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Background: Pregnancy complications have been recognized as a window to future health. Though cesarean delivery is common, it is unknown whether labor duration and mode of delivery are associated with maternal long-term mortality., Objective: To examine whether labor duration and mode of delivery were associated with all-cause and cause-specific mortality., Study Design: Participants were mothers from the multisite Collaborative Perinatal Project (CPP) cohort (1959-1966; n=43,646, limited to last CPP delivery). We ascertained all-cause and specific causes of death as of 2016 via linkage to the National Death Index and Social Security Death Master File. Hazard ratios (HR) testing mode of delivery and labor duration were estimated using Cox proportional hazards models adjusted for demographic and clinical characteristics. We further stratified analyses by parity., Results: Among participants with a recorded delivery mode, 5.9% (2486/42,335) had a cesarean delivery. Participants who had a cesarean were older (26.9 vs 24.3 years), with higher body mass index (24.0 vs 22.7 kg/m 2 ), were less likely to be nulliparous (21% vs 30%), and more likely to have a household income of at least $6000 (22% vs 17%), to smoke ≥1 pack/d (18% vs 15%), to have diabetes mellitus (12% vs 1%) and to have a prior medical condition (47% vs 34%), compared to participants with a vaginal delivery. Delivery mode was similar by race/ethnicity, marital status, and education. Median labor duration was 395 minutes among participants who had an intrapartum cesarean delivery and 350 minutes among participants delivered vaginally. By 2016, 52.2% of participants with a cesarean delivery and 38.5% of participants with a vaginal delivery had died. Cesarean vs vaginal delivery was significantly associated with increased risk for all-cause mortality (HR=1.16 (95% confidence interval [CI]: 1.09, 1.23); in nulliparas, HR=1.27 (95% CI: 1.09, 1.47); in multiparas, HR=1.13 (95% CI: 1.06, 1.21) as well as increased risk of death from cardiovascular disease, diabetes, respiratory disease, infection, and kidney disease. Associations with death from cardiovascular disease, infection, and kidney disease were stronger for multiparas than nulliparas, though the association with death from diabetes was stronger among nulliparas. Labor duration was not significantly related to overall mortality., Conclusion: In a historic United States cohort with a low cesarean delivery rate, cesarean delivery was an indicator for subsequent increased mortality risk, particularly related to cardiovascular disease and diabetes. Future studies with long-term follow-up are warranted given the current high prevalence of cesarean delivery., (Published by Elsevier Inc.)

Background: Antenatal maternal depression is associated with poor pregnancy outcomes and long-term effects on the offspring. Previous studies have identified links between antenatal depression and placental DNA methylation and between placental epigenetic aging and poor pregnancy outcomes, such as preterm labor and preeclampsia. The relationship between antenatal depression and poor pregnancy outcomes may be partly mediated via placental aging., Objective: This study aimed to investigate whether antenatal depressive symptoms are associated with placental epigenetic age acceleration, an epigenetic aging clock measure derived from the difference between methylation age and gestational age at delivery., Study Design: The study included 301 women who provided placenta samples at delivery as part of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies - Singletons that recruited participants from diverse race and ethnic groups at 12 US clinical sites (2009-2013). Women underwent depression screening using the Edinburgh Postnatal Depression Scale up to 6 times across the 3 trimesters of pregnancy. Depressive symptoms status was determined for each pregnancy trimester using an Edinburgh Postnatal Depression Scale score, in which a score of ≥10 was defined as having depressive symptoms and a score of <10 was defined as not having depressive symptoms. Placental DNA methylation was profiled from placenta samples. Placental epigenetic age was estimated using a methylation-based age estimator (placental "epigenetic clock") that has previously been found to have high placental gestational age prediction accuracy for uncomplicated term pregnancies. Placental age acceleration was defined to be the residual upon regressing the estimated epigenetic age on gestational age at delivery. Associations between an Edinburgh Postnatal Depression Scale score of ≥10 and an Edinburgh Postnatal Depression Scale score of <10 in the first, second, and third trimesters of pregnancy (ie, depressive symptoms vs none in each trimester) and placental age acceleration were tested using multivariable linear regression adjusting for maternal age, parity, race and ethnicity, and employment., Results: There were 31 (10.3%), 48 (16%), and 49 (16.4%) women with depressive symptoms (ie, Edinburgh Postnatal Depression Scale score of ≥10) in the first, second, and third trimesters of pregnancy, respectively. Of these women, 21 (7.2%) had sustained first- and second-trimester depressive symptoms, 19 (7%) had sustained second- and third-trimester depressive symptoms, and 12 (4.8%) had sustained depressive symptoms throughout pregnancy. Women with depressive symptoms in the second trimester of pregnancy had 0.41 weeks higher placental age acceleration than women without depressive symptoms during the second trimester of pregnancy (β=0.21 weeks [95% confidence interval, -0.17 to 0.58; P=.28] during the first trimester of pregnancy; β=0.41 weeks [95% confidence interval, 0.10-0.71; P=.009] during the second trimester of pregnancy; β=0.17 weeks [95% confidence interval, -0.14 to 0.47; P=.29] during the third trimester of pregnancy). Sustained first- and second-trimester depressive symptoms were associated with 0.72 weeks higher placental age acceleration (95% confidence interval, 0.29-1.15; P=.001) than no depressive symptom in the 2 trimesters. The association between second-trimester depressive symptoms and higher placental epigenetic age acceleration strengthened in the analysis of pregnancies with male fetuses (β=0.53 weeks; 95% confidence interval, 0.06-1.08; P=.03) but was not significant in pregnancies with female fetuses., Conclusion: Antenatal depressive symptoms during the second trimester of pregnancy were associated with an average of 0.41 weeks of increased placental age acceleration. Accelerated placental aging may play an important role in the underlying mechanism linking antenatal depression to pregnancy complications related to placental dysfunction., (Published by Elsevier Inc.)

