The placenta facilitates vital nutrient and gas exchange between mother and fetus. Metals such as cadmium (Cd), lead (Pb) and arsenic (As) have been associated with decreased placental vascularization, suboptimal invasion, and poorer birth outcomes. Although exposure to these chemical stressors often co-occurs with social stressors, few studies have evaluated the effects of these chemical stressors in the context of social stressors. Herein, we evaluate relationships between chemical stressors and birthweight, gestational age at delivery, and placental weight in the context of social stress. We used Inductively coupled plasma mass spectrometry (ICP-MS) to measure a suite of metals including Cd, Pb and As in fetal placentae of three groups: 62 non-Hispanic white (NHW), 164 non-Hispanic black (NHB), and 84 Hispanic participants. We used Kruskal-Wallis tests to assess overall differences in toxic metal concentrations by for each group, followed by pairwise Wilcoxon rank-sum tests for comparisons between specific groups. Multivariable linear regression models were used to evaluate whether the associations between toxic metals and birth outcomes varied in the offspring of women with or without adverse childhood experiences (ACEs), financial stress, and perceived discrimination. Placental Cd levels for NHB were significantly higher than in Hispanic and NHW participants (p < 0.05), a difference not explained by established exposures such as maternal smoking or obesity. Further analyses revealed that in NHB, significant effects of Cd on shorter gestational age at delivery, birthweight and lower placental weight were apparent only in offspring of parents reporting the existence of ACEs. (p < 0.05). While sample size limits inference, these data support the hypothesis that social stressors interact with environmental contaminants to influence poor birth outcomes. Larger studies are needed to clarify these findings.

OBJECTIVE: To evaluate the risks of adverse maternal and neonatal outcomes associated with pregnancies complicated by hepatitis C virus (HCV) infection. METHODS: This is a secondary analysis of a multicenter prospective cohort study of HCV infection in pregnancy. Participants were screened for HCV infection with serum antibody tests, and each participant with a positive HCV result (case group) was matched with up to two individuals with negative HCV results (control group) prospectively by gestational age (±2 weeks) at enrollment. Maternal outcomes included gestational diabetes, abruption, preeclampsia or gestational hypertension, cholestasis, and preterm delivery. Neonatal outcomes included hyperbilirubinemia, admission to neonatal intensive care (NICU); small-for-gestational-age (SGA) birth weight; and neonatal infection , defined as sepsis or pneumonia. Models were adjusted for maternal age, body mass index, injection drug use, and maternal medical comorbidities. RESULTS: The 249 individuals in the case group were prospectively matched to 486 individuals in the control group who met eligibility criteria. There were significant differences in demographic characteristics between the groups, including race, socioeconomic markers, education, insurance status, and drug and tobacco use. The frequencies of maternal outcomes of gestational diabetes, preeclampsia, and abruption were similar between the case and control groups. Preterm birth was similar between groups, but neonates born to individuals in the case group were more likely to be admitted to the NICU (45.1% vs 19.0%, adjusted odds ratio [aOR] 2.6, 95% CI, 1.8–3.8) and to have SGA birth weights below the 5th percentile (10.6% vs 3.1%, aOR 2.9, 95% CI, 1.4–6.0). There were no increased odds of hyperbilirubinemia or neonatal infection. CONCLUSION: Despite no increased odds of preterm birth or other adverse maternal outcomes in adjusted analyses, maternal HCV infection was associated with twofold increased odds of NICU admission and nearly threefold increased odds of SGA birth weight below the 5th percentile.

To describe how the UNC Horizons program, a comprehensive women-centered program for pregnant and parenting women with substance use disorders, and its patient population have changed over time and summarize basic neonatal outcomes for infants born to women in treatment at Horizons. Yearly Annual Reports from fiscal years of 1994 to 2017 were abstracted. Patient characteristics and infant outcomes compared to normative North Carolina data were examined. Highlights of findings include: The percentage of women for whom opioids were the primary substance of use increased from 0

