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Fetal electrocardiogram (ECG) ST changes are associated with fetal cardiac hypoxia. Our objective was to evaluate ST changes by maternal diabetic status and stage of labor. This was a secondary analysis of a multicentered randomized-controlled trial in which laboring patients with singleton gestations underwent fetal ECG scalp electrode placement and were randomly assigned to masked or unmasked ST-segment readings. Our primary outcome was the frequency of fetal ECG tracings with ST changes by the stage of labor. ECG tracings were categorized into mutually exclusive groups (ST depression, ST elevation without ST depression, or no ST changes). We compared participants with DM, gestational diabetes mellitus (GDM), and no DM. Of the 5,436 eligible individuals in the first stage of labor (95 with pregestational DM and 370 with GDM), 4,427 progressed to the second stage. ST depression occurred more frequently in the first stage of labor in participants with pregestational DM (15%, adjusted odds ratio [aOR] 2.20, 95% confidence interval [CI] 1.14-4.24) and with GDM (9.5%, aOR 1.51, 95% CI 1.02-2.25) as compared with participants without DM (5.7%). The frequency of ST elevation was similar in participants with pregestational DM (33%, aOR 0.79, 95% CI 0.48-1.30) and GDM (33.2%, aOR 0.91, 95% CI 0.71-1.17) as compared with those without DM (34.2%). In the second stage, ST depression did not occur in participants with pregestational DM (0%) and occurred more frequently in participants with GDM (3.5%, aOR 2.01, 95% CI 1.02-3.98) as compared with those without DM (2.0%). ST elevation occurred more frequently in participants with pregestational DM (30%, aOR 1.81, 95% CI 1.02-3.22) but not with GDM (19.0%, aOR 1.06, 95% CI 0.77-1.47) as compared with those without DM (17.8%). ST changes in fetal ECG occur more frequently in fetuses of diabetic mothers during labor.gov number, NCT01131260. ST changes in fetal ECG, a marker of fetal cardiac hypoxia, occur more frequently in fetuses of diabetic parturients.· Fetal hypertrophic cardiomyopathy (HCM) and cardiac dysfunction occur frequently among fetuses of diabetic patients.. · Fetal ECG changes such as ST elevation and depression reflect cardiac hypoxia.. · Fetuses of diabetic patients demonstrate a higher prevalence of fetal ECG tracings with ST changes..

Objective The aim of this study was to evaluate the association of mild gestational diabetes mellitus (GDM) and obesity with metabolic and cardiovascular markers 5 to 10 years after pregnancy. Study Design This was a secondary analysis of 5- to 10-year follow-up study of a mild GDM treatment trial and concurrent observational cohort of participants ineligible for the trial with abnormal 1-hour glucose challenge test only. Participants with 2-hour glucose tolerance test at follow-up were included. The primary exposures were mild GDM and obesity. The outcomes were insulinogenic index (IGI), 1/homeostatic model assessment of insulin resistance (HOMA-IR), and cardiovascular markers vascular endothelial growth factor, (VEGF), vascular cell adhesion molecule 1 (VCAM-1), cluster of differentiation 40 ligand (CD40L), growth differentiation factor 15 (GDF-15), and suppression of tumorgenesis 2 (ST-2). Multivariable linear regression estimated the association of GDM and obesity with biomarkers. Results Of 951 participants in the parent study, 642 (68%) were included. Lower 1/HOMA-IR were observed in treated and untreated GDM groups, compared with non-GDM (mean differences, −0.24 and −0.15; 95% confidence intervals [CIs], −0.36 to −0.12 and −0.28 to −0.03, respectively). Lower VCAM-1 (angiogenesis) was observed in treated GDM group (mean difference, −0.11; 95% CI, −0.19 to −0.03). GDM was not associated with IGI or other biomarkers. Obesity was associated with lower 1/HOMA-IR (mean difference, −0.42; 95% CI, −0.52 to −0.32), but not other biomarkers. Conclusion Prior GDM and obesity are associated with more insulin resistance but not insulin secretion or consistent cardiovascular dysfunction 5 to 10 years after delivery. Key Points

Objective: To measure the association between hypertensive disorders of pregnancy (HDP) and long-term maternal metabolic and cardiovascular biomarkers. Study Design: Follow-up study of patients who completed glucose tolerance testing 5-10 years after enrollment in a mild GDM treatment trial or concurrent non-GDM cohort. Maternal serum insulin concentrations and cardiovascular markers VCAM-1, VEGF, CD40L, GDF-15 and ST-2 were measured, and insulinogenic index (IGI, pancreatic -cell function) and 1/HOMA (insulin resistance) were calculated. Biomarkers were compared by presence of HDP (gestational hypertension or preeclampsia) during pregnancy. Multivariable linear regression estimated the association of HDP with biomarkers, adjusting for GDM, baseline BMI, and years since pregnancy. Results: Of 642 patients, 66 (10%) had HDP: 42 with gestational hypertension and 24 with preeclampsia. Patients with HDP had higher baseline and follow-up BMI, higher baseline BP and more chronic hypertension at follow-up. HDP was not associated with metabolic or cardiovascular biomarkers at follow-up. However, when HDP type was evaluated, patients with preeclampsia had lower GDF-15 levels (oxidative stress/cardiac ischemia), compared to patients without HDP (adjusted mean difference -0.24, 95%CI -0.44, -0.03). There were no differences between gestational hypertension and no HDP. Conclusion: In this cohort, metabolic and cardiovascular biomarkers 5-10 years after pregnancies did not differ by HDP. Patients with preeclampsia may have less oxidative stress/cardiac ischemia postpartum; however, this may have been observed due to chance alone given multiple comparisons. Longitudinal studies are needed to define the impact of HDP during pregnancy and interventions postpartum.

Objectives During obstetric hemorrhage, peripheral vasoconstriction maintains heart rate and blood pressure until compensatory mechanisms are overwhelmed and patients deteriorate rapidly. Real-time perfusion measurements could quantify vasoconstriction, improving early recognition of hemorrhage and facilitating early intervention to reduce morbidity and mortality. The AccuFlow device makes rapid, non-invasive, quantitative measurements of perfusion, but has not been studied for hemorrhage detection or used in surgical settings. This study evaluated feasibility, tolerability, and preliminary efficacy of the AccuFlow for assessment of blood loss at cesarean delivery (CD). Methods In this pilot study, sensors were applied to the wrist, forearm, bicep, and chest wall of 25 patients undergoing scheduled CD. Postoperatively, sensors were removed and patients rated the AccuFlow and the standard anesthesia monitoring equipment on a validated comfort rating scale for wearable computers (CRS). Blood loss was estimated by the surgical team (EBL) and calculated from change in hematocrit, weight, and height (CBL). CRS scores were compared via Wilcoxon signed ranks tests. Coefficients of correlation between sensor readings and CBL, and between EBL and CBL, were compared using Fisher’s R-to-z transformation. Results There were no safety events; no participants requested device removal. CRS ratings of the AccuFlow and the standard monitoring equipment were similar (7.2 vs. 8.8, p=0.25). Change in wrist perfusion from delivery to dressing placement was more strongly correlated with CBL than was EBL (R=−0.48 vs. R=0.087, p=0.03). Conclusions The AccuFlow sensor is well-tolerated and shows promise in detecting intrapartum hemorrhage, though larger studies are needed.

