean of the subsequent three measurements was calculated. Twenty-one Shirodkar and ten McDonald operations were done. The mean (+/- standard deviation) precerclage cervical length was 2.7+/-0.9 cm and the postcerclage cervical length was 3.6+/-0.9 cm (P<.001, paired t test). Prophylactic cerclage results in measurable increases in cervical length, which might contribute to the success of the procedure. Further study is needed to determine whether the degree of cervical lengthening after cerclage predicts term delivery.
To determine whether adrenomedullin levels in amniotic fluid were associated with preterm labor. We measured immunoreactive adrenomedullin in amniotic fluid collected by amniocentesis from 36 women with clinical diagnosis of preterm labor or preterm premature rupture of membranes (PROM) and from 18 normal pregnant women. Amniotic fluid from cases of PROM and failure to respond to tocolysis were associated significantly with higher amniotic fluid adrenomedullin concentrations (177.0 +/- 22.5 pg/mL and 182.7 +/- 22.0 pg/mL, respectively, P < .01) than that from uncomplicated pregnancies (101.2 +/- 28.1 pg/mL) or preterm labor responsive to tocolysis (102.3 +/- 26.8 pg/mL). Amniotic fluid adrenomedullin is higher than normal in cases of PROM and preterm labor unresponsive to tocolysis, perhaps indicating enhanced synthesis from placenta or fetal membranes being stimulated by bacterial products.
Our goal was to study the effect of therapeutic McDonald cerclage on cervical length with the use of transvaginal ultrasonography. Cervical length was measured serially in singleton pregnancies in which there were doubts regarding cervical competence. When shortening of the cervix was substantial before 27 weeks' gestation a McDonald cerclage was applied. Wilcoxon signed rank test was used, and 1-tailed P <.05 was considered significant. In the 34 pregnancies studied, the mean cervical length measured at a mean gestational age of 14 weeks had decreased significantly (P <.0001) from 42 mm (95% confidence interval 38-47) to 21 mm (95% confidence interval 19-23) at a mean gestational age of 20 weeks 5 days, when a cerclage was applied. After the cerclage the mean cervical length increased significantly (P <.0001) to 34 mm (95% confidence interval 30-38) at a mean gestational age of 22 weeks 1 day (95% confidence interval 21 weeks 1 day-23 weeks 2 days). Therapeutic McDonald cerclage results in a longer cervical length as measured by transvaginal ultrasonography.
Martius JA et al., 1998·Eur J Obstet Gynecol Reprod Biol·
The study was conducted to identify medical, obstetrical and social risk factors associated with early preterm births (<32+0 gestational weeks). The Statewide Perinatal Survey of Bavaria is a collection of perinatal data from all Bavarian maternity units using a uniform numbered questionnaire. Data on 106345 singleton births from the 1994 Survey were analysed using univariate and multivariate logistic regression analysis. In the multivariate analysis, early preterm birth was associated with premature rupture of the membranes (odds ratio (OR) 1.6, 95% confidence interval (CI) 1.37-1.86), treatment for infertility (OR 1.7, 95% CI 1.19-2.34), previous induced abortion (OR 1.8, 95% CI 1.57-2.13), maternal age >35 years (OR 1.8, 95% CI 1.47-2.16), premature cervical dilatation (OR 2.3, 95% CI 1.86-2.94), a history of stillbirth (OR 3.2, 95% CI 2.13-4.83), a history of preterm birth (OR 3.3, 95% CI 2.45-4.48), maternal age <18 years (OR 3.4, 95% CI 2.03-5.61), malpresentation (OR 3.9, 95% CI 3.10-4.93), preeclampsia (OR 4.0, 95% CI 3.20-4.94), uterine bleeding (OR 5.0, 95% CI 4.08-6.02), preterm labour (OR 7.0, 95% CI 5.94-8.22), and chorioamnionitis (OR 22.3, 95% CI 17.40-28.66). These data identify a subgroup of women at an increased risk for early preterm birth and may benefit from an intensified prenatal care. Risk factors related to the obstetrical history, genital infections, preeclampsia and maternal age are the most relevant for early preterm birth.
The purpose of our study was to analyze the efficacy of serum C-reactive protein (CRP), white blood cell count (WBC) and erythrocyte sedimentation rate (ESR) serial evaluations in the prediction of chorioamnionitis in cases of premature rupture of membranes (PROM). A group of 80 patients with PROM before 35 weeks' gestation were evaluated prospectively and managed expectantly. We applied the expectant management with the permanent use of tocolysis, antibiotics, steroids, amnioinfusions of artificial amniotic fluid and intravaginal chemotherapeutics. Patients were monitored with frequent vital signs, fetal heart rate evaluation and everyday blood tests as follows: CRP, WBC and ESR. All afterbirths were examined to establish the presence of histologic chorioamnionitis (gold standard of intrauterine infection). S: 59 (73.7%) patients had significant chorioamnionitis on histopathology and only 15 of them had clinical chorioamnionitis. Serum CRP serial determinations (definition of abnormal tests: 1) > 1.2 mg/dl; 2) > 2.0 mg/dl; 3) > 1.2 mg/dl and increasing in two consecutive days) were found the most reliable with a sensitivity 1) 91.5%; 2) 85%; 3) 88%, specificity 57%; 76%; 86%, positive predictive value 86%; 90%; 94.5%, negative predictive value 70.5%; 64%; 72% and accuracy 82.5%; 82.5%; 87.5% respectively. The efficacy of WBC (abnormal tests: > 12500/mm3; > 15000/mm3; > 12500/mm3 and increasing in two consecutive days) and ESR (abnormal tests: > 60 mm/h; > 60 mm/h and increasing in two consecutive days) serial evaluations was significantly lower. Moreover, in cases of chorioamnionitis CRP increased above the upper limit of normal 3 days earlier than WBC or ESR. S: CRP was found the most reliable indicator of histologic chorioamnionitis and indicated the presence of intrauterine infection earlier than WBC or ESR.
beta-mimetics have been prescribed by physicians to arrest or prevent premature labor for more than 20 years. Although not approved by the Food and Drug Administration (FDA) for tocolytic use, terbutaline sulfate has been the most widely prescribed beta-mimetic in the United States. Recently, the role of terbutaline in the treatment and prevention of preterm labor has been questioned by the FDA. Because the off-label use of drugs is a formally accepted practice in medicine when scientific studies support such use, we reviewed the currently available clinical literature on terbutaline use in various routes of delivery: intravenous, oral, and subcutaneous via infusion pump. This review describes the clinical evidence that supports the safe and effective use of terbutaline as a tocolytic agent in certain patient populations. Practicing physicians should continue to have unrestricted use of terbutaline for tocolysis as one of the few remaining therapeutic options remaining in the fight against preterm birth.
Preterm birth, which occurs in 11 percent of all pregnancies, is responsible for the majority of neonatal deaths and nearly one half of all cases of congenital neurologic disability, including cerebral palsy.1Although all births before 37 weeks of gestation are considered premature, births before 32 weeks' gestation (2 percent of all births) account for most neonatal deaths and disorders.2 State and national vital statistics indicate that the incidence of preterm birth has risen over the past 15 years (Figure 1), and it remains twice as high among black women as among white women.35 Preterm birth is commonly categorized . . .
To assess the cervicovaginal fetal fibronectin test to predict preterm delivery. We searched MEDLINE, Current Contents, Index Medicus, and proceedings of meetings for studies published between 1991 and June 1997. Inclusion criteria were prospective cohort study; test performed between 20 and 36 weeks' gestation; fetal fibronectin measured by a previously described assay, with a cutoff level set at 50 ng/mL; test results not disclosed to women or physicians; and fewer than 20% of study participants excluded from the analysis. TABULATION, INTEGRATION, Twenty-nine relevant studies were stratified according to the prevalence of preterm delivery, the number of tests performed, and delivery before 34, 35, or 37 weeks. Sensitivities, specificities, and likelihood ratios were calculated in each study. The summary estimates of the likelihood ratio for tests yielding positive results or tests yielding negative results along with their 95% confidence intervals (CIs) were computed in each stratum according to a random-effects model. All summary likelihood ratios for a test yielding positive results indicated a significant association with preterm delivery. The strongest association was found between a single test with positive results and delivery before 37 weeks in a low-risk population (likelihood ratio 7.5; 95% CI 4.6, 12.3). This association also was found in high-risk women (likelihood ratio 3.5; 95% CI 2.6, 4.6). In high-risk women, a test yielding negative results was associated with a reduction in risk of preterm delivery (likelihood ratio 0.4; 95% CI 0.3, 0.5). Fetal fibronectin in cervicovaginal secretions is associated with preterm delivery in both high-risk and low-risk women.
To test the effect of telephone calls from registered nurses to low-income pregnant women on the rates of low birth weight (LBW) and preterm births. A total of 1554 women receiving prenatal care in a public clinic who met study criteria and who consented were assigned randomly to intervention and control groups. Women in the intervention group received telephone calls from a registered nurse, one or two times weekly from 24 weeks' through 37 weeks' gestation. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated. Low birth weight rates were 10.9% in the intervention group and 14.0% in the control group (RR 0.75; 95% CI 0.55, 1.03; P = .072). For gestational age less than 37 weeks, rates were 9.7 in the intervention group and 11.0 in the control group (RR .87; 95% CI 0.62, 1.22; P = .415). In the subgroup of low-income black women 19 years of age and older, a statistically significant difference was found in preterm birth rates before 37 weeks (8.7% in the intervention group versus 15.4% in the controls [RR 0.56; 95% CI 0.38, 0.84; P = .004]). There was no difference in LBW or preterm births between intervention and control groups in the total sample. In a secondary analysis of black subjects 19 years of age and older, there was a significant difference in preterm birth rates.
This study was undertaken to determine the relationship between fetal fibronectin, short cervix, bacterial vaginosis, other traditional risk factors, and spontaneous preterm birth. From 1992 through 1994, 2929 women were screened at the gestational age 22 to 24 weeks. The odds ratios for spontaneous preterm birth were highest for fetal fibronectin, followed by a short cervix and history of preterm birth. These factors, as well as bacterial vaginosis, were more strongly associated with early than with late spontaneous preterm birth. Bacterial vaginosis was more common--and a stronger predictor of spontaneous preterm birth--in Black women, while body mass index less than 19.8 was a stronger predictor in non-Black women. This analysis suggests a pathway leading from Black race through bacterial vaginosis and fetal fibronectin to spontaneous preterm birth. Prior preterm birth is associated with spontaneous preterm birth through a short cervix. Fetal fibronectin and a short cervix are stronger predictors of spontaneous preterm birth than traditional risk factors. Bacterial vaginosis was found more often in Black than in non-Black women and accounted for 40% of the attributable risk for spontaneous preterm birth at less than 32 weeks.
To determine whether serum interleukin-6 concentrations predict impending preterm delivery. Blood samples were collected from 130 gravidas at 22-34 weeks' gestation. The study group consisted of 89 women evaluated for preterm contractions or premature rupture of membranes, and these women were compared with 41 outpatient controls without evidence of labor or infection, chosen by clinicians at the time of routine prenatal visits. Serum interleukin-6 concentrations were measured using a specific enzyme-linked immunosorbent assay kit. Analyses were by the Mann-Whitney U and the Kruskal-Wallis tests. All 41 control subjects had serum interleukin-6 concentrations less than 8 pg/mL. Sixteen of the 89 study patients had serum interleukin-6 concentrations greater than or equal to 8 pg/mL and 73 had values less than 8 pg/mL. When the serum interleukin-6 concentration was at least 8 pg/mL, the median interval from collection to delivery was significantly shorter than that among study and control subjects with serum interleukin-6 less than 8 pg/mL (5.5 versus 240 and 1801 hours, respectively; P < .001). The median gestational age at delivery was significantly lower when the serum interleukin-6 concentration was at least 8 pg/mL, compared with study and control subjects with serum interleukin-6 concentrations less than 8 pg/mL (29.6 versus 33.4 and 39.0 weeks, respectively; P < .001). In patients with preterm contractions, the interval from collection to delivery was significantly shorter when the serum interleukin-6 concentration was at least 8 pg/mL than when it was less than 8 pg/mL (3 versus 600 hours, P < .001). Similarly, the median gestational age at delivery was significantly lower when serum interleukin-6 was at least 8 pg/mL (29.0 versus 36.1 weeks, P < .001). Maternal serum interleukin-6 concentrations appear to be elevated in women destined to deliver prematurely. Measurement of this cytokine may prove useful in treating patients at high risk for preterm delivery.
