Search

BACKGROUND: The association between obesity (body mass index (BMI) ≥ 30 kg/m(2)) and pattern of medication use during pregnancy in the United States is not well-studied. Higher prepregnancy BMI may be associated with increases or decreases in medication use across pregnancy as symptoms (e.g. reflux) or comorbidities (e.g. gestational diabetes) requiring treatment that may be associated with higher BMI could also change with advancing gestation. OBJECTIVES: To determine whether prenatal medication use, by the number and types of medications, varies by pre-pregnancy obesity status. METHODS: In a secondary data analysis of a racially/ethnically diverse prospective cohort of pregnant women with low risk for fetal abnormalities enrolled in the first trimester of pregnancy and followed to delivery (singleton, 12 United States clinical sites), free text medication data were obtained at enrollment and up to five follow-up visits and abstracted from medical records at delivery. RESULTS: In 436 women with obesity and 1750 women without obesity (pre-pregnancy BMI, 19–29.9 kg/m(2)), more than 70% of pregnant women (77% of women with and 73% of women without obesity) reported taking at least one medication during pregnancy, respectively (adjusted risk ratio (aRR)=1.10, 95% confidence interval (CI)=1.01, 1.20), with 81% reporting two and 69% reporting three or more. A total of 17 classes of medications were identified. Among medication classes consumed by at least 5% of all women, the only class that differed between women with and without obesity was hormones and synthetic substitutes (including steroids, progesterone, diabetes, and thyroid medications) in which women with obesity took more medications (11 vs. 5%, aRR = 1.9, 95% CI = 1.38, 2.61) compared to women without obesity. Within this class, a higher percentage of women with obesity took diabetes medications (2.3 vs. 0.7%) and progesterone (3.4 vs. 1.3%) than their non-obese counterparts. Similar percentages of women with and without obesity reported consuming medications in the remaining medication classes including central nervous system agents (50 and 46%), gastrointestinal drugs (43 and 40%), anti-infective agents (23 and 21%), antihistamines (20 and 17%), autonomic drugs (10 and 9%), and respiratory tract agents (7 and 6%), respectively (p > 0.05 for all adjusted comparisons). There were no differences in medication use by obesity status across gestation. Since the study exclusion criteria limited the non-obese group to women without thyroid disease, in a sensitivity analysis we excluded all women who reported thyroid medication intake and still a higher proportion of women with obesity took the hormones and synthetic substitutes class compared to women without obesity. CONCLUSION: Our findings suggest that pre-pregnancy obesity in otherwise healthy women is associated with a higher use of only selected medications (such as diabetes medications and progesterone) during pregnancy, while the intake of other more common medication types such as analgesics, antibiotics, and antacids does not vary by pre-pregnancy obesity status. As medication safety information for prenatal consumption is insufficient for many medications, these findings highlight the need for a more in-depth examination of factors associated with prenatal medication use.

Objective Prior data suggest that there are racial and ethnic disparities in postpartum readmission among individuals, especially among those with hypertensive disorders of pregnancy. Existing reports commonly lack granular information on social determinants of health. The objective of this study was to investigate factors associated with postpartum readmission for individuals and address whether such risk factors differed by whether an individual had an antecedent diagnosis of a hypertensive disorder of pregnancy (HDP). Study Design This is a secondary analysis of a large, multicenter prospective cohort study of 10,038 nulliparous participants. The primary outcome of this analysis was postpartum readmission. A priori, participants were analyzed separately based on whether they had HDP. Participant characteristics previously associated with a greater risk of perinatal morbidity or readmission (including social determinants of health, preexisting and chronic comorbidities, and intrapartum characteristics) were compared with bivariable analyses and retained in multivariable models if p Results Of 9,457 participants eligible for inclusion, 1.7% (n = 165) were readmitted following initial hospital discharge. A higher proportion of individuals with HDP were readmitted compared with individuals without HDP (3.4 vs 1.3%, p Conclusion In this diverse cohort of nulliparous pregnant individuals, there was a higher frequency of postpartum readmission among participants with HDP. Preexisting comorbidity and intrapartum complications were associated with postpartum readmission among this population engaged in a longitudinal study. Key Points

OBJECTIVE This study aimed to describe the overall quantity and type of supplements and medications used during pregnancy in a low-risk cohort and to examine any racial/ethnic differences in intake. STUDY DESIGN We used data from 2,164 racially/ethnically diverse, nonobese, and low-risk pregnant women participating without pre-pregnancy chronic conditions in a prospective cohort study at 12 sites across the United States. Medication data were self-reported as free text in enrollment, follow-up visit questionnaires, and abstracted from medical records at delivery. Supplements and medications data were mapped to their active ingredients and categorized into corresponding classes using the Slone Drug Dictionary. The total number and classes of supplements and medications consumed during pregnancy were calculated. Modified Poisson regression models were used to estimate the racial/ethnic differences in supplements and medications intake. All models were adjusted for maternal sociodemographic factors and study site. RESULTS 98% of women took at least one supplement during pregnancy, with prenatal vitamins/multivitamins being most common. While only 31% reported taking no medications during pregnancy, 23% took one, 18% took two, and 28% took three or more. The percentage of women taking at least one medication during pregnancy was highest among non-Hispanic white women and lowest among Asians (84 vs. 55%, p

This study aimed to determine whether specific factors of the built environment related to physical activity and diet are associated with inadequate and excessive gestational weight gain (GWG). This analysis is based on data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be, a prospective cohort of nulliparous women who were followed from the beginning of their pregnancies through delivery. At each study visit, home addresses were recorded and geocoded. Locations were linked to several built-environment characteristics such as the census tract National Walkability Score (the 2010 Walkability Index) and the number of gyms, parks, and grocery stores within a 3-km radius of residential address. The primary outcome of GWG (calculated as the difference between prepregnancy weight and weight at delivery) was categorized as inadequate, appropriate, or excessive based on weight gained per week of gestation. Multinomial regression (generalized logit) models evaluated the relationship between each factor in the built environment and excessive or inadequate GWG. Of the 8,182 women in the analytic sample, 5,819 (71.1%) had excessive GWG, 1,426 (17.4%) had appropriate GWG, and 937 (11.5%) had inadequate GWG. For the majority of variables examined, built environments more conducive to physical activity and healthful food availability were associated with a lower odds of excessive or inadequate GWG category. For example, a higher number of gyms or parks within 3 km of a participant's residential address was associated with lower odds of having excessive (gyms: adjusted odds ratio [aOR] = 0.93 [0.89-0.96], parks: 0.94 [0.90-0.98]) or inadequate GWG (gyms: 0.91 [0.86-0.96]; parks: 0.91 [0.86-0.97]). Similarly, a higher number of grocery stores was associated with lower odds of having excessive GWG (0.94 [0.91-0.97]). Among a diverse population of nulliparous women, multiple aspects of the built environment are associated with excessive and inadequate GWG.· There are little data on the association between the built environment and pregnancy outcomes.. · Multiple aspects of the built environment are associated with excessive and inadequate GWG.. · These results suggest the role that neighborhood investment may play in improving pregnancy outcomes..

The objective of the study was to determine whether adding longitudinal measures of fundal height (FH) to the standard cross-sectional FH to trigger third trimester ultrasound estimated fetal weight (EFW) would improve small for gestational age (SGA) prediction. We developed a longitudinal FH calculator in a secondary analysis of a prospective cohort study of 1,939 nonobese pregnant women who underwent serial FH evaluations at 12 U.S. clinical sites. We evaluated cross-sectional FH measurement ≤ -3 cm at visit 3 (mean: 32.0 ± 1.6 weeks) versus the addition of longitudinal FH up to and including visit 3 to trigger an ultrasound to diagnose SGA defined as birth weight10th percentile. If the FH cut points were not met, the SGA screen was classified as negative. If FH cut points were met and EFW was10th percentile, the SGA screen was considered positive. If EFW was ≥10th percentile, the SGA screen was also considered negative. Sensitivity, specificity, and positive predictive value (PPV) and negative predictive value (NPV) were computed. In a comparison of methods, 5.8% of women were classified as at risk of SGA by both cross-sectional and longitudinal classification methods; cross-sectional FH identified an additional 4.0%, and longitudinal fundal height identified a separate, additional 4.5%.Using cross-sectional FH as an ultrasound trigger, EFW had a PPV and NPV for SGA of 69 and 92%, respectively. After adding longitudinal FH, PPV increased to 74%, whereas NPV of 92% remained unchanged; however, the number of women who underwent triggered EFW decreased from 9.7 to 5.7%. An innovative approach for calculating longitudinal FH to the standard cross-sectional FH improved identification of SGA birth weight, while simultaneously reducing the number of triggered ultrasounds. As an essentially free-of-charge screening test, our novel method has potential to decrease costs as well as perinatal morbidity and mortality (through better prediction of SGA).· We have developed an innovative calculator for fundal height trajectory.. · Longitudinal fundal height improves detection of SGA.. · As a low cost screening test, the fundal height calculator may decrease costs and morbidity through better prediction of SGA..