Objective We have previously described a model using maternal, antenatal, and ultrasonographic characteristics to assess the risk of delivery within 7 days following diagnosis of abnormal umbilical artery Doppler (UAD) in pregnancies affected by fetal growth restriction (FGR). Therefore, we sought to validate this model in an independent cohort. Study Design Retrospective, single referral center study of liveborn singleton pregnancies from 2016 to 2019 complicated by FGR and abnormal UAD (systolic/diastolic ratio ≥95th percentile for gestational age [GA]). Prediction probabilities were calculated by applying the original model (Model 1) to the current cohort (Brigham and Women's Hospital [BWH] cohort). The variables of this model include GA at first abnormal UAD, severity of first abnormal UAD, oligohydramnios, preeclampsia, and prepregnancy body mass index. Model fit was assessed with area under the curve (AUC). Two alternative models (Models 2 and 3) were created to identify a model with better predictive characteristics than Model 1. The receiver operating characteristics curves were compared using the DeLong test. Results A total of 306 patients were assessed for eligibility, 223 of whom were included in the BWH cohort. Median GA at eligibility was 31.3 weeks, and median interval from eligibility to delivery was 17 days (interquartile range: 3.5–33.5). Eighty-two (37%) patients delivered within 7 days of eligibility. Applying Model 1 to the BWH cohort resulted in an AUC of 0.865. Using the previously determined probability cutoff of 0.493, the model was 62% sensitive and 90% specific in predicting the primary outcome in this independent cohort. Models 2 and 3 did not perform better than Model 1 (p = 0.459). Conclusion A previously described prediction model to predict risk of delivery in patients with FGR and abnormal UAD performed well in an independent cohort. With high specificity, this model could assist in identifying low-risk patients and improve antenatal corticosteroid timing. Key Points

ImportancePregnancy induces unique physiologic changes to the immune response and hormonal changes leading to plausible differences in the risk of developing post-acute sequelae of SARS-CoV-2 (PASC), or Long COVID. Exposure to SARS-CoV-2 during pregnancy may also have long-term ramifications for exposed offspring, and it is critical to evaluate the health outcomes of exposed children. The National Institutes of Health (NIH) Researching COVID to Enhance Recovery (RECOVER) Multi-site Observational Study of PASC aims to evaluate the long-term sequelae of SARS-CoV-2 infection in various populations. RECOVER- Pregnancy was designed specifically to address long-term outcomes in maternal-child dyads.MethodsRECOVER-Pregnancy cohort is a combined prospective and retrospective cohort that proposes to enroll 2,300 individuals with a pregnancy during the COVID-19 pandemic and their offspring exposed and unexposed in utero, including single and multiple gestations. Enrollment will occur both in person at 27 sites through theEunice Kennedy ShriverNational Institutes of Health Maternal-Fetal Medicine Units Network and remotely through national recruitment by the study team at the University of California San Francisco (UCSF). Adults with and without SARS-CoV-2 infection during pregnancy are eligible for enrollment in the pregnancy cohort and will follow the protocol for RECOVER-Adult including validated screening tools, laboratory analyses and symptom questionnaires followed by more in-depth phenotyping of PASC on a subset of the overall cohort. Offspring exposed and unexposed in utero to SARS-CoV-2 maternal infection will undergo screening tests for neurodevelopment and other health outcomes at 12, 18, 24, 36 and 48 months of age. Blood specimens will be collected at 24 months of age for SARS-CoV-2 antibody testing, storage and anticipated later analyses proposed by RECOVER and other investigators.DiscussionRECOVER-Pregnancy will address whether having SARS-CoV-2 during pregnancy modifies the risk factors, prevalence, and phenotype of PASC. The pregnancy cohort will also establish whether there are increased risks of adverse long-term outcomes among children exposed in utero.RegistrationNCT05172024

OBJECTIVE: Antenatal and early neonatal nutritional environment may influence later metabolic health. Infants of mothers with gestational diabetes mellitus (GDM) have higher risk for childhood obesity and metabolic syndrome (MetS). Leptin and adiponectin are known biomarkers for MetS and may guide interventions to reduce later obesity. We sought to examine the relationship between birthweight, early infancy feeding practices, and biomarkers for MetS in offspring of women with mild GDM. STUDY DESIGN: Secondary analysis of a prospective observational follow-up study on the offspring of women who participated in a multicenter randomized treatment trial on mild GDM. Children were evaluated by research coordinators and biospecimens collected at the age of 5 to 10. Plasma concentrations of leptin and adiponectin were compared between large for gestational age (LGA) and average birthweight (AGA) infants, and according to whether solid foods were introduced early (

The randomized controlled trial has long been recognized as the gold standard of research designs. As small or underpowered trials have become increasingly common in obstetrics and gynecology, it is essential to appraise the trial design and results with a critical eye and understand the limitations of these trials including the potential for selection bias, inability to discriminate uncommon outcomes and the imprecision of point estimates. When small or underpowered trials are designed to be assessed in combination with other trials in high-quality meta-analysis, some of these limitations are minimized.

OBJECTIVE To evaluate race and ethnicity differences in cesarean birth and maternal morbidity in low-risk nulliparous people at term. METHODS We conducted a secondary analysis of a randomized trial of expectant management compared with induction of labor in low-risk nulliparous people at term. The primary outcome was cesarean birth. Secondary outcome was maternal morbidity, defined as: transfusion of 4 or more units of red blood cells, any transfusion of other products, postpartum infection, intensive care unit admission, hysterectomy, venous thromboembolism, or maternal death. Multivariable modified Poisson regression was used to evaluate associations between race and ethnicity, cesarean birth, and maternal morbidity. Indication for cesarean birth was assessed using multivariable multinomial logistic regression. A mediation model was used to estimate the portion of maternal morbidity attributable to cesarean birth by race and ethnicity. RESULTS Of 5,759 included participants, 1,158 (20.1%) underwent cesarean birth; 1,404 (24.3%) identified as non-Hispanic Black, 1,670 (29.0%) as Hispanic, and 2,685 (46.6%) as non-Hispanic White. Adjusted models showed increased relative risk of cesarean birth among non-Hispanic Black (adjusted relative risk [aRR] 1.21, 95% CI 1.03-1.42) and Hispanic (aRR 1.26, 95% CI 1.08-1.46) people compared with non-Hispanic White people. Maternal morbidity affected 132 (2.3%) individuals, and was increased among non-Hispanic Black (aRR 2.05, 95% CI 1.21-3.47) and Hispanic (aRR 1.92, 95% CI 1.17-3.14) people compared with non-Hispanic White people. Cesarean birth accounted for an estimated 15.8% (95% CI 2.1-48.7%) and 16.5% (95% CI 4.0-44.0%) of excess maternal morbidity among non-Hispanic Black and Hispanic people, respectively. CONCLUSION Non-Hispanic Black and Hispanic nulliparous people who are low-risk at term undergo cesarean birth more frequently than low-risk non-Hispanic White nulliparous people. This difference accounts for a modest portion of excess maternal morbidity.

