Multiethnic growth standards for fetal body composition and organ volumes derived from 3D ultrasonography.

BACKGROUND: A major goal of contemporary obstetrical practice is to optimize fetal growth and development throughout pregnancy. To date, fetal growth during prenatal care is assessed by performing ultrasonographic measurement of 2-dimensional fetal biometry to calculate an estimated fetal weight. Our group previously established 2-dimensional fetal growth standards using sonographic data from a large cohort with multiple sonograms. A separate objective of that investigation involved the collection of fetal volumes from the same cohort. OBJECTIVE: The Fetal 3D Study was designed to establish standards for fetal soft tissue and organ volume measurements by 3-dimensional ultrasonography and compare growth trajectories with conventional 2-dimensional measures where applicable. STUDY DESIGN: The National Institute of Child Health and Human Development Fetal 3D Study included research-quality images of singletons collected in a prospective, racially and ethnically diverse, low-risk cohort of pregnant individuals at 12 U.S. sites, with up to 5 scans per fetus (N=1730 fetuses). Abdominal subcutaneous tissue thickness was measured from 2-dimensional images and fetal limb soft tissue parameters extracted from 3-dimensional multiplanar views. Cerebellar, lung, liver, and kidney volumes were measured using virtual organ computer aided analysis. Fractional arm and thigh total volumes, and fractional lean limb volumes were measured, with fractional limb fat volume calculated by subtracting lean from total. For each measure, weighted curves (fifth, 50th, 95th percentiles) were derived from 15 to 41 weeks' using linear mixed models for repeated measures with cubic splines. RESULTS: Subcutaneous thickness of the abdomen, arm, and thigh increased linearly, with slight acceleration around 27 to 29 weeks. Fractional volumes of the arm, thigh, and lean limb volumes increased along a quadratic curvature, with acceleration around 29 to 30 weeks. In contrast, growth patterns for 2-dimensional humerus and femur lengths demonstrated a logarithmic shape, with fastest growth in the second trimester. The mid-arm area curve was similar in shape to fractional arm volume, with an acceleration around 30 weeks, whereas the curve for the lean arm area was more gradual. The abdominal area curve was similar to the mid-arm area curve with an acceleration around 29 weeks. The mid-thigh and lean area curves differed from the arm areas by exhibiting a deceleration at 39 weeks. The growth curves for the mid-arm and thigh circumferences were more linear. Cerebellar 2-dimensional diameter increased linearly, whereas cerebellar 3-dimensional volume growth gradually accelerated until 32 weeks followed by a more linear growth. Lung, kidney, and liver volumes all demonstrated gradual early growth followed by a linear acceleration beginning at 25 weeks for lungs, 26 to 27 weeks for kidneys, and 29 weeks for liver. CONCLUSION: Growth patterns and timing of maximal growth for 3-dimensional lean and fat measures, limb and organ volumes differed from patterns revealed by traditional 2-dimensional growth measures, suggesting these parameters reflect unique facets of fetal growth. Growth in these three-dimensional measures may be altered by genetic, nutritional, metabolic, or environmental influences and pregnancy complications, in ways not identifiable using corresponding 2-dimensional measures. Further investigation into the relationships of these 3-dimensional standards to abnormal fetal growth, adverse perinatal outcomes, and health status in postnatal life is warranted.

Nutritional Intake in Dichorionic Twin Pregnancies: A Descriptive Analysis of a Multisite United States Cohort.

INTRODUCTION: Twin gestations have greater nutritional demands than singleton gestations, yet dietary intakes of women with twin gestations have not been well described. METHODS: In a prospective, multi-site US study of 148 women with dichorionic twin gestations (2012-2013), we examined longitudinal changes in diet across pregnancy. Women completed a food frequency questionnaire during each trimester of pregnancy. We examined changes in means of total energy and energy-adjusted dietary components using linear mixed effects models. RESULTS: Mean energy intake (95% CI) across the three trimesters was 2010 kcal/day (1846, 2175), 2177 kcal/day (2005, 2349), 2253 kcal/day (2056, 2450), respectively (P = 0.01), whereas the Healthy Eating Index-2010 was 63.9 (62.1, 65.6), 64.5 (62.6, 66.3), 63.2 (61.1, 65.3), respectively (P = 0.53). DISCUSSION: Women with twin gestations moderately increased total energy as pregnancy progressed, though dietary composition and quality remained unchanged. These findings highlight aspects of nutritional intake that may need to be improved among women carrying twins.