Gestational weight gain (GWG) and anthropometric trajectories may affect foetal programming and are potentially modifiable.To assess concomitant patterns of change in weight, circumferences and adiposity across gestation as an integrated prenatal exposure, and determine how they relate to neonatal body composition.Data are from a prospective cohort of singleton pregnancies (n = 2182) enrolled in United States perinatal centres, 2009-2013. Overall and by prepregnancy BMI group (overweight/obesity and healthy weight), joint latent trajectory models were fit with prenatal weight, mid-upper arm circumference (MUAC), triceps (TSF) and subscapular (SSF) skinfolds. Differences in neonatal body composition by trajectory class were assessed via weighted least squares.Six trajectory patterns reflecting co-occurring changes in weight and MUAC, SSF and TSF across pregnancy were identified overall and by body mass index (BMI) group. Among people with a healthy weight BMI, some differences were observed for neonatal subcutaneous adipose tissue, and among individuals with overweight/obesity some differences in neonatal lean mass were found. Neonatal adiposity measures were higher among infants born to individuals with prepregnancy overweight/obesity.Six integrated trajectory patterns of prenatal weight, subcutaneous adipose tissue and circumferences were observed that were minimally associated with neonatal body composition, suggesting a stronger influence of prepregnancy BMI.

OBJECTIVE The aim of this study was to compare duration of labor induction between diabetic and nondiabetic women receiving dinoprostone vaginal insert (10 mg). STUDY DESIGN This is a secondary analysis of two large randomized controlled trials using dinoprostone vaginal inserts for labor induction. We compare time to active labor, overall delivery, and vaginal delivery between diabetic and nondiabetic women undergoing induction of labor with a 10-mg dinoprostone vaginal insert. RESULTS Diabetic women receiving dinoprostone vaginal insert had a longer time to onset of active labor, overall delivery, and vaginal delivery than their nondiabetic counterparts. There was no difference in abnormal labor affecting fetal heart rate pattern in diabetic women compared with nondiabetic women. The rates of neonatal hyperbilirubinemia were higher in diabetic women. CONCLUSION Diabetes may represent an independent factor associated with prolonged induction among women undergoing induction of labor with dinoprostone. Dinoprostone is well tolerated in both diabetic and nondiabetic women. KEY POINTS · Diabetic women receiving DVI have slower labor curves than nondiabetic women.. · Nulliparous diabetic women took longer to achieve active labor, overall delivery, and vaginal delivery than nondiabetic women.. · Parous diabetic women took longer to achieve vaginal delivery than nondiabetic women..

Background Evidence documenting whether diet quality, particularly dietary fatty acids, is associated with preterm birth (PTB) is limited. Objective The aim was to measure associations between dietary fatty acid intake prior to pregnancy, specifically n–3 (ɷ-3) PUFAs and odds of PTB in US women and determine if associations differed by prepregnancy BMI. Methods We designed a secondary analysis of dietary intake in nulliparous women enrolled in a longitudinal cohort (NCT01322529). Participants completed an FFQ, modified to assess detailed PUFA intake, during the 3 mo preceding pregnancy. Inclusion in this analytic cohort required total energy intake within 2 SDs of the group mean. Prepregnancy BMI was categorized as underweight, normal, overweight, or obese. The primary exposure was estimated intake of EPA and DHA (combined EPA+DHA), in the context of a recommended intake of 250 mg. The primary outcome was PTB (, Self-reported intake of EPA + DHA in nulliparous US women is much lower than recommended. In that context, n–3 fatty acid intake was associated with preterm birth risk.

The Dietary Guidelines for Americans rely on summaries of the effect of dietary pattern on disease risk, independent of other population characteristics. We explored the modifying effect of prepregnancy body mass index (BMI; weight (kg)/height (m)2) on the relationship between fruit and vegetable density (cup-equivalents/1,000 kcal) and preeclampsia using data from a pregnancy cohort study conducted at 8 US medical centers (n = 9,412; 2010–2013). Usual daily periconceptional intake of total fruits and total vegetables was estimated from a food frequency questionnaire. We quantified the effects of diets with a high density of fruits (≥1.2 cups/1,000 kcal/day vs.

Bariatric surgery is a widely used treatment option for obesity that often provides long-term weight control and health benefits. Although a growing number of women are becoming pregnant after bariatric surgery, only a few population-based studies have assessed the impact thereof on perinatal outcomes.This study aimed to examine the association between bariatric surgery and adverse perinatal outcomes in pregnant women and to examine whether the risk for adverse perinatal outcomes is modified by the postsurgery weight, gestational weight gain, type of bariatric surgery, timing of pregnancy after bariatric surgery, and maternal comorbidities.A retrospective cohort study was performed with the use of the Bariatric Surgery Registry and hospital inpatient and outpatient physician encounter records. The International Classification of Diseases, Ninth and Tenth Revision codes from hospitalizations during pregnancy and infant birth records were used to ascertain the outcomes of interest. Women eligible for BS who delivered at ≥20 weeks of gestation (n=20,213) at Kaiser Permanente Southern California hospitals (January 1, 2007 to December 31, 2018) were included in the study. Adjusted odds ratios were derived from logistic regression models with inverse probability of treatment weighting to adjust for confounding using propensity scores.Bariatric surgery was associated with a reduction in the risks for gestational diabetes (adjusted odds ratio, 0.60; 95% confidence interval, 0.53-0.69; P.001), preeclampsia (adjusted odds ratio, 0.53; 95% confidence interval, 0.46-0.61; P.001), chorioamnionitis (adjusted odds ratio, 0.45; 95% confidence interval, 0.32-0.63; P.001), cesarean delivery (adjusted odds ratio, 0.65; 95% confidence interval, 0.59-0.72; P.001), large for gestational age neonate (adjusted odds ratio, 0.23; 95% confidence interval, 0.19-0.29; P.001), macrosomia (adjusted odds ratio, 0.24; 95% confidence interval, 0.19-0.30; P.001), and neonatal intensive care unit admission (adjusted odds ratio, 0.70; 95% confidence interval, 0.61-0.81; P.001). However, bariatric surgery was also associated with a significantly increased risk for small for gestational age neonates (adjusted odds ratio, 2.46; 95% confidence interval, 2.16-2.79; P.001). The risk for the adverse outcomes is independent of the time interval between the surgery and subsequent pregnancy.These data suggest that there are many pregnancy outcome benefits for women with severe obesity who undergo bariatric surgery; however, women who have undergone bariatric surgery before pregnancy should be monitored closely to reduce the risk for small for gestational age neonates and postpartum hemorrhage.

Background Accumulating evidence indicates that maternal diets are important for optimizing maternal and offspring health. Existing research lacks comprehensive profiles of maternal diets throughout pregnancy, especially in a racially/ethnically diverse obstetrical population. Objective The aim was to characterize diets in a longitudinal US pregnancy cohort by trimester, race/ethnicity, and prepregnancy BMI. Methods Data were obtained from pregnant women in the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Studies-Singleton cohort (2009-2013). A food-frequency questionnaire (FFQ) at 8-13 wk of gestation assessed periconception and first-trimester diet (n = 1615). Automated, self-administered, 24-h dietary recalls targeted at 16-22, 24-29, 30-33, and 34-37 wk of gestation assessed second- and third-trimester diets (n = 1817 women/6791 recalls). The Healthy Eating Index-2010 (HEI-2010) assessed diet quality (i.e., adherence to US Dietary Guidelines). Variations in weighted energy-adjusted means for foods and nutrients were examined by trimester, self-identified race/ethnicity, and self-reported prepregnancy BMI. Results Mean (95% CI) HEI-2010 was 65.9 (64.9, 67.0) during periconception to the first trimester assessed with an FFQ and 51.6 (50.8, 52.4) and 51.5 (50.7, 52.3) during the second trimester and third trimester, respectively, assessed using 24-h recalls. No significant differences were observed between the second and third trimester in macronutrients, micronutrients, foods, or HEI-2010 components (P ≥ 0.05). Periconception to first-trimester HEI-2010 was highest among Asian/Pacific Islander [67.2 (65.9, 68.6)] and lowest among non-Hispanic Black [58.7 (57.5, 60.0)] women and highest among women with normal weight [67.2 (66.1, 68.4)] and lowest among women with obesity [63.5 (62.1, 64.9)]. Similar rankings were observed in the second/third trimesters. Conclusions Most pregnant women in this cohort reported dietary intakes that, on average, did not meet US Dietary Guidelines for nonpregnant individuals. Also, diet differed across race/ethnic groups and by prepregnancy BMI, with the lowest overall dietary quality in all trimesters among non-Hispanic Black women and women with obesity. No meaningful changes in dietary intake were observed between the second and third trimesters.