Background: To examine the incidence of overt hypothyroidism 1 and 5 years after pregnancies where screening before 21 weeks identified subclinical hypothyroidism (SH) or hypothyroxinemia (HT). Methods: Secondary analysis of two multicenter treatment trials for either SH or HT diagnosed between 8 and 20 weeks gestation. Current analyses focus only on individuals randomized to the placebo groups in the two parallel studies. SH was diagnosed with thyrotropin (TSH) >= 4.0 mU/L and normal free T4 (fT4) (0.86-1.9 ng/dL). HT was diagnosed with normal TSH (0.08-3.99 mU/L) but fT4 <0.86 ng/dL. Serum from initial testing was stored for later thyroid peroxidase (TPO) antibody assay; results were not returned for clinical management. At 1 and 5 years after delivery, participants were asked whether they had either been diagnosed with or were being treated for a thyroid condition. Maternal serum was collected at these visits and thyroid function measured. Subsequent overt hypothyroidism was defined as TSH >= 4.0 mU/L with fT4 <0.86 ng/dL. Results: Data for 1- and 5-year follow-up were available in 307 of the 338 participants with SH and 229 of the 261 with HT. Subsequent hypothyroidism was more common both at year 1 (13.4% vs. 3.1%, p < 0.001) and year 5 (15.6% vs. 2.6%, p < 0.001) for participants with SH compared with those with HT. This progression was more common in individuals with TSH values >10 mIU/mL. Baseline TPO level >50 IU/mL in participants with SH was associated with higher rates of hypothyroidism at year 1 (26.7% vs. 6.5%, odds ratio [OR] = 5.3 [confidence interval (CI) 2.6-10.7]) and year 5 (30.5% vs. 7.5%, OR = 5.4 [CI: 2.8-10.6]) compared with those with TPO levels <= 50 IU/mL. For participants with HT, no differences in overt hypothyroidism were seen at 1 year related to baseline TPO level >50 IU/mL (1/10 (10%) vs. 6/218 (2.8%), OR = 3.9 [CI: 0.43-36.1]), but more participants with TPO levels >50 IU/mL developed hypothyroidism by year 5 (2/10 (20%) vs. 4/218 (1.8%), OR = 13.4 [CI: 2.1-84.1]). Conclusion: SH is associated with higher rates of overt hypothyroidism or thyroid replacement therapy within 5 years of delivery than is HT when these conditions are diagnosed in the first half of pregnancy.

OBJECTIVE:To characterize breastfeeding behaviors and identify factors associated with breastfeeding initiation among people with hepatitis C virus (HCV) infection. METHODS:We conducted a secondary analysis of a multicenter observational cohort of pregnant people with singleton gestations and HCV seropositivity. This analysis includes individuals with data on breastfeeding initiation and excludes those with human immunodeficiency virus (HIV) co-infection. The primary outcome was self-reported initiation of breastfeeding or provision of expressed breast milk. Secondary outcomes included duration of breastfeeding. Demographic and obstetric characteristics were compared between those who initiated breastfeeding and those who did not to identify associated factors. Univariable and multivariable analyses were performed. RESULTS:Overall, 579 individuals (75.0% of participants in the parent study) were included. Of those, 362 (62.5%) initiated breastfeeding or provided breast milk to their infants, with a median duration of breastfeeding of 1.4 months (interquartile range 0.5-6.0). People with HCV viremia , defined as a detectable viral load at any point during pregnancy, were less likely to initiate breastfeeding than those who had an undetectable viral load (59.4 vs 71.9%, adjusted odds ratio [aOR] 0.61, 95% CI, 0.41-0.92). People with private insurance were more likely to initiate breastfeeding compared with those with public insurance or no insurance (80.0 vs 60.1%; aOR 2.43, 95% CI, 1.31-4.50). CONCLUSION:Although HCV seropositivity is not a contraindication to breastfeeding regardless of viral load, rates of breastfeeding initiation were lower among people with HCV viremia than among those with an undetectable viral load. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov , NCT01959321 .