Preterm birth is a major cause of perinatal morbidity and mortality. Whether the rate of preterm birth can be reduced by frequent contact between nurses and pregnant women or home monitoring of uterine activity is not known. We randomly assigned 2422 pregnant women with known risk factors for preterm labor (including 844 women who were pregnant with twins) to receive education and to have one of the following: weekly contact with a nurse, daily contact with a nurse, or daily contact with a nurse and home monitoring of uterine activity. The nurses elicited the women's own assessments of their symptoms and signs of preterm labor. The primary end point was the incidence of birth at less than 35 weeks' gestation. Secondary end points included cervical status at the time preterm labor was diagnosed and birth weight. There were no significant differences among the groups in the incidence of birth at less than 35 weeks (14 percent in the weekly-contact group, 13 percent in the daily-contact group, and 14 percent in the home-monitoring group), in the mean amount of cervical dilatation at the time preterm labor was diagnosed (1.8 cm, 1.5 cm, and 1.4 cm, respectively), or in such neonatal outcomes as birth weights of less than 1500 g or less than 2500 g. However, daily contact with a nurse increased the mean number of unscheduled visits to obstetricians (1.2 in the weekly-contact group, 1.8 in the daily-contact group, and 2.3 in the home-monitoring group) and the proportion of women who received prophylactic tocolytic drugs (12 percent, 14 percent, and 19 percent, respectively). Women who have daily contact with a nurse, with or without home monitoring of uterine activity, have no better pregnancy outcomes than women who have weekly contact with a nurse.
Preterm infants are at 8 times higher risk than term infants for pre- and perinatal brain damage, resulting in cerebral palsy. In this paper we have analysed the influence of prenatal and birth-related risk factors on cerebral palsy in preterm infants. In a register-based study, 175 preterm singleton infants with cerebral palsy, born in 1982-86, were compared with 687 controls matched by gestational age and year of birth. Statistically significant higher rates in cases were found in parity > or = 3 (22% vs. 16%, p < 0.05), Cesarean section (67% vs. 56%, p < 0.01), and low Apgar scores at 1 minute (45% vs. 36%, p < 0.05). By multivariate analyses, two variables remained statistically significant: parity > or = 3 (adjusted OR = 1.53 (95% CI 1.00-2.34), p < 0.05) and Cesarean section (adjusted OR = 1.57 (95% CI 1.07-2.32), p < 0.05). Pregnancy complications preceding preterm birth did not imply a higher risk of cerebral palsy. Delivery by Cesarean section was a prognostic factor for developing cerebral palsy, and the predictive value of Apgar scores was highly limited.
Thyroid and Metabolic Function · Insulin and Metabolism
To evaluate the complications and outcome of pregnancy in women with polycystic ovary disease (PCOD). The course and outcome of 47 singleton pregnancies in women with well-documented PCOD were compared with those in 100 healthy controls. Women with PCOD had a significantly higher body mass index as compared to the control group (P < .05); however, the proportion of lean versus obese subjects in the two groups was similar. The incidence of an abnormal glucose challenge test, gestational diabetes mellitus and pregnancy-induced hypertension was significantly increased in pregnant women with PCOD (P < .05). When lean PCOD subjects were compared with lean control subjects, the difference in the incidence of the above complications was still significant (P < .05). The incidence of pregnancy complications was similar when obese PCOD subjects were compared with obese controls. Women with PCOD were at increased risk of gestational diabetes and pregnancy-induced hypertension, and this risk appeared to be independent of body mass index.
To examine the risk of preterm birth for mothers who themselves were born before term. Data were taken from a linked data base of birth certificates composed of two cohorts: 1) a parental cohort of women born between 1947 and 1957 and 2) their offspring born between 1970 and 1992. "Preterm mothers" were women in the parental cohort who were born at less than 37 weeks' gestation. "Term mothers" were women in the parental cohort born at or after 38 weeks' gestation. Preterm mothers and term mothers were matched for birth year, county of birth, marital status, parity, and age. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for the risk of preterm delivery in preterm mothers. Multiple logistic regression was used to assess the interaction of concomitant variables with the risk of premature delivery. The risk of preterm birth was significantly higher in preterm mothers than in term mothers (OR 1.18; 95% CI 1.02, 1.37). The risk increased as the gestational age at the mothers' birth decreased (less than 30 weeks'; OR 2.38; 95% CI 1.37, 4.16). The interaction between maternal age and parity increased the risk of preterm delivery at less than 34 weeks in some age and parity strata. An increased risk of preterm delivery exists for women who themselves were born before 37 weeks' gestation. The risk is inversely correlated with the maternal gestational age at birth and is influenced by maternal age and parity.
Oleszczuk J et al., 1997·Eur J Obstet Gynecol Reprod Biol·
We estimated the levels of interleukin 6 (IL-6) and neopterin, in serum of twelve nonpregnant (group A) and 28 pregnant women between 28-36 weeks of pregnancy. Group B consisted of eight patients with uncomplicated pregnancy, group C consisted of thirteen pregnant women with clinical signs of preterm labour and without laboratory markers of infection and group D consisted of seven pregnant women with signs of preterm labour and with laboratory markers of infection. The levels of IL-6 and neopterin were significantly higher in group D compared to groups A, B and C (p < 0.05). Similarly, the level of C-reactive protein (CRP) and total white blood cell count (the laboratory markers of infection) were significantly higher in group D than in groups A, B and C. Total white blood cell count was significantly lower in group A than in group B and D (p < 0.05). There were no significant differences in values of IL-6, neopterin and CRP between groups A, B and C (p > 0.05). In all groups, significant correlations were found between IL-6 and neopterin as well as total white blood cell count and CRP. Our results suggest that IL-6 and neopterin may be the markers of preterm labour caused by infection. On the other hand, cell-mediated immune response may be involved in the mechanisms of preterm labour.
To report the occurrence of an unusual case of successful pregnancy achieved by oocyte donation in a woman > 60 years of age. Case report. University-based assisted reproductive technology program. PATIENT(S): Sixty-three-year old nulligravida, married for 16 years to her 60-year-old husband. Throughout her infertility treatment, the patient was believed to be 10 years younger, as she claimed. She revealed her true age of 63 only upon being referred for obstetric care at 13 weeks of gestational age. INTERVENTION(S): Oocyte donation, IVF, embryo cryopreservation, and ET. MAIN OUTCOME MEASURE(S): Attainment of pregnancy and subsequent delivery. RESULT(S): The patient underwent two cycles of oocyte donation. During the second attempt, the fresh transfer resulted in a clinical miscarriage at approximately 8 weeks of gestational age. A subsequent transfer of three frozen-thawed embryos resulted in an ongoing singleton gestation. The pregnancy was complicated by gestational diabetes (controlled by diet) and mild pregnancy-induced hypertension. Delivery by cesarean section at 38 weeks of gestational age resulted in the birth of a healthy female infant weighing 2,844 g with Apgar scores of 9 and 9. CONCLUSION(S): This case demonstrates that the uterus is capable of supporting nidation and subsequent gestation for many years beyond natural menopause. It shows that other aspects of human physiology are capable of adapting to the stresses and changes of pregnancy sufficiently well to achieve a normal birth at the age of 63 years. This case also exemplifies the difficulty in attempting to regulate the age of recipients in oocyte donation. As in other aspects of human life, when age limits are applied to the provision of certain services, human beings whose age falls outside of these limits become motivated to deceive the providers of those services to avail themselves of the services.
To test whether subfertile women may be at higher risk of preterm delivery. We used data from two population-based cohort studies on risk factors and pregnancy outcome for approximately 20,000 deliveries in three major Danish obstetric departments. The Aalborg-Odense study comprised all pregnant women attending routine antenatal care at two obstetric departments from 1984 to 1987. In all, 11,850 women (86%) filled in a questionnaire at about 36 weeks' gestation. The Aarhus study addressed women at the routine visit near 16 weeks' gestation from 1989 to 1991; a study questionnaire was returned by 6857 (80%). Both studies excluded women with chronic illnesses, multiple fetuses, and inability to speak Danish. Only women with planned pregnancies were included in the analysis. In all, 8855 and 3985 women from Aalborg-Odense and Aarhus, respectively, were eligible for the analyses. In both cohorts, women were categorized according to their waiting time to pregnancy (0-6 months, 7-12 months, and greater than 1 year) and according to examination or treatment for infertility (yes, no). Preterm delivery was defined as birth before 37 completed weeks. Compared with women who tried for 6 months or less before they conceived, women who tried for 7-12 months had 1.3 times (95% confidence interval [CI] 0.8, 2.1) the adjusted risk of preterm delivery in both cohorts, and women with a time to pregnancy of greater than 12 months had adjusted relative risks for preterm delivery of 1.6 (95% CI 1.1, 2.2) for Aalborg-Odense and 1.7 (95% CI 1.1, 2.6) for Aarhus. The results remained similar after excluding women with infertility treatment. Pregnant women with subfertility and clinically defined infertility are more prone to preterm delivery, even in the absence of infertility treatment.
C-reactive protein (CRP) levels were evaluated during spontaneous labour, in imminent premature parturition (IPP) and after preterm rupture of oocyst membranes (PROM). Increasing CRP level during spontaneous labour was found in 16.6% parturients. Elevated CRP level in patients with IPP makes it impossible to predict premature labour. In parturients with PROM, increase in CRP level makes further infection predictable only in a few cases.
To compare the effectiveness of routine management of patients at high risk for preterm delivery to the effectiveness of routine management in combination with daily telephone nursing contact. The control group, 1 (n = 21), had education and frequent prenatal visits and cervical examinations. The study group, 2 (n = 21), had education, frequent prenatal visits and cervical examination, and daily telephone contact. Group 3 (n = 22) received education but refused to participate. There were no significant differences (SD) between groups in race, smoking, age, multiple gestation, visits, diagnosis of premature labor, mean days gained after diagnosis of premature labor, tocolytic use or bed rest. There was also no SD in preterm birth rate, mode of delivery, number of maternal or neonatal hospital days, mean neonatal weight or gestational age at delivery between groups. While not reducing the overall incidence of preterm birth, this management for all groups resulted in a more advanced gestational age at the time of delivery (mean change = 7.5 weeks, P < .0001) when compared to the patient's first preterm birth. This study indicated that daily contact, while providing reassurance and support, did not change the outcome when the study group was compared to women managed similarly but without daily contact.
To evaluate the presence of fetal fibronectin in the cervix and vagina as a screening test for spontaneous preterm birth. Two thousand nine hundred twenty-nine women at ten centers were routinely screened every 2 weeks from 22-24 to 30 weeks for cervical and vaginal fetal fibronectin. A positive test was defined as a value equal to or greater than 50 ng/mL. The relation between a positive test at four gestational ages and spontaneous preterm birth at various intervals after the test was determined. In each testing period, 3-4% of the fetal fibronectin tests were positive. The correlation between cervical and vaginal fetal fibronectin at the same visit was always approximately 0.7 (P < .001), and that between cervical or vaginal fetal fibronectin in consecutive visits was between 0.17 and 0.25 (P < .001). The sensitivity of fetal fibronectin at 22-24 weeks to predict spontaneous preterm birth at less than 28 weeks was 0.63, and the relative risk for a positive versus negative test was 59. The specificity was always 96-98%, whereas the positive predictive value rose from 13% to 36% as the upper limit of the definition of preterm birth was increased from less than 28 to less than 37 weeks. The relative risk for spontaneous preterm birth after a positive fetal fibronectin test compared with a negative fetal fibronectin test varied substantially by testing period and by the definition of spontaneous preterm birth, but always remained greater than 4 and statistically significant. A positive cervical or vaginal fetal fibronectin test at 22-24 weeks predicted more than half of the spontaneous preterm births at less than 28 weeks (sensitivity 0.63). As the definition of spontaneous preterm birth was extended to include later gestational ages or when the fetal fibronectin test was performed later in pregnancy, the level of association between a positive fetal fibronectin test and spontaneous preterm birth, while remaining highly significant, tended to decrease. Although fetal fibronectin is an excellent test for predicting spontaneous preterm birth, we present no evidence that the use of this test will result in a reduction in spontaneous preterm birth.
The role of the cervix in the pathogenesis of premature delivery is controversial. In a prospective, multicenter study of pregnant women, we used vaginal ultrasonography to measure the length of the cervix; we also documented the incidence of spontaneous delivery before 35 weeks' gestation. At 10 university-affiliated prenatal clinics, we performed vaginal ultrasonography at approximately 24 and 28 weeks of gestation in women with singleton pregnancies. We then assessed the relation between the length of the cervix and the risk of spontaneous preterm delivery. We examined 2915 women at approximately 24 weeks of gestation and 2531 of these women again at approximately 28 weeks. Spontaneous preterm delivery (at less than 35 weeks) occurred in 126 of the women (4.3 percent) examined at 24 weeks. The length of the cervix was normally distributed at 24 and 28 weeks (mean [+/- SD], 35.2 +/- 8.3 mm and 33.7 +/- 8.5 mm, respectively). The relative risk of preterm delivery increased as the length of the cervix decreased. When women with shorter cervixes at 24 weeks were compared with women with values above the 75th percentile, the relative risks of preterm delivery among the women with shorter cervixes were as follows: 1.98 for cervical lengths at or below the 75th percentile (40 mm), 2.35 for lengths at or below the 50th percentile (35 mm), 3.79 for lengths at or below the 25th percentile (30 mm), 6.19 for lengths at or below the 10th percentile (26 mm), 9.49 for lengths at or below the 5th percentile (22 mm), and 13.99 for lengths at or below the 1st percentile (13 mm) (P < 0.001 for values at or below the 50th percentile; P = 0.008 for values at or below the 75th percentile). For the lengths measured at 28 weeks, the corresponding relative risks were 2.80, 3.52, 5.39, 9.57, 13.88, and 24.94 (P < 0.001 for values at or below the 50th percentile; P = 0.003 for values at the 75th percentile). The risk of spontaneous preterm delivery is increased in women who are found to have a short cervix by vaginal ultrasonography during pregnancy.