Background Adherence to alternate Healthy Eating Index (AHEI), alternate Mediterranean diet (AMED), and Dietary Approaches to Stop Hypertension (DASH) has been linked to lower risks of chronic diseases. However, their associations with common pregnancy complications are unclear. Objectives This study investigates the associations of AHEI, AMED, and DASH during periconception and pregnancy with common pregnancy complication risks. Methods The study included 1887 pregnant women from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons. Women responded to an FFQ at 8-13 gestational weeks, and they performed a 24-h dietary recall at 16-22 and 24-29 wk. Gestational diabetes (GDM), gestational hypertension, preeclampsia, and preterm delivery were ascertained using medical records. Results Healthier diet indicated by higher AHEI, AMED, and DASH scores was generally related to lower risks of pregnancy complications. Significant inverse associations were observed between AHEI score reported at 16-22 wk and GDM risk [adjusted RR (95% CI), highest (Q4) vs. lowest quartile (Q1): 0.32 (0.16, 0.66), P-trend = 0.002]; DASH score reported at both 8-13 [adjusted RR (95% CI), Q4 vs. Q1: 0.45 (0.17, 1.17), P-trend = 0.04] and 16-22 wk [adjusted RR (95% CI), Q4 vs. Q1: 0.19 (0.05, 0.65), P-trend = 0.01] and gestational hypertension risk; AHEI score reported at 24-29 wk and preeclampsia risk [adjusted RR (95% CI), Q4 vs. Q1: 0.31 (0.11, 0.87), P-trend = 0.03]; AMED score reported at 8-13 wk [adjusted RR (95% CI), Q4 vs. Q1: 0.50 (0.25, 1.01), P-trend = 0.03] and DASH score reported at 24-29 wk [adjusted RR (95% CI), Q4 vs. Q1: 0.50, (0.26, 0.96), P-trend = 0.03] and preterm delivery risk. Conclusions Adherence to AHEI, AMED, or DASH during periconception and pregnancy was related to lower risks of GDM, gestational hypertension, preeclampsia, and preterm delivery.This study was registered at ClinicalTrials.gov as NCT00912132.

Background: Several features of the neighborhood built environment have been shown to promote leisure-time physical activity (PA) in the general population, but few studies have examined its impact on PA during pregnancy. Methods: Data were extracted from 8362 Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort participants (2010–2013). Residential address information was linked to 3 built environment characteristics: number of gyms and recreation areas within a 3-km radius of residence and census block level walkability. Self-reported leisure-time PA was measured in each trimester and dichotomized as meeting PA guidelines or not. Relative risks for cross-sectional associations between neighborhood characteristics and meeting PA guidelines were estimated using Poisson regression. Results: More gyms and recreation areas were each associated with a greater chance of meeting PA guidelines in models adjusted for sociodemographic characteristics and preexisting conditions. Associations were strongest in the third trimester where each doubling in counts of gyms and recreation areas was associated with 10% (95% confidence interval, 1.07–1.13) and 8% (95% confidence interval, 1.03–1.12), respectively, greater likelihood of meeting PA guidelines. Associations were similar though weaker for walkability. Conclusions: Results from a large, multisite cohort suggest that these built environment characteristics have similar PA-promoting benefits in pregnant women as seen in more general populations.

Background Cesarean delivery reduces the risk of infant and maternal morbidity and mortality when medically indicated, however, the cesarean delivery rate is estimated to be two to three times higher than medically necessary. The World Health Organization and American College of Obstetricians and Gynecologists have expressed concern over the high rates of cesarean delivery, citing evidence that cesarean delivery has negative short- and long-term consequences for the health of the infant, mother, and for future pregnancies. Infants delivered by cesarean are at an increased risk of metabolic disease and immune dysfunction throughout the lifespan. Preliminary research suggests that the hypothalamic pituitary adrenal (HPA) axis is a plausible pathway linking cesarean delivery to poor health later in life. The present study examines the relation between mode of delivery and HPA axis function in six-month-old infants. We also examine whether the cesarean delivery was elective or indicated altered to the relation between mode of delivery and infant cortisol profiles. Methods The sample included 136 mother/infant pairs. Thirty-nine women delivered by cesarean and 97 delivered vaginally. Maternal and infant medical records were reviewed for prenatal medical history and birth outcomes. Infant saliva was collected for cortisol analysis at a 6-month well-baby checkup. Samples were collected upon arrival to the appointment (baseline) and 20 min after exposure to a painful stressor, the inoculation procedure (response). A mixed model ANCOVA was conducted to determine whether salivary cortisol concentrations differed between the two delivery groups. To examine whether complications related to having an indicated cesarean delivery contributed to any association between mode of delivery and cortisol production, cortisol concentrations were compared between the subgroup of infants whose cesarean deliveries were elective (e.g. maternal request or previous cesarean delivery) to infants delivered vaginally. Results Infants delivered by cesarean had lower cortisol concentrations at baseline and after the inoculation procedure compared to those delivered vaginally. Further, the relation between mode of delivery and cortisol levels persisted even when the analyses were restricted to compare only the elective cesarean deliveries (e.g. maternal request or previous cesarean delivery) to those delivered vaginally. Discussion This study provides evidence for an association between cesarean delivery and infant HPA axis function in infancy. Findings are consistent with the hypothesis that the HPA axis is a plausible pathway that links cesarean delivery with long-term health outcomes.

Background Nearly half of all women exceed the 2009 Institute of Medicine guidelines for gestational weight gain. Excess gestational weight gain is associated with adverse pregnancy outcomes. Objective Our objective was to determine whether having a personal gestational weight gain goal consistent with the Institute of Medicine’s recommendations for appropriate gestational weight gain and whether having a discussion with one’s obstetrical provider regarding that goal were associated with appropriate gestational weight gain. Study Design This is a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study, a prospective cohort study of nulliparous women. We asked women at their first study visit (between 6 and 13 weeks’ gestation) whether they had a gestational weight gain goal and what that goal was. Furthermore, we asked whether their provider discussed a gestational weight gain goal and what that goal was. We classified personal and provider-recommended gestational weight gain goals as consistent or inconsistent with the Institute of Medicine guidelines, taking into account a woman’s initial body mass index category (underweight, normal weight, overweight, and obese). We included women with live singleton term deliveries (between 37 and 43 weeks’ gestation) in this analysis. We classified the primary outcome, which was gestational weight gain (defined as the difference between first visit weight and final weight before delivery), as inadequate, appropriate, or excessive, based on the Institute of Medicine guidelines and initial body mass index category. We used Student t, Wilcoxon rank-sum, and chi-square tests for bivariable analyses, and multinomial logistic regression was performed to control for confounding variables. Results Of 6727 eligible women, 3799 (56.5% of all eligible women) stated they had a gestational weight gain goal. Of the 3799 women with a stated goal, 2589 (38.5% of all women) had a goal consistent with the Institute of Medicine’s recommendations. In addition, of the 6727 eligible women, 2188 (32.5%) reported that they discussed gestational weight gain with their provider, and 1548 of these (23.0% of all women) recalled that their provider gave a gestational weight gain goal in accordance with the Institute of Medicine guidelines. Although having any gestational weight gain goal was not associated with appropriate gestational weight gain, having a gestational weight gain goal that was consistent with the Institute of Medicine’s recommendations was associated with a reduced risk of excessive (adjusted relative risk ratio, 0.77; 95% confidence interval, 0.64–0.92) and inadequate weight gain (adjusted relative risk ratio, 0.66; 95% confidence interval, 0.53–0.82). Conversely, discussing gestational weight gain goals with a provider was not associated with either inadequate or excessive gestational weight gain even if the provider’s recommendations for gestational weight gain were consistent with the guidelines. Conclusion Nulliparas who delivered singleton pregnancies at term who had a personal gestational weight gain goal consistent with the Institute of Medicine’s recommendations were less likely to have excessive or inadequate gestational weight gain. Further study is required to evaluate the most effective way to communicate this information to patients.