Objective The fetal consequences of intrapartum fetal tachycardia with maternal fever or clinical chorioamnionitis are not well studied. We evaluated the association between perinatal morbidity and fetal tachycardia in the setting of intrapartum fever. Study Design Secondary analysis of a multicenter randomized control trial that enrolled 5,341 healthy laboring nulliparous women ≥36 weeks' gestation. Women with intrapartum fever ≥ 38.0°C (including those meeting criteria for clinical chorioamnionitis) after randomization were included in this analysis. Isolated fetal tachycardia was defined as fetal heart rate (FHR) ≥160 beats per minute for at least 10 minutes in the absence of other FHR abnormalities. FHR abnormalities other than tachycardia were excluded from the analysis. The primary outcome was a perinatal composite (5-minute Apgar's score ≤3, intubation, chest compressions, or mortality). Secondary outcomes included low arterial cord pH (pH < 7.20), base deficit ≥12, and cesarean delivery. Results A total of 986 (18.5%) of women in the trial developed intrapartum fever, and 728 (13.7%) met criteria to be analyzed; of these, 728 women 336 (46.2%) had maternal-fetal medicine (MFM) reviewer-defined fetal tachycardia, and 349 of the 550 (63.5%) women during the final hour of labor had validated software (PeriCALM) defined fetal tachycardia. After adjusting for confounders, isolated fetal tachycardia was not associated with a significant difference in the composite perinatal outcome (adjusted odds ratio [aOR] = 3.15 [0.82–12.03]) compared with absence of tachycardia. Fetal tachycardia was associated with higher odds of arterial cord pH <7.2, aOR = 1.48 (1.01–2.17) and of infants with a base deficit ≥ 12, aOR = 2.42 (1.02–5.77), but no significant difference in the odds of cesarean delivery, aOR = 1.33 (0.97–1.82). Conclusion Fetal tachycardia in the setting of intrapartum fever or chorioamnionitis is associated with significantly increased fetal acidemia defined as a pH <7.2 and base excess ≥12 but not with a composite perinatal morbidity. Key Points

Objective 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. Methods 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. Results 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%). Conclusion ST changes in fetal ECG occur more frequently in fetuses of diabetic mothers during labor. ClinicalTrials.gov number, NCT01131260. Precis: ST changes in fetal ECG, a marker of fetal cardiac hypoxia, occur more frequently in fetuses of diabetic parturients. Key Points

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

Objective: Our objective was to evaluate whether iodine status in pregnant patients with either subclinical hypothyroidism or hypothyroxinemia in the first half of pregnancy is associated with measures of behavior and neurodevelopment in children through the age of 5 years.Study design: This is a secondary analysis of a multicenter study consisting of two randomized, double-masked, placebo-controlled treatment trials conducted in parallel. Patients with a singleton gestation before 20 weeks' gestation underwent thyroid screening using serum thyrotropin and free thyroxine. Participants with subclinical hypothyroidism or hypothyroxinemia were randomized to levothyroxine replacement or an identical placebo. At randomization, maternal urine was collected and stored for subsequent urinary iodine excretion analysis. Urinary iodine concentrations greater than 150 mu g/L were considered iodine sufficient, and concentrations of 150 mu g/L or less were considered iodine insufficient. The primary outcome was a full-scale intelligence quotient (IQ) score at the age of 5 years, the general conceptual ability score from the Differential Ability Scales-II at the age of 3 if IQ was not available, or death before 3 years.Results: A total of 677 pregnant participants with subclinical hypothyroidism and 526 with hypothyroxinemia were randomized. The primary outcome was available in 1,133 (94%) of children. Overall, 684 (60%) of mothers were found to have urinary iodine concentrations >150 mu g/L. Children of iodine-sufficient participants with subclinical hypothyroidism had similar primary outcome scores when compared to children of iodine-insufficient participants (95 [84-105] vs. 96 [87-109], P (adj )= 0.73). After adjustment, there was also no difference in IQ scores among children of participants with hypothyroxinemia at 5 to 7 years of age (94 [85 - 102] and 91 [81 - 100], P-adj 1/4 0.11). Treatment with levothyroxine was not associated with neurodevelopmental or behavioral outcomes regardless of maternal iodine status (p > 0.05).Conclusion: Maternal urinary iodine concentrations <= 150 mu g/L were not associated with abnormal cognitive or behavioral outcomes in offspring of participants with either subclinical hypothyroidism or hypothyroxinemia.