To compare the diagnostic and prognostic performance of maternal blood C-reactive protein, white blood cell count (WBC), and temperature with that of amniotic fluid (AF) WBC in preterm labor. One hundred two women with preterm labor and intact membranes were studied. Maternal blood was collected to measure C-reactive protein concentration and WBC, and maternal temperature was also measured. Amniotic fluid obtained by amniocentesis was cultured and WBC determined. Receiver operating characteristic curve, logistic regression, and survival techniques were used for analysis. Patients with acute histologic chorioamnionitis had significantly higher median C-reactive protein concentration, WBC, temperature, and AF WBC than patients without this lesion (P < .05). Receiver operating characteristic curve and survival analysis demonstrated that an elevated C-reactive protein, WBC, or AF WBC was strongly associated with the likelihood of histologic chorioamnionitis, shorter interval to delivery, clinical chorioamnionitis, and neonatal morbidity (P < .05 for each). Of all the tests, AF WBC was the best independent predictor of a positive AF culture (odds ratio [OR] 16.8), interval to delivery (hazard ratio 5.7), clinical chorioamnionitis (OR 15.2), neonatal sepsis (OR 16.8), and significant neonatal complications (OR 7.4), after other confounding variables were adjusted (P < .05 for each). An elevated C-reactive protein, WBC, or AF WBC identified patients with intrauterine infection and adverse perinatal outcomes. Amniotic fluid WBC was a better independent predictor of these outcomes than C-reactive protein, WBC, or temperature.
The aim of this study was to investigate the correlation between the cytokine levels in the amniotic fluid (AF) and the histological stage of chorioamnionitis (CAM) in premature labor. AF of 6 cases (7 samples of AF were obtained as one was a twin pregnancy) in whom CAM was diagnosed histologically, and 12 cases without CAM were included in this study. Amniotic fluid was obtained within 24 hours prior to delivery. Cytokine levels (IL-2, -4, -6, TNF-alpha, IFN-gamma) in AF were measured by an ELISA method. Levels of IL-2 and -6 in the CAM-positive group (mean +/-S.E., 52.9 +/- 83.9 pg/ml, and 20,537.9 +/- 8853.7 pg/ml, respectively) were higher than those in the CAM-negative group (i.e. undetectable, and 65.6 +/- 27.5, respectively) with a statistical significance of p < 0.05, p < 0.001, respectively. There was a positive linear relationship between IL-6 levels of AF and the placental histological inflammatory stages of Blanc in the CAM-positive group. From these results it would appear that the IL-6 level in AF is the most sensitive test in the detection of extraamniotic infection or intraamniotic infection in preterm labor with intact membranes and also indicates the severity infection.
Preterm birth complicates 8-10% of all pregnancies in the United States and is the leading cause of infant morbidity and mortality. Neonatal morbidity and mortality is concentrated among very low-birthweight and extremely premature infants, particularly those delivered prior to 30 weeks' gestational age. In addition to the contribution of preterm birth to neonatal morbidity and mortality, the economic costs associated with this pregnancy complication are staggering. Efforts to reduce the preterm birth rate have been largely focused on prevention and early intervention with treatment for preterm labor. Mixed results regarding the success of prematurity prevention programs have been reported, and controversy continues to surround the efficacy of tocolytic therapy in the treatment of preterm labor. Although neonatal survival for infants born at early gestational ages has steadily improved in recent years, survival of infants delivered prior to 24 weeks' gestation remains very poor. Additionally, despite this decline in neonatal mortality, the United States still lags behind most industrialized nations in infant mortality, and no change in the rate of low birthweight has occurred in recent decades. Multiple lines of evidence support a role for infection as an etiologic factor in preterm labor. Although this association has been well known for many years, a wealth of new data is emerging, linking subclinical genital tract infection with spontaneous preterm birth, particularly among pregnancies that result in birth prior to 30 weeks' gestational age as a result of spontaneous preterm labor or preterm, premature rupture of membranes. Conversely, preterm birth that occurs closer to term is less likely to be associated with genital tract infection. Improved understanding of the link between genital tract infection and preterm birth now provides an exciting potential for the development of sensitive new markers to identify women at risk and effective interventions to prevent preterm birth. A review and comment on this growing literature is provided.
Rossi AM et al., 1995·Eur J Obstet Gynecol Reprod Biol·
The outcome of 103 pregnancies in 64 women with constant hyperprolactinemia was evaluated. Seventy-eight pregnancies had been induced with bromocriptine and 25 occurred without any treatment. In all, 66% of the pregnancies ended in delivery, 17% in miscarriage, 10% in tubal pregnancy and 7% in induced abortion. The pregnancy of women with untreated hyperprolactinemia was more frequently ectopic when compared to those in women treated by bromocriptine. Obstetric complications as well as signs of tumoral enlargement during pregnancy were rare in hyperprolactinemic women treated or untreated with bromocriptine. Untreated hyperprolactinemia as a risk factor in tubal pregnancy is proposed.
To describe the relationship between pregnancy complications and fetal outcome in first and second pregnancies, focusing on idiopathic and indicated preterm birth of singleton infants in either pregnancy. Included in the study were 13,967 women in Denmark who gave birth to their first singleton infant in 1982 and a second infant in 1982-1987. Information on pregnancy and birth was obtained by linking the National Medical Birth Register and the National Register of Hospital Discharges, based on personal identification numbers. The risk of a preterm second birth in women with idiopathic and indicated preterm first birth did not differ significantly (15.2 and 12.8%, respectively). However, women with idiopathic preterm birth in the first pregnancy tended to repeat idiopathic preterm birth twice as often as women with indicated preterm birth repeated indicated preterm birth (11.3 versus 6.4%). Adjustment by logistic regression analysis for other risk factors for preterm birth did not influence the relative risk (6.0 before 32 weeks and 4.8 for 32-36 weeks) of a second preterm birth after a first preterm birth. Women with idiopathic preterm delivery in their first and second pregnancies gave birth to infants with lower birth weight than in previous or subsequent pregnancies. Emergency cesarean delivery in a first term pregnancy was a risk factor for subsequent idiopathic preterm birth. Idiopathic preterm birth is associated with emergency cesarean delivery at term in previous pregnancies and infants with lower birth weight in previous and subsequent pregnancies.
To evaluate whether preterm-birth prevention educational programs are effective at reducing neonatal mortality, low birth weight (LBW), and preterm delivery. A MEDLINE literature search of English-language studies was performed, supplemented by a bibliography search of original research and review articles to locate studies assessing preterm-birth prevention programs. We identified 31 studies that reported results from trials evaluating preterm-birth prevention programs. From this group, only the six randomized controlled trials evaluating preterm-birth prevention education programs satisfied criteria of homogeneity to be included in a meta-analysis. One of these six studies was a subset of another study and was excluded except when reporting outcomes that were not included in the larger report. Two independent reviewers assessed study methodology and identified the following outcomes: LBW frequency, preterm birth frequency, neonatal survival, birth weight, gestational age at delivery, and preterm labor diagnosis rates. When data were combined using meta-analytic techniques, no significant benefits were found for preterm-birth education programs in preventing neonatal death (cumulative relative risk [RR] 1.00, 95% confidence interval [CI] 0.99-1.01), LBW rates (RR 0.99, 95% CI 0.88-1.11), or preterm delivery rates (RR 1.08, 95% CI 0.92-1.27). The only statistically significant effect of preterm birth education programs appears to be an increase in the frequency at which preterm labor is diagnosed (RR 1.71, 95% CI 1.41-2.08). Preterm-birth prevention educational programs appear to have little benefit in reducing preterm birth and may result in an increased rate of diagnosis of preterm labor.
To describe the characteristics of pregnancies and children at birth resulting from IVF-ET and to assess whether they differ from those after natural conception. Prospective multicenter survey. A national registry, representing 80% of all French IVF-ET activity for the period 1986 to 1990. Data on 7,024 pregnancies, 5,371 deliveries, and 6,879 newborn infants. A form is completed for every clinical pregnancy. Spontaneous abortion, ectopic pregnancy, multiple pregnancy, prematurity, hypotrophy, perinatal and neonatal mortality, and congenital malformations rates. The spontaneous abortion and ectopic pregnancy rates were, respectively, 17.6% and 5.8%. More than a quarter (26.8%) of the deliveries were multiple births. The preterm birth rate (29.3%), the low birth weight rate (36.2%), and the perinatal and neonatal mortality rates were higher than the national average. The rate of malformations (2.8%) was comparable with the general population (2.1%). Assisted conception frequently results in multiple pregnancy, and this is the main determinant of pregnancy outcome. Nevertheless, it is not the only risk factor for prematurity, which is also more frequent among IVF singleton newborn. The prevalence of congenital malformations is not higher than after natural conception.
Anti-Infective and Anti-Inflammatory Agents · Antibiotics in Reproductive Care
To compare ampicillin with and without sulbactam with respect to the effect on the latency period after preterm premature rupture of membranes (PROM). Patients with PROM at 25-35 weeks' gestation were offered participation in a randomized blinded trial comparing ampicillin-sulbactam with ampicillin. Evaluations for cervical pathogens were performed on admission and patients were followed-up with daily maternal and fetal evaluation. Maternal and neonatal outcomes were analyzed using indicated techniques. Fifty-three women were studied, with 25 receiving ampicillin-sulbactam and 28 receiving ampicillin. The ampicillin-sulbactam group had a significantly longer latency period (433 +/- 625 versus 143 +/- 165 hours, P = .03) and significantly fewer neonatal complications (five versus 20, P < .001). Although no neonatal infectious complications were observed in sulbactam-treated cases, there were four cases of neonatal sepsis and two of neonatal pneumonia in the ampicillin group. Also, significantly more neonates in the ampicillin group required prolonged oxygen and ventilatory support. There was no significant difference in maternal morbidity. In our population with preterm PROM, a broad-spectrum antibiotic that provides anaerobic coverage appears to extend latency and decrease neonatal morbidity without increasing adverse maternal outcome.
To evaluate catalase activity as a rapid predictor of microbial invasion of amniotic fluid (AF). The study population consisted of 74 patients before 36 weeks' gestation with preterm labor or premature rupture of membranes (PROM). Subjects were excluded if there was evidence of clinical chorioamnionitis or fetal distress at admission. Amniocentesis was done within 24 hours of admission, and the AF was cultured for aerobic and anaerobic bacteria and for Mycoplasma species. All AF samples were Gram stained, and slides were examined by microbiology technologists. Amniotic fluid catalase activity was measured immediately after amniocentesis using a commercially available kit. The sensitivity of the Gram stain and catalase activity were compared using McNemar exact test. Amniotic fluid cultures were positive in 12 of 37 (32%) patients presenting with preterm labor and in 21 of 37 (56%) patients with PROM. Catalase activity was significantly more sensitive than Gram stain in detecting positive AF cultures in cases of PROM (P < .001) and preterm labor (P < .04). Catalase activity is a simple, rapid test that is useful in identifying subclinical intra-amniotic infection in patients with preterm labor or PROM.
In this study we evaluated different markers of infection and their relationship to preterm delivery. Forty-four consecutive women with singleton pregnancies in uncomplicated preterm labor were investigated. C-reactive protein (CRP) in peripheral maternal blood, amniotic fluid cytokines, amniotic fluid leukocyte count, and amniotic fluid culture were performed in all patients. Thirty-six patients responded to standard tocolytic therapy and delivered after 34 weeks' gestation. In eight patients treatment failed and they delivered before 34 weeks' gestation. Two of these eight patients had a positive amniotic fluid culture for Ureaplasma urealyticum. The positive culture was accompanied by an elevated neutrophil count in the amniotic fluid. Elevated amniotic fluid levels of tumor necrosis factor (TNF) (more than 23 pg/mL), interleukin-6 (IL-6) (more than 2292 pg/mL) and interleukin-8 (more than 164 pg/mL) correlated with early preterm delivery. CRP levels in serum had a low sensitivity (38%) but a high specificity (94%) in predicting preterm delivery. This study indicates that preterm labor can be initiated by infection. Markers of infection obtained by amniocentesis have a better sensitivity and positive predictive value than noninvasive markers. Elevated IL-6 (more than 2292 pg/mL) seems to be the best predictor for preterm delivery, with a sensitivity of 75% and a specificity of 97%.