OBJECTIVE To compare maternal and neonatal outcomes after preterm prelabor rupture of membranes (PROM) from 23 to 34 weeks of gestation in twin compared with singleton gestations. METHODS We conducted a secondary analysis of an obstetric cohort of 115,502 individuals and their singleton or twin neonates born in 25 hospitals nationwide (2008-2011). Those with preterm PROM from 23 0/7 through 33 6/7 weeks of gestation were included; neonates with major fetal anomalies were excluded. The coprimary outcomes for this analysis were composite maternal morbidity (chorioamnionitis, blood transfusion, postpartum endometritis, wound infection, sepsis, venous thromboembolism, intensive care unit admission, or death) and composite major neonatal morbidity (persistent pulmonary hypertension, intraventricular hemorrhage grade III or IV, seizures, hypoxic-ischemic encephalopathy, necrotizing enterocolitis stage II or III, bronchopulmonary dysplasia, stillbirth subsequent to admission, or neonatal death before discharge). Logistic regression was used to estimate unadjusted and adjusted odds ratios (ORs) with 95% CIs for twin compared with singleton gestations. RESULTS Of 1,531 (1.3%) individuals who met eligibility criteria for this analysis, 218 (14.2%) had twin gestations. The median gestational age at preterm PROM was similar between those with twins and singletons (31.2 weeks [interquartile range 27.4-32.9] vs 30.6 weeks [interquartile range 26.9-32.7], P=.23); however, those with twin gestations had a shorter median latency period (2.0 days [interquartile range 1.0-5.0] vs 3.0 days [interquartile range 2.0-8.0], P

Summary Background Women with HIV face an increased risk of preterm birth. 17 alpha-hydroxyprogesterone caproate (17P) has been shown in some trials to reduce early delivery among women with a history of spontaneous preterm birth. We investigated whether 17P would reduce this risk among women with HIV. Methods We did a randomised, double-blind, placebo-controlled trial in pregnant women with HIV at the University Teaching Hospital and Kamwala District Health Centre in Lusaka, Zambia. Eligible patients were women aged 18 years or older with confirmed HIV-1 infection, viable intrauterine singleton pregnancy at less than 24 weeks of gestation, and were receiving or intending to commence antiretroviral therapy during pregnancy. Exclusion criteria were major uterine or fetal anomaly; planned or in situ cervical cerclage; evidence of threatened miscarriage, preterm labour, or ruptured membranes at screening; medical contraindication to 17P; previous participation in the trial; or history of spontaneous preterm birth. Eligible participants provided written informed consent and were randomly assigned (1:1) to receive 250 mg intramuscular 17P or placebo once per week, starting between 16 and 24 weeks of gestation until delivery, stillbirth, or reaching term (37 weeks). Participants and study staff were masked to assignment, except for pharmacy staff who did random assignment and prepared injections but did not interact with participants. The primary outcome was a composite of delivery before 37 weeks or stillbirth at any gestational age. Patients attended weekly visits for study drug injections and antenatal care. We estimated the absolute and relative difference in risk of the primary outcome and safety events between treatment groups by intention to treat. This trial is registered with ClinicalTrials.gov , NCT03297216 , and is complete. Findings Between Feb 7, 2018 and Jan 13, 2020, we assessed 1042 women for inclusion into the study. 242 women were excluded after additional assessments, and 800 eligible patients were enrolled and randomly assigned to receive intramuscular 17P (n=399) or placebo (n=401). Baseline characteristics were similar between groups. Adherence to study drug injections was 98% in both groups, no patients were lost to follow-up, and the final post-partum visit was on Aug 6, 2020. 36 (9%) of 399 participants assigned to 17P had preterm birth or stillbirth, compared with 36 (9%) of 401 patients assigned to placebo (risk difference 0·1, 95% CI −3·9 to 4·0; relative risk 1·0, 95% CI 0·6 to 1·6; p=0·98). Intervention-related adverse events were reported by 140 (18%) of 800 participants and occurred in similar proportions in both randomisation groups. No serious adverse events were reported. Interpretation Although 17P seems to be safe and acceptable to participants, available data do not support the use of the drug to prevent preterm birth among women whose risk derives solely from HIV infection. The low risk of preterm birth in both randomisation groups warrants further investigation. Funding US National Institutes of Health and the Bill and Melinda Gates Foundation.

Objective To evaluate intrapartum resuscitation interventions and improvement in category II fetal heart rate (FHR) tracings. Methods This secondary analysis of a randomized trial of intrapartum fetal electrocardiographic ST-segment analysis included all participants with category II FHR tracings undergoing intrauterine resuscitation: maternal oxygen, intravenous fluid bolus, amnioinfusion, or tocolytic administration. Fetal heart rate pattern-recognition software was used to confirm category II FHR tracings 30 minutes before intervention and to analyze the subsequent 60 minutes. The primary outcome was improvement to category I within 60 minutes. Secondary outcomes included FHR tracing improvement to category I 30-60 minutes after the intervention and composite neonatal outcome. Results Of 11,108 randomized participants, 2,251 (20.3%) had at least one qualifying intervention for category II FHR tracings: 63.7% improved to category I within 60 minutes and 50.5% improved at 30-60 minutes. Only 3.4% underwent cesarean delivery and 4.1% an operative vaginal delivery for nonreassuring fetal status within 60 minutes after the intervention. Oxygen administration was the most common intervention (75.4%). Among American College of Obstetricians and Gynecologists-defined subgroups that received oxygen, the absent FHR accelerations and absent-minimal FHR variability subgroup (n=332) was more likely to convert to category I within 60 minutes than the FHR accelerations or "moderate FHR variability" subgroup (n=1,919) (77.0% vs 63.0%, odds ratio [OR] 2.0, 95% CI 1.4-2.7). The incidence of composite neonatal adverse outcome for category II tracings was 2.9% (95% CI 2.2-3.7%) overall; 2.8% (95% CI 2.0-3.8%) for improvement to category I within 60 minutes (n=1,433); and 3.2% (95% CI 2.1-4.6%) for no improvement within 60 minutes (n=818). However, the group with improvement had 29% lower odds for higher level neonatal care (11.8% vs 15.9%, OR 0.71, 95% CI 0.55-0.91). Conclusion Nearly two thirds of category II FHR tracings improved to category I within 60 minutes of intervention with a relatively low overall rate of the composite neonatal adverse outcome. Funding source Funded in part by Neoventa Medical.

BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks’ gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI], 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks’ gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.)

Our understanding and management of gestational hypertension and its variants are substantially hindered by a reliance on antiquated terminology and on practice recommendations based largely on tradition rather than outcomes-based evidence. Unsurprisingly, gestational hypertension remains a major contributor to maternal and neonatal morbidity and mortality rates, with little improvement seen over the past half century except as it relates to better newborn care. Reliance on a binary classification of vastly disparate types and degrees of organ dysfunction (severe or not severe) and the use of nonphysiological and largely arbitrary gestational age cutoffs are particularly problematic. If this situation is to improve, it will be necessary to abandon current misleading terminology and non-evidence-based traditional practice patterns and start again, building on management approaches validated by outcomes-based data.