Summary Background The timepoint at which fetal growth begins to differ by maternal glycaemic status is not well understood. To address this lack of data, we examined gestational diabetes, impaired glucose tolerance, and early pregnancy glucose concentrations in relation to fetal growth trajectories. Methods This cohort study included 2458 pregnant women from the NICHD Fetal Growth Studies-Singletons study, which took place between 2009 and 2013. Women were recruited from 12 clinical centres in the USA. Women aged 18–40 years without major chronic conditions when entering pregnancy were included and those with records of neither glucose screening test or glucose tolerance test were excluded from the study. Women were enrolled at gestational weeks 8–13 and randomly assigned to four ultrasonogram schedules (Group A; weeks 16, 24, 30, 34; Group B: weeks 18, 26, 31, 35, 39; Group C: weeks 20, 28, 32, 36; Group D: weeks 22, 29, 33, 37, 41) to capture weekly fetal growth. Gestational diabetes, impaired glucose tolerance, and normal glucose tolerance were defined by medical record review. Glucose was measured in a subsample of women at weeks 10–14. We modelled fetal growth trajectories using linear mixed models with cubic splines. This study is registered with ClinicalTrials.gov , NCT00912132 . Findings Of the 2458 women included in this study, 107 (4·4%) had gestational diabetes, 118 (4·8%) had impaired glucose tolerance, and 2020 (82·2%) had NGT. 213 women were excluded from the main analysis. The cohort with gestational diabetes was associated with a larger estimated fetal weight that started at week 20 and was significant at week 28–40 (at week 37: 3061 g [95% CI 2967–3164] for women with gestational diabetes vs 2943 g [2924–2962] for women with normal glucose tolerance, adjusted p=0·02). In addition, glucose levels at weeks 10–14 were positively associated with estimated fetal weight starting at week 23 and the association became significant at week 27 (at week 37: 3073 g [2983–3167] in the highest tertile vs 2853 g [2755–2955] in the lowest tertile, adjusted p=0·0009. Interpretation Gestational diabetes was associated with a larger fetal size that started at week 20 and became significant at gestational week 28. Efforts to mitigate gestational diabetes-related fetal overgrowth should start before 24–28 gestational weeks, when gestational diabetes is typically screened for in the USA. Funding National Institutes of Health.

CONTEXT: Antenatal corticosteroids are commonly administered to pregnant women at risk for delivering between 23 and 34 gestational weeks; they provide crucial benefits to fetal lung maturation and reduce risk for neonatal morbidity and mortality. Corticosteroids are maximally efficacious for lung maturation when administered within 2 to 7 days of delivery. Accurately identifying the timing of preterm delivery is thus critical to ensure that antenatal corticosteroids are administered within a week of delivery and to avoid unnecessary administration to women who will deliver at term. A plausible biomarker for predicting time of delivery is placental corticotropin-releasing hormone (pCRH). OBJECTIVE: To assess whether pCRH concentrations predict time to delivery and specifically which women will deliver within a week of treatment. DESIGN: pCRH concentrations were evaluated before administration of the corticosteroid betamethasone, and timing of delivery was recorded. PARTICIPANTS: A total of 121 women with singleton pregnancies who were prescribed betamethasone. RESULTS: Elevated pCRH concentrations were associated with a shorter time from treatment to delivery. Receiver-operating characteristic curves revealed that pCRH may improve the precision of predicting preterm delivery. CONCLUSIONS: In the current sample, pCRH concentrations predicted the likelihood of delivering within 1 week of corticosteroid treatment. Current findings suggest that pCRH may be a diagnostic indicator of impending preterm delivery. Increasing the precision in predicting time to delivery could inform when to administer antenatal corticosteroids, thus maximizing benefits and reducing the likelihood of exposing fetuses who will be delivered at term.

ObjectiveTo characterize prescription and other medication use in a geographically and ethnically diverse cohort of women in their first pregnancy.MethodsIn a prospective, longitudinal cohort study of nulliparous women followed through pregnancy from the first trimester, medication use was chronicled longitudinally throughout pregnancy. Structured questions and aids were used to capture all medications taken as well as reasons they were taken. Total counts of all medications taken including number in each category and class were captured. Additionally, reasons the medications were taken were recorded. Trends in medications taken across pregnancy and in the first trimester were determined.ResultsOf the 9,546 study participants, 9,272 (97.1%) women took at least one medication during pregnancy with 9,139 (95.7%) taking a medication in the first trimester. Polypharmacy, defined as taking at least five medications, occurred in 2,915 (30.5%) women. Excluding vitamins, supplements, and vaccines, 73.4% of women took a medication during pregnancy with 55.1% taking one in the first trimester. The categories of drugs taken in pregnancy and in the first trimester include the following: gastrointestinal or antiemetic agents (34.3%, 19.5%), antibiotics (25.5%, 12.6%), and analgesics (23.7%, 15.6%, which includes 3.6%; 1.4% taking an opioid pain medication).ConclusionIn this geographically and ethnically diverse cohort of nulliparous pregnant women, medication use was nearly universal and polypharmacy was common.Clinical trial registrationClinicalTrials.gov, NCT01322529.

To assess the relationships between self-reported psychosocial stress and preterm birth, hypertensive disease of pregnancy, and small-for-gestational-age (SGA) birth and to assess the extent to which these relationships account for racial and ethnic disparities in these adverse outcomes.Self-reported measures of psychosocial stress (perceived stress, depression, racism, anxiety, resilience, and social support) were collected during pregnancy among a racially and ethnically diverse cohort of women enrolled in a prospective observational study of nulliparous women with singleton pregnancies, from eight clinical sites across the United States, between October 2010 and May 2014. The associations of preterm birth, hypertensive disease of pregnancy, and SGA birth with the self-reported measures of psychosocial stress as well as with race and ethnicity were evaluated.The study included 9,470 women (60.4% non-Hispanic white, 13.8% non-Hispanic black, 16.7% Hispanic, 4.0% Asian, and 5.0% other). Non-Hispanic black women were significantly more likely to experience any preterm birth, hypertensive disease of pregnancy, and SGA birth than were non-Hispanic white women (12.2% vs 8.0%, 16.7% vs 13.4%, and 17.2% vs 8.6%, respectively; P.05 for all). After adjusting for potentially confounding factors, including the six different psychosocial factors singly and in combination, non-Hispanic black women continued to be at greater risk of any preterm birth and SGA birth compared with non-Hispanic white women.Among a large and geographically diverse cohort of nulliparous women with singleton gestations, non-Hispanic black women are most likely to experience preterm birth, hypertensive disease of pregnancy, and SGA birth. These disparities were not materially altered for preterm birth or SGA birth by adjustment for demographic differences and did not appear to be explained by differences in self-reported psychosocial factors.

Antenatal depression affects approximately 1 of 7 pregnancies, with an increasing prevalence across gestation. Data regarding the associations between antenatal depression and adverse pregnancy outcomes yielded conflicting results. However, previous studies evaluated the cross-sectional prevalence of depression at various time points and not the depressive symptom trajectory across gestation.This study aimed to identify whether the trajectory of antenatal depressive symptoms is associated with different risks of adverse pregnancy outcomes.This was a secondary analysis of a large multisite prospective cohort of nulliparous women across the United States. The Edinburgh Postpartum Depression Scale was administered at 2 study visits: between 6 and 14 weeks' gestation and between 22 and 30 weeks' gestation. The Edinburgh Postpartum Depression Scale score trajectories were categorized as improved, stable, or worsened based on whether the scores changed by at least 1 standard deviation between the 2 visits. The frequencies of adverse pregnancy outcomes (hypertensive disorders of pregnancy, abruption, cesarean delivery, preterm birth [ie,37 weeks' gestation], small for gestational age neonates, neonatal intensive care unit admission, and maternal readmission) were compared with depression trajectories across gestation in bivariable and multivariable analyses. Secondary analyses evaluated the frequencies of spontaneous and medically indicated preterm births and frequencies of spontaneous and medically indicated preterm births before 35, 32, and 28 weeks' gestation.Of the 8784 women who completed the 2 antenatal Edinburgh Postpartum Depression Scale screens, 1141 (13.0%) had improved, 6663 (75.9%) had stable, and 980 (11.2%) had worsened depressive symptom trajectories across gestation. Compared with women with improved or stable depressive symptoms, those with worsened symptoms were more likely to experience preterm birth (8.3% vs 7.4% vs 9.9%, respectively; P=.018). After controlling for potential confounders, worsened depressive symptoms remained associated with more frequent preterm birth (adjusted odds ratio, 1.68; 95% confidence interval, 1.10-2.57).Women with depression symptoms that worsen as pregnancy progresses have increased odds of preterm birth. Future research is warranted to optimize and implement effective prevention, screening, and treatment protocols for antenatal depressive symptoms as a strategy to prevent preterm birth.