BACKGROUND:In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes-including from >1 individual-to be considered concurrently. OBJECTIVE:This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to maternal-perinatal paired (dyadic) outcomes in which both individuals may be affected by an intervention but may experience discordant outcomes (eg, an obstetrical intervention may improve perinatal but worsen maternal outcomes). STUDY DESIGN:This secondary analysis applies the desirability of outcome ranking methodology to data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ARRIVE trial. The original analysis found no substantial difference in the primary (perinatal composite) outcome, but a decreased risk of the secondary outcome of cesarean delivery with elective induction at 39 weeks. In the present desirability-of-outcome-ranking analysis, dyadic outcomes ranging from spontaneous vaginal delivery without severe neonatal complication (most desirable) to cesarean delivery with perinatal death (least desirable) were classified into 8 categories ranked by overall desirability by experienced investigators. Distributions of the desirability of outcome ranking were compared by estimating the probability of having a more desirable dyadic outcome with elective induction at 39 weeks of gestation than with expectant management. To account for various perspectives on these outcomes, a complementary analysis, called the partial credit strategy, was used to grade outcomes on a 100-point scale and estimate the difference in overall treatment scores between groups using a t test. RESULTS:All 6096 participants from the trial were included. The probability of a better dyadic outcome for a randomly selected patient who was randomized to elective induction was 53% (95% confidence interval, 51-54), implying that elective induction led to a better overall outcome for the dyad when taking multiple outcomes into account concurrently. Furthermore, the desirability-of-outcome-ranking probability of averting cesarean delivery with elective induction was 52% (95% confidence interval, 51-53), which was not at the expense of an operative vaginal delivery or a poorer outcome for the perinate (ie, survival with a severe neonatal complication or perinatal death). Randomization to elective induction was also advantageous in most of the partial credit score scenarios. CONCLUSION:Desirability-of-outcome-ranking methodology is a useful tool for obstetrical trials because it provides a concurrent view of the effect of an intervention on multiple dyadic outcomes, potentially allowing for better translation of data for decision-making and person-centered care.

Abstract Objective This study aimed to evaluate whether there are genetic variants associated with adverse neurodevelopmental outcomes in extremely low birth weight (ELBW) infants. Study Design We conducted a candidate gene association study in two well-defined cohorts of ELBW infants (<1,000 g). One cohort was for discovery and the other for replication. The discovery case–control analysis utilized anonymized DNA samples and evaluated 1,614 single-nucleotide polymorphisms (SNPs) in 145 genes concentrated in inflammation, angiogenesis, brain development, and oxidation pathways. Cases were children who died by age one or who were diagnosed with cerebral palsy (CP) or neurodevelopmental delay (Bayley II mental developmental index [MDI] or psychomotor developmental index [PDI] < 70) by 18 to 22 months. Controls were survivors with normal neurodevelopment. We assessed significant epidemiological variables and SNPs associated with the combined outcome of CP or death, CP, mental delay (MDI < 70) and motor delay (PDI < 70). Multivariable analyses adjusted for gestational age at birth, small for gestational age, sex, antenatal corticosteroids, multiple gestation, racial admixture, and multiple comparisons. SNPs associated with adverse neurodevelopmental outcomes with p < 0.01 were selected for validation in the replication cohort. Successful replication was defined as p < 0.05 in the replication cohort. Results Of 1,013 infants analyzed (452 cases, 561 controls) in the discovery cohort, 917 were successfully genotyped for >90% of SNPs and passed quality metrics. After adjusting for covariates, 26 SNPs with p < 0.01 for one or more outcomes were selected for replication cohort validation, which included 362 infants (170 cases and 192 controls). A variant in SERPINE1, which encodes plasminogen activator inhibitor (PAI1), was associated with the combined outcome of CP or death in the discovery analysis ( p = 4.1 × 10 −4 ) and was significantly associated with CP or death in the replication cohort (adjusted odd ratio: 0.4; 95% confidence interval: 0.2–1.0; p = 0.039). Conclusion A genetic variant in SERPINE1, involved in inflammation and coagulation, is associated with CP or death among ELBW infants. Key Points Early preterm and ELBW infants have dramatically increased risks of CP and developmental delay. A genetic variant in SERPINE1 is associated with CP or death among ELBW infants. The SERPINE1 gene encodes the serine protease inhibitor plasminogen activator inhibitor.