Objective Administration of antenatal corticosteroids (ANCS) is recommended for individuals expected to deliver between 24 and 34 weeks of gestation. Properly timed administration of ANCS achieves maximal benefit. However, more than 50% of individuals receive ANCS outside the recommended window. This study aimed to examine maternal and hospital factors associated with suboptimal receipt of ANCS among individuals who deliver between 24 and 34 weeks of gestation. Study Design Secondary analysis of the Assessment of Perinatal Excellence (APEX), an observational study of births to 115,502 individuals at 25 hospitals in the United States from March 2008 to February 2011, was conducted. Data from 3,123 individuals who gave birth to a nonanomalous live-born infant between 240/7 to 340/7 weeks of gestation, had prenatal records available at delivery, and data available on the timing of ANCS use were included in this analysis. Eligible individuals' ANCS status was categorized as optimal (full course completed >24 hours after ANCS but not >7 days before birth) or suboptimal (none, too late, or too early). Maternal and hospital-level variables were compared using optimal as the referent group. Hierarchical multinomial logistic regression models, with site as a random effect, were used to identify maternal and hospital-level characteristics associated with optimal ANCS use. Results Overall, 83.6% (2,612/3,123) of eligible individuals received any treatment: 1,216 (38.9%) optimal and 1,907 (61.1%) suboptimal. Within suboptimal group, 495 (15.9%) received ANCS too late, 901 (28.9%) too early, and 511 (16.4%) did not receive any ANCS. Optimal ANCS varied depending on indication for hospital admission (p Conclusion Optimal ANCS use varied by maternal and hospital factors and by hospital site, indicating opportunities for improvement. Key Points

We aimed to evaluate whether delivering during the early the coronavirus disease 2019 (COVID-19) pandemic was associated with increased risk of maternal death or serious morbidity from common obstetric complications compared with a historical control period.This was a multicenter retrospective cohort study with manual medical-record abstraction performed by centrally trained and certified research personnel at 17 U.S. hospitals. Individuals who gave birth on randomly selected dates in 2019 (before the pandemic) and 2020 (during the pandemic) were compared. Hospital, health care system, and community risk-mitigation strategies for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in response to the early COVID-19 pandemic are described. The primary outcome was a composite of maternal death or serious morbidity from common obstetric complications, including hypertensive disorders of pregnancy (eclampsia, end organ dysfunction, or need for acute antihypertensive therapy), postpartum hemorrhage (operative intervention or receipt of 4 or more units blood products), and infections other than SARS-CoV-2 (sepsis, pelvic abscess, prolonged intravenous antibiotics, bacteremia, deep surgical site infection). The major secondary outcome was cesarean birth.Overall, 12,133 patients giving birth during and 9,709 before the pandemic were included. Hospital, health care system, and community SARS-CoV-2 mitigation strategies were employed at all sites for a portion of 2020, with a peak in modifications from March to June 2020. Of patients delivering during the pandemic, 3% had a positive SARS-CoV-2 test result during pregnancy through 42 days postpartum. Giving birth during the pandemic was not associated with a change in the frequency of the primary composite outcome (9.3% vs 8.9%, adjusted relative risk [aRR] 1.02, 95% CI 0.93-1.11) or cesarean birth (32.4% vs 31.3%, aRR 1.02, 95% CI 0.97-1.07). No maternal deaths were observed.Despite substantial hospital, health care, and community modifications, giving birth during the early COVID-19 pandemic was not associated with higher rates of serious maternal morbidity from common obstetric complications.ClinicalTrials.gov, NCT04519502.

Objective This study aimed to assess the association of maternal body mass index (BMI) with a composite of severe maternal outcomes. Study Design Secondary analysis of a cohort of deliveries on randomly selected days at 25 hospitals from 2008 to 2011. Data on comorbid conditions, intrapartum events, and postpartum course were collected. The reference group (REF, BMI: 18.5–29.9kg/m2), obese (OB; BMI: 30–39.9kg/m2), morbidly obese (MO; BMI: 40–49.9kg/m2), and super morbidly obese (SMO; BMI ≥ 50kg/m2) women were compared. The composite of severe maternal outcomes was defined as death, intensive care unit (ICU) admission, ventilator use, deep venous thrombosis/pulmonary embolus (DVT/PE), sepsis, hemorrhage, disseminated intravascular coagulation (DIC), unplanned operative procedure, or stroke. Patients in the REF group were matched 1:1 with those in all other obesity groups based on propensity score using the baseline characteristics of age, race/ethnicity, previous cesarean, preexisting diabetes, chronic hypertension, parity, cigarette use, and insurance status. Multivariable Poisson's regression was used to estimate adjusted relative risks (aRRs) and 95% confidence intervals (CIs) for the association between BMI and the composite outcome. Because cesarean delivery may be in the causal pathway between obesity and adverse maternal outcomes, models were then adjusted for mode of delivery to evaluate potential mediation. Results A total of 52,162 pregnant patients are included in the analysis. Risk of composite maternal outcomes was increased for SMO compared with REF but not for OB and MO [OB: aRR=1.06, 95% CI: 0.99–1.14; MO: aRR=1.10, 95% CI: 0.97–1.25; SMO: aRR=1.32, 95% CI: 1.02–1.70]. However, in the mediation analysis, cesarean appears to mediate 46% (95% CI: 31–50%) of the risk of severe morbidity for SMO compared with REF. Conclusion Super morbid obesity is significantly associated with increased serious maternal morbidity and mortality; however, cesarean appears to mediate this association. Obesity and morbid obesity are not associated with maternal morbidity and mortality. Key Points

We sought to (1) use the Robson 10-Group Classification System (TGCS), which classifies deliveries into 10 mutually exclusive groups, to characterize the groups that are primary contributors to cesarean delivery frequencies, (2) describe inter-hospital variations in cesarean delivery frequencies, and (3) evaluate the contribution of patient characteristics by TGCS group to hospital variation in cesarean delivery frequencies. This was a secondary analysis of an observational cohort of 115,502 deliveries from 25 hospitals between 2008 and 2011. The TGCS was applied to the cohort and each hospital. We identified and compared the TGCS groups with the greatest relative contributions to cohort and hospital cesarean delivery frequencies. We assessed variation in hospital cesarean deliveries attributable to patient characteristics within TGCS groups using hierarchical logistic regression. A total of 115,211 patients were classifiable in the TGCS (99.7%). The cohort cesarean delivery frequency was 31.4% (hospital range: 19.1-39.3%). Term singletons in vertex presentation with a prior cesarean delivery (group 5) were the greatest relative contributor to cohort (34.8%) and hospital cesarean delivery frequencies (median: 33.6%; range: 23.8-45.5%). Nulliparous term singletons in vertex (NTSV) presentation (groups 1 [spontaneous labor] and 2 [induced or absent labor]: 28.9%), term singletons in vertex presentation with a prior cesarean delivery (group 5: 34.8%), and preterm singletons in vertex presentation (group 10: 9.8%) contributed to 73.2% of the relative cesarean delivery frequency for the cohort and were correlated with hospital cesarean delivery frequencies (Spearman's rho = 0.96). Differences in patient characteristics accounted for 34.1% of hospital-level cesarean delivery variation in group 2. The TGCS highlights the contribution of NTSV presentation to cesarean delivery frequencies and the impact of patient characteristics on hospital-level variation in cesarean deliveries among nulliparous patients with induced or absent labor.· We report on the cesarean delivery frequencies in a multicenter U.S.. · NTSV gestations (groups 1 and 2) are a primary driver of cesarean deliveries.. · Patient characteristics contributed most to hospital variation in cesarean deliveries in group 2..