Background Lifestyle changes are recommended for women diagnosed with gestational diabetes mellitus (GDM), yet there are few data available documenting whether women change their diet and exercise after GDM diagnosis. Objective The aim of this study was to assess whether, and to what extent, pregnant women receiving usual prenatal care change their diet and exercise after a GDM diagnosis. Design This study was a post-hoc secondary analysis using data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies–Singletons (2009-2013), a prospective pregnancy cohort study. Participants/setting Pregnant US women without major chronic medical conditions were enrolled from 12 participating hospital centers at 8 to 13 weeks’ gestation. Diet analyses were based on 5,194 dietary recalls from 1,371 women. Exercise analyses were based on 6,440 physical activity assessments from 1,875 women. GDM was ascertained from medical records according to Carpenter and Coustan criteria. Women completed 24-hour dietary recalls and exercise assessments at weeks 16 to 22, 24 to 29, 30 to 33, 34 to 37, and 38 to 41 (exercise only). Main outcome measures The main outcome was the diet and exercise change from before to after GDM diagnosis or screening. Statistical analyses Diet and exercise changes with 95% CIs from before to after GDM diagnosis or screening for women with and without GDM were estimated using weighted multivariable linear mixed models. Results Women with GDM (n = 72) significantly reduced their total energy intake (–184 kcal/d; 95% CI –358 to –10 kcal/d) and carbohydrate intake (–47.6 g/d; 95% CI –71.4 to –23.7 g/d) from before to after GDM diagnosis; these changes were unique to women with GDM and not observed among women without GDM (n = 1,299). Women with GDM decreased intakes of juice (–0.4 cups/d; 95% CI –0.7 to –0.2 cups/d) and added sugar (–3.2 teaspoons/d; 95% CI –5.5 to –0.5 teaspoons/d) and increased cheese (0.3 cups/d; 95% CI 0.1 to 0.6 cups/d) and artificially sweetened beverages (0.2 cups/d; 95% CI 0.0 to 0.3 cups/d). Women with GDM (n = 84) did not change their exercise duration after diagnosis; women without GDM (n = 1,791) significantly decreased moderate (–19.5 min/wk; 95% CI –24.7 to –14.3 min/wk) and vigorous exercise (–8.8 min/wk; 05% CI –10.6 to –6.9 min/wk) after GDM screening. Conclusions Women with GDM made modest dietary improvements and maintained their prediagnosis exercise routine, yet opportunities remain to further improve dietary intake and exercise after a diagnosis of GDM.

To evaluate the association between hypertensive (HTNsive) disorders of pregnancy and outcomes of labor induction, in two cohorts of women induced with either misoprostol vaginal insert (MVI) or dinoprostone vaginal insert (DVI).This investigation was a post-hoc analysis of data from three Phase II and III, multi-center, double blind, randomized controlled trials of women induced with identical efficacy endpoints. A competing risk framework investigated the association between HTNsive disorders of pregnancy and the time-to-event endpoints of onset of active labor and vaginal delivery. We analyzed the overall incidence of the competing risk, cesarean delivery, by logistic regression to identify potential differences between the proportion of patients with cesarean and vaginal deliveries for each cohort.401 women with HTNsive disorders during pregnancy underwent induction of labor in these studies (175 with DVI and 226 with MVI). Significant differences were noted in the cumulative incidence of vaginal delivery 24 hours following insertion between the non-HTNsive and HTNsive groups for both treatments, (57.1% vs. 47.4% (p=0.023) among MVI patients and 39.9% vs. 27.2% (p=0.017) among DVI patients). However, upon adjusting for potential confounders, the estimated relative rates of vaginal delivery among HTNsive vs. non-HTNsive patients was 0.947 (95% CI (0.637, 1.371), p=0.631) and 0.904 (95% CI (0.735, 1.113) p=0.341) within the MVI and DVI sub-groups respectively.After adjustment for confounders, such as BMI, baseline modified Bishop score and gestational age, time-to-event outcomes for induction of labor using MVI or DVI in HTNsive women are not significantly different from non-HTNsive women.

Key Points Question Is maternal health literacy associated with maternal and neonatal health outcomes? Findings In this cohort study of 10 038 nulliparous individuals, those with inadequate health literacy had greater odds of cesarean delivery, major perineal lacerations, and neonates with small for gestational age status, low birth weight, and low 5-minute Apgar score, although absolute differences were generally small. Meaning These findings suggest that inadequate health literacy is common among pregnant individuals in the US and is associated with a variety of adverse maternal and neonatal outcomes., This cohort study examines the association between maternal health literacy and maternal and neonatal outcomes among nulliparous individuals in the US., Importance Health literacy is considered an important social determinant of health that may underlie many health disparities, but it is unclear whether inadequate health literacy among pregnant individuals is associated with adverse maternal and neonatal outcomes. Objective To assess the association between maternal health literacy and maternal and neonatal outcomes among nulliparous individuals. Design, Setting, and Participants This was a secondary analysis of a large, multicenter cohort study of 10 038 nulliparous individuals in the US (2010-2013). Participants underwent 3 antenatal study visits and had detailed maternal and neonatal data abstracted. Data analysis was performed from July to December 2019. Exposures Between 16 and 21 weeks of gestation, health literacy was assessed using the Rapid Estimate of Adult Literacy in Medicine–Short Form, a validated 7-item word recognition test. In accordance with standard scoring, results were dichotomized as inadequate vs adequate health literacy. Main Outcomes and Measures On the basis of theoretical causal pathways between health literacy and health outcomes, a priori maternal and neonatal outcomes (determined via medical records) were selected for this analysis. Multivariable Poisson regression models were constructed to estimate the associations between health literacy and outcomes. Sensitivity analyses in which education was removed from models and that excluded individuals who spoke English as a second language were performed. Results Of 9341 participants who completed the Rapid Estimate of Adult Literacy in Medicine–Short Form, the mean (SD) age was 27.0 (5.6) years, and 2540 (27.4%) had publicly funded prenatal care. Overall, 1638 participants (17.5%) had scores indicative of inadequate health literacy. Participants with inadequate health literacy were more likely to be younger (mean [SD] age, 22.9 [5.0] vs 27.9 [5.3] years), have less educational attainment (some college education or greater, 1149 participants [73.9%] vs 5279 participants [94.5%]), have publicly funded insurance (1008 participants [62.2%] vs 1532 participants [20.0%]), and report they were a member of an underrepresented racial or ethnic group (non-Hispanic Black, 506 participants [30.9%] vs 780 participants [10.1%]; Hispanic, 516 participants [31.5%] vs 948 participants [12.3%]) compared with those with adequate health literacy. Participants who had inadequate health literacy had greater risk of cesarean delivery (adjusted risk ratio [aRR], 1.11; 95% CI, 1.01-1.23) and major perineal laceration (aRR, 1.44; 95% CI, 1.03-2.01). The adjusted risks of small-for-gestational-age status (aRR, 1.34; 95% CI, 1.14-1.58), low birth weight (aRR, 1.33; 95% CI, 1.07-1.65), and 5-minute Apgar score less than 4 (aRR, 2.78; 95% CI, 1.16-6.65) were greater for neonates born to participants with inadequate health literacy. Sensitivity analyses confirmed these findings. Conclusions and Relevance These findings suggest that inadequate maternal health literacy is associated with a variety of adverse maternal and neonatal outcomes.

Induction of labor is a common procedure undertaken whenever the benefits of prompt delivery outweigh the risks of expectant management. Cervical assessment is essential to determine the optimal approach. Indication for induction, clinical presentation and history, safety, cost, and patient preference may factor into the selection of methods. For the unfavorable cervix, several pharmacologic and mechanical methods are available, each with associated advantages and disadvantages. In women with a favorable cervix, combined use of amniotomy and intravenous oxytocin is generally the most effective approach. The goal of labor induction is to ensure the best possible outcome for mother and newborn.

Objectives To evaluate the frequency with which gestational weight gain and estimated fetal weight do not track across gestation and to assess the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) birth weight as a function of tracking. Methods This study included a pregnancy cohort (2009–2013) of 2438 women from 4 racial/ethnic groups in the United States. We calculated race- and trimester-specific gestational weight gain and estimated fetal weight z scores. The prevalence of how often gestational weight gain and estimated fetal weight did not or did directly track was examined by grouping z scores into measure-specific categories ( 1 SD) and then examining 2-measure combinations. Trimester-specific relative risks for SGA and LGA births were estimated with a gestational weight gain and estimated fetal weight z score interaction. We estimated coefficients for selected gestational weight gain and estimated fetal weight values (–1 SD, 0 SD, and +1 SD) compared with the referent of 0 SD for both measures. Small and large for gestational age were calculated as birth weight below the 10th and at or above the 90th percentiles, respectively. Results Gestational weight gain and estimated fetal weight were within 1 SD 55.5%, 51.5%, and 48.2% of the time in the first, second, and third trimesters, respectively. There was no significant interaction between gestational weight gain and estimated fetal weight on the risk of SGA in the first and second trimesters (interaction term P = .48; P = .79). In the third trimester, there was a significant interaction (P = .002), resulting in a 71% (95% confidence interval, 1.45–2.02) increased risk of SGA when estimated fetal weight was low and gestational weight gain was high. These relationships were similar for the risk of LGA. Conclusions Deviations in either measure, even in the presence of average gestational weight gain or estimated fetal weight, still suggest an increased risk of SGA and LGA.