BACKGROUND: Hypertensive disorders of pregnancy are the leading cause of indicated preterm birth; however, the optimal delivery approach for pregnancies complicated by preterm hypertensive disorders of pregnancy remains uncertain.OBJECTIVE: This study aimed to compare maternal and neonatal morbidity in patients with hypertensive disorders of pregnancy who either went induction of labor or prelabor cesarean delivery at <33 weeks' gestation. In addition, we aimed to quantify the length of induction of labor and rate of vaginal delivery in those who underwent induction of labor.STUDY DESIGN: This is a secondary analysis of an observational study which included 115,502 patients in 25 hospitals in the United States from 2008 to 2011. Patients were included in the secondary analysis if they were delivered for pregnancy associated hypertension (gestational hypertension or preeclampsia) between 23(0) and <33(0) weeks' gestation; and were excluded for known fetal anomalies, multiple gestation, fetal malpresentation or demise, or a contraindication to labor. Maternal and neonatal adverse composite outcomes were evaluated by intended mode of delivery. Secondary outcomes were duration of labor induction and rate of cesarean delivery in those who underwent labor induction.RESULTS: A total of 471 patients met inclusion criteria, of whom 271 (58%) underwent induction of labor and 200 (42%) underwent prelabor cesarean delivery. Composite maternal morbidity was 10.2% in the induction group and 21.1% in the cesarean delivery group (unadjusted odds ratio, 0.42 [0.25-0.72]; adjusted odds ratio, 0.44 [0.26-0.76]). Neonatal morbidity in the induction group vs the cesarean delivery was 51.9% and 63.8 %, respectively (unadjusted odds ratio, 0.61 [0.42-0.89]; adjusted odds ratio, 0.71 [0.48-1.06]). The frequency of vaginal delivery in the induction group was 53% (95% confidence interval, 46.8-58.7) and the median duration of labor was 13.9 hours (interquartile range, 8.7 -22.2). The frequency of vaginal birth was higher in patients at or beyond 29 weeks (39.9% at 24(0)-28(6) weeks, 56.3% at 29(0)-<33(0) weeks; P=.01).CONCLUSION: Among patients delivered for hypertensive disorders of pregnancy <33(0) weeks, labor induction compared with prelabor cesarean delivery is associated with significantly lower odds of maternal but not neonatal morbidity. More than half of patients induced delivered vaginally, with a median duration of labor induction of 13.9 hours.

BACKGROUND: Maternal obesity complicates a high number of preg-nancies. The degree to which neonatal outcomes are adversely affected is unclear.OBJECTIVE: This study aimed to evaluate neonatal outcomes of preg-nancies complicated by maternal obesity. STUDY DESIGN: This study was a secondary analysis of a cohort of deliveries occurring on randomly selected days at 25 hospitals from 2008 to 2011. Data were collected by certified abstractors. This analysis included singleton deliveries between 24 and 42 weeks of gestation. Body mass index was calculated on the basis of maternal height and most recent weight before delivery. Normal and overweight (reference group; body mass index, 18.5-29.9 kg/m2), obese (body mass index, 30.0-39.9 kg/m2), morbidly obese (body mass index, 40.0-49.9 kg/m2), and super morbidly obese (body mass index, >= 50 kg/m2) patients were compared. Patients in the ref-erence group were matched in a 1:1 ratio with those in all other groups with obesity using the baseline characteristics of age, race and ethnicity, pre-vious cesarean delivery, preexisting diabetes mellitus, chronic hypertension, parity, cigarette use, and insurance status. The primary outcome was com-posite neonatal morbidity, including fetal or neonatal death, hypoxic-ischemic encephalopathy, respiratory distress syndrome, intraventricular hemorrhage grade 3 or 4, necrotizing enterocolitis, sepsis, birth injury, seizures, or ventila-tor use. We used a modified Poisson regression to examine the associations between body mass index and composite neonatal outcome. Preterm delivery at <37 weeks of gestation and the presence of maternal preeclampsia or eclampsia were included in the final model because of their known associa-tions with neonatal outcomes.RESULTS: Overall, 52,162 patients and their neonates were included after propensity score matching. Of these, 21,704 (41.6%) were obese, 3787 (7.3%) were morbidly obese, and 590 (1.1%) were super morbidly obese. A total of 2103 neonates (4.0%) had the composite outcome. Neo-nates born to pregnant people with morbid obesity had a 33% increased risk of composite neonatal morbidity compared with those in the reference group (adjusted odds ratio, 1.33; 95% confidence interval, 1.17-1.52), but no significant association was observed for persons with obesity (adjusted odds ratio, 1.05; 95% confidence interval, 0.97-1.14) or with super morbid obesity (adjusted odds ratio, 1.18; 95% confidence interval, 0.86-1.64).CONCLUSION: Compared with the reference group, gravidas with morbid obesity were at higher risk of composite neonatal morbidity.