We report the existence of a 'placental clock', which is active from an early stage in human pregnancy and determines the length of gestation and the timing of parturition and delivery. Using a prospective, longitudinal cohort study of 485 pregnant women we have demonstrated that placental secretion of corticotropin-releasing hormone (CRH) is a marker of this process and that measurement of the maternal plasma CRH concentration as early as 16-20 weeks of gestation identifies groups of women who are destined to experience normal term, preterm or post-term delivery. Further, we report that the exponential rise in maternal plasma CRH concentrations with advancing pregnancy is associated with a concomitant fall in concentrations of the specific CRH binding protein in late pregnancy, leading to a rapid increase in circulating levels of bioavailable CRH at a time that coincides with the onset of parturition, suggesting that CRH may act directly as a trigger for parturition in humans.
To determine whether long-term intravenous (IV) tocolysis using combined terbutaline and magnesium sulfate is safe and effective. One thousand consecutive women in preterm labor were treated with combination IV tocolytic therapy. Terbutaline was initiated with an infusion rate of 1.75 micrograms/minute and increased to a maximum of 80 micrograms/minute. Magnesium sulfate was infused at 2 g/hour without any bolus and increased to maintain a serum level of 6.5-7.5 mg/dL. Tocolysis was continued until fetal lung maturity was achieved or delivery occurred. Combination tocolytic therapy prolonged pregnancy by a mean (+/- standard deviation) of 61 +/- 23.6 days in 751 women with intact membranes and by 20.5 +/- 17.4 days in 249 with ruptured membranes. The longest durations of continuous IV tocolysis were 123 days in a patient with intact membranes and 77 days in one with ruptured membranes. The most common side effects were nausea and vomiting, followed by chest tightness and shortness of breath. Long-term IV tocolysis appeared to be safe and to have acceptable side effects, allowing patients to receive combined terbutaline and magnesium sulfate until delivery.
Pregnancy Complications · Premature Rupture of Membranes
To examine the relationship of subfertility with miscarriage, low birth weight, and preterm delivery. Comparison of time to pregnancy distributions between pregnancies that had different outcomes. Three comparisons were made: (a) miscarriages with live births; within live births, (b) low birth weight infant (up to 2,500 grams) or not low birth weight; (c) preterm birth (37 weeks or less) or not preterm. Cox regression was used to adjust for covariates. All first pregnancies were analyzed from the National Child Development Study, a large survey of young adults aged 33 years, which is nationally representative of the British-born population. The distribution of the time taken to conceive (time to pregnancy), miscarriage, birth weight, and preterm delivery. Pregnancies that ended in miscarriage tended to take 23% longer to conceive, after adjustment for the other variables. Pregnancies that resulted in preterm delivery tended to take 15% longer to conceive. There was no statistically significant association with low birth weight. Delay in time to conception is a risk factor for poor obstetric outcome, irrespective of medical intervention.
The primary objective of this prospective study was to test whether preterm birth prevention education plus increased clinic visits and selected prophylactic interventions reduce preterm birth. Eight West Los Angeles prenatal county clinics, comparable with respect to selected demographics, were randomized to be either experimental or control clinics. High-risk patients in all clinics were identified with a risk scoring system derived from a similar population. High-risk patients (N = 1774) in experimental clinics were offered a program of education and more frequent visits and were randomized to receive various secondary intervention protocols in addition to the basic interventions of education and more frequent visits. Control clinic patients (N = 880) received standard county care. Preterm birth rates were 19% lower among the experimental high-risk patients (7.4% vs 9.1%), and differences were significant (p < 0.05) when preterm risk was taken into account. There was no evidence to suggest that the secondary interventions provided added benefit over the primary intervention protocol of preterm birth prevention education and increased visits. The 19% reduction in preterm birth rate observed in the experimental clinics suggest an overall program benefit from a protocol that offered education, more frequent visits, and greater attention given to patients while the selected interventions were applied.
To compare the effect of fertility drugs and IVF on the outcome of triplet pregnancies. Prospective clinical study. A single university medical center. One hundred six consecutive triplet pregnancies treated from 1984 through 1992. The frequency of pregnancy loss, livebirths, and antenatal and neonatal complications was compared in spontaneous, clomiphene citrate (CC), menotropins, and IVF triplet pregnancies. Eighty-one of the 106 (76.4%) triplet pregnancies progressed beyond 25 weeks, comprising 6 of 7 (85.7%) spontaneous pregnancies, 13 of 16 (81.2%) CC induced, 44 of 56 (78.6%) menotropin induced, and 18 of 27 (66.6%) IVF gestations. There were no significant differences in the stillbirth and neonatal mortality rates according to the mode of conception. The mean gestational ages and the mean birth weights were similar in the four groups. The frequency of premature contractions, premature rupture of membranes, cesarean section, and neonatal complications were similar in the ovulation induction and IVF pregnancies. Triplet pregnancies after ovulation induction and IVF have a similar outcome.
To establish a nomogram for the length of the uterocervical canal and to determine whether this can be used to predict preterm delivery. Cervical length was measured by transvaginal ultrasonography in 32 women (21 primigravid, 11 multigravid) with threatened preterm delivery, and in 177 normal singleton pregnancies between 18-37 weeks' gestation. Regression analysis was used to create the nomogram. Student t test was used to compare the groups. A linear relationship was found between cervical length and gestational age (r = -0.4, P < .001). Comparison of cervical length on admission in the patients with threatened preterm delivery showed that 11 preterm deliveries occurred in women who had a mean cervical length of 23.2 mm (range 17-29), whereas 21 term deliveries occurred in women with a mean cervical length of 31.7 mm (range 21-42). The difference was significant (P < .001). A cervical length of less than 20 mm on admission had a positive predictive value of 100%. These patients had preterm delivery despite tocolytic therapy during hospitalization. The risk of preterm delivery is high in women whose cervical length on admission is less than 30 mm, and strict management is required for those with a cervical length of less than 20 mm.
Anti-Infective and Anti-Inflammatory Agents · Nonsteroidal Anti-Inflammatory Drugs
Although low-dose aspirin has been reported to reduce the incidence of preeclampsia among women at high risk for this complication, its efficacy and safety in healthy, nulliparous pregnant women are not known. We studied 3135 normotensive nulliparous women who were 13 to 26 weeks pregnant to determine whether treatment with aspirin reduced the incidence of preeclampsia. Of this group, 1570 women received 60 mg of aspirin per day and 1565 received placebo for the remainder of their pregnancies. We also evaluated the effect of aspirin on maternal and neonatal morbidity. Of the original group of 3135 women, 2985 (95 percent) were followed throughout pregnancy and the immediate puerperium. The incidence of preeclampsia was lower in the aspirin group (69 of 1485 women [4.6 percent]) than in the placebo group (94 of 1500 women [6.3 percent]) (relative risk, 0.7; 95 percent confidence interval, 0.6 to 1.0; P = 0.05), whereas the incidence of gestational hypertension was 6.7 and 5.9 percent, respectively. There were no significant differences in the infants' birth weight or in the incidence of fetal growth retardation, postpartum hemorrhage, or neonatal bleeding problems between the two groups. Subgroup analysis showed that preeclampsia occurred primarily in women whose initial systolic blood pressure was 120 to 134 mm Hg (incidence among such women, 5.6 percent in the aspirin group vs. 11.9 percent in the placebo group; P = 0.01). The incidence of abruptio placentae was greater among the women who received aspirin (11 women, vs. 2 in the placebo group; P = 0.01). Low-dose aspirin decreases the incidence of preeclampsia among nulliparous women, primarily through its effect in those who have elevated systolic blood pressure initially. This treatment does not decrease perinatal morbidity but increases the risk of abruptio placentae.
The purpose of this study was to determine the relationship between C-reactive protein (CRP) levels and intraamniotic infection in 48 women presenting with preterm labor and intact membranes. Blood samples for CRP tests were obtained immediately before the performance of transabdominal amniocentesis. The prevalence of amniotic fluid cultures positive for organisms was 14.6%. In 16 women (33.3%) positive CRP levels were obtained. There were no significant differences in the prematurity rate or the prevalence of microbial invasion of the amniotic cavity between women with positive CRP levels and women with negative levels. The sensitivity, specificity, and positive and negative predictive values for the detection of amniotic infection were 71.5%, 73.2%, 31.3% and 93.8%, respectively. Based on these results, we suggest that in women with preterm labor and negative CRP levels, routine amniocentesis may not be essential to the initial workup.
To evaluate clinical, microbiologic, and histologic findings associated with elevated C-reactive protein levels among women in preterm labor or with preterm premature rupture of the membranes (PROM). Obstetric data, serum C-reactive protein levels, and amniotic fluid (AF) and chorioamniotic membrane cultures and histology were obtained on 203 women presenting between 22-34 weeks' gestation in preterm labor or with PROM. Women with C-reactive protein greater than 1.5 mg/dL were more likely to deliver within 7 days of enrollment (54 of 68, 79%) than were women with normal C-reactive protein levels (45 of 135, 33%) (P < .001). The median C-reactive protein levels and association with rapid delivery did not differ between women with intact versus ruptured membranes. Elevated C-reactive protein levels were associated with a positive AF culture among women in preterm labor with intact membranes. To control for confounding by a long interval to delivery, only the group delivering within 7 days was considered for evaluation of C-reactive protein levels and placental and infant outcome. Among women delivering within 7 days, elevated C-reactive protein was associated with the development of clinical chorioamnionitis and with infant death before hospital discharge, but not with a positive membrane culture or histologic chorioamnionitis. Elevated C-reactive protein appears to be associated with AF infection, delivery within 7 days of admission, and infant death among women delivering preterm, but not with membrane infection or inflammation. Elevated C-reactive protein may be helpful in determining the need for AF culture and in targeting studies of antibiotic therapy among women in preterm labor or with preterm PROM.
To assess the outcome of pregnancy following assisted conception. Cohort descriptive study. Unit of Reproductive Medicine, Ninewells Hospital and Medical School. One hundred and forty-eight consecutive assisted conceptions. Patient characteristics and outcome of pregnancy. Seventy-nine percent of mothers were aged between 26 and 35 years (mean 31.4). The main causes of infertility were tubal (48%), unexplained (35%), anovulatory (8%) and male factor (8%). Primary infertility accounted for 61% of cases and 82% of pregnancies occurred within 3 treatment cycles. Thirty-five (24%) pregnancies miscarried before 14 weeks and 7 (5%) between 15 and 24 weeks gestation. One hundred and three pregnancies resulted in 136 liveborn infants. There was one neonatal death. Thirty-five babies were admitted to SCBU. Antenatally, 13% of patients were admitted to hospital with hypertension and 8% with APH; 50% of multiple and 13% of singleton pregnancies were delivered prematurely, 68% following preterm labour. There were 28 sets of twins (four miscarried at less than 24 weeks) and four sets of triplets. Multiple pregnancy was not associated with cause of infertility, treatment, age or ovarian hyperstimulation syndrome. Seventy-eight per cent of singletons and 50% of multipara were delivered vaginally. Our data confirm the high incidence of pregnancy loss and preterm delivery associated with assisted conception once allowing for the high rate of multiple pregnancies. The effect of assisted conception programme on health services is discussed.
MRC/RCOG Working Party on Cervical Cerclage, 1993·Br J Obstet Gynaecol·
To assess whether cervical cerclage in women deemed to be at increased risk of cervical incompetence prolongs pregnancy and thereby improves fetal and neonatal outcome. Multicentre randomised controlled trial. Hospitals in the United Kingdom, France, Hungary, Norway, Italy, Belgium, Zimbabwe, South Africa, Iceland, Ireland, the Netherlands and Canada. One thousand two hundred and ninety-two pregnant women whose obstetricians were uncertain whether to recommend cervical cerclage, most of whom had a history of early delivery or cervical surgery. Cervical cerclage was compared with a policy of withholding the operation unless it was considered to be clearly indicated. Delivery before 33 completed weeks, preterm delivery (< 37 weeks), and vital status of the baby after completion of the pregnancy. The overall preterm delivery rate was 28%. There were fewer deliveries before 33 weeks in the cerclage group (83 (13%) compared with 110 (17%), P = 0.03) and this difference reflected deliveries characterised by features of cervical incompetence (painless cervical dilatation and prelabour rupture of the membranes). There was a corresponding difference in very low birthweight deliveries (63 (10%) compared with 86 (13%), P = 0.05). The difference in the overall rate of miscarriage, stillbirth or neonatal death (55 (9%) compared with 68 (11%)) was less marked and was not statistically significant. The use of cervical cerclage was associated with increased medical intervention and a doubling of the risk of puerperal pyrexia. These results suggest that the operation had an important beneficial effect in 1 in 25 cases in the trial (95% confidence interval (CI) 1 in 12 to 1 in 300 sutures). Its use is associated with increased medical intervention and puerperal pyrexia. Nevertheless, this trial suggests that, on balance, cervical cerclage should be offered to women at high risk, such as those with a history of three or more pregnancies ending before 37 weeks gestation.