Objective In the antenatal late preterm steroids (ALPS) trial betamethasone significantly decreased short-term neonatal respiratory morbidity but increased the risk of neonatal hypoglycemia, diagnosed only categorically ( Study Design Secondary analysis of infants from ALPS, a multicenter trial randomizing women at risk for late preterm delivery to betamethasone or placebo. This study was a reabstraction of all available charts from the parent trial, all of which were requested. Unreviewed charts included those lost to follow-up or from sites not participating in the reabstraction. Duration of hypoglycemia ( Results Of 2,831 randomized, 2,609 (92.2%) were included. There were 387 (29.3%) and 223 (17.3%) with hypoglycemia in the betamethasone and placebo groups, respectively (relative risk [RR]: 1.69, 95% confidence interval [CI]: 1.46–1.96). Hypoglycemia generally occurred in the first 24 hours in both groups: 374/385 (97.1%) in the betamethasone group and 214/222 (96.4%) in the placebo group (p = 0.63). Of 387 neonates with hypoglycemia in the betamethasone group, 132 (34.1%) received treatment, while 73/223 (32.7%) received treatment in placebo group (p = 0.73). The lowest recorded blood sugar was similar between groups. Most hypoglycemia resolved by 24 hours in both (93.0 vs. 89.3% in the betamethasone and placebo groups, respectively, p = 0.18). Among infants with hypoglycemia in the first 24 hours, the time to resolution was shorter in the betamethasone group (2.80 [interquartile range: 2.03–7.03) vs. 3.74 (interquartile range: 2.15–15.08) hours; p = 0.002]. Persistence for >72 hours was rare and similar in both groups, nine (2.4%, betamethasone) and four (1.9%, placebo, p = 0.18). Conclusion In this cohort, hypoglycemia was transient and most received no treatment, with a quicker resolution in the betamethasone group. Prolonged hypoglycemia was uncommon irrespective of steroid exposure. Key Points

BACKGROUND: Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.METHODS: We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.FINDINGS: Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture INTERPRETATION: Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.FUNDING: Patient-Centered Outcomes Research Institute.

Pregnant patients with severe or critical coronavirus disease 2019 (COVID-19), but not those with mild or moderate COVID-19, were at increased risk for perinatal complications compared with asymptomatic patients., OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race–ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2–11%) incidence of venous thromboembolism among those with severe–critical illness compared with 0.2% in mild–moderate and 0% in asymptomatic (P

OBJECTIVE To compare risks of maternal and perinatal outcomes by completed week of gestation from 39 weeks in low-risk nulliparous patients undergoing expectant management. METHODS We conducted a secondary analysis of a multicenter randomized trial of elective induction of labor at 39 weeks of gestation compared with expectant management in low-risk nulliparous patients. Participants with nonanomalous neonates, who were randomized to and underwent expectant management and attained 39 0/7 weeks of gestation, were included. Delivery gestation was categorized by completed week: 39 0/7-39 6/7 (39 weeks), 40 0/7-40 6/7 (40 weeks), and 41 0/7-42 2/7 (41-42 weeks) (none delivered after 42 2/7). The coprimary outcomes were cesarean delivery and a perinatal composite (death, respiratory support, 5-minute Apgar score 3 or less, hypoxic ischemic encephalopathy, seizure, sepsis, meconium aspiration syndrome, birth trauma, intracranial or subgaleal hemorrhage, or hypotension requiring vasopressor support). Other outcomes included a maternal composite (blood transfusion, surgical intervention for postpartum hemorrhage, or intensive care unit admission), hypertensive disorders of pregnancy, peripartum infection, and neonatal intermediate or intensive care unit admission. For multivariable analysis, P

SARS-CoV-2 infection during pregnancy is associated with adverse pregnancy outcomes, including fetal death and preterm birth. It is not known whether that risk occurs only during the time of acute infection or whether the risk persists later in pregnancy.This study aimed to evaluate whether the risk of SARS-CoV-2 infection during pregnancy persists after an acute maternal illness.A retrospective cohort study of pregnant patients with and without SARS-CoV-2 infection delivering at 17 hospitals in the United States between March 2020 and December 2020. Patients experiencing a SARS-CoV-2-positive test at or before 28 weeks of gestation with a subsequent delivery hospitalization were compared with those without a positive SAR-CoV-2 test at the same hospitals with randomly selected delivery days during the same period. Deliveries occurring at20 weeks of gestation in both groups were excluded. The study outcomes included fetal or neonatal death, preterm birth at37 weeks of gestation and34 weeks of gestation, hypertensive disorders of pregnancy (HDP), any major congenital malformation, and size for gestational age of5th or10th percentiles at birth based on published standards. HDP that were collected included HDP and preeclampsia with severe features, both overall and with delivery at37 weeks of gestation.Of 2326 patients who tested positive for SARS-CoV-2 during pregnancy and were at least 20 weeks of gestation at delivery from March 2020 to December 2020, 402 patients (delivering 414 fetuses or neonates) were SARS-CoV-2 positive before 28 weeks of gestation and before their admission for delivery; they were compared with 11,705 patients without a positive SARS-CoV-2 test. In adjusted analyses, those with SARS-CoV-2 before 28 weeks of gestation had a subsequent increased risk of fetal or neonatal death (2.9% vs 1.5%; adjusted relative risk, 1.97; 95% confidence interval, 1.01-3.85), preterm birth at37 weeks of gestation (19.6% vs 13.8%; adjusted relative risk, 1.29; 95% confidence interval, 1.02-1.63), and HDP with delivery at37 weeks of gestation (7.2% vs 4.1%; adjusted relative risk, 1.74; 95% confidence interval, 1.19-2.55). There was no difference in the rates of preterm birth at34 weeks of gestation, any major congenital malformation, and size for gestational age of5th or10th percentiles. In addition, there was no significant difference in the rate of gestational hypertension overall or preeclampsia with severe features.There was a modest increase in the risk of adverse pregnancy outcomes after SARS-CoV-2 infection.

OBJECTIVE To study the association between nicotine or cannabis metabolite presence in maternal urine and child neurodevelopmental outcomes. METHODS We conducted a secondary analysis of two parallel multicenter randomized controlled trials of treatment for hypothyroxinemia or subclinical hypothyroidism among pregnant individuals enrolled at 8-20 weeks of gestation. All maternal-child dyads with a maternal urine sample at enrollment and child neurodevelopmental testing were included (N=1,197). Exposure was urine samples positive for nicotine (cotinine) or cannabis 11-nor-9-carboxy-delta-9-tetrahydrocannabinol [THC-COOH]) or both metabolites. Primary outcome was child IQ at 60 months. Secondary outcomes included cognitive, motor and language, attention, behavioral and social competency, and differential skills assessments at 12, 24, 36, and 48 months. Quantile regression analysis was performed with confounder adjustment. RESULTS Of 1,197 pregnant individuals, 99 (8.3%) had positive cotinine samples and 47 (3.9%) had positive THC-COOH samples; 33 (2.8%) were positive for both. Groups differed in self-reported race and ethnicity, education, marital status, insurance, and thyroid status. Median IQ was similar between cotinine-exposed and -unexposed children (90 vs 95, adjusted difference in medians -2.47, 95% CI -6.22 to 1.29) and THC-COOH-exposed and -unexposed children (89 vs 95, adjusted difference in medians -1.35, 95% CI -7.76 to 5.05). In secondary outcome analysis, children with THC-COOH exposure compared with those unexposed had higher attention scores at 48 months of age (57 vs 49, adjusted difference in medians 6.0, 95% CI 1.11-10.89). CONCLUSIONS Neither prenatal nicotine nor cannabis exposure was associated with a difference in IQ. Cannabis exposure was associated with worse attention scores in early childhood. Longitudinal studies assessing associations between child neurodevelopmental outcomes and prenatal nicotine and cannabis exposure with a focus on timing and quantity of exposure are needed. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT00388297.