The Influence of Diabetes on Labor Induction with Dinoprostone Vaginal Inserts.

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..

Combination of Fundal Height and Ultrasound to Predict Small for Gestational Age at Birth.

OBJECTIVE: 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. STUDY DESIGN: 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 weight <10th percentile. If the FH cut points were not met, the SGA screen was classified as negative. If FH cut points were met and EFW was <10th 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. RESULTS: 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%. CONCLUSION: 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). KEY POINTS: · 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..

Association of Social Determinants of Health and Clinical Factors with Postpartum Hospital Readmissions among Nulliparous Individuals.

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 < 0.05. Social determinants of health evaluated in this analysis included insurance status, self-identified race and ethnicity (as a proxy for structural racism), income, marital status, primary language, and educational attainment. 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 < 0.001). Among participants without HDP, the only factors associated with postpartum readmission were chorioamnionitis and cesarean delivery. Among participants with HDP, gestational diabetes and postpartum hemorrhage requiring transfusion were associated with postpartum readmission. While the number of postpartum readmissions included in our analysis was relatively small, social determinants of health that we examined were not associated with postpartum readmission for either group. 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: · Non-HDP patients had higher odds of PPR with chorioamnionitis or cesarean.. · HDP patients had higher odds of PPR if they had GDM or PPH.. · Characterizing PPR may identify and highlight modifiable factors..

Maternal Morbidity Risk Factors in Nulliparas.

OBJECTIVE: For every incidence of maternal mortality, maternal morbidity is thought to occur in another 50 to 100 individuals in the United States. Multiple risk factors for severe maternal morbidity have been identified, but counseling about specific risk in pregnancy remains difficult, particularly nulliparous individuals as prior obstetric history is one of the factors influencing risk for severe maternal morbidity. The objective of this study is to examine the association between sociodemographic and laboratory assessments in the first trimester and maternal morbidity in nulliparas. STUDY DESIGN: This was a secondary analysis of a large, multicenter prospective observational cohort of nulliparas. The primary maternal outcome was a composite of hypertensive disorders of pregnancy (HDP), hemorrhage (transfusion, hemorrhage, hysterectomy, other surgery, readmission for bleeding), infection (endometritis, wound infection or dehiscence, pneumonia, sepsis, infection during labor and delivery, readmission for infection through day 14), venous thromboembolic events (VTE) (deep venous thrombosis, or pulmonary embolus), or maternal death within 14 days of delivery. Sociodemographic and clinical factors were compared between people with and without maternal morbidity. Relative risk and 95% confidence interval for maternal morbidity was calculated using log-binomial regression, adjusted for baseline characteristics that had a significant independent relationship with maternal morbidity with a p-value <0.05. RESULTS: Of 9,445 pregnant people in the analysis, 18.2% (n = 1,716) experienced the composite maternal morbidity; the most common component was HDP (13.1%, n = 1,244) followed by infection (4.43%, n = 420), hemorrhage (2.27%, n = 215), VTE (0.12%, n = 11), and death (0.01%, n = 1). In a multivariable model, self-identified Black race, first trimester obesity, pregestational diabetes, chronic hypertension, and chronic kidney disease were significantly associated with the primary maternal outcome. CONCLUSION: More than one in six nulliparas experienced the composite maternal morbidities. Maternal morbidity was associated with self-identified Black race, obesity, and multiple preexisting medical comorbidities. KEY POINTS: · One in six nulliparas experience maternal morbidity in their first pregnancy related to hypertensive disorders of pregnancy, infection, hemorrhage, and venous thromboembolism.. · Risk factors for maternal morbidity in nulliparas include Black race, prepregnancy body mass index, and preexisting medical conditions.. · The preexisting medical conditions with the strongest association with maternal morbidity included pregestational diabetes, chronic hypertension, and chronic kidney disease..