Prescribing Safety · Medication Safety in Pregnancy
Our aim was to determine the efficacy and safety of tocolytic agents currently used to treat premature labor. We carried out a comprehensive review of tocolytic agents in the treatment of premature labor. Three hundred twenty-eight studies published between 1933 and 1992 were analyzed. An analysis of randomized, placebo-controlled, clinical trials showed that magnesium sulfate is not better than placebo in the treatment of premature labor. beta-Adrenergic receptor agonists effectively stop premature labor for only 24 to 48 hours. Calcium channel blockers and oxytocin antagonists inhibit uterine contractions, but their role in stopping labor is undefined. Prostaglandin inhibitors appear to be effective in treating premature labor and have few adverse side effects. The only tocolytic drugs that might be effective are the prostaglandin inhibitors. Tocolytic agents should be used only between 24 and 32 completed weeks of gestation. Magnesium sulfate should not be used to treat premature labor. Oxytocin antagonists should be used only in experimental clinical trials. Calcium channel blockers and beta-adrenergic receptor agonists inhibit uterine contractions but do not prolong gestation for longer than 48 hours.
Preterm labor is defined as the onset of uterine contractions in a woman who has completed less than 37 weeks of pregnancy. It may be due to maternal, placental, fetal, or idiopathic causes, and it is associated with a number of risk factors. Nondrug measures such as bedrest and hydration have been used alone or in combination with drug therapy to treat the disorder. Pharmacologic (tocolytic) agents include ethanol, progesterone, indomethacin, nifedipine, beta-adrenergic agonists, and magnesium salts. The three most commonly used drugs are ritodrine, terbutaline, and magnesium.
Prescribing Safety · Medication Safety in Pregnancy
To compare the tocolytic efficacy and side effects of parenteral and oral magnesium and terbutaline. Ninety-eight patients in labor between 23-35 weeks were prospectively entered into a controlled trial of intravenous and oral magnesium versus subcutaneous and oral terbutaline. Tocolytic effectiveness was judged by delay of delivery for 48 hours or 1 week, and to 37 weeks or more. The need to change therapy to the alternate drug was identified, as were side effects. Entrance characteristics of the population, initial pelvic examination, and concomitant infection or cervicovaginal isolates were noted. Outcomes included gestational age at delivery, birth weights, and Apgar scores. Outcome analysis was based on initial tocolytic therapy. Significantly more patients in the magnesium group delivered at 37 weeks or more: 34 of 46 versus 27 of 52 (P < .05). No significant differences were found for delivery by 48 hours or 1 week. The interval between treatment and delivery was greater for magnesium: 7.1 +/- 3.9 versus 5.0 +/- 3.2 weeks (P < .005). Failure to achieve 37 completed weeks was more often due to obstetric complications than to preterm labor itself. Tocolytic effectiveness was reduced if secondary therapy or re-treatment was required or if the patient had cervical dilatation of 3 cm or greater. Infectious complications were common but were not associated with tocolytic effectiveness. Side effects were more noticeable with oral magnesium and subcutaneous terbutaline. For short-term tocolysis, no significant difference was found between magnesium and terbutaline. Magnesium was associated with a higher term delivery rate. Idiopathic preterm labor accounted for only a small part of the overall prematurity in the study population.
To compare the obstetric outcome of in vitro fertilization pregnancies with normally conceived pregnancies. The obstetric outcome of in vitro fertilization pregnancies achieved in 763 British residents at two in vitro fertilization clinics resulting in the births of 961 babies were compared by means of the relative risk statistic with a control group of naturally conceived primiparous pregnancies matched by maternal age and multiplicity of pregnancy. Twenty-five percent of in vitro fertilization pregnancies were multiple pregnancies. The incidence of singleton term breech presentation was similar to that among controls. As compared with controls there was an increased incidence among in vitro fertilization pregnancies of vaginal bleeding and hypertension requiring hospitalization (p less than 0.001) and cesarean births (p less than 0.001) and, among in vitro fertilization singleton pregnancies, an increased incidence of intrauterine growth retardation (p less than 0.05), placenta previa (p less than 0.05), and preterm delivery (p less than 0.001). The congenital malformation, stillbirth, and perinatal mortality rates were comparable with maternal age-standardized national rates. Although the majority of in vitro fertilization pregnancies have a satisfactory obstetric outcome, there are a number of increased obstetric risks that may reflect the history of infertility, the relatively high incidence of poor obstetric history, and the lower threshold for obstetric intervention in in vitro fertilization patients.
Premature birth causes high rates of neonatal morbidity and mortality. There are multiple causes of preterm birth. This article reviews the evidence linking subclinical infection and premature birth. Although maternal genital tract colonization with specific organisms has been inconsistently associated with preterm birth and/or premature rupture of membranes, some infections have been consistently associated with preterm delivery. The association of histologic chorioamnionitis with prematurity is a consistent finding, but the mechanisms require further study. The relationship between histologic chorioamnionitis infection and the chorioamnionitis of prematurity requires additional research. A varying number of patients in "idiopathic" preterm labor have positive amniotic fluid cultures (0% to 30%), but it is not clear whether infection preceded labor or occurred as a result of labor. Evidence of subclinical infection as a cause of preterm labor is raised by finding elevated maternal serum C-reactive protein and abnormal amniotic fluid organic acid levels in some patients in preterm labor. Biochemical mechanisms for preterm labor in the setting of infection are suggested by both in vitro and in vivo studies of prostaglandins and their metabolites, endotoxin and cytokines. Some, but by no means all, antibiotic trials conducted to date have reported decreases in prematurity. These results support the hypothesis that premature birth results in part from infection caused by genital tract bacteria. In the next few years, research efforts must be prioritized to determine the role of infection and the appropriate prevention of this cause of prematurity.
To review the maternal morbidity and neonatal morbidity and mortality associated with in vitro fertilization (IVF) multiple pregnancies. Retrospective analysis of data collected from office and hospital records and from questionnaires sent to patients, their obstetricians, and pediatricians. Patients (all with private insurance carriers) enrolled in an academic IVF program (The Jones Institute for Reproductive Medicine). PATIENTS, All IVF pregnancies resulting in one or more gestational sacs on the initial ultrasound at 6 to 7 weeks were reviewed. The frequency and severity of obstetrical and neonatal complications and the perinatal mortality of IVF twins, triplets, and quadruplets were compared. These were also compared with non-IVF multiple pregnancies. From 1982 to 1990, 629 IVF pregnancies progressed beyond 20 weeks; 115 twins (18.3%), 15 triplets (2.4%), and 4 quadruplets (0.6%). There was a high incidence of antenatal complications such as abortions (30.3%, 42%, and 20%), premature labor (41.5%, 92.3%, and 75%), pregnancy-induced hypertension (17.0%, 38.6%, and 50%), and gestational diabetes mellitus (3.1%, 38.5%, and 25%) for twins, triplets, and quadruplets, respectively. The mean gestational age at delivery was 35.5 +/- 3.7, 31.8 +/- 2.7, and 31.0 +/- 1.7 weeks, respectively. There was also a proportionate progressive increase in neonatal complications. The mean weights were 2,473 +/- 745, 1,666 +/- 441 and 1,414 +/- 368 g, respectively. Twins (22.7%), 64.1% of triplets, and 75% of quadruplets needed admission to the neonatal intensive care unit and remained for an average of 12.0 +/- 2.3, 17.4 +/- 14.0, and 57.8 +/- 17.9 days, respectively. There was no difference in the mean Apgar scores or the incidence of congenital malformations in the three groups. The corrected perinatal mortality rates were 38.5, 0.0, and 0.0 per thousand live births, respectively. Triplet and quadruplet IVF pregnancies have increased obstetrical and neonatal complications compared with IVF twins. The perinatal mortality and the incidence of congenital malformations are, however, comparable in all three groups.
The Medical Research Council In-Vitro Fertilization (IVF) Register report on births resulting from assisted conception in Great Britain demonstrated a high incidence of preterm and low birthweight babies. This incidence remained high even when the analysis was restricted to singleton babies. The present paper investigates possible risk factors for prematurity, low birthweight and small-for-gestational-age (SGA) in singleton IVF births. Thirteen per cent of singleton IVF babies were preterm, 11% low birthweight and 17% small-for-gestational-age. Analysis by multiple regression indicated that hypertension during pregnancy was an independent risk for preterm delivery, low birthweight and SGA, bleeding during pregnancy for preterm delivery, and the number of embryos transferred and the type of infertility for low birthweight.
There are no absolute objective diagnostic criteria for cervical incompetence. Abdominal and endovaginal ultrasonographic assessment of endocervical length, both of which have been associated with technical problems, have been used to establish the diagnosis. Cervical cerclage may be useful in preventing silent cervical dilatation; however, no prospective trials with and without cerclage have been performed when endocervical shortening has been demonstrated by ultrasonography.
Home uterine activity monitoring has been proposed as an effective technique for reducing the incidence of preterm birth by early recognition of incipient labor. Five randomized controlled trials evaluating this technique have been published in peer review journals. As judged by accepted criteria for such trials, all have serious methodologic deficiencies. Four of the five trials demonstrated no significant benefit from this monitoring. Two other trials not published in peer review journals support the hypothesis that home uterine activity monitoring is no more effective than daily nursing contact. Until the efficacy of this technology has been established, home uterine activity monitoring should not be used clinically.
Infertility, spontaneous abortions and trisomic anomalies increase with maternal age, as do ectopic pregnancy, low birth weight, macrosomia, abruptio placentae and labor dysfunction. However, those phenomena are multifactorial in origin and cannot be ascribed solely to advancing age. Older pregnant women are also at increased risk for diabetes and hypertension. Whereas the older gravida is at increased risk for maternal mortality and morbidity and for fetal and infant mortality, those problems are explainable in large part by coexisting medical complications. The healthy older pregnant woman who receives appropriate prepregnancy counseling and up-to-date perinatal care can achieve results comparable to those achieved by younger ones.
Fifty-one consecutive twin pregnancies studied prospectively were compared with 153 consecutive control twin gestations that were concurrently delivered, but chosen retrospectively. Study patients were managed by a protocol that used weekly ultrasound surveillance combined with clinical assessment. Control subjects were not managed by protocol or ultrasound surveillance. Seven of 51 study patients (13.7%) were diagnosed as having cervical incompetency before 30 weeks' gestation (range 18-28 weeks, mean 24). In comparison, 14 of 153 controls (9.2%) delivered before 30 weeks' gestation (range 18-29 weeks, mean 25). The mean cervical length, dilatation, and membrane herniation (funneling) at diagnosis were 1.9, 2.2, and 3.6 cm, respectively, for patients with cervical incompetency. There was a significant difference in perinatal mortality. All study twins survived, whereas nine control subjects delivered at a mean gestational age of 22.7 weeks, with a loss of 17 infants. Life table analysis demonstrated that a significantly greater proportion of controls delivered very low birth weight, premature twins. The use of ultrasound and clinical criteria to select patients for cerclage placement helped prevent birth of the youngest and smallest twins and significantly decreased perinatal mortality in the study group. Routine cerclage placement is not recommended for twin gestations, but multifetal gestations may benefit from ultrasound surveillance for cervical incompetency.
Home uterine activity monitoring has been described as an effective means of detecting uterine contractions, but controversy exists whether it is home uterine activity monitoring or increased nursing support in conjunction with it that contributes to earlier detection of preterm labor. In this study 377 women at risk for preterm labor from three centers were prospectively, randomly assigned to high-risk prenatal care alone (not monitored) or to the same care with twice-daily home uterine activity monitoring without increased nursing support (monitored). The two groups were medically and demographically similar at entry into the study. Routine visits, nonroutine visits, and gestational age at diagnosis of preterm labor were similar in both groups. Preterm labor occurred in 41 of 198 monitored and 39 of 179 not monitored patients. Mean cervical dilatation was 1.4 cm in 41 monitored compared with 2.5 cm for 37 not monitored (p = 0.0006); 73.1% of monitored and 27.5% of not monitored had preterm labor detected before 2 cm dilatation (p = 0.00009). Neonatal outcome of singleton pregnancies showed greater birth weight, fewer days in the neonatal intensive care unit, and fewer babies requiring oxygen therapy and mechanical ventilation in the monitored group. The better outcomes are probably due to the increased likelihood of diagnosis of preterm labor before advanced cervical dilatation with home uterine activity monitoring, thus providing the clinician with a better chance to initiate tocolytic therapy directed at improving pregnancy outcome.
We evaluated the association between subfertility and low birth weight infants. Women in this analysis participated in a cross-sectional investigation of maternal risk factors for adverse pregnancy outcomes. Medical and obstetric history and life style information were obtained from women who delivered at the Boston Hospital for Women, 1977 to 1980. PATIENTS, Our analysis was restricted to nondiabetic married women who planned their pregnancies and subsequently delivered viable singletons (3,622). The 644 "subfertile" women (no conception during a year of unprotected intercourse) were compared with 2,978 "fertile" women (conception within 1 year). MAIN OUTCOME MEASURE(S): The relative risk of low birth weight was estimated using the cumulative incidence risk ratio. After adjusting for confounding, the relative risk of delivering a low birth weight infant (less than 2,500 g) for subfertile women versus fertile women was 1.9 (95% confidence interval [CI], 1.3 to 2.8). The adjusted relative risk of delivering a term low birth weight (intrauterine growth retarded) infant was 2.3 (95% CI, 1.2 to 4.4). In these data, subfertility is a predictor for low birth weight. The association may result from endocrinological, immunological, cervical, or other factors that interfere with optimal fetal growth.