Background: Limited data exist about the potential developmental delays in appropriately grown twins; furthermore, twins may be at higher risk of developmental delay than singletons. Small-for-gestational age is a risk factor for developmental delay and is based on singleton birthweight references, which may misclassify small-for-gestational age in a subset of appropriately grown twins., Objective: This study aimed to evaluate the risk of developmental delay in twins classified as small-for-gestational age according to the twin and singleton birthweight references (<10th percentile)., Study Design: In a birth cohort (2008-2010) of twins (n=1790) and singletons (n=3829) where parents completed Ages & Stages Questionnaires for child development between 4 and 36 months, we used a US population-based birthweight reference to categorize singletons and twins as small-for-gestational age. Uncertain small-for-gestational age twins were defined as small-for-gestational age by a singleton reference (<10th percentile) and not by a twin reference, and twin-reference small-for-gestational age twins were defined as small-for-gestational age by a twin reference. Adjusted generalized linear mixed-effects models were used to estimate the odds of failure on any Ages & Stages Questionnaires domain and on each of the 5 domains (fine motor, gross motor, communication, personal-social, and problem-solving domains); random intercepts accounted for repeated measures and twin clustering., Results: Compared with non-small-for-gestational age twins (>10th percentile), uncertain small-for-gestational age twins did not have higher odds of Ages & Stages Questionnaires failure (adjusted odds ratio, 1.28; 95% confidence interval, 0.91-1.80). Compared with non-small-for-gestational age singletons, both twin-reference and uncertain small-for-gestational age twins had higher odds of Ages & Stages Questionnaires failure, with the highest risk conferred to twin-reference small-for-gestational age twins (twin-reference adjusted odds ratio, 3.14 [95% confidence interval, 1.94-5.10]; uncertain adjusted odds ratio, 2.35 [95% confidence interval, 1.69-3.26]; P<.01 for trend). Results remained consistent when limiting analyses to term births (≥37 weeks' gestation)., Conclusion: Although a singleton reference may overestimate small-for-gestational age in twins, the findings indicated that a singleton birthweight reference may be appropriate for twins because it identifies more twins at risk of developmental delay than a twin reference., (Published by Elsevier Inc.)

Background: Although the neonatal morbidity associated with shoulder dystocia are well known, the maternal morbidity caused by this obstetrical emergency is infrequently reported., Objective: This study aimed to assess the composite adverse maternal and neonatal outcomes among vaginal deliveries (at 34 weeks or later) with and without shoulder dystocia., Study Design: This is a secondary analysis of the Consortium of Safe Labor, an observational obstetrical cohort of all vaginal deliveries occurring at 19 hospitals (from 2002-2008) and for which data on the occurrence of shoulder dystocia were available. The composite adverse maternal outcome included third- or fourth-degree perineal laceration, postpartum hemorrhage (>500 cc blood loss for a vaginal delivery and >1000 cc blood loss for cesarean delivery), blood transfusion, chorioamnionitis, endometritis, thromboembolism, admission to intensive care unit, or maternal death. The composite adverse neonatal outcome included an Apgar score of <7 at 5 minutes, a birth injury, neonatal seizure, hypoxic ischemic encephalopathy, or neonatal death. A multivariable Poisson regression was used to estimate the adjusted relative risks with 95% confidence intervals. The area under the receiver operating characteristic curve was constructed to determine if clinical factors would identify shoulder dystocia., Results: Of the 228,438 women in the overall cohort, 130,008 (59.6%) met the inclusion criteria, and among them, shoulder dystocia was documented in 2159 (1.7%) cases. The rate of composite maternal morbidity was significantly higher among deliveries with shoulder dystocia (14.7%) than without (8.6%; adjusted relative risk, 1.71; 95% confidence interval, 1.64-2.01). The most common maternal morbidity with shoulder dystocia was a third- or fourth-degree laceration (adjusted relative risk, 2.82; 95% confidence interval, 2.39-3.31). The risk of composite neonatal morbidity with shoulder dystocia (12.2%) was also significantly higher than without shoulder dystocia (2.4%) (adjusted relative risk, 5.18; 95% confidence interval, 4.60-5.84). The most common neonatal morbidity was birth injury (adjusted relative risk, 5.39; 95% confidence interval, 4.71-6.17). The area under the curve for maternal characteristics to identify shoulder dystocia was 0.66 and it was 0.67 for intrapartum factors., Conclusion: Although shoulder dystocia is unpredictable, the associated morbidity affects both mothers and newborns. The focus should be on concurrently averting the composite morbidity for the maternal-neonatal dyad with shoulder dystocia., (Copyright © 2021 Elsevier Inc. All rights reserved.)