Associations of the Neighborhood Built Environment with Gestational Weight Gain.

OBJECTIVE: 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). STUDY DESIGN: 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. RESULTS: 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]). CONCLUSION: Among a diverse population of nulliparous women, multiple aspects of the built environment are associated with excessive and inadequate GWG. KEY POINTS: · 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..

Use of a Doubly Robust Machine-Learning-Based Approach to Evaluate Body Mass Index as a Modifier of the Association Between Fruit and Vegetable Intake and Preeclampsia.

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. <1.2 cups/1,000 kcal/day) and vegetables (≥1.3 cups/1,000 kcal/day vs. <1.3 cups/1,000 kcal/day) on preeclampsia risk, conditional on BMI, using a doubly robust estimator implemented in 2 stages. We found that the protective association of higher fruit density declined approximately linearly from a BMI of 20 to a BMI of 32, by 0.25 cases per 100 women per each BMI unit, and then flattened. The protective association of higher vegetable density strengthened in a linear fashion, by 0.3 cases per 100 women for every unit increase in BMI, up to a BMI of 30, where it plateaued. Dietary patterns with a high periconceptional density of fruits and vegetables appear more protective against preeclampsia for women with higher BMI than for leaner women.

Trajectories of antenatal depression and adverse pregnancy outcomes.

BACKGROUND: 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. OBJECTIVE: This study aimed to identify whether the trajectory of antenatal depressive symptoms is associated with different risks of adverse pregnancy outcomes. STUDY DESIGN: 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. RESULTS: 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). CONCLUSION: 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.

Perinatal outcomes after bariatric surgery.

BACKGROUND: 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. OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSION: 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.

Fetal Growth Biometry as Predictors of Shoulder Dystocia in a Low-Risk Obstetrical Population.

OBJECTIVE: This study aimed to evaluate fetal biometrics as predictors of shoulder dystocia (SD) in a low-risk obstetrical population. STUDY DESIGN: Participants were enrolled as part of a U.S.-based prospective cohort study of fetal growth in low-risk singleton gestations (n = 2,802). Eligible women had liveborn singletons ≥2,500 g delivered vaginally. Sociodemographic, anthropometric, and pregnancy outcome data were abstracted by research staff. The diagnosis of SD was based on the recorded clinical impression of the delivering physician. Simple logistic regression models were used to examine associations between fetal biometrics and SD. Fetal biometric cut points, selected by Youden's J and clinical determination, were identified to optimize predictive capability. A final model for SD prediction was constructed using backward selection. Our dataset was randomly divided into training (60%) and test (40%) datasets for model building and internal validation. RESULTS: A total of 1,691 women (98.7%) had an uncomplicated vaginal delivery, while 23 (1.3%) experienced SD. There were no differences in sociodemographic or maternal anthropometrics between groups. Epidural anesthesia use was significantly more common (100 vs. 82.4%; p = 0.03) among women who experienced SD compared with those who did not. Amniotic fluid maximal vertical pocket was also significantly greater among SD cases (5.8 ± 1.7 vs. 5.1 ± 1.5 cm; odds ratio = 1.32 [95% confidence interval: 1.03,1.69]). Several fetal biometric measures were significantly associated with SD when dichotomized based on clinically selected cut-off points. A final prediction model was internally valid with an area under the curve of 0.90 (95% confidence interval: 0.81, 0.99). At a model probability of 1%, sensitivity (71.4%), specificity (77.5%), positive (3.5%), and negative predictive values (99.6%) did not indicate the ability of the model to predict SD in a clinically meaningful way. CONCLUSION: Other than epidural anesthesia use, neither sociodemographic nor maternal anthropometrics were significantly associated with SD in this low-risk population. Both individually and in combination, fetal biometrics had limited ability to predict SD and lack clinical usefulness. KEY POINTS: · SD unpredictable in low-risk women.. · Fetal biometry does not reliably predict SD.. · Epidural use associated with increased SD risk.. · SD prediction models clinically inefficient..