Noblot G et al., 1991·Eur J Obstet Gynecol Reprod Biol·
The results of a study concerning the treatment of acute menace of preterm labor are given: beta-mimetics were administered intravenously in all cases (44) and micronized progesterone or placebo was administered orally after classical double-blind randomization (22 cases in each group). The mean index of pregnancy prolongation was the same in both groups. However the mean duration of the intravenous perfusion and the mean quantity of beta-mimetics administered intravenously were significantly reduced in the progesterone group (P less than 0.01). The mean duration of hospital stay was also significantly reduced (P less than 0.05). Cost and risks are finally significantly lessened.
At an interdisciplinary workshop on home monitoring of uterine activity, participants reviewed the basis of this technology and its use in the identification of women at high risk of preterm delivery and in the prevention of preterm birth. Although the guard-ring devices in current use appear capable of detecting uterine activity, they do not clearly distinguish between Braxton Hicks contractions and the contractions of early labor. There was agreement that women destined for preterm delivery have more uterine activity on average than do other women of comparable gestational age but that there is substantial overlap between the two groups. Thus it is uncertain whether this difference can be used effectively for screening purposes. Conferees agreed that there is considerable evidence that twice-daily monitoring of very-high-risk women, in conjunction with daily nursing support and high-quality obstetric care, may prevent preterm births. Available evidence does not clearly distinguish the contribution of tocodynamometry from that of nursing support. A number of areas were identified in which further research is needed.
The relative contributions of home tokodynamometry and daily nursing telephone contact to the success of preterm birth prevention programs remains a subject of debate. Because investigators have obtained conflicting data, a reinterpretation of published results was undertaken by proposing a dynamic interface between the nurse and the machine. Experience gained from the technology and the development of nursing expertise with assessment of patient symptoms are presented as interdependent factors, both of which are critical to a therapeutic nurse-patient relationship. It is proposed that this combined interactive expertise increases sensitivity to the early recognition of preterm labor. The nurse's role in providing social support to high-risk pregnant women is then identified as a potential additional independent contributing factor to reported observed reductions in preterm births. Discussion focuses on future research, public policy issues, and the need for expanding nurse-patient interactions into the home.
A randomized prospective trial was performed to compare the efficacy and safety of ritodrine and indomethacin in the long-term treatment of preterm labor. Forty patients with intact membranes in preterm labor at 23 to 34 weeks' gestation were randomized to receive either intravenous ritodrine or oral indomethacin as the first-line tocolytic agent. Successful intravenous ritodrine therapy was followed by oral terbutaline therapy, and indomethacin-treated patients continued to receive oral indomethacin. Treatment failures were defined as progressive preterm labor or patient intolerance, and these patients were treated with intravenous magnesium sulfate. Ritodrine and indomethacin were equally successful in delaying preterm birth as defined by interval to delivery, gestational age at delivery, delivery delayed greater than 7 days, attainment of 35 weeks of gestation, percentage of patients who required magnesium sulfate therapy, percentage of patients who were readmitted with premature rupture of membranes, absence of recurrent preterm labor, and infant birth weight. More than 80% of mothers who received ritodrine voiced complaints of beta-sympathomimetic side effects, and one patient discontinued treatment as the result of intolerance. There were minimal patient complaints with indomethacin use. No statistically significant differences were noted in neonatal outcome as defined by Apgar scores, umbilical cord pH, intensive care days, ventilator days, or neonatal deaths. However, three cases of primary pulmonary hypertension were observed in the indomethacin group. We had not previously observed this problem with short-term (24 to 48 hours) indomethacin therapy.
A total of 394 patients were enrolled in a study to assess the effectiveness of an educational preterm delivery prevention program and to determine whether the addition of home uterine monitoring to the program improved results in patients at high risk of preterm labor. Both the educational program and home uterine monitoring were found to increase the percentage of women with preterm labor who sought care while still favorable for long-term suppression, resulting in a decreased incidence of preterm births and improved outcome when compared with similar high-risk patients who did not participate in these programs. In a randomized, prospective study, addition of home uterine monitoring to the educational program was found to significantly improve outcome in twin gestations but not in singleton gestations. However, the number of singleton pregnancies was too small to rule out possible benefit from home uterine monitoring in that group.
A preterm birth prevention program consisting of risk scoring, intensive weekly observation including cervical examinations, and detailed education about preterm labor signs and symptoms was tested in a predominantly black, indigent population. One thousand high-risk women were randomized to treatment or control groups. Although more preterm labor was diagnosed and treated in the treatment group, there were no significant differences between the groups with respect to mean birth weight or gestational age, spontaneous preterm delivery rates, or low or very low birth weight rates. The rates of respiratory distress syndrome and fetal and neonatal mortality, although greater in the treatment group, were not statistically different. However, the treatment-group infants had significantly more intracranial hemorrhages and spent more days on ventilators. At this institution, the preterm birth prevention program was not effective.
Ninety pregnancies conceived by infertile couples using assisted reproductive technologies and 86 pregnancies conceived by infertile couples with routine infertility treatment were analyzed to determine the outcome of and the complications experienced during the pregnancies. Pregnancies ending after 24 weeks' gestation were evaluated for the following complications: pregnancy-induced hypertension, diabetes mellitus, preterm labor, premature rupture of membranes, placenta previa, and fetal growth retardation. A matched control group of normal fertile patients admitted to the obstetric service at Vanderbilt University Medical Center was used to compare the incidence of pregnancy complications among the groups. In the group treated by assisted reproduction, 81 pregnancies were singleton and nine were multiple gestations, whereas in the routine group, 84 were singleton and two were multiple gestations. In the group treated by assisted reproduction, 29 of 90 gestations (32%) ended before 24 weeks, compared with 18 of 86 (21%) in the routine group, a nonsignificant difference. Mean birth weight and gestational age were similar among the three groups for singleton gestations. Among multiple gestations, the mean (+/- standard error of the mean [SEM]) birth weights were 2513 +/- 115, 724 +/- 57, and 2282 +/- 132 g in the group treated by assisted reproduction, the group receiving routine methods, and the control group, respectively (P less than .001 when those treated by routine methods were compared with the other two groups). The mean (+/- SEM) gestational ages were 36 +/- 1.2, 26.5 +/- 2.0, and 35.5 +/- 1.2 weeks, respectively (P less than .01 comparing those treated by routine methods and the other two groups).(ABSTRACT TRUNCATED AT 250 WORDS)
Patient and staff education concerning the subtle signs and symptoms that precede a clinical diagnosis of preterm labor have not been well established. Therefore we interviewed 100 patients for the presence or absence of various symptoms and signs during the 7 days preceding diagnosis of preterm labor. An additional 100 patients without preterm labor matched for gestation were chosen at random as control subjects. A history of increased uterine contractions, menstrual cramps, constant backache, constant pelvic pressure, increased amount and consistency and color change of vaginal discharge, and increased frequency of urination were present with a statistically significant higher frequency in patients with preterm labor compared with controls. Twenty-nine percent of patients did not report any uterine contractions and only half described them as painful. Fewer than 50% of the women reported contractions as frequently as every 10 minutes or more.
Two recently published meta-analyses of controlled trials of a wide variety of progestational agents, used in pregnancy (Daya 1989; Goldstein et al. 1989), prompted this third meta-analysis of placebo-controlled trials involving the prophylactic use of a single agent, 17 alpha-hydroxyprogesterone caproate. Of seven relevant published reports of controlled trials, six had involved women considered to be a high risk of miscarriage or preterm birth. This analysis provides no support for the view that 17 alpha-hydroxyprogesterone caproate protects against miscarriage, but suggests that it does reduce the occurrence of preterm birth. The latter effect was reflected in a reduced rate of low birthweight babies, but not in a statistically significant reduction in perinatal mortality and morbidity. The difference between this meta-analysis and the two earlier meta-analyses illustrates the problems both of selective sub-grouping and of comprehensive pooling of data from small trials.
Selective fetal reduction was performed in the first trimester of pregnancy in 20 women with multifetal gestations after ovulation induction with human menopausal gonadotropin (hMG). In 10 women (group A) reduction was performed transabdominally, and in 10 women (group B) the transvaginal approach was used. The transvaginal technique achieved penetration of several gestational sacs without withdrawing the needle from the uterus. Fetal termination using either procedure occurred with intrafetal injection of potassium chloride. Six (60%, group A) and eight (80%, group B) patients delivered healthy newborns. One patient (group B) is at 30 weeks' gestation. Four (40%, group A) and one (10%, group B) aborted 1 day to 8 weeks after the procedure (1 septic abortion, each group). Our results suggest that transvaginal fetal reduction offers a better outcome, with minimal complications, to patients referred for selective continuation of pregnancy.
The relationship between asymptomatic bacteriuria and prematurity/low birth weight (LBW) is still a controversial issue, despite many studies. Meta-analysis, a research tool designed to analyze and combine the results of previous studies, may resolve this discrepancy among contradictory results of clinical trials. The purpose of this study was to examine the relationship between asymptomatic bacteriuria and preterm delivery/LBW using meta-analysis. Reports from the literature were classified according to study design into cohort or randomized-treatment control trials. Meta-analysis of cohort studies showed that untreated asymptomatic bacteriuria during pregnancy significantly increased rates of LBW and preterm delivery. Nonbacteriuric patients had only about two-thirds the risk (typical relative risk = 0.65; 95% confidence interval 0.57, 0.74) of LBW and half the risk (typical relative risk = 0.50; 95% confidence interval 0.36, 0.70) of preterm delivery of those with untreated asymptomatic bacteriuria. These reduced risks correspond to a 3.4 (confidence interval 1.8, 5.0) percentage-point difference in LBW and a 3.8 (1.1, 6.4) percentage-point difference in preterm delivery. The analysis of randomized clinical trials showed that antibiotic treatment significantly reduced the risk of LBW (typical relative risk = 0.56; 95% confidence interval 0.43, 0.73), with a substantial reduction of 6.4 (confidence interval 3.3, 9.5) percentage points in the rate of LBW. We conclude that clinical and epidemiologic evidence indicates a strong association between untreated asymptomatic bacteriuria and LBW/preterm delivery and that antibiotic treatment is effective in reducing the occurrence of LBW.
Tocolytics were administered in 66 consecutive women in uncomplicated preterm labour with intact fetal membranes (53 singleton and 13 twin pregnancies). C-reactive protein (CRP), a marker of infection, was determined daily and used retrospectively to investigate the role of subclinical infection in preterm labour and to predict the efficacy of tocolysis and the development of a clinical perinatal infection. CRP was also determined in 66 women in uncomplicated labour at term (53 singleton and 13 twin pregnancies). The placenta was examined for histological evidence of infection in all patients who were delivered before 36 weeks (n = 21) and in all women in the control group (n = 66). Elevated CRP levels were more often found in patients who were refractory to tocolysis, suggesting an underlying infectious morbidity. Placental infection was found in 62% of the preterm delivery group and in 12% of the control group. There was an association between elevated CRP levels and histological evidence of placental infection. However, confounding factors such as urinary tract infections limit the usefulness of the CRP test. Because CRP cannot predict clinical perinatal infection accurately, its clinical relevance is very limited.
Two runners who were not aware they had conceived continued their intense running regimens during the first and second trimesters of pregnancy. Both women assumed that their amenorrhea was due to endurance training. When their pregnancies were diagnosed, both women markedly reduced their training mileage during the third trimester because they feared that intense exercise might harm the fetus. Retrospective data were collected on their antenatal and intrapartum courses. Both women delivered healthy infants of normal weight. Although these two cases suggest that strenuous anaerobic exercise during pregnancy is not harmful, more studies are needed to determine if these cases are isolated.
Measurement and Statistics · Instrument Development and Validation
Despite recognition that estimation of gestational age (GA) based on maternal recollection of the last normal menstrual period (LNMP) is fraught with error, it is not generally appreciated that the magnitude and direction of this error vary as a function of the LNMP estimate. Early second-trimester (16 to 18 weeks) ultrasound determinations of the fetal biparietal diameter were used as the "gold standard" to test the validity of LNMP-based GA estimates in 11,045 women. The large majority of deliveries occurring at or near term showed LNMP estimates that were valid within plus or minus seven days of the ultrasound estimate. As the LNMP GA deviated progressively toward earlier or later GAs, however, the discrepancies became quite marked, especially for postterm dates. The positive predictive values of the LNMP GA estimates decreased dramatically from term (.949) to preterm (.775) to postterm (.119) deliveries. These systematic errors in menstrual GA estimates have profound implications for unnecessary induction, dysfunctional labor and cesarean section, and resultant neonatal and maternal morbidity.