Objectives To determine whether longitudinal fetal growth is altered among pregnant women reporting greater perceived stress or more symptoms of depression. Methods This analysis was based on a multicenter longitudinal study of fetal growth. Women were screened at gestational ages of 8 weeks to 13 weeks 6 days for low-risk status and underwent serial sonographic examinations. At each study visit during pregnancy, women were asked to complete the Cohen Perceived Stress Scale (PSS) and Edinburgh Postpartum Depression Survey (EPDS). Growth curves for estimated fetal weight and individual biometric parameters were created by using linear mixed models with cubic splines and compared on the basis of whether women scored 15 or higher on the PSS or 10 or higher on the EPDS either at the start of or at any time during pregnancy. Results Of the 2334 women enrolled in the study, 2088 (89%) and 2108 (90%) completed the PSS and EPDS, respectively, at least once in all trimesters. The longitudinal growth curves of estimated fetal weight as well as all individual biometric parameters were similar (P > .05) regardless of whether the participants reported PSS of 15 or higher or EPDS of 10 or higher in the first trimester or whether these scores persisted throughout the pregnancy. Similarly, effect modification by race/ethnicity was not statistically significant for the biometric parameters under study (P > .05 for all race/ethnicity interactions). Conclusions More depressive symptoms and greater perceived stress, as quantified by the EPDS and the PSS, respectively, are not associated with alterations in fetal growth throughout gestation.

Objective To evaluate the relationship between acculturation and adverse pregnancy outcomes, and whether these relationships differ across racial or ethnic groups. Methods This is a planned secondary analysis of the nuMoM2b study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be), a prospective observational cohort study of 10,038 pregnant women at eight academic health care centers in the United States. Nulliparous pregnant women with singleton gestations were recruited between 6 0/7 and 13 6/7 weeks of gestation from October 2010-September 2013. Acculturation was defined by birthplace (United States vs non-United States), language used during study visits (English or Spanish), and self-rated English proficiency. The adverse pregnancy outcomes of interest were preterm birth (less than 37 weeks of gestation, both iatrogenic and spontaneous), preeclampsia or eclampsia, gestational hypertension, gestational diabetes, stillbirth, small for gestational age, and large for gestational age. Multivariable regression modeling was performed, as was an interaction analysis focusing on the relationship between acculturation and adverse pregnancy outcomes by maternal race or ethnicity. Results Of the 10,006 women eligible for this analysis, 8,100 (80.9%) were classified as more acculturated (eg, born in the United States with high English proficiency), and 1,906 (19.1%) were classified as having less acculturation (eg, born or not born in the United States with low proficiency in English or use of Spanish as the preferred language during study visits). In multivariable logistic regression modeling, more acculturation was significantly associated with higher frequency of preterm birth (odds ratio [OR] 1.46, adjusted odds ratio [aOR] 1.50, 95% CI 1.16-1.95); spontaneous preterm birth (OR 1.54, aOR 1.62, 95% CI 1.14-2.24); preeclampsia or eclampsia (OR 1.39, aOR 1.31, 95% CI 1.03-1.67); preeclampsia without severe features (OR 1.44, aOR 1.43, 95% CI 1.03-2.01); and gestational hypertension (OR 1.68, aOR 1.48, 95% CI 1.22-1.79). These associations did not differ by self-described race or ethnicity. Conclusion In a large cohort of nulliparous women, more acculturation, regardless of self-described race or ethnicity, was associated with increased odds of several adverse pregnancy outcomes. Clinical trial registration ClinicalTrials.gov, NCT01322529.

BACKGROUND: Preterm birth remains the leading cause of neonatal morbidity and mortality, with complex biochemical pathways requiring continued understanding and assessment. OBJECTIVE: To assess the associations between maternal cortisol and placental corticotropin releasing hormone (placental CRH) concentrations with birth outcomes when stratified by placental histopathology. MATERIALS & METHODS: We conducted an analysis of 112 singleton pregnancies who received betamethasone between 23 and 34 weeks’ gestation. Maternal blood and saliva were collected prior to betamethasone administration and samples assayed for plasma cortisol (pCort), salivary cortisol (sCort), and placental CRH levels. Placental findings were characterized as inflammatory, maternal vascular underperfusion (MVU), or no pathology, and compared for the outcomes of placental CRH, pCort and sCort levels, gestational age at birth (GAB), and birthweight percentiles (BWP). RESULTS: Thirty-six subjects were characterized as inflammatory, 38 as MVU and 38 without placental abnormalities. Histopathology groups differed significantly on placental CRH levels, GAB, and BWP. Post hoc tests suggested that the MVU group had higher placental CRH than the inflammatory or no pathology groups and, despite delivering earlier than the other two groups, the inflammatory group had infants with significantly higher BWP. No differences existed between groups in terms of mean plasma or sCort levels. Higher placental CRH and pCort levels were associated with earlier GAB in the overall sample but, when split by group, these associations remained significant only among the MVU group. Higher placental CRH was also associated with lower BWP in the overall sample but did not remain significant when split by group. Higher sCort was associated with lower BWP only in the MVU group. CONCLUSION: There is differentiation of placental CRH, cortisol and birth outcomes when evaluated by placental histopathology. This highlights the importance of evaluating birth outcomes within the context of placental histopathology.

Objective This study aimed to determine if hyperemesis gravidarum (HG) is associated with autism spectrum disorder (ASD) risk, and how this association is influenced by race, ethnicity, sex, exposure timing, and medication used to treat it. Study Design This is a retrospective cohort study using records from 469,789 mother–child pairs who delivered at Kaiser Permanente Southern California (KPSC) hospital (1991–2014). Singleton-born children were followed longitudinally from 2 to 17 years of age. Clinical records were used to determine the diagnosis of HG and specialist-confirmed diagnosis of ASD. Results Children exposed to HG in-utero had higher rates of ASD than unexposed children (2.87 vs. 1.71/1,000 person-years; adjusted hazard ratio [adj.HR]: 1.53; 95% confidence interval [CI]: 1.37–1.70). Children exposed at first and second trimester of pregnancies were more likely to develop ASD; 1.58-fold (95% CI: 1.40–1.79), and 1.36-fold (95% CI: 1.05–1.75), respectively, compared with unexposed children. HG was associated with ASD for boys (adj.HR: 1.50; 95% CI: 1.33–1.70) and girls (adj.HR: 1.62; 95% CI: 1.28–2.05). HG was significantly associated with ASD risk in white and Hispanic children. The medications used to treat HG did not contribute to ASD risk. Conclusion HG diagnosis is associated with ASD risk and may be helpful in identifying at-risk children who could benefit from enhanced surveillance and earlier diagnosis and intervention.

Objective Pleckstrin homology-like domain, family A, member 2 (PHLDA2) is a maternally expressed imprinted gene. Loss of imprinting in PHLDA2 is associated with abnormal placental development and fetal growth restriction. Our objective was to determine whether genetic variation in PHLDA2 is also associated with risk of HELLP syndrome and preeclampsia (PE) with severe features. Study design Case (n = 162) and control (n = 33) mother-father-child triads were recruited using an internet-based method. Medical records were reviewed to verify clinical diagnosis of self-reported cases. DNA was genotyped for three polymorphisms in the PHLDA2 gene using TaqMan assays: rs13390, rs1056819, rs2583435. Main outcome measures To examine the association between minor alleles and haplotypes with HELLP syndrome and PE with severe features, relative risks and 95% confidence intervals were estimated using log-linear models, adjusting for the correlation between familial genotypes, using HAPLIN. Results There was no association identified between PHLDA2 gene polymorphisms or haplotypes and HELLP syndrome and PE with severe features. No parent-of-origin effects were observed. Conclusion Genetic variation in the PHLDA2 gene is not associated with HELLP syndrome or PE with severe features.

Objective To evaluate the prevalence of cesarean delivery in women with hypertensive disorders of pregnancy (HDP), and explore whether maternal, sociodemographic, or obstetric comorbidities contribute to cesarean delivery rates. Study Design This is a retrospective cohort study of nulliparous, term, singleton, vertex women using the 2013 U.S. National Vital Statistics Report. We compared prevalence of risk factors for cesarean delivery between women with and without HDP, and then calculated probabilities of cesarean delivery after controlling for these risk factors. Results In this cohort of 1,439,977 women, the unadjusted probability of cesarean delivery in women with HDP was 39.5 versus 26.8% in those without the diagnosis (p Conclusion Even after controlling for multiple comorbidities, hypertension remained a significant risk factor for cesarean delivery in nulliparous women at term. Hypertensive women may therefore represent an important target population in efforts aimed at reduction of cesarean rates.

