Keith, L. G., Oleszczuk, J. J., & Keith, D. M. (2000). Multiple gestation: reflections on epidemiology, causes, and consequences. International journal of fertility and women's medicine, 45(3), 206-214.
Keith LG, Oleszczuk JJ, Keith DM. Multiple gestation: reflections on epidemiology, causes, and consequences. Int J Fertil Womens Med. 2000;45(3):206-214.
Keith, L. G., et al. "Multiple gestation: reflections on epidemiology, causes, and consequences." International journal of fertility and women's medicine, vol. 45, no. 3, 2000, pp. 206-214.
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Multiple births (of all orders) increased in epidemic proportions in the years 1971-1997. Twins increased 53%, 32%, 31%, and 83% in white, Afro-American, Native American and Mexican American women, respectively. Triplet, quadruplet, and quintuplet+ births increased >400%, >1,100%, and >500%, respectively, in the same years. The principal causes of these changes are related to the increasing age of the maternal cohort and an increasing incidence of fertility-inhibiting diseases and conditions in association with advancing maternal age. Major immediate consequences of these changes include disproportionately large numbers of infants born at <33 weeks' gestation (1.7% for singletons vs. 41.2% for triplets) and at <1,500 g birth weight (1.1% for singletons vs. 31.9% for triplets). Additional short-term consequences include an almost 2,000% increase in infant deaths (per 1,000 live births) among triplets compared with singletons (190.4 vs. 11.2). Long-term risks include a 300% increase in the relative risk of handicap in triplets compared with singletons (2.9 vs. 1.0), and a 650% increase in the rate of cerebral palsy per 1,000 live births in triplets compared with singletons (26.6 vs. 1.6). Peripartum costs relate to prematurity rather than plurality, as do lifetime survivorship costs, which relate to morbidities and subsequent health-related problems.
Kimber-Trojnar Ż et al., 2014·Current pharmaceutical biotechnology
The clinical recognition and adequate treatment of women with hyperglycemia during pregnancy is significant in order to reduce neonatal complications correlated with gestational diabetes mellitus (GDM). The traditional management of pregnant patients with GDM in whom diet restriction is not sufficient enough involves subcutaneous insulin administration. However, insulin therapy has several disadvantages. It is therefore highly desirable to find an effective alternative to insulin. Glyburide (also known as glibenclamide) is currently classified as Category C by the U.S. Food and Drug Administration (FDA) for use in pregnancy. Despite the fact that the FDA does not approve glyburide for the treatment of GDM, the American College of Obstetricians and Gynecologists (ACOG) recommended in 2013 that: "when pharmacologic treatment of GDM is indicated, insulin and oral medications are equivalent in efficacy, and either can be an appropriate first-line therapy". These conflicting standpoints result from published contradictory data concerning the risks and benefits of the use of glyburide for the treatment of women with GDM. In this focused review we first present the current state of knowledge about the pharmacokinetics and pharmacodynamics of glyburide, including aspects of the transplacental transport and placental metabolism of the drug, and then we comment on several clinical studies describing the use of glyburide for the treatment of women with GDM. Since the contradictory data primarily concern the transfer of glyburide across the placenta, further rigorous scientific researches focusing on this issue are required in order to develop evidence-based recommendations for the use of glyburide for the treatment of women with GDM.
To more precisely understand the changes in triplet births in recent years. Analysis of recent government and medical publications pertaining to triplets. Triplet births are at much greater risk than singletons of poor birth outcomes. More than 9 of 10 triplet births are born preterm (< 37 completed weeks of gestation) as compared with < 1 of 10 singleton infants. The average weight of a triplet newborn (1,698 g) is one-half that of a singleton newborn (3,358 g). The infant death rate for triplet and other higher-order multiple births is 12 times higher than that for singletons (93.7 as compared with 7.8 infant deaths per 1,000 live births). Based on their frequency of preterm birth, low birth weight and infant death rate, it is appropriate to characterize all triplet pregnancies as high risk.
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.
In the United States, pregnancies associated with assisted reproductive technology (ART) or ovulation-inducing drugs are more likely to result in multiple births than spontaneously conceived pregnancies (1). In addition, triplet and higher-order multiple births are at greater risk than singleton births to be preterm (< or = 37 completed weeks' gestation), low birthweight (LBW) (i.e., < or = 2500 g), or very low birthweight (i.e., < 1500 g), resulting in higher infant morbidity and mortality (2). Because preterm and LBW infants often require costly neonatal care and long-term developmental follow-up, the continuing increase in triplet and higher-order multiple births causes concern among health-care providers and policymakers (3). This report provides estimates of the contribution of ART and ovulation-inducing drugs to these birth outcomes for 1996 and 1997, and summarizes trends during 1980-1997, which indicate that the ratio of triplet and higher-order multiple births has more than quadrupled and that a large proportion of this increase can be attributed to ART or the use of ovulation-inducing drugs.
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.
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.
Luke B et al., 2007·Fertility and sterility·Free full text on PubMed Central
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.
PMID 10929683 10929683 Keith et al. 2000, Keith 2000
Cite this article
Keith, L. G., Oleszczuk, J. J., & Keith, D. M. (2000). Multiple gestation: reflections on epidemiology, causes, and consequences. International journal of fertility and women's medicine, 45(3), 206-214.
Keith LG, Oleszczuk JJ, Keith DM. Multiple gestation: reflections on epidemiology, causes, and consequences. Int J Fertil Womens Med. 2000;45(3):206-214.
Keith, L. G., et al. "Multiple gestation: reflections on epidemiology, causes, and consequences." International journal of fertility and women's medicine, vol. 45, no. 3, 2000, pp. 206-214.
Keywords
Female, Fertilization in Vitro, Humans, Infant Mortality, Infant, Newborn, Infant, Premature, Infant, Very Low Birth Weight, Maternal Age, Pregnancy, Pregnancy Outcome/epidemiology, Pregnancy, Multiple/statistics & Numerical Data, United States/epidemiology
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