Nine patients in preterm labor requiring long-term tocolysis were managed with subcutaneous terbutaline administered via a portable infusion pump. All had failed oral tocolytic therapy and were therefore faced with prolonged hospitalization. In this feasibility study, the patients were treated at home and monitored with portable tocodynamometers and home nursing visits. Uterine activity data were transmitted via telephone to the study center and terbutaline pump infusion rates were adjusted accordingly. Terbutaline pump therapy consisted of a combination of low-dose continuous basal infusion supplemented with intermittent high-dose boluses. Total daily drug dosage remained exceptionally low (less than 3 mg/24 hours). The mean gestational age at initiation of therapy was 29.6 +/- 3.7 weeks, and pregnancy was prolonged an average of 9.2 +/- 4.3 weeks. The minimum gestational age at delivery was 37.3 weeks. Patient tolerance was excellent and, in a total 394 patient-days of therapy, there were no significant complications. We conclude that the portable subcutaneous terbutaline pump may be a promising new method for long-term outpatient tocolysis in patients who cannot be maintained on oral therapy.
Kornman L et al., 1988·Aust N Z J Obstet Gynaecol·
This study was designed to derive the predictive value of C-reactive protein (CRP) in peripheral venous serum of patients admitted to hospital with suspected premature rupture of the membranes (PROM). CRP was assayed by each of 4 separate methods and the results have been compared for accuracy and practical value with respect to clinical outcome and the histopathology of the placenta. Of the 4 techniques used only the latex test had characteristics suitable for a diagnostic screen. While the results were only semiquantitative, when comparisons were made to other techniques no significant change in clinical diagnosis would have been made. The results have confirmed that chorioamnionitis and preterm labour are often associated, but in some instances the extent of inflammatory infiltration was greater than might have been expected from the short time interval between documented membrane rupture and delivery. Thus it may be speculated that some cases of PROM are secondary to, rather than causative of, infection. Finally it is suggested that a controlled therapeutic trial of active intervention in those cases of PROM with elevated CRP in the absence of other clinical parameters suggestive of intrauterine infection should be undertaken.
Pregnancy following a period of infertility was considered to be an increased risk for the fetus. During a period of 3 years (1983-85), 748 couples were seen at this infertility clinic; 515 women (68.9%) conceived, and were followed up and studied prospectively. Fifteen of these women moved out of the area. We analysed the results of pregnancies for the remaining 500, (Group 1) and compared them with the outcome for the total obstetric population (Group 2) during the same period. Mean age at conception in the infertility group (Group 1) was 31.8 (+/- 2.7, 2 SD) years, as compared with 23.7 (+/- 2.9, 2 SD) in the total hospital obstetric population (Group 2) (p less than 0.05). The incidences of spontaneous abortion for the two groups (8 and 6.2%) did not differ (p greater than 0.05). However, the incidence of ectopic pregnancy was higher (3.0%) in Group 1 than in Group 2 (1.5%) (p less than 0.01). The incidence of pre-existing hypertensive vascular disease (7.7%) complicating pregnancy and multiple pregnancy (4.1%) was significantly higher in Group 1 than in Group 2 (1.5% and 1.4% respectively), (p less than 0.01). The incidences of induction of labor (29.5%) and elective operative delivery (10.6%) were higher in Group 1 (p less than 0.01). The incidences of infants with birth weight below the tenth centile (12.9%), of fetal distress in labor (14.6%) and a low Apgar score (0-5) (9.5%), were higher in Group 1, but there was no difference in the perinatal mortality rate between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Anti-Infective and Anti-Inflammatory Agents · Antibiotics in Reproductive Care
To determine the best method of preventing ascending infection in the management of premature rupture of membranes, antibiotics such as latamoxef sodium, cefoperazone sodium, and cefotaxime sodium were infused directly into the amniotic cavity in 64 patients undergoing induction of labor at term. A single infusion of 100 or 500 mg of each drug resulted in a concentration of 200 to 1000 micrograms/ml immediately after infusion, and the concentration remained above 10 micrograms/ml for about 24 hours without significant increase in fetal or maternal blood levels. Consequently, a daily single dose of 100 mg or more is probably effective prophylaxis in cases of premature rupture of membranes. When intrauterine infection is suspected, the dose can be increased to 500 mg or more, and transplacental administration may be added to achieve a higher concentration in fetal blood. The present study simulates well premature rupture of membranes, and an amnioinfusion of antibiotics will be reliable and effective in managing premature rupture of membranes.
The value of maternal C-reactive protein (CRP) levels as predictors of fetal and maternal infective morbidity and fetal mortality was assessed prospectively over a 6-month period in all cases of premature rupture of the fetal membranes or suspected premature labour. Statistical analysis of results showed that CRP at a level of 1.32 mg/dl is a sensitive marker of infective morbidity in mother and neonate. Furthermore, there was a significant association between raised CRP levels and low-birth-weight babies, suggesting that intra-uterine infection is a major cause of prematurity in the study population.
We studied 500 women who conceived after investigation and treatment for different infertility problems and compared the outcome of the 5 infertility groups (Group 1 to 5), the ovulatory dysfunction (Group 1), male infertility (Group 2), A.I.D. (Group 3), tubal surgery and IVF (Group 4) and no treatment (Group 5) with the outcome in the hospital group during a period of 3 years. The incidence of abortion in Group 3 is significantly higher (13.8%), the incidence of ectopic pregnancy is significantly higher in Group 4 (21.7%) as compared with the incidence in the hospital group (P less than 0.01). The rate of pre-existing hypertension and gestational diabetes is significantly higher in all the 5 infertility groups as compared with the incidence in the hospital group (P less than 0.05). The incidence of preterm labor in general is less in the infertility group as compared with the incidence in the hospital group (P greater than 0.05). The incidence of older women, multiple pregnancy, induction of labor, operative deliveries, fetal distress, low Apgar score, babies with birth weight below the tenth centile were higher in the infertility groups (P less than 0.05). But the perinatal mortality or major or minor fetal anomalies were not significantly different in the infertility groups as compared with the rate in the hospital groups (P greater than 0.05).
Cervical incompetence is one of the main contributors to repeated pregnancy loss, accounting for approximately 25% of the cases. Typically it results in progressive cervical dilatation, leading to a painless second- or early-third-trimester abortion. In most instances cervical incompetence is the result of previous obstetric or gynecologic trauma; a congenital etiology is unusual. Despite the various reported diagnostic procedures, the obstetric history and frequent visual and digital examinations during pregnancy remain the most important factors in arriving at the correct diagnosis. In spite of the fact that numerous procedures have been advocated as treatment, the McDonald purse string closure technique is by far the most simple and effective corrective surgical technique, yielding an overwhelming number of successful pregnancies.
A study to evaluate whether ambulatory tocodynamometry at home could enhance the management of oral tocolysis was performed. On discharge from the hospital, after completing parenteral tocolysis, 60 patients received a lightweight tocodynamometer, designed for storage and transmission of uterine activity data. Sixty additional contemporary patients, who were matched for maternal age, parity, and risk factors, served as a control group. In addition to instructions regarding self-detection of recurrent preterm labor, monitored patients recorded uterine activity for greater than or equal to 200 min/day and then transmitted the data to the study center. Tocolytic dosage was adjusted to maintain mean uterine contraction frequency of less than 4/hr. Persistent uterine contractions of greater than or equal to 4/hr lead to in-hospital evaluation for recurrent preterm labor. The results indicate that the monitored group had a lower incidence of preterm births mostly because of a decrease in the proportion of patients with failed tocolysis. It is suggested that surveillance of uterine activity at home during oral treatment for preterm labor may be instrumental in improving perinatal outcome in high-risk patients.
The potential tocolytic effect of natural progesterone administration on premature labor was investigated in a double-blind study. An oral progesterone formulation was used because its ability to increase both plasma and myometrial concentration of progesterone in pregnant women had been previously demonstrated. Furthermore, no commercial intravenous or intramuscular natural progesterone formulation is currently available in France. Fifty-seven patients in two obstetric clinics, admitted because of the risk of premature delivery, were included in the study, and uterine contractility and fetal cardiac rhythm were monitored in all of them. At random and after 30 minutes' rest, 29 women absorbed four capsules of 100 mg of progesterone each and 28 women absorbed four capsules of a placebo. Plasma progesterone levels were evaluated in all cases after 30 minutes' rest and 1 hour after absorption of the capsules. The results showed that bed rest and placebo administration decrease uterine activity in 42% of the cases and oral progesterone decreases activity in 75% to 88% of cases, depending on the initial severity of the menace of premature delivery. The difference between the effects of progesterone and of placebo is significant. The tocolytic effect of oral progesterone is not as intense or as rapid as the effect of intravenous beta-mimetics but is sufficient in 80% of cases, on the average, to stop the premature labor without any detectable side effects. This tocolytic effect of oral progesterone is related not just to an increase in plasma progesterone levels but probably to an increase in myometrial progesterone concentration.
The role of subclinical intrauterine infection in preterm labor was evaluated prospectively in 40 patients and appropriate control subjects. The 24 preterm labor patients (60%) with a negative C-reactive protein value responded to tocolysis 95.8% of the time, with a mean delay of delivery of 35.5 days and a mean gestational age of 36.9 weeks. The 16 patients (40%) with a positive C-reactive protein value responded to tocolysis only 37.5% of the time, with a mean delay of delivery of 14.4 days and a mean gestational age of 33.2 weeks. Pathologic evidence of chorioamnionitis was present in 32.9% of 310 preterm deliveries as compared to only 22.3% of 1631 term deliveries. The presence of subclinical infection must be considered in cases of preterm labor, especially among patients for whom tocolytic therapy is unsuccessful.
A system capable of ambulatory home monitoring of uterine activity and data transmission was evaluated in a group of pregnant patients. The evaluation focused on three questions: 1) Is the information as reliable as that obtained by the current stationary monitors; 2) Does the information obtained by the tested system relate to that obtained by direct intrauterine pressure measurements; and 3) Is the system simple enough to be used by the unsupervised gravida at home? The results indicate that the tested system can provide reliable information about uterine activity in ambulatory patients. A good correlation between the intensity of contractions and the recording of uterine activity by this system could be demonstrated, particularly in the presence of mild to moderate contractions. The tested monitor proved to be simple to use even in the untrained gravida. Additional studies to determine the role of ambulatory home monitoring of uterine activity in patients with cervical cerclage, placenta previa, and preterm labor will need to be performed to establish its role in current obstetric practice.
The medical records of 330 patients treated with terbutaline infusion for the inhibition of preterm labor were reviewed over a five-year period. In patients with intact membranes the results were uniformly good, particularly when treatment was instituted before the 30th week. Half these patients had a prolonged labor of six weeks or more; in most cases of treatment failure complications already existed on admission. In only nine patients (2.7%) terbutaline treatment was stopped due to side effects: predominantly maternal tachycardia or vomiting. Two patients had chest symptoms, but in no case was pulmonary edema diagnosed. The results suggested that a low incidence of severe side effects can be obtained if the following precautions are taken: glucose is used as the infusion medium, instead of sodium chloride; concentrated solutions are given to avoid fluid overload; the patients are carefully controlled; and the infusion is immediately reduced or stopped if signs of severe side effects appear.
Eighty pregnant women at high risk of giving birth prematurely were divided randomly into two groups. Treatment with either 17 alpha-hydroxyprogesterone caproate, 250 mg by intramuscular injection once a week, or a placebo was given in a double-blind fashion. Imminent premature labor occurred in 29.0% of the treated group and in 59.4% of the control group (p less than 0.025). The rate of premature deliveries was also significantly lower in the treated group (16.1%) than in the control group (37.82%) (p less than 0.05). There were no cases of perinatal death or fetal malformations in either group. The mean birth weight of all infants of the treated group was significantly higher than in those of the control group (3111.9 +/- 905 gm versus 2680 +/- 813.4 gm, p less than 0.05). The results support treatment with progesterone caproate for the prevention of premature labor.
Although major advances have been made in both obstetric care of the high-risk patient and in neonatal care, prematurity and its consequences remain the major contributor to perinatal mortality. The identification of maternal or obstetric risk factors associated with preterm delivery has enhanced our ability to provide special obstetric care to gravidas at increased risk. The selective management of patients at increased risk for preterm delivery may ultimately reduce the incidence of preterm births. Maternal genital infections are also associated with preterm delivery. Further research is needed to explore the pathogenesis of preterm delivery associated with genital infections, since infections may represent a potentially preventable cause of prematurity.
The effect of cervical suture on pregnancy outcome was studied in 194 women with a high risk (approximately 30%) of having a late abortion or a preterm delivery. The women were randomly allocated either to have a cervical suture inserted (n = 96) or to be managed without a suture (n = 98). There was no evidence that cervical cerclage either prolonged gestation or improved survival. Patients allocated to receive cerclage spent significantly longer in hospital, even when the period of admission for insertion was excluded. The patients in the cerclage group were more likely to receive tocolytic drugs, and more of them experienced puerperal pyrexia, although these differences between the groups were not statistically significant.