Racial/Ethnic Differences in Prenatal Supplement and Medication Use in Low-Risk Pregnant Women.

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 < 0.001). All racial/ethnic groups reported taking the same top four medication classes including central nervous system agents, gastrointestinal drugs, anti-infective agents, and antihistamines. Compared with non-Hispanic white women, Hispanic (adjusted relative risk [aRR]: 0.84, 95% confidence interval [CI]: 0.71-0.98), and Asian women (aRR: 0.83, 95% CI: 0.70-0.98) were less likely to take central nervous system agents, as well as gastrointestinal drugs (Hispanics aRR: 0.79, 95% CI: 0.66-0.94; Asians aRR = 0.75, 95% CI: 0.63-0.90), and antihistamines (Hispanics aRR: 0.65, 95% CI: 0.47-0.92). CONCLUSION: Supplement intake was nearly universal. Medication use was also common among this low-risk pregnancy cohort and differed by race/ethnicity. GOV IDENTIFIER: NCT00912132. KEY POINTS: · In women without chronic conditions, medication use is common.. · Racial/ethnic differences exist in prenatal medications use.. · Almost all women use supplements during pregnancy..

Autism Spectrum Disorders in Children Exposed in Utero to Hyperemesis Gravidarum.

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.

Gestational Weight Gain and Pregnancy Outcomes among Nulliparous Women.

OBJECTIVE: To determine the association between total gestational weight gain and perinatal outcomes. STUDY DESIGN: Data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be (NuMoM2b) study were used. Total gestational weight gain was categorized as inadequate, adequate, or excessive based on the 2009 Institute of Medicine guidelines. Outcomes examined included hypertensive disorders of pregnancy, mode of delivery, shoulder dystocia, large for gestational age or small for-gestational age birth weight, and neonatal intensive care unit admission. RESULTS: Among 8,628 women, 1,666 (19.3%) had inadequate, 2,945 (34.1%) had adequate, and 4,017 (46.6%) had excessive gestational weight gain. Excessive gestational weight gain was associated with higher odds of hypertensive disorders (adjusted odds ratio [aOR] = 2.05, 95% confidence interval [CI]: 1.78-2.36) Cesarean delivery (aOR = 1.24, 95% CI: 1.09-1.41), and large for gestational age birth weight (aOR = 1.49, 95% CI: 1.23-1.80), but lower odds of small for gestational age birth weight (aOR = 0.59, 95% CI: 0.50-0.71). Conversely, inadequate gestational weight gain was associated with lower odds of hypertensive disorders (aOR = 0.75, 95% CI: 0.62-0.92), Cesarean delivery (aOR = 0.77, 95% CI: 0.65-0.92), and a large for gestational age birth weight (aOR = 0.72, 95% CI: 0.55-0.94), but higher odds of having a small for gestational age birth weight (aOR = 1.64, 95% CI: 1.37-1.96). CONCLUSION: Both excessive and inadequate gestational weight gain are associated with adverse maternal and neonatal outcomes.

Quality of periconceptional dietary intake and maternal and neonatal outcomes.