BACKGROUND: Ultrasound is indispensable to gestational age estimation and thus to quality obstetrical care, yet high equipment cost and the need for trained sonographers limit its use in low-resource settings. METHODS: From September 2018 through June 2021, we recruited 4695 pregnant volunteers in North Carolina and Zambia and obtained blind ultrasound sweeps (cineloop videos) of the gravid abdomen alongside standard fetal biometry. We trained a neural network to estimate gestational age from the sweeps and, in three test data sets, assessed the performance of the artificial intelligence (AI) model and biometry against previously established gestational age. RESULTS: In our main test set, the mean absolute error (MAE) (±SE) was 3.9±0.12 days for the model versus 4.7±0.15 days for biometry (difference, −0.8 days; 95% confidence interval [CI], −1.1 to −0.5; P

Objective To assess whether neonatal morbidities evident by the time of hospital discharge are associated with subsequent cerebral palsy (CP) or death. Study Design This is a secondary analysis of data from a multicenter placebo-controlled trial of magnesium sulfate for the prevention of CP. The association between prespecified intermediate neonatal outcomes (n = 11) and demographic and clinical factors (n = 10) evident by the time of discharge among surviving infants (n = 1889) and the primary outcome of death or moderate/severe CP at age 2 (n = 73) was estimated, and a prediction model was created. Results Gestational age in weeks at delivery (odds ratio [OR]: 0.74, 95% confidence interval [CI]: 0.67–0.83), grade III or IV intraventricular hemorrhage (IVH) (OR: 5.3, CI: 2.1–13.1), periventricular leukomalacia (PVL) (OR: 46.4, CI: 20.6–104.6), and male gender (OR: 2.5, CI: 1.4–4.5) were associated with death or moderate/severe CP by age 2. Outcomes not significantly associated with the primary outcome included respiratory distress syndrome, bronchopulmonary dysplasia, seizure, necrotizing enterocolitis, neonatal hypotension, 5-minute Apgar score, sepsis, and retinopathy of prematurity. Using all patients, the receiver operating characteristic curve for the final prediction model had an area under the curve of 0.84 (CI: 0.78–0.89). Using these data, the risk of death or developing CP by age 2 can be calculated for individual surviving infants. Conclusion IVH and PVL were the only neonatal complications evident at discharge that contributed to an individual infant's risk of the long-term outcomes of death or CP by age 2. A model that includes these morbidities, gestational age at delivery, and gender is predictive of subsequent neurologic sequelae. Key Points

Background Clinicians caring for the nearly 10% of patients in the United States with non-severe hypertensive disorders in late pregnancy need better evidence to balance risks and benefits of clinician-initiated delivery. Methods We conducted a record-based cohort study of maternal and infant health outcomes among deliveries from 2002-2013 at Women & Infants Hospital of Rhode Island. Participants had gestational hypertension or non-severe preeclampsia before 39 weeks' gestation (N=4,295). For each gestational week from 34 to 38, we compared outcomes between clinician-initiated deliveries (induction of labor or prelabor cesarean) and those not initiated in that week, using propensity score models to control confounding by indication. Results The analysis predicted an increment in risk of adverse maternal and infant outcomes sustained through week 37 if all patients underwent clinician-initiated delivery, with risk differences on the order of 0.2 for maternal outcomes and 0.3 for infant outcomes weeks 34 and 35. For women undergoing clinician-initiated delivery, the analysis identified increased risk of progression to severe disease in weeks 35 and 36, increases in all adverse infant outcomes only in week 34, increases in NICU admission and infant hospital stay in weeks 35 and 36, and no meaningful increase in any of the adverse outcomes in weeks 37 or 38. Conclusions We estimate that hypertensive pregnancies chosen for intervention were minimally harmed by early delivery after 34 weeks' gestation but predict benefit from extension to 37 weeks. Our study also showed adverse infant health consequences associated with routine delivery prior to 37 weeks.

Objective This study aimed to develop and validate a model to predict the probability of vaginal delivery (VD) in low-risk term nulliparous patients, and to determine whether it can predict the risk of severe maternal and neonatal morbidity. Methods Secondary analysis of an obstetric cohort of patients and their neonates born in 25 hospitals across the United States (n = 115,502). Trained and certified research personnel abstracted the maternal and neonatal records. Nulliparous patients with singleton, nonanomalous vertex fetuses, admitted with an intent for VD ≥ 37 weeks were included in this analysis. Patients in active labor (cervical exam > 5 cm), those with prior cesarean and other comorbidities were excluded. Eligible patients were randomly divided into a training and test sets. Based on the training set, and using factors available at the time of admission for delivery, we developed and validated a logistic regression model to predict the probability of VD, and then estimated the prevalences of severe morbidity according to the predicted probability of VD. Results A total of 19,611 patients were included. Based on the training set (n = 9,739), a logistic regression model was developed that included maternal age, body mass index (BMI), cervical dilatation, and gestational age on admission. The model was internally validated on the test set (n = 9,872 patients) and yielded a receiver operating characteristic-area under the curve (ROC-AUC) of 0.71 (95% confidence interval [CI]: 0.70–0.72). Based on a subset of 18,803 patients with calculated predicted probabilities, we demonstrated that the prevalences of severe morbidity decreased as the predicted probability of VD increased (p Conclusion In a large cohort of low-risk nulliparous patients in early labor or undergoing induction of labor, at term with singleton gestations, we developed and validated a model to calculate the probability of VD, and maternal and neonatal morbidity. If externally validated, this calculator may be clinically useful in helping to direct level of care, staffing, and adjustment for case-mix among various systems. Key Points

Objective Our objective was to compare outcomes among low-risk parous women who underwent elective labor induction at 39 weeks versus expectant management. Study Design This is a secondary analysis of an observational cohort of 115,502 mother–infant dyads who delivered at 25 hospitals between 2008 and 2011. The inclusion criteria for this analysis were low-risk parous women with nonanomalous singletons with at least one prior vaginal delivery after 20 weeks, who delivered at ≥390/7 weeks. Women who electively induced between 390/7 and 396/7 weeks were compared with women who expectantly managed ≥390/7 weeks. The primary outcome for this analysis was cesarean delivery. Secondary outcomes were composites of maternal adverse outcome and neonatal adverse outcome. Multivariable logistic regression was used to estimate adjusted odds ratios (aOR). Results Of 20,822 women who met inclusion criteria, 2,648 (12.7%) were electively induced at 39 weeks. Cesarean delivery was lower among women who underwent elective induction at 39 weeks than those who did not (2.4 vs. 4.6%, adjusted odds ratio [aOR]: 0.70, 95% confidence interval [CI]: 0.53–0.92). The frequency of the composite maternal adverse outcome was significantly lower for the elective induction cohort as well (1.6 vs. 3.1%, aOR: 0.66, 95% CI: 0.47–0.93). The composite neonatal adverse outcome was not significantly different between the two groups (0.3 vs. 0.6%; aOR: 0.60, 95% CI: 0.29–1.23). Conclusion In low-risk parous women, elective induction of labor at 39 weeks was associated with decreased odds of cesarean delivery and maternal morbidity, without an increase in neonatal adverse outcomes. Key Points