BACKGROUND:Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS:We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS:A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P = 0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS:Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).

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 (<40 mg/dL). We sought to better characterize the nature, duration, and treatment for hypoglycemia. 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 (<40 mg/dL), lowest value and treatment, if any, were assessed by group. Measures of association and regression models were used where appropriate. 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.

IMPORTANCE:Pregnancy 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. METHODS:RECOVER-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 the Eunice Kennedy Shriver National 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. DISCUSSION:RECOVER-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. CLINICAL TRIALS.GOV IDENTIFIER:Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT05172011.

Objective This study aimed to evaluate maternal and neonatal outcomes by method of cervical ripening for labor induction among low-risk nulliparous individuals. Study Design This is a secondary analysis of a multicenter randomized trial of labor induction at 39 weeks versus expectant management in low-risk nulliparous participants. Participants undergoing cervical ripening for labor induction in either group were included. Participants were excluded for preripening membrane rupture, abruption, chorioamnionitis, fetal demise, or cervical dilation ≥3.5 cm. Cervical ripening was defined by the initial method used: prostaglandin only (PGE; referent), Foley with concurrent prostaglandin (Foley-PGE), Foley only (Foley), and Foley with concurrent oxytocin (Foley-oxytocin). Coprimary outcomes were adverse maternal and neonatal composites. Secondary outcomes included cesarean delivery and length of labor and delivery (L&D) stay. Multivariable analysis was used to adjust for patient characteristics. Results Of 6,106 participants included in the trial, 2,376 (38.9%) met criteria for this analysis. Of these, 1,247 (52.4%) had cervical ripening with PGE, 290 (12.2%) had Foley-PGE, 385 (16.2%) had Foley, and 454 (19.1%) had Foley-oxytocin. The maternal composite outcome was similar among participants who received Foley-PGE (24.1%, adjusted relative risk [aRR] = 1.21, 95% confidence interval [CI]: 0.96–1.52), Foley (21.3%, aRR = 1.16, 95% CI: 0.92–1.45), or Foley-oxytocin (19.4%, aRR = 1.04, 95% CI: 0.83–1.29), compared with PGE (19.7%). The neonatal composite outcome was less frequent in participants who received the Foley-PGE (2.4%, aRR = 0.35, 95% CI: 0.16–0.75) or Foley (3.6%, aRR = 0.51, 95% CI: 0.29–0.89) but did not reach statistical significance for participants who received Foley-oxytocin (4.6%, aRR = 0.63, 95% CI: 0.40–1.01) compared with PGE only (6.8%). Participants who received Foley-PGE or Foley-oxytocin had a shorter L&D stay (adjusted mean difference = −1.97 hours, 95% CI: −3.45 to −0.49 and −5.92 hours, 95% CI: −7.07 to −4.77, respectively), compared with PGE. Conclusion In term low-risk nulliparous participants, Foley alone or concurrent with PGE is associated with a lower risk of adverse neonatal outcomes than with PGE alone. Length of L&D stay was the shortest with concurrent Foley-oxytocin. Key Points