ObjectiveTo characterize the association of longitudinal changes in maternal anthropometric measures with neonatal anthropometry and to assess to what extent late-gestational changes in maternal anthropometry are associated with neonatal body composition.DesignIn a prospective cohort of pregnant women, maternal anthropometry was measured at six study visits across pregnancy and after birth, neonates were measured and fat and lean mass calculated. We estimated maternal anthropometric trajectories and separately assessed rate of change in the second (15–28 weeks) and third trimester (28–39 weeks) in relation to neonatal anthropometry. We investigated the extent to which tertiles of third-trimester maternal anthropometry change were associated with neonatal outcomes.SettingWomen were recruited from twelve US sites (2009–2013).ParticipantsNon-obese women with singleton pregnancies (n 2334).ResultsA higher rate of increase in gestational weight gain was associated with larger-birth-weight infants with greater lean and fat mass. In contrast, higher rates of increase in maternal anthropometry measures were not associated with infant birth weight but were associated with decreased neonatal lean mass. In the third trimester, women in the tertile of lowest change in triceps skinfold (−0·57 to −0·06 mm per week) had neonates with 35·8 g more lean mass than neonates of mothers in the middle tertile of rate of change (−0·05 to 0·06 mm per week).ConclusionsThe rate of change in third-trimester maternal anthropometry measures may be related to neonatal lean and fat mass yet have a negligible impact on infant birth weight, indicating that neonatal anthropometry may provide additional information over birth weight alone.

Objective To examine the association between exposures to perinatal factors and autism spectrum disorders (ASD). Study Design A retrospective cohort study of ASD among children born in Kaiser Permanente Southern California hospitals between 1991 and 2009 (n = 594,638). Medical records were used to determine exposure to perinatal (antepartum and intrapartum) complications. ASD was diagnosed using DSM-IV criteria. Multivariable Cox regression was used to estimate hazard ratios (HRs). Result Children with ASD were more likely to be exposed to perinatal complications (HR = 1.15, 95% confidence interval [CI]: 1.09–1.21) than neurotypical children. Children exposed to antepartum (HR = 1.22, 95% CI: 1.10–1.36) and intrapartum (HR = 1.10, 95% CI: 1.04–1.17) complications were at increased risk of ASD. The risk was even greater when both antepartum and intrapartum conditions were present (HR = 1.44, 95% CI: 1.26–1.63). Conclusion Exposure to antepartum or intrapartum complications increases the risk of ASD in the offspring. Therefore, pregnancy complications may help identify children who could benefit from early screening and intervention for this common neurodevelopmental condition.

Endogenous hydrogen sulfide (H2S) synthesized via metabolizing L-cysteine by cystathionine-beta-synthase (CBS) and cystathionine-gamma-lyase (CSE) is a potent vasodilator and angiogenic factor. The objectives of this study were to determine if human uterine artery (UA) H2S production increases with augmented expression and/or activity of CBS and/or CSE during the menstrual cycle and pregnancy and whether exogenous H2S dilates UA. Uterine arteries from nonpregnant (NP) premenopausal proliferative (pPRM) and secretory (sPRM) phases of the menstrual cycle and pregnant (P) women were studied. H2S production was measured by the methylene blue assay. CBS and CSE mRNAs were assessed by quantitative real-time PCR, and proteins were assessed by immunoblotting and semiquantitative immunofluorescence microscopy. Effects of H2S on rat UA relaxation were determined by wire myography ex vivo. H2S production was greater in NP pPRM and P than NP sPRM UAs and inhibited by the specific CBS but not CSE inhibitor. CBS but not CSE mRNA and protein were greater in NP pPRM and P than NP sPRM UAs. CBS protein was localized to endothelium and smooth muscle and its levels were in a quantitative order of P >NP UAs of pPRM>sPRM. CSE protein was localized in UA endothelium and smooth muscle with no difference among groups. A H2S donor relaxed P > NP UAs but not mesentery artery. Thus, human UA H2S production is augmented with endothelium and smooth muscle CBS upregulation, contributing to UA vasodilation in the estrogen-dominant physiological states in the proliferative phase of the menstrual cycle and pregnancy.

Preterm Premature Rupture of Membranes (PPROM) precedes many deliveries and experts agree with expectant management until 34 weeks gestation. However, there is controversy regarding the gestational age (GA) for administration of corticosteroids.We performed a retrospective cohort study in the University of California Fetal Consortium (UCfC). We searched available charts of singleton pregnancies with PPROM between 32 and 33 6/7 weeks GA. Outcomes from the groups were analyzed.Of 191 women with PPROM at 32 to 33 6/7 weeks, 150 received corticosteroids. The median GA at admission was earlier for the exposed versus unexposed group (32 4/7 versus 33 0/7 weeks, respectively, p = 0.001). The mean GA at delivery in the exposed was 33 2/7 (32 0/7 to 35 0/7) weeks versus 33 5/7 (32 0/7 to 36 1/7) weeks in the unexposed (p = 0.001). There was no difference in chorioamnionitis or RDS.In women with PPROM at 32 to 33 6/7 weeks, our data suggests that corticosteroids are associated with similar outcomes despite earlier GA at delivery and no differences in major morbidities. A larger prospective study is needed to determine if the benefit of corticosteroids outweighs the potential risks in PPROM.

© 2016 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc.OBJECTIVE: To estimate whether ultrasound measurement of the fetal adrenal gland remote from delivery in asymptomatic women can accurately predict spontaneous preterm birth. METHODS: We conducted a prospective multicenter observational nested cohort study of asymptomatic nulliparous women with a singleton pregnancy to study adverse pregnancy outcomes. Between 22 0/7 and 30 6/7 weeks of gestation, credentialed ultrasonographers measured the width (width), length (length), and, when able, depth (depth) of the "fetal zone" of the fetal adrenal gland as well as the width (Width), length (Length), and depth (Depth) of the total gland. We used the ratios of each measurement (width/Width, length/Length, and depth/Depth) to control for variation in adrenal size by gestational age. The accuracy of each ratio measurement in predicting spontaneous preterm birth at less than 37 0/7 weeks of gestation and spontaneous preterm birth at less than 34 0/7 weeks of gestation was assessed by receiver operating characteristic curves using area under the curve. RESULTS: Pregnancy outcomes were available for 1,697 women with one or more fetal adrenal gland measurements. Spontaneous preterm birth at less than 37 0/7 weeks of gestation and spontaneous preterm birth at less than 34 0/7 weeks of gestation occurred in 82 (4.8%) and six women (0.4%), respectively. None of the fetal adrenal gland measurements distinguished spontaneous preterm birth from term birth. The areas under the curve (95% confidence intervals) for spontaneous preterm birth at less than 37 0/7 weeks of gestation were 0.51 (0.45-0.58), 0.50 (0.44-0.56), and 0.52 (0.41-0.63) for width/Width, length/Length, and depth/Depth ratios, respectively. The areas under the curve for spontaneous preterm birth at less than 34 0/7 weeks of gestation were 0.52 (0.25-0.79) and 0.55 (0.31-0.79) for width/Width and length/Length ratios, respectively. Additionally, none of the means of the gland measurements were statistically different between those delivering at term and spontaneous at preterm (P>.05). CONCLUSION: Fetal adrenal size, as measured by ultrasonography between 22 0/7 and 30 6/7 weeks of gestation, is not predictive of spontaneous preterm birth in asymptomatic nulliparous women.

Spontaneous preterm birth is a leading cause of infant mortality. Prediction, largely based on prior pregnancy outcomes, is not possible in women pregnant for the first time. To assess the accuracy of universal screening to predict spontaneous preterm birth in nulliparous women using serial measurements of vaginal fetal fibronectin levels and cervical length. A prospective observational cohort study of nulliparous women with singleton pregnancies, from 8 clinical sites across the United States between October 2010 and May 2014. Women and clinicians were blinded to results unless cervical shortening less than 15 mm was identified. Transvaginal cervical length and quantitative vaginal fetal fibronectin levels were reviewed at 2 study visits 4 or more weeks apart. Spontaneous preterm birth at less than 37 weeks was the primary outcome. Cervical length and quantitative fetal fibronectin were considered independently and together at each visit. Measurement distributions were compared for spontaneous preterm birth vs all other births. Spontaneous preterm birth before 32 weeks was a secondary outcome. The study included 9410 women (median age, 27.0 [interquartile range, 9.0] years; 60.7% non-Hispanic white, 13.8% non-Hispanic black, 16.5% Hispanic, 4.0% Asian, and 5.1% other), of whom 474 (5.0%) had spontaneous preterm births, 335 (3.6%) had medically indicated preterm births, and 8601 (91.4%) had term births. Among women with spontaneous preterm birth, cervical length of 25 mm or less occurred in 35 of 439 (8.0%) at 16 to 22 weeks' gestation and in 94 of 403 (23.3%) at 22 to 30 weeks' gestation. Fetal fibronectin levels of 50 ng/mL or greater at 16 to 22 weeks identified 30 of 410 women (7.3%) with spontaneous preterm birth and 31 of 384 (8.1%) at 22 to 30 weeks. The area under the receiver operating characteristic curve for screening between 22 and 30 weeks for fetal fibronectin level alone was 0.59 (95% CI, 0.56-0.62), for transvaginal cervical length alone was 0.67 (95% CI, 0.64-0.70), and for the combination as continuous variables was 0.67 (95% CI, 0.64-0.70). Among nulliparous women with singleton pregnancies, quantitative vaginal fetal fibronectin and serial transvaginal ultrasound cervical length had low predictive accuracy for spontaneous preterm birth. These findings do not support routine use of these tests in such women.