Objective This study aimed to the assess risk of respiratory morbidity in neonates born to women with gestational diabetes mellitus (GDM) delivered after labor compared with those delivered without exposure to labor. Study Design This is a secondary analysis of a prospective single-center cohort study of singleton pregnancies complicated by GDM. Neonates who were liveborn and delivered at ≥34 weeks' gestation were included. The primary outcome was respiratory morbidity defined as respiratory distress syndrome (RDS) or transient tachypnea of the newborn (TTN) resulting in neonatal intensive care unit (NICU) admission. Neonates born after labor (either spontaneous or induced) were compared with those delivered by cesarean delivery without labor. Associations between labor and neonatal morbidities were estimated using logistic regression. Covariates were adjusted for if they differed significantly between neonates exposed to and not exposed to labor (p Results Of the 581 neonates meeting study inclusion criteria, 23.2% delivered without exposure to labor. Those who did and did not experience labor delivered at similar gestational ages (38.6 vs. 38.4 weeks). Thirty-six neonates (6.2%) developed RDS or TTN and were admitted to the NICU. Exposure to labor was associated with a lower frequency of respiratory morbidity requiring admission to NICU, 4.9% (22/446) versus 10.4% (14/135) (p = 0.04). After adjusting for parity, body mass index, birth weight, gestational weight gain more than Institute of Medicine guidelines, race, and exposure to labor were associated with an adjusted odds ratio of 0.41 (95% confidence interval: 0.18–0.89). Conclusion Exposure to labor was associated with decreased odds of respiratory morbidity in neonates born to mothers with GDM. Limiting elective cesarean in this population can reduce health care costs and optimize neonatal health. Key Points

Objective To estimate whether the frequency of adverse maternal and neonatal outcomes differs between low-risk nulliparous and multiparous women at 39-41 weeks of gestation. Methods This is a secondary analysis of an observational obstetrics cohort of maternal-neonatal dyads at 25 hospitals. Low-risk women with nonanomalous singletons who delivered between 39 0/7 and 41 6/7 weeks of gestation were included. The composite neonatal adverse outcome included 5-minute Apgar score less than five, ventilator support or cardiopulmonary resuscitation, seizure, hypoxic ischemic encephalopathy, sepsis, bronchopulmonary dysplasia, persistent pulmonary hypertension, necrotizing enterocolitis, birth injury or perinatal death. The composite maternal adverse outcome included infection, third- or fourth-degree perineal laceration, thromboembolism, transfusion of blood products, or maternal death. Small for gestational age (SGA), large for gestational age (LGA), and shoulder dystocia requiring maneuvers were also evaluated. Multivariable regression was used to estimate adjusted relative risks (aRRs) and adjusted odds ratios (aORs) with 95% CIs. Results Of the 115,502 women in the overall cohort, 39,870 (34.5%) met eligibility criteria for this analysis; 18,245 (45.8%) were nulliparous. The risk of the composite neonatal adverse outcome (1.5% vs 1.0%, aRR 1.80, 95% CI 1.48-2.19), composite maternal adverse outcome (15.1% vs 3.3%, aRR 5.04, 95% CI 4.62-5.49), and SGA (8.9% vs 5.8%, aOR 1.45, 95% CI 1.33-1.57) was significantly higher in nulliparous than multiparous patients. The risk of LGA (aOR 0.65, 95% CI 0.60-0.71) and shoulder dystocia with maneuvers (aRR 0.68, 95% CI 0.60-0.77) was significantly lower in nulliparous rather than multiparous patients. Conclusion The risk of composite adverse outcomes and SGA among low-risk nulliparous women at 39-41 weeks of gestation is significantly higher than among multiparous counterparts. However, nulliparous women had a lower risk of shoulder dystocia with maneuvers and LGA.

Objective The objective of this study was to determine whether antenatal corticosteroid exposure has a differential association with preterm neonatal morbidity among women with and without diabetes. Study design Secondary analysis of an observational cohort of 115,502 women and their neonates born in 25 U.S. hospitals (2008-2011). Women who delivered at 230/7 to 336/7 weeks' gestation and received antenatal corticosteroids were compared with those who did not receive antenatal corticosteroids. Women with a stillbirth and women who delivered a neonate that was not resuscitated were excluded. The primary outcome was neonatal respiratory distress syndrome or death within 48 hours. Secondary outcomes included composite neonatal morbidity (respiratory distress syndrome, necrotizing enterocolitis, grades 3-4 intraventricular hemorrhage, sepsis, or death) and mechanical ventilation. Multivariable modified Poisson regression was used to estimate the association between antenatal corticosteroid exposure and neonatal outcomes. Maternal diabetes (pregestational and gestational) was evaluated as a potential effect modifier, and sensitivity analyses were conducted to evaluate whether receipt of a partial, single, or multiple course(s) of antenatal corticosteroids influenced results. Results A total of 4,429 women with 5,259 neonates met inclusion criteria: 3,716 (83.9%) women received antenatal corticosteroids and 713 (16.1%) did not. Of the 510 diabetic women (181 pregestational and 329 gestational), 439 (86.1%) received antenatal corticosteroids. Of the 3,919 nondiabetic women, 3,277 (83.6%) received antenatal corticosteroids. Antenatal corticosteroid exposure was not associated with respiratory distress syndrome or early death (adjusted relative risk [aRR] = 0.94, 95% confidence interval [CI]: 0.85-1.04), composite neonatal morbidity (aRR = 0.98, 95% CI: 0.89-1.07), or mechanical ventilation (aRR = 0.95, 95% CI: 0.86-1.05). There was no significant effect modification of maternal diabetes on the relationship between antenatal corticosteroids and neonatal outcomes (p > 0.05), and outcomes were similar in sensitivity analyses of partial, single, or multiple courses of corticosteroids. Discussion Antenatal corticosteroid administered to reduce preterm neonatal morbidity does not appear to have a differential association among women with diabetes compared with those without. Key points · Antenatal corticosteroids are used ubiquitously in women with and without diabetes.. · Maternal diabetes does not appear to modify the neonatal effect of antenatal corticosteroids.. · Larger studies of antenatal corticosteroids are needed to confirm our findings in diabetic women..

Objective We sought to determine if there is an association between fibroblast growth factor 21 (FGF21) levels and a history of gestational diabetes mellitus (GDM) in women with and without metabolic dysfunction, defined as a diagnosis of metabolic syndrome or type 2 diabetes (T2DM), 5 to 10 years following participation in a multiple cohort GDM study. Study Design At 5 to 10 years after index pregnancy, women underwent a follow-up visit and were categorized as having no metabolic syndrome, metabolic syndrome, or T2DM. FGF21 levels were compared between women who did and did not have a history of GDM using multivariable linear regression. Results Among 1,889 women, 950 underwent follow-up and 796 had plasma samples analyzed (413 GDM and 383 non-GDM). Total 30.7% of women had been diagnosed with T2DM or metabolic syndrome. Overall, there was no difference in median FGF21 levels in pg/mL between the prior GDM and non-GDM groups (p = 0.12), and the lack of association was observed across all three metabolic categories at follow-up (p for interaction = 0.70). Conclusion There was no association between FGF21 levels and prior history of mild GDM in women with and without metabolic dysfunction 5 to 10 years after the index pregnancy (ClinicalTrials.gov number, NCT00069576, original trial).

Objective The aim of the study is to evaluate the association between amniotomy at various time points during labor induction and maternal and neonatal outcomes among term, nulliparous women. Study Design Secondary analysis of a randomized trial of term labor induction versus expectant management in low-risk, nulliparous women (2014–2017) was conducted. Women met inclusion criteria if they underwent induction ≥38 weeks' gestation using oxytocin with documented time and type of membrane rupture. Women with antepartum stillbirth or fetal anomaly were excluded. The primary outcome was cesarean delivery. Secondary outcomes included maternal and neonatal complications. Maternal and neonatal outcomes were compared among women with amniotomy versus women with intact membranes and no amniotomy at six 2-hour time intervals: before oxytocin initiation, 0 to Results Of 6,106 women in the parent trial, 2,854 (46.7%) women met inclusion criteria. Of these 2,340 (82.0%) underwent amniotomy, and majority of the women had amniotomy performed between 2 and 24 hours. Amniotomy at time intervals ≥2 hours and 3 days. Amniotomy was not associated with postpartum or neonatal complications. Conclusion Among a contemporary cohort of nulliparous women undergoing term labor induction, amniotomy was associated with either lower or similar odds of cesarean delivery and other adverse outcomes, compared with no amniotomy.

