The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System
R Sauvé , K Demissie , Michael S Kramer
R Liston , Robert W Platt, Huanming Yang
Author affiliations (2)
Department of Pediatrics, McGill University Faculty of Medicine, Montreal, Quebec, Canada.ROR
The World Health Organization defines preterm birth as birth at less than 37 completed gestational weeks, but most studies have focused on very preterm infants (birth at <32 weeks) because of their high risk of mortality and serious morbidity. However, infants born at 32 through 36 weeks are more common and their public health impact has not been well studied.
Objective
To assess the quantitative contribution of mild (birth at 34-36 gestational weeks) and moderate (birth at 32-33 gestational weeks) preterm birth to infant mortality.
DESIGN, SETTING, AND
Participants
Population-based cohort study using linked singleton live birth-infant death cohort files for US birth cohorts for 1985 and 1995 and Canadian birth cohorts (excluding Ontario) for 1985-1987 and 1992-1994.
Main Outcome Measures
Relative risks (RRs) and etiologic fractions (EFs) for overall and cause-specific early neonatal (age 0-6 days), late neonatal (age 7-27 days), postneonatal (age 28-364 days), and total infant death among mild and moderate preterm births vs term births (at >/=37 gestational weeks).
Results
Relative risks for infant death from all causes among singletons born at 32 through 33 gestational weeks were 6.6 (95% confidence interval [CI], 6.1-7.0) in the United States in 1995 and 15.2 (95% CI, 13.2-17.5) in Canada in 1992-1994; among singletons born at 34 through 36 gestational weeks, the RRs were 2.9 (95% CI, 2.8-3.0) and 4.5 (95% CI, 4.0-5.0), respectively. Corresponding EFs were 3.2% and 4.8%, respectively, at 32 through 33 gestational weeks and 6.3% and 8.0%, respectively, at 34 through 36 gestational weeks; the sum of the EFs for births at 32 through 33 and 34 through 36 gestational weeks exceeded those for births at 28 through 31 gestational weeks. Substantial RRs were observed overall for the neonatal (eg, for early neonatal deaths, 14.6 and 33.0 for US and Canadian infants, respectively, born at 32-33 gestational weeks; EFs, 3.6% and and 6. 2% for US and Canadian infants, respectively) and postneonatal (RRs, 2.1-3.8 and 3.0-7.0 for US and Canadian infants, respectively, born at 32-36 gestational weeks; EFs, 2.7%-5.8% and 3.0%-7.0% for the same groups, respectively) periods and for death due to asphyxia, infection, sudden infant death syndrome, and external causes. Except for a reduction in the RR and EF for neonatal mortality due to infection, the patterns have changed little since 1985 in either country.
Conclusions
Mild- and moderate-preterm birth infants are at high RR for death during infancy and are responsible for an important fraction of infant deaths. JAMA. 2000;284:843-849
mild moderate preterm birth infant mortality population based, late preterm birth 34-36 weeks neonatal death risk, etiologic fraction preterm birth infant death contribution, Kramer preterm birth infant mortality Canada United States, moderate preterm 32-33 weeks relative risk infant death, SIDS infection asphyxia cause-specific mortality preterm infants, postneonatal mortality preterm birth population cohort study, Canadian Perinatal Surveillance System preterm birth outcomes, singleton live birth infant death linked cohort analysis, public health impact near-term preterm birth mortality
PMID 10938173 10938173 DOI 10.1001/jama.284.7.843 10.1001/jama.284.7.843 Kramer et al. 2000, Kramer 2000
Cite this article
Kramer, M. S., Demissie, K., Yang, H., Platt, R. W., Sauvé, R., & Liston, R. (2000). The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. JAMA, 284(7), 843-849. https://doi.org/10.1001/jama.284.7.843
Kramer MS, Demissie K, Yang H, Platt RW, Sauvé R, Liston R. The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System. JAMA. 2000;284(7):843-849. doi:10.1001/jama.284.7.843
Kramer, M. S., et al. "The contribution of mild and moderate preterm birth to infant mortality. Fetal and Infant Health Study Group of the Canadian Perinatal Surveillance System." JAMA, vol. 284, no. 7, 2000, pp. 843-849.
Keywords
Canada/epidemiology, Cause of Death, Cohort Studies, Gestational Age, Humans, Infant, Infant Mortality/trends, Infant, Newborn, Infant, Premature, Infant, Premature, Diseases/mortality, Morbidity, Risk, United States/epidemiology
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.
pregnancy/preterm-birth/predictionbirth-and-delivery/birth-outcomes/maternal-morbidity
Open Access
Preston M et al., 2024·European journal of obstetrics, gynecology, and reproductive biology
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.
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.