To describe the multidisciplinary approaches to placenta accreta spectrum (PAS) across five tertiary care centers that comprise the University of California fetal Consortium (UCfC) and to identify potential best practices. Retrospective review of all cases of pathologically confirmed invasive placenta delivered from 2009 to 2014 at UCfC. Differences in intraoperative management and outcomes based on prenatal suspicion were compared. Interventions assessed included ureteral stent use, intravascular balloon use, anesthetic type, gynecologic oncology (Gyn Onc) involvement, and cell saver use. Intervention variation by institution was also assessed. Analyses were adjusted for final pathologic diagnosis. Chi-square, Fisher���s exact, Student���s t-test, and Mann���Whitney���s U-test were used as appropriate. Binary logistic regression and multivariable linear regression were used to adjust for confounders. One hundred and fifty-one cases of pathologically confirmed invasive placenta were identified, of which 82% (123) were suspected prenatally. There was no correlation between the degree of invasion on prenatal imaging and use of each intervention. Ureteral stents were placed in 33% (41) of cases and did not reduce GU injury. Intravascular balloons were placed in 29% (36) of cases and were associated with shorter OR time (161 versus 236 min, p p p = .02) while OR time and intraoperative complications did not differ. Cell saver was used in 20% (24) and was associated with longer OR time (296 versus 200 min, p Intravascular interventions such as uterine artery balloons and the inclusion of Gynecologic Oncologists as part of a multidisciplinary approach to treating PAS reduce EBL. Additionally, the placement of intravascular balloons may reduce OR time. No significant differences were seen in outcomes when comparing the use of ureteral stents, general anesthesia, or institutions. A team of experienced operators with a standard approach may be more significant than specific practices.

Background Amniotic fluid is essential to normal fetal development and is estimated clinically with ultrasound scanning to identify pregnancies that are at risk for poor perinatal outcome. Objective Our goal was to develop a United States standard for amniotic fluid volume that is estimated by the amniotic fluid index and single deepest pocket. Study Design We performed a planned secondary analysis of a multicenter observational study of 2334 low-risk women with normal singleton gestations from 1 of 4 self-reported racial/ethnic groups. Eligible women had confirmed first-trimester dating criteria with health status, lifestyles, and medical and obstetric histories that were associated with normal fetal growth. Consenting women underwent serial (up to 5) sonographic evaluations of amniotic fluid between 15 and 40 weeks of gestation after being assigned randomly to 1 of 4 gestational age observation schedules. Twelve United States perinatal centers participated, and all sonograms were performed by credentialed sonographers who used identical, high-resolution equipment; caregivers were unaware of results but were notified for oligohydramnios. Women (n=597) who were subsequently found to have clinically significant antepartum complications were excluded. Racial/ethnic–specific nomograms for amniotic fluid index and single deepest pocket across gestation were developed with the use of linear mixed models with cubic splines; racial/ethnic differences were evaluated both with global and between-group tests. Median, 3rd, 5th, 10th, 90th, 95th and 97th percentile values were also estimated. We further considered the possible confounding effects of selected maternal characteristics and the estimated fetal weight at each sonogram. Results A total of 1719 pregnant women met inclusion criteria and had available data. These included 480 non-Hispanic white women, 418 non-Hispanic black women, 485 Hispanic women, and 336 Asian women. Both the amniotic fluid index and the single deepest pocket varied across gestation with maximal values at 26 and 33 weeks of gestation, respectively. Statistically significant differences were observed by maternal race/ethnicity. The between-group differences that were observed at 17–22 and 35–40 weeks of gestation remained statistically significant after adjustment for maternal characteristics and estimated fetal weight. These between-group racial/ethnic differences were most prominent after 35 weeks of gestation and at the extremes of dispersion (3rd and 97th percentiles). All 3rd and 97th percentile amniotic fluid index values were within the range of commonly used cutoffs to define oligohydramnios (≤5 cm) and polyhydramnios (≥25 cm). However, the 3rd percentile values ranged between 5.9 cm at 40 weeks of gestation and 10.1 cm at 25–27 weeks of gestation; the 97th percentile values ranged between 24.8 cm at 38 weeks of gestation and 15.7 cm at 15 weeks of gestation. Conclusion Sonographic amniotic fluid volume estimates vary by racial/ethnic group, but the absolute differences appear to be small and may not be clinically significant. Selected maternal characteristics and estimated fetal weight did not affect the racial/ethnic differences. Between-group differences are maximal after 35 weeks of gestation and at the extremes of the upper and lower dispersion estimates. Given the observed variability in extreme (3rd and 97th percentile) dispersion values over the gestation, use of single cutoffs to define out-of-range measurements may not be appropriate clinically. These data might form a contemporary United States standard for amniotic fluid estimation that uses the amniotic fluid index and the single deepest pocket.

Childhood exposure to traumatic events has a profound and disruptive impact on mental and physical health, including stress physiology. In the current study, we evaluate 90 pregnant women at risk for preterm delivery and assess the association between history of exposure to traumatic events and hair cortisol concentrations, an integrated measure of cortisol production. Exposure to more traumatic events in childhood and in adulthood independently predicted elevated hair cortisol concentrations in pregnancy. Notably, the impact of childhood exposure to traumatic events remained after accounting for more proximal traumatic events in adulthood. Further, there was a significant interaction between childhood and adult exposures. Traumatic experiences in adulthood were more strongly associated with hair cortisol concentrations among mothers with a history of greater childhood trauma. Findings suggest that not only do proximal adult exposures impact HPA-axis functioning during pregnancy, but that childhood traumatic experiences have persisting consequences for HPA-axis functioning during pregnancy. Maternal HPA- axis dysregulation in pregnancy has consequences for both maternal health and for fetal development. Therefore, we consider prenatal maternal HPA-axis functioning as a potential biological pathway underlying intergenerational consequences of childhood trauma.

OBJECTIVE To assess the relationship between first-trimester vaginal bleeding and fetal growth patterns. METHODS We conducted a secondary analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Fetal Growth Studies-Singletons, a prospective cohort study of low-risk, nonobese women with healthy lifestyles. Duration of bleeding was self-reported at enrollment (10 0/7 to 13 6/7 weeks of gestation) and categorized as 0, 1, or more than 1 day. Longitudinal measures of fetal biometrics were obtained in up to six study visits, and estimated fetal weight was computed. Growth trajectories were created for biometrics and estimated fetal weight. When global tests among groups was significant (P

Background Sleep-disordered breathing (SDB) is common in pregnancy, but there are limited data on predictors. Objectives The objective of this study was to develop predictive models of sleep-disordered breathing during pregnancy. Study Design Nulliparous women completed validated questionnaires to assess for symptoms related to snoring, fatigue, excessive daytime sleepiness, insomnia, and restless leg syndrome. The questionnaires included questions regarding the timing of sleep and sleep duration, work schedules (eg, shift work, night work), sleep positions, and previously diagnosed sleep disorders. Frequent snoring was defined as self-reported snoring ≥3 days per week. Participants underwent in-home portable sleep studies for sleep-disordered breathing assessment in early (6–15 weeks gestation) and mid pregnancy (22–31 weeks gestation). Sleep-disordered breathing was characterized by an apnea hypopnea index that included all apneas, plus hypopneas with ≥3% oxygen desaturation. For primary analyses, an apnea hypopnea index ≥5 events per hour was used to define sleep-disordered breathing. Odds ratios and 95% confidence intervals were calculated for predictor variables. Predictive ability of the logistic models was estimated with area under the receiver-operating-characteristic curves, along with sensitivities, specificities, and positive and negative predictive values and likelihood ratios. Results Among 3705 women who were enrolled, data were available for 3264 and 2512 women in early and mid pregnancy, respectively. The corresponding prevalence of sleep-disordered breathing was 3.6% and 8.3%, respectively. At each time point in gestation, frequent snoring, chronic hypertension, greater maternal age, body mass index, neck circumference, and systolic blood pressure were associated most strongly with an increased risk of sleep-disordered breathing. Logistic regression models that included current age, body mass index, and frequent snoring predicted sleep-disordered breathing in early pregnancy, sleep-disordered breathing in mid pregnancy, and new onset sleep-disordered breathing in mid pregnancy with 10-fold cross-validated area under the receiver-operating-characteristic curves of 0.870, 0.838, and 0.809. We provide a supplement with expanded tables, integrated predictiveness, classification curves, and an predicted probability calculator. Conclusion Among nulliparous pregnant women, logistic regression models with just 3 variables (ie, age, body mass index, and frequent snoring) achieved good prediction of prevalent and incident sleep-disordered breathing. These results can help with screening for sleep-disordered breathing in the clinical setting and for future clinical treatment trials.