It has long been observed that neonates born between 39 and 40 gestational weeks have the best perinatal outcomes. What has not been known, until recently, is whether these ideal perinatal outcomes would be achieved in neonates whose delivery was brought on intentionally in this window by labor induction. Recent randomized trials and large observational cohorts have answered this question: labor induction, as compared with expectant management, lowers the rate of cesarean delivery (without increasing other adverse maternal outcomes) and improves perinatal outcomes. For those women still pregnant, delivery at 39 weeks of gestation would simultaneously lower the number of cesarean deliveries and reduce the number of stillbirths and neonatal deaths in the United States.

Objective To estimate the effect of antenatal treatment of subclinical hypothyroidism on maternal depressive symptoms. Methods We conducted an ancillary study to a multicenter trial in women with singleton pregnancies diagnosed with subclinical hypothyroidism randomized to antenatal thyroxine therapy or placebo. Treatment was discontinued at the end of pregnancy. Women with overt thyroid disease, diabetes, autoimmune disease, and those diagnosed with depression were excluded. Participants were assessed for depressive symptoms using the Center for Epidemiological Studies-Depression scale (CES-D) before starting the study drug (between 11 and 20 weeks of gestation), between 32 and 38 weeks of gestation, and at 1 year postpartum. The primary outcome was maternal depressive symptoms score as assessed using the CES-D. Secondary outcome was the percentage of women who scored 16 or higher on the CES-D, as such a score is considered screen-positive for depression. Results Two hundred forty-five (36.2% of parent trial) women with subclinical hypothyroidism were allocated to thyroxine (n=124) or placebo (n=121). Median CES-D scores and the proportion of participants with positive scores were similar at baseline between the two groups. Treatment with thyroxine was not associated with differences in CES-D scores (10 [5-15] vs 10 [5-17]; P=.46) or in odds of screening positive in the third trimester compared with placebo, even after adjusting for baseline scores (24.3% vs 30.1%, adjusted odds ratio 0.63, 95% CI 0.31-1.28, P=.20). At 1 year postpartum, CES-D scores were not different (6 [3-11] vs 6 [3-12]; P=.79), nor was the frequency of screen-positive CES-D scores in the treated compared with the placebo group (9.7% vs 15.8%; P=.19). Treatment with thyroxine during pregnancy was also not associated with differences in odds of screening positive at the postpartum visit compared with placebo even after adjusting for baseline scores. Sensitivity analysis including women who were diagnosed with depression by the postpartum visit did not change the results. Conclusions This study did not achieve its planned sample size, thus our conclusions may be limited, but in this cohort of pregnant women with subclinical hypothyroidism, antenatal thyroxine replacement did not improve maternal depressive symptoms.

IMPORTANCE: It remains unknown whether SARS-CoV-2 infection specifically increases the risk of serious obstetric morbidity. OBJECTIVE: To evaluate the association of SARS-CoV-2 infection with serious maternal morbidity or mortality from common obstetric complications. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 14 104 pregnant and postpartum patients delivered between March 1, 2020, and December 31, 2020 (with final follow-up to February 11, 2021), at 17 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development’s Gestational Research Assessments of COVID-19 (GRAVID) Study. All patients with SARS-CoV-2 were included and compared with those without a positive SARS-CoV-2 test result who delivered on randomly selected dates over the same period. EXPOSURES: SARS-CoV-2 infection was based on a positive nucleic acid or antigen test result. Secondary analyses further stratified those with SARS-CoV-2 infection by disease severity. MAIN OUTCOMES AND MEASURES: The primary outcome was a composite of maternal death or serious morbidity related to hypertensive disorders of pregnancy, postpartum hemorrhage, or infection other than SARS-CoV-2. The main secondary outcome was cesarean birth. RESULTS: Of the 14 104 included patients (mean age, 29.7 years), 2352 patients had SARS-CoV-2 infection and 11 752 did not have a positive SARS-CoV-2 test result. Compared with those without a positive SARS-CoV-2 test result, SARS-CoV-2 infection was significantly associated with the primary outcome (13.4% vs 9.2%; difference, 4.2% [95% CI, 2.8%-5.6%]; adjusted relative risk [aRR], 1.41 [95% CI, 1.23-1.61]). All 5 maternal deaths were in the SARS-CoV-2 group. SARS-CoV-2 infection was not significantly associated with cesarean birth (34.7% vs 32.4%; aRR, 1.05 [95% CI, 0.99-1.11]). Compared with those without a positive SARS-CoV-2 test result, moderate or higher COVID-19 severity (n = 586) was significantly associated with the primary outcome (26.1% vs 9.2%; difference, 16.9% [95% CI, 13.3%-20.4%]; aRR, 2.06 [95% CI, 1.73-2.46]) and the major secondary outcome of cesarean birth (45.4% vs 32.4%; difference, 12.8% [95% CI, 8.7%-16.8%]; aRR, 1.17 [95% CI, 1.07-1.28]), but mild or asymptomatic infection (n = 1766) was not significantly associated with the primary outcome (9.2% vs 9.2%; difference, 0% [95% CI, −1.4% to 1.4%]; aRR, 1.11 [95% CI, 0.94-1.32]) or cesarean birth (31.2% vs 32.4%; difference, −1.4% [95% CI, −3.6% to 0.8%]; aRR, 1.00 [95% CI, 0.93-1.07]). CONCLUSIONS AND RELEVANCE: Among pregnant and postpartum individuals at 17 US hospitals, SARS-CoV-2 infection was associated with an increased risk for a composite outcome of maternal mortality or serious morbidity from obstetric complications.

A trial of progesterone to prevent preterm birth among HIV-infected Zambian women [Improving Pregnancy Outcomes with Progesterone (IPOP)] found no treatment effect, but the risk of the primary outcome was among the lowest ever documented in women with HIV. In this secondary analysis, we compare the risks of preterm birth (37 weeks), stillbirth, and a composite primary outcome comprising the two in IPOP versus an observational pregnancy cohort [Zambian Preterm Birth Prevention Study (ZAPPS)] in Zambia, to evaluate reasons for the low risk in IPOP.Both studies enrolled women before 24 gestational weeks, during August 2015-September 2017 (ZAPPS) and February 2018-January 2020 (IPOP). We used linear probability and log-binomial regression to estimate risk differences and risk ratios (RR), before and after restriction and standardization with inverse probability weights.The unadjusted risk of composite outcome was 18% in ZAPPS (N = 1450) and 9% in IPOP (N = 791) (RR = 2.0; 95% CI = 1.6, 2.6). After restricting and standardizing the ZAPPS cohort to the distribution of IPOP baseline characteristics, the risk remained higher in ZAPPS (RR = 1.6; 95% CI = 1.0, 2.4). The lower risk of preterm/stillbirth in IPOP was only partially explained by measured risk factors.Possible benefits in IPOP of additional monetary reimbursement, more frequent visits, and group-based care warrant further investigation.