Objective This study aimed to evaluate whether racial and ethnic disparities in adverse perinatal outcomes exist at term. Study Design We performed a secondary analysis of a multicenter observational study of 115,502 pregnant patients and their neonates (2008–2011). Singleton, nonanomalous pregnancies delivered from 37 to 41 weeks were included. Race and ethnicity were abstracted from the medical record and categorized as non-Hispanic White (White; referent), non-Hispanic Black (Black), non-Hispanic Asian (Asian), or Hispanic. The primary outcome was an adverse perinatal composite defined as perinatal death, Apgar score < 4 at 5 minutes, ventilator support, hypoxic–ischemic encephalopathy, subgaleal hemorrhage, skeletal fracture, infant stay greater than maternal stay (by ≥ 3 days), brachial plexus palsy, or facial nerve palsy. Results Of the 72,117 patients included, 48% were White, 20% Black, 5% Asian, and 26% Hispanic. The unadjusted risk of the primary outcome was highest for neonates of Black patients (3.1%, unadjusted relative risk [uRR] = 1.16, 95% confidence interval [CI]: 1.04–1.30), lowest for neonates of Hispanic patients (2.1%, uRR = 0.80, 95% CI: 0.71–0.89), and no different for neonates of Asian (2.6%), compared with those of White patients (2.7%). In the adjusted model including age, body mass index (BMI), smoking, obstetric history, and high-risk pregnancy, differences in risk for the primary outcome were no longer observed for neonates of Black (adjusted relative risk [aRR] = 1.06, 95% CI: 0.94–1.19) and Hispanic (aRR = 0.92, 95% CI: 0.81–1.04) patients. Adding insurance to the model lowered the risk for both groups (aRR = 0.85, 95% CI: 0.75–0.96 for Black; aRR = 0.68, 95% CI: 0.59–0.78 for Hispanic). Conclusion Although neonates of Black patients have the highest frequency of adverse perinatal outcomes at term, after adjustment for sociodemographic factors, this higher risk is no longer observed, suggesting the importance of developing strategies that address social determinants of health to lessen extant health disparities. Key Points

OBJECTIVE: To compare health care medical resource utilization in low-risk nulliparous pregnancies according to body mass index (BMI, calculated as weight in kilograms divided by height in meters squared) categories. METHODS: This is a secondary analysis of a multicenter randomized controlled trial of induction of labor between 39 0/7 39 and 4/7 weeks of gestation compared with expectant management in low-risk nulliparous pregnant people, defined as those without standard obstetric indications for delivery at 39 weeks. Body mass index at randomization was categorized into four groups (lower than 25, 25–29, 30–39, and 40 or higher). The primary outcome of this analysis was time spent in the labor and delivery department from admission to delivery. Secondary outcomes included length of stay (LOS) postdelivery, total hospital LOS, and antepartum, intrapartum, and postpartum resource utilization, which were defined a priori. Multivariable generalized linear modeling and logistic regressions were performed, and 99% CIs were calculated. RESULTS: A total of 6,058 pregnant people were included in the analysis; 640 (10.6%) had BMIs of lower than 25, 2,222 (36.7%) had BMIs between 25 and 29, 2,577 (42.5%) had BMIs of 30–39, and 619 (10.2%) had BMIs of 40 or higher. Time spent in the labor and delivery department increased from 15.1±9.2 hours for people with BMIs of lower than 25 to 23.5±13.6 hours for people with BMIs of 40 or higher, and every 5-unit increase in BMI was associated with an average 9.8% increase in time spent in the labor and delivery department (adjusted estimate per 5-unit increase in BMI 1.10, 99% CI 1.08–1.11). Increasing BMI was not associated with an increase in antepartum resource utilization, except for blood tests and urinalysis. However, increasing BMI was associated with higher odds of intrapartum resource utilization, longer total hospital LOS, and postpartum resource utilization. For example, every 5-unit increase in BMI was associated with an increase of 26.1% in the odds of antibiotic administration, 57.6% in placement of intrauterine pressure catheter, 5.1% in total inpatient LOS, 31.0 in postpartum emergency department visit, and 23.9% in postpartum hospital admission. CONCLUSION: Among low-risk nulliparous people, higher BMI was associated with longer time from admission to delivery, total hospital LOS, and more frequent utilization of intrapartum and postpartum resources. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01990612.

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 < 0.001). Individuals who were admitted with intent to deliver were less likely to receive optimal ANCS while individuals admitted for hypertensive diseases of pregnancy were most likely to receive optimal ANCS (10 vs. 35%). The median gestational age of individuals who received optimal ANCS was 31.0 weeks. Adjusting for hospital factors, hospitals with electronic medical records and who receive transfers have fewer eligible individuals who did not receive ANCS. ANCS administration and timing varied substantially by hospital, optimal frequencies ranged from 9.1 to 51.3%, and none frequencies from 6.1 to 61.8%. When evaluating variation by hospital site, models with maternal and hospital factors did not explain any of the variation in ANCS use. Conclusion Optimal ANCS use varied by maternal and hospital factors and by hospital site, indicating opportunities for improvement. Key Points