Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas.

Adverse pregnancy outcomes (APOs) affect a large proportion of pregnancies and represent an important cause of morbidity and mortality worldwide. Yet the pathophysiology of APOs is poorly understood, limiting our ability to prevent and treat these conditions. To search for genetic markers of maternal risk for four APOs, we performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia. We clustered participants by their genetic ancestry and focused our analyses on three sub-cohorts with the largest sample sizes: European, African, and Admixed American. Association tests were carried out separately for each sub-cohort and then meta-analyzed together. Two novel loci were significantly associated with an increased risk of pregnancy loss: a cluster of SNPs located downstream of the TRMU gene (top SNP: rs142795512), and the SNP rs62021480 near RGMA. In the GWAS of gestational length we identified two new variants, rs2550487 and rs58548906 near WFDC1 and AC005052.1, respectively. Lastly, three new loci were significantly associated with gestational diabetes (top SNPs: rs72956265, rs10890563, rs79596863), located on or near ZBTB20, GUCY1A2, and RPL7P20, respectively. Fourteen loci previously correlated with preterm birth, gestational diabetes, and preeclampsia were found to be associated with these outcomes as well.

Adverse Pregnancy Outcomes and Predicted 30-Year Risk of Maternal Cardiovascular Disease 2-7 Years After Delivery.

OBJECTIVE: To determine whether adverse pregnancy outcomes are associated with a higher predicted 30-year risk of atherosclerotic cardiovascular disease (CVD; ie, coronary artery disease or stroke). METHODS: This was a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. The exposures were adverse pregnancy outcomes during the first pregnancy (ie, gestational diabetes mellitus [GDM], hypertensive disorder of pregnancy, preterm birth, and small- and large-for-gestational-age [SGA, LGA] birth weight) modeled individually and secondarily as the cumulative number of adverse pregnancy outcomes (ie, none, one, two or more). The outcome was the 30-year risk of atherosclerotic CVD predicted with the Framingham Risk Score assessed at 2-7 years after delivery. Risk was measured both continuously in increments of 1% and categorically, with high predicted risk defined as a predicted risk of atherosclerotic CVD of 10% or more. Linear regression and modified Poisson models were adjusted for baseline covariates. RESULTS: Among 4,273 individuals who were assessed at a median of 3.1 years after delivery (interquartile range 2.5-3.7), the median predicted 30-year atherosclerotic CVD risk was 2.2% (interquartile range 1.4-3.4), and 1.8% had high predicted risk. Individuals with GDM (least mean square 5.93 vs 4.19, adjusted ß=1.45, 95% CI, 1.14-1.75), hypertensive disorder of pregnancy (4.95 vs 4.22, adjusted ß=0.49, 95% CI, 0.31-0.68), and preterm birth (4.81 vs 4.27, adjusted ß=0.47, 95% CI, 0.24-0.70) were more likely to have a higher absolute risk of atherosclerotic CVD. Similarly, individuals with GDM (8.7% vs 1.4%, adjusted risk ratio [RR] 2.02, 95% CI, 1.14-3.59), hypertensive disorder of pregnancy (4.4% vs 1.4%, adjusted RR 1.91, 95% CI, 1.17-3.13), and preterm birth (5.0% vs 1.5%, adjusted RR 2.26, 95% CI, 1.30-3.93) were more likely to have a high predicted risk of atherosclerotic CVD. A greater number of adverse pregnancy outcomes within the first birth was associated with progressively greater risks, including per 1% atherosclerotic CVD risk (one adverse pregnancy outcome: 4.86 vs 4.09, adjusted ß=0.59, 95% CI, 0.43-0.75; two or more adverse pregnancy outcomes: 5.51 vs 4.09, adjusted ß=1.16, 95% CI, 0.82-1.50), and a high predicted risk of atherosclerotic CVD (one adverse pregnancy outcome: 3.8% vs 1.0%, adjusted RR 2.33, 95% CI, 1.40-3.88; two or more adverse pregnancy outcomes: 8.7 vs 1.0%, RR 3.43, 95% CI, 1.74-6.74). Small and large for gestational age were not consistently associated with a higher atherosclerotic CVD risk. CONCLUSION: Individuals who experienced adverse pregnancy outcomes in their first birth were more likely to have a higher predicted 30-year risk of CVD measured at 2-7 years after delivery. The magnitude of risk was higher with a greater number of adverse pregnancy outcomes experienced.

Community-level social determinants of health and pregestational and gestational diabetes.

BACKGROUND: Individual adverse social determinants of health are associated with increased risk of diabetes in pregnancy, but the relative influence of neighborhood or community-level social determinants of health is unknown. OBJECTIVE: This study aimed to determine whether living in neighborhoods with greater socioeconomic disadvantage, food deserts, or less walkability was associated with having pregestational diabetes and developing gestational diabetes. STUDY DESIGN: We conducted a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be. Home addresses in the first trimester were geocoded at the census tract level. The exposures (modeled separately) were the following 3 neighborhood-level measures of adverse social determinants of health: (1) socioeconomic disadvantage, defined by the Area Deprivation Index and measured in tertiles from the lowest tertile (ie, least disadvantage [T1]) to the highest (ie, most disadvantage [T3]); (2) food desert, defined by the United States Department of Agriculture Food Access Research Atlas (yes/no by low income and low access criteria); and (3) less walkability, defined by the Environmental Protection Agency National Walkability Index (most walkable score [15.26-20.0] vs less walkable score [<15.26]). Multinomial logistic regression was used to model the odds of gestational diabetes or pregestational diabetes relative to no diabetes as the reference, adjusted for age at delivery, chronic hypertension, Medicaid insurance status, and low household income (<130% of the US poverty level). RESULTS: Among the 9155 assessed individuals, the mean Area Deprivation Index score was 39.0 (interquartile range, 19.0-71.0), 37.0% lived in a food desert, and 41.0% lived in a less walkable neighborhood. The frequency of pregestational and gestational diabetes diagnosis was 1.5% and 4.2%, respectively. Individuals living in a community in the highest tertile of socioeconomic disadvantage had increased odds of entering pregnancy with pregestational diabetes compared with those in the lowest tertile (T3 vs T1: 2.6% vs 0.8%; adjusted odds ratio, 2.52; 95% confidence interval, 1.41-4.48). Individuals living in a food desert (4.8% vs 4.0%; adjusted odds ratio, 1.37; 95% confidence interval, 1.06-1.77) and in a less walkable neighborhood (4.4% vs 3.8%; adjusted odds ratio, 1.33; 95% confidence interval, 1.04-1.71) had increased odds of gestational diabetes. There was no significant association between living in a food desert or a less walkable neighborhood and pregestational diabetes, or between socioeconomic disadvantage and gestational diabetes. CONCLUSION: Nulliparous individuals living in a neighborhood with higher socioeconomic disadvantage were at increased odds of entering pregnancy with pregestational diabetes, and those living in a food desert or a less walkable neighborhood were at increased odds of developing gestational diabetes, after controlling for known covariates.

The Effect of Body Mass Index on Post-Bolus Magnesium Levels in the Obstetric Patient.

OBJECTIVE: In the setting of a growing obese obstetric population, we sought to determine whether differences in body mass index (BMI) and obesity class influenced both serum magnesium levels and the likelihood of achieving therapeutic levels for eclampsia prophylaxis after standard boluses of magnesium sulfate. STUDY DESIGN: This is a retrospective cohort study of patients treated with magnesium sulfate in the setting of either preeclampsia with severe features or preterm labor between 2010 and 2016. Subjects were categorized by BMI: Normal (BMI < 30 kg/m2), Class 1 (BMI 30-34.9 kg/m2), Class 2 (BMI 35-39.9 kg/m2), and Class 3 (BMI ≥ 40 kg/m2). Study participants' demographics, intrapartum characteristics, and adverse reactions were compared among the groups. Logistic regression models were used to calculate unadjusted and adjusted odds ratios comparing the likelihood of each BMI class reaching therapeutic eclamptic prophylactic levels. Linear regression models were also evaluated to determine the relationship between BMI and post-bolus serum magnesium levels. RESULTS: Of the 760 people who met the inclusion criteria, 313 (41.1%) had normal BMI, 190 (25.0%) had Class 1 obesity, 135 (17.8%) had Class 2 obesity, and 122 (16.1%) had Class 3 obesity. When adjusted for confounders, those with Class 1 obesity were 54% less likely to achieve serum levels deemed therapeutic for seizure prophylaxis compared with normal BMI counterparts. Meanwhile, those with Class 2 or 3 obesity were 90% less likely. Linear regression models also demonstrated an inverse association between BMI and post-bolus serum magnesium levels. CONCLUSION: Increasing BMI has a significant effect on post-bolus serum magnesium levels regardless of standard loading dose used. Immediately after bolus administration, obese gravidas are significantly less likely to reach levels effective for eclamptic seizure prophylaxis. When considering which bolus to administer in an obese gravida, it may be more beneficial to choose a 6 g load. KEY POINTS: · BMI has an inverse relationship with post-bolus serum magnesium levels.. · Obese gravidas were less likely to reach eclampsia prophylaxis levels regardless of bolus type.. · Obesity class, not just the presence or absence of obesity, plays a role in serum magnesium levels..

Cannabis Exposure and Adverse Pregnancy Outcomes Related to Placental Function.

Importance: Cannabis use is increasing among reproductive-age individuals and the risks associated with cannabis exposure during pregnancy remain uncertain. Objective: To evaluate the association between maternal cannabis use and adverse pregnancy outcomes known to be related to placental function. Design, Setting, and Participants: Ancillary analysis of nulliparous individuals treated at 8 US medical centers with stored urine samples and abstracted pregnancy outcome data available. Participants in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort were recruited from 2010 through 2013; the drug assays and analyses for this ancillary project were completed from June 2020 through April 2023. Exposure: Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-Δ9-tetrahydrocannabinol using frozen stored urine samples from study visits during the pregnancy gestational age windows of 6 weeks and 0 days to 13 weeks and 6 days (visit 1); 16 weeks and 0 days to 21 weeks and 6 days (visit 2); and 22 weeks and 0 days to 29 weeks and 6 days (visit 3). Positive results were confirmed with liquid chromatography tandem mass spectrometry. The timing of cannabis exposure was defined as only during the first trimester or ongoing exposure beyond the first trimester. Main Outcome and Measure: The dichotomous primary composite outcome included small-for-gestational-age birth, medically indicated preterm birth, stillbirth, or hypertensive disorders of pregnancy ascertained by medical record abstraction by trained perinatal research staff with adjudication of outcomes by site investigators. Results: Of 10 038 participants, 9257 were eligible for this analysis. Of the 610 participants (6.6%) with cannabis use, 32.4% (n = 197) had cannabis exposure only during the first trimester and 67.6% (n = 413) had ongoing exposure beyond the first trimester. Cannabis exposure was associated with the primary composite outcome (25.9% in the cannabis exposure group vs 17.4% in the no exposure group; adjusted relative risk, 1.27 [95% CI, 1.07-1.49]) in the propensity score-weighted analyses after adjustment for sociodemographic characteristics, body mass index, medical comorbidities, and active nicotine use ascertained via urine cotinine assays. In a 3-category cannabis exposure model (no exposure, exposure only during the first trimester, or ongoing exposure), cannabis use during the first trimester only was not associated with the primary composite outcome; however, ongoing cannabis use was associated with the primary composite outcome (adjusted relative risk, 1.32 [95% CI, 1.09-1.60]). Conclusions and Relevance: In this multicenter cohort, maternal cannabis use ascertained by biological sampling was associated with adverse pregnancy outcomes related to placental dysfunction.

Neighborhood Socioeconomic Disadvantage and Abnormal Birth Weight.

OBJECTIVE: To examine whether exposure to community or neighborhood socioeconomic disadvantage as measured by the ADI (Area Deprivation Index) is associated with risk of abnormal birth weight among nulliparous individuals with singleton gestations. METHODS: This was a secondary analysis from the prospective cohort NuMoM2b study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be). Participant addresses at cohort enrollment between 6 and 13 weeks of gestation were geocoded at the Census tract level and linked to the 2015 ADI. The ADI, which incorporates the domains of income, education, employment, and housing quality into a composite national ranking of neighborhood socioeconomic disadvantage, was categorized by quartiles (quartile 1, least disadvantaged, reference; quartile 4, most disadvantaged). Outcomes were large for gestational age (LGA; birth weight at or above the 90th percentile) and small for gestational age (SGA; birth weight below the 10th percentile) compared with appropriate for gestational age (AGA; birth weight 10th-90th percentile) as determined with the 2017 U.S. natality reference data, standardized for fetal sex. Multinomial logistic regression models were adjusted for potential confounding variables. RESULTS: Of 8,983 assessed deliveries in the analytic population, 12.7% (n=1,143) were SGA, 8.2% (n=738) were LGA, and 79.1% (n=7,102) were AGA. Pregnant individuals living in the highest ADI quartile (quartile 4, 17.8%) had an increased odds of delivering an SGA neonate compared with those in the lowest referent quartile (quartile 1, 12.4%) (adjusted odds ratio [aOR] 1.32, 95% CI 1.09-1.55). Pregnant individuals living in higher ADI quartiles (quartile 2, 10.3%; quartile 3, 10.7%; quartile 4, 9.2%) had an increased odds of delivering an LGA neonate compared with those in the lowest referent quartile (quartile 1, 8.2%) (aOR: quartile 2, 1.40, 95% CI 1.19-1.61; quartile 3, 1.35, 95% CI 1.09-1.61; quartile 4, 1.47, 95% CI 1.20-1.74). CONCLUSION: Neonates of nulliparous pregnant individuals living in U.S. neighborhoods with higher area deprivation were more likely to have abnormal birth weights at both extremes.

Sodium intake and the development of hypertensive disorders of pregnancy.

BACKGROUND: In nonpregnant populations, sodium intake has been associated with the development of chronic hypertension, and sodium restriction has been identified as a strategy to reduce blood pressure. Data regarding the relationship between sodium intake and the development of hypertensive disorders of pregnancy are limited and conflicting. OBJECTIVE: This study aimed to assess the association between daily periconceptional sodium intake and the risk of hypertensive disorders of pregnancy. STUDY DESIGN: This was a secondary analysis of the prospective Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study. Individuals with nonanomalous, singleton pregnancies who completed food frequency questionnaires with recorded sodium intake in the 3 months before pregnancy were included in the analysis. Individuals whose pregnancies did not progress beyond 20 weeks of gestation were excluded from the analysis. Sodium intake was categorized as low (<2 g per day), medium (2 to <3 g per day), or high (≥3 g per day), based on thresholds used in the nonpregnant population. The primary outcome was the development of a new-onset hypertensive disorder of pregnancy, including gestational hypertension; preeclampsia; hemolysis, elevated liver enzymes, and low platelet count syndrome; superimposed preeclampsia; or eclampsia. Bivariable analyses were performed using Kruskal-Wallis and chi-square tests. Poisson regression was used to estimate adjusted incidence risk ratios with 95% confidence intervals after controlling for potentially confounding factors. RESULTS: Among 7458 individuals included in this analysis, 2336 (31%) reported low sodium intake, 2792 (37%) reported medium sodium intake, and 2330 (31%) reported high sodium intake. Individuals with high sodium intake were more likely to have chronic hypertension, to use tobacco, and to be living with obesity. The risk of developing a hypertensive disorder of pregnancy was similar among groups (medium vs low adjusted incidence risk ratio: 1.10 [95% confidence interval, 0.94-1.28]; high vs low adjusted incidence risk ratio: 1.17 [95% confidence interval, 1.00-1.37]). There was no difference in neonatal outcomes by sodium intake, including preterm birth, small-for-gestational-age neonate, and admission to the neonatal intensive care unit. CONCLUSION: Sodium intake was not associated with the risk of developing a hypertensive disorder of pregnancy. This lack of association