BACKGROUND: Periconceptional diet quality is commonly suboptimal and sociodemographic disparities in diet quality exist. However, it is unknown whether individual periconceptional diet quality is associated with obstetric outcomes. OBJECTIVE: Our objective was to assess differences in maternal and neonatal outcomes according to maternal periconceptional diet quality. STUDY DESIGN: This is a secondary analysis of a large, multicenter prospective cohort study of 10,038 nulliparous women receiving obstetrical care at 8 United States centers. Women underwent 3 antenatal study visits and had detailed maternal and neonatal data abstracted by trained research personnel. In the first trimester (between 6 and 13 weeks), women completed the modified Block 2005 Food Frequency Questionnaire, a semiquantitative assessment of usual dietary intake for the 3 months around conception. Responses were scored using the Healthy Eating Index-2010, which assesses adherence to the 2010 Dietary Guidelines for Americans. Higher scores on the Healthy Eating Index represent better adherence. Healthy Eating Index scores were analyzed by quartile; quartile 4 represents the highest dietary quality. Bivariable and multivariable analyses were performed to assess associations between diet quality and outcomes. A sensitivity analysis in which markers of socioeconomic status were included in the multivariable Poisson regression models was performed. RESULTS: In the cohort of 8259 women with Healthy Eating Index data, the mean Healthy Eating Index score was 63 (±13) of 100. Women with the lowest quartile Healthy Eating Index scores were more likely to be younger, non-Hispanic black and Hispanic, publicly insured, low income, and tobacco users. They were more likely to have comorbidities (obesity, chronic hypertension, pregestational diabetes, mental health disorders), a higher prepregnancy body mass index, and less education. Women with lowest quartile scores experienced less frequent major perineal lacerations and more frequent postpartum hemorrhage requiring transfusion and hypertensive disorders of pregnancy, which persisted on multivariable analyses (controlling for age, body mass index, tobacco use, chronic hypertension, pregestational diabetes mellitus, and mental health disorders) comparing women in each quartile with quartile 4. Additionally, women in quartiles 1 and 2 experienced greater adjusted relative risk of cesarean delivery compared with women in quartile 4. Neonatal outcomes also differed by dietary quartile, with women in the lowest Healthy Eating Index quartile experiencing greater adjusted relative risk of preterm birth, neonatal intensive care unit admission, small for gestational age infant, and low birthweight, and lower risk of macrosomia; all neonatal findings also persisted in multivariable analyses. The sensitivity analysis with inclusion of markers of socioeconomic status (race/ethnicity, insurance status, marital status) in the multivariable models supported these findings. CONCLUSION: Periconceptional diet quality among women in the United States is poor. Poorer periconceptional dietary quality is associated with adverse maternal and neonatal outcomes, even after controlling for potential comorbidities and body mass index, suggesting periconceptional diet may be an important social or biological determinant of health underlying existing health disparities.

Prospective, randomized, double-blind, placebo-controlled evaluation of the Pharmacokinetics, Safety and Efficacy of Recombinant Antithrombin Versus Placebo in Preterm Preeclampsia.

BACKGROUND: Despite expectant management, preeclampsia remote from term usually results in preterm delivery. Antithrombin, which displays antiinflammatory and anticoagulant properties, may have a therapeutic role in treating preterm preeclampsia, a disorder characterized by endothelial dysfunction, inflammation, and activation of the coagulation system. OBJECTIVE: This randomized, placebo-controlled clinical trial aimed to evaluate whether intravenous recombinant human antithrombin could prolong gestation and therefore improve maternal and fetal outcomes. STUDY DESIGN: We performed a double-blind, placebo-controlled trial at 23 hospitals. Women were eligible if they had a singleton pregnancy, early-onset or superimposed preeclampsia at 23 0/7 to 30 0/7 weeks' gestation, and planned expectant management. In addition to standard therapy, patients were randomized to receive either recombinant human antithrombin 250 mg loading dose followed by a continuous infusion of 2000 mg per 24 hours or an identical saline infusion until delivery. The primary outcome was days gained from randomization until delivery. The secondary outcome was composite neonatal morbidity score. A total of 120 women were randomized. RESULTS: There was no difference in median gestational age at enrollment (27.3 weeks' gestation for the recombinant human antithrombin group [range, 23.1-30.0] and 27.6 weeks' gestation for the placebo group [range, 23.0-30.0]; P=.67). There were no differences in median increase in days gained (5.0 in the recombinant human antithrombin group [range, 0-75] and 6.0 for the placebo group [range, 0-85]; P=.95). There were no differences between groups in composite neonatal morbidity scores or in maternal complications. No safety issues related to recombinant human antithrombin were noted in this study, despite the achievement of supraphysiological antithrombin concentrations. CONCLUSION: The administration of recombinant human antithrombin in preterm preeclampsia neither prolonged pregnancy nor improved neonatal or maternal outcomes.