Thirty-seven consecutive patients with singleton pregnancies in "uncomplicated" preterm labor with intact membranes suitable for tocolysis were evaluated for evidence of silent chorioamnionitis by means of maternal serum C-reactive protein and amniotic fluid white blood cell count, Gram stain, and cultures. Abnormalities in these markers of infection were found to be significantly more common in cases that were refractory to tocolysis. These cases also showed both pathologic evidence of chorioamnionitis and a significantly greater neonatal early infectious morbidity. We conclude that silent chorioamnionitis is a significant cause of "uncomplicated" preterm labor refractory to conventional methods of tocolysis.
A total of 506 women at moderate risk of preterm delivery were randomly allocated to either cervical cerclage or a control group. Significantly more women in the group allocated to cerclage were admitted to hospital for reasons other than the operation and more received oral tocolytic drugs. There were also more caesarean sections and more preterm deliveries in the women allocated to cerclage although the differences between the two groups were small and not statistically significant.
Subclinical intrauterine infection is an important cause of preterm labor, specifically where tocolysis has failed. Fifty patients in preterm labor with singleton pregnancies were studied prospectively to determine whether the presence or absence of C-reactive protein, a nonspecific marker for infection, would correlate with success or failure of tocolysis. Of the 50 patients, tocolysis failed in 11 of 15 women with a positive C-reactive protein determination. Tocolysis succeeded in 33 of 35 cases where C-reactive protein was negative (P less than .0005). Urinary tract infection occurred in 40% of the study patients, but was not a confounding factor in the interpretation of C-reactive protein.
The principal function of muscular tissue is contraction. This is also true for the uterus this function begins with sexual maturation. During pregnancy special conditions are brought about by the increasing distention of the uterine cavity. For clinical practice, external tocography is of importance for the recognition of uterine motility Data in the literature on the normal frequency of contractions during pregnancy vary greatly and caused us to study this topic. Moreover, most cases of prematurity independent of other causes suppose a prematurely increased uterine motility. In order to register this activity a portable recording apparatus was developed. We studied in particular the question for how long and how often uterine contractions should be recorded. A one hour daily recording was found to be sufficient. In order to gain information on the average number of contractions it suffices to record during one week. In 26 healthy primiparous and 28 multiparous women the number of contractions from the 25th to 41st gestation week was recorded. A notable finding was the frequency peak about the 32nd week. The number of pregnancy contractions as a sole parameter for the recognition of impending premature delivery is not sufficient. However, the information may be important when taking in conjunction with the previous history and the state of the cervix. We considered tocolysis indicated when as a weekly average there are more than two contractions per hour with beginning cervical dilation or more than three contractions per hour regardless of cervical findings.(ABSTRACT TRUNCATED AT 250 WORDS)
Congenital Uterine Anomalies · Anomalies and Pregnancy Outcomes
Fifteen women with diminished fertility as a result of congenital uterine anomalies were treated by cervical suture (cerclage) in the 11th-12th week of pregnancy without surgical correction of the uterine anomaly. None of these women had either clinical or radiological evidence of cervical incompetence. As a result of the treatment, 13 of the women delivered live full-term mature infants. None of the women aborted, only two women delivered prematurely, and both infants were alive and well. Comparison of these good results to the very poor outcome of previous pregnancies in these women points to a distinct advantage to be gained by cervical suture. As a result of this experience, we recommend cervical suture in cases of diminished fertility as a result of congenital uterine anomaly. We recommend that the suture be performed before considering surgical repair of the anomaly and irrespective of lack of evidence of cervical incompetence. Only in cases where cervical suture is unsuccessful, would we recommend surgical correction according to the accepted techniques.
Rats which were subjected to ovariectomy on day 18 of pregnancy and were treated with 17 beta-estradiol underwent delivery prematurely at 0900 +/- 1.9 hours on the morning of day 18. All animals had in plasma and uterine tissue a precipitate and highly significant progesterone withdrawal and a corresponding significant increase in prostaglandin F and prostaglandin F metabolite. Progesterone replacement therapy given to a second group of castrated animals prevented progesterone withdrawal and premature labor, because the hormonal profile in plasma and uterine tissue of these animals was identical with that of the intact pregnant vehicle controls. Electron microscopy of longitudinal and circular myometrial layers showed a precipitate and highly significant increase in the number, size, and area of gap junctions in the uteri of the group undergoing premature delivery. In the uteri of the progesterone-treated and vehicle control groups (both intact pregnant), gap junctions were conspicuously scarce. Thus the extensive regulatory imbalance, provoked by progesterone withdrawal, induced a significant increase in myometrial gap junctions. This structural change established contacts between individual myometrial cell which could transform the multibillion cell community of the uterus into a syncytium, to generate low-resistance pathways to the flow of current and thus promote the propagation of trains of electrical discharge in support of labor.
Congenital Uterine Anomalies · Anomalies and Pregnancy Outcomes
Heinonen PK et al., 1982·Acta Obstet Gynecol Scand·
A total of 182 women with uterine anomalies were observed over a period of 18 years. In all, 126 women had 265 pregnancies, fetal survival rate was 66%, perinatal mortality 8% and premature labors occurred in 23%. When the uterine anomalies were grouped according to degree of failure of normal and uterine development, the complete septate uteri had the best fetal survival rate (86%), complete bicornuate uteri (50%) and unicornuate (40%) poorest. Cervical cerclage was applied most in the partial bicornuate uteri (17%), where fetal survival in operated cases was: before operation, 53% and after, 100%. The frequency of breech presentation was 40-50% in all groups except complete septate uteri (25%) and complete bicornuate (0%). The highest cesarean section rate (82%) was in deliveries of patients with uterus didelphys. The frequency of cesarean section among total deliveries was 53%. Metroplasty was carried out on 19 patients. The obstetric outcome improved from 10% successful pregnancies before surgery to 88% postoperatively.
A case-control study of the epidemiology of preterm delivery was undertaken at Yale-New Haven Hospital in Connecticut during 1977. The study population consisted of 175 mothers of singleton preterm infants and 313 mothers of singleton term infants. Significant risk factors of a preterm delivery included low socioeconomic status; low pregravid weight; inadequate weight gain during the pregnancy; a previous preterm delivery; a history of infertility problems; an induced abortion terminating the previous pregnancy; vaginal spotting or light bleeding during the pregnancy; antepartum hemorrhage and abnormal placental implantation; lack of leisure-time physical activities during the pregnancy; alcohol consumption prior to the third trimester of pregnancy; and negative attitudinal expression toward the pregnancy.
A shift in progesterone-to-estradiol balance to estradiol dominance is assumed to be a prerequisite for regular uterine contractions. To antagonize this effect in premature labor 24 consecutive women were treated with intravenous cortisol for 3 days and with weekly intramuscular injections of 17 alpha-hydroxyprogesterone caproate (17 OHP-C). Twenty-four similar patients treated with ritodrine served as a reference group. The delivery was postponed by at least 1 week in 21 patients (87.5%) in the steroid treatment group and in 18 patients (75%) in the ritodrine group. The premature labor lasted for 5.1 +/- 0.4 hours (mean +/- SEM) with steroid therapy and for 2.2 +/- 0.3 hours with ritodrine. In singleton pregnancies the gestational length and birth weight of the newborn infants were greater in the steroid treatment group (N = 23, 39.1 +/- 0.3 weeks, 3,460 +/- 119 gm) than in the ritodrine group (N = 24, 37.7 +/- 0.4 weeks, 3,106 +/- 118 gm). Steroid treatment suppressed serum estradiol concentrations (maximally by 60%) and, to a lesser extent, testosterone, estriol, and progresterone levels (maximally by 30%).
Studies have been undertaken regarding the efficacy and modus operandi of 17 alpha-hydroxyprogesterone caproate (17 alpha-OHP-C) in preventing premature labor in high-risk patients. In a total of 70 patients, the treated patient population had a prematurity rate (12.8%) and a perinatal mortality rate (5%) which were significantly lower than those of the total placebo or untreated patient group (40.9 and 25%, respectively). In addition, sequential plasma steroid values were determined in 21 patients, 10 of whom delivered prematurely. The results indicate that low plasma progesterone (P) and 17 alpha-hydroxyprogesterone (17 alpha-OHP) levels precede the onset of preterm labor by weeks. Successful treatment with 17 alpha-OHP-C was characterized by elevated P levels. Plasma estradiol (E2) and cortisol (C) values did not vary with time of delivery or treatment. These findings support the progesterone block theory as an important mechanism affecting preterm delivery in this high-risk population.
Conflicting results have been published regarding changes in plasma progesterone during the last trimester of pregnancy. Some have demonstrated a fall in plasma progesterone before labor, and this has been taken as a possible explanation of the onset of labor. It has been suggested that the various results could be due to differences in methods for progesterone determination. In this study the progesterone levels were determined by both RIA and CPB. In 11 women the plasma progesterone, human placenta lactogen, and serum estriol were measured weekly during the last trimester of normal pregnancies and immediately after delivery. All samples were analysed radioimmunologically. In order to compare the radioimmunoassay and competitive protein binding techniques (RIA and CPB), the progesterone levels were determined by both methods. This was also done for 80 successive plasma progesterone routine samples drawn from women who were not pregnant or who were in the early stages of pregnancy. Both methods showed a significant rise in the plasma progesterone level during the last 6 weeks before spontaneous labor. However, the values obtained were lower when assayed by CPB than by RIA, presumably because of a higher specificity and a cross reaction in RIA. Serum estriol exhibited increasing values throughout pregnancy, but without a significant rise during the last few weeks. Plasma HPL settled at a constant level during the last few weeks before labor.
Data from 25,958 consecutive UCLA deliveries were analyzed to determine the effect of prior abortions and premature births on current pregnancy outcome. Perinatal death rate, combining stillbirths and neonatal deaths, increased more than threefold among women with at least one prior premature in birth and at least one prior abortion and approached 18 per cent of current deliveries when there were three or more prior premature births. Abnormal live births, defined as infants with either birth weight under 2,501 grams, gestational age less than 37 weeks, or congenital anomalies, significantly increased as the number of prior abortions and premature births increased, each in a range of 0 through 3 or more. For example, among women with at least three prior premature births, there were greater than 50 per cent abnormal live births. The risk was mostly that of low birth weight and low gestational age, although there was a slight increase in congenital anomalies. The risk was reduced considerably when there were previous term births and was influenced variably by race, clinic classification, maternal illness, and prior pregnancy complications. This empirical data on pregnancy outcome should be useful in reproductive counseling among women with pregnancy losses and premature births.
We conducted a double-blind study to determine the efficacy of 17alpha-hydroxyprogesterone caproate in preventing premature delivery in 43 high-risk patients. Premature delivery did not occur in 18 patients receiving the progestational agent, whereas 41 per cent of the 22 receiving the palcebo had premature delivery (P less than 0.01). The mean duration of pregnancy and the mean birth weight in the former group (38.6 weeks +/- 1.6 S.D., and 2836 g +/- 412 S.D.) were both significantly greater (P less than 0.025) than that in the latter (35.2 weeks +/- 6.7 S.D.; 2361 g +/- 1085 S.D.). The perinatal mortality rate in the group given the progestational agent (O per cent) was significantly less than that observed in the placebo group (27 per cent) (P less than 0.05). Although there were no complications attributable to the progestational drug, the study population was too small for assessment of immediate or long term safety. However, the results indicate a possible obstetric use for this drug.
Eighty-six women reached at least 20 weeks' pregnancy in 96 instances, after ovulation induced by clomiphene citrate. Although 37 of the women had 44 previous pregnancies, there had been a high pregnancy wastage (70.5%) producing only 13 live infants prior to the successful clomiphene therapy. After clomiphene therapy, pregnancies were normal except for a high incidence of toxemia (16.7%) and a possibly increased incidence of prediabetes. The pregnancies resulted in 88 single and 8 twin births. The total fetal and neonatal loss was 6.7%. The loss of single births (3.1%) included two stillbirth infants of prediabetic mothers. The twin loss of 25% was due to prematurity. The incidence of congenital malformations was within normal limits.
One hundred and seventy-two plasma progesterone determinations were performed in normal pregnancy, labor, and the puerperium. One hundred and nineteen of the assays were done on isolated samples; 53 of the assays were done in 11 serial studies. While the concentration of progresterone in peripheral blood increased progressively with advancing pregnancy, no apparent decrease in the hormone level occurred at or near the onset of labor or during its progress. A significant decrease in plasma progesterone one hour after the delivery of the placenta continued to decline to menstrual cycle levels by 72 hours post partum.
Pregnancy Complications · Premature Rupture of Membranes
The concept that a cervix could be inadequate or incompetent for retaining a normal pregnancy was publicized by Lash and Lash in 1950. It did not catch the fancy of the majority of obstetricians to any extent until the introduction of the relatively simple corrective procedure advocated by Shirodkar in 1955 and publicized by Barter et al. Since then there has been a constantly increasing number of reports discussing this problem. Incompetent cervical os is estimated to represent only a small percentage of all causes of fetal wastage …