A contemporary amniotic fluid volume chart for the United States: The NICHD Fetal Growth Studies-Singletons.

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.

Fetal growth patterns in pregnancy-associated hypertensive disorders: NICHD Fetal Growth Studies.

BACKGROUND: Fetal growth patterns in pregnancy-associated hypertensive disorders is poorly understood because prospective longitudinal data are lacking. OBJECTIVE: The objective of the study was to compare longitudinal fetal growth trajectories between normotensive women and those with pregnancy-associated hypertensive disorders. STUDY DESIGN: This is a study based on data from a prospective longitudinal cohort study of fetal growth performed at 12 US sites (2009-2013). Project gestational age was confirmed by ultrasound between 8 weeks 0 days and 13 weels 6 days, and up to 6 ultrasounds were performed across gestation. Hypertensive disorders were diagnosed based on 2002 American College of Obstetricians and Gynecologists guidelines and grouped hierarchically as severe preeclampsia (including eclampsia or HELLP [hemolysis, elevated liver enzymes, and low platelet count] syndrome), mild preeclampsia, severe gestational hypertension, mild gestational hypertension, or unspecified hypertension. Women without any hypertensive disorder constituted the normotensive group. Growth curves for estimated fetal weight and individual biometric parameters including biparietal diameter, head circumference, abdominal circumference, and femur and humerus length were calculated for each group using linear mixed models with cubic splines. Global and weekly pairwise comparisons were performed between women with a hypertensive disorder compared with normotensive women to analyze differences while adjusting for confounding variables. Delivery gestational age and birthweights were compared among groups. RESULTS: Of 2462 women analyzed, 2296 (93.3%) were normotensive, 63 (2.6%) had mild gestational hypertension, 54 (2.2%) mild preeclampsia, 32 (1.3%) severe preeclampsia, and 17 (0.7%) unspecified hypertension. Compared with normotensive women, those with severe preeclampsia had estimated fetal weights that were reduced between 22 and 38 weeks (all weekly pairwise values of P < .008). Women with severe preeclampsia compared with those without hypertension also had significantly smaller fetal abdominal circumference between 23-31 and 33-37 weeks' gestation (weekly pairwise values of P < .04). Scattered weekly growth differences were noted on other biometric parameters between these 2 groups. The consistent differences in estimated fetal weight and abdominal circumference were not observed between women with other hypertensive disorders and those who were normotensive. Women with severe preeclampsia delivered significantly earlier (mean gestational age 35.9 ± 3.2 weeks) than the other groups (global P < .0001). Birthweights in the severe preeclampsia group were also significantly lower (mean -949.5 g [95% confidence interval, -1117.7 to -781.2 g]; P < .0001) than in the normotensive group. CONCLUSION: Among women with pregnancy-associated hypertensive disorders, only those destined to develop severe preeclampsia demonstrated a significant and consistent difference in fetal growth (ie, smaller estimated fetal weight and abdominal circumference) when compared with normotensive women.

Longitudinal changes in maternal anthropometry in relation to neonatal anthropometry.

OBJECTIVE: To 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. DESIGN: In 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. SETTING: Women were recruited from twelve US sites (2009-2013).ParticipantsNon-obese women with singleton pregnancies (n 2334). RESULTS: A 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). CONCLUSIONS: The 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.

Disparate Rates of Cesarean Delivery in Term Nulliparous Women with Hypertensive Disorders of Pregnancy.

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 < 0.01). Hypertensive women had more risk factors for cesarean delivery, most notably morbid obesity (9.0 vs. 3.1%, p < 0.01), diabetes (9.9 vs. 4.4%, p < 0.01), and induction of labor (59.2 vs. 26.9%, p < 0.01). Despite this, after controlling for these risk factors, hypertensive women remained significantly more likely to undergo cesarean delivery (35.1 vs. 26.4%, p < 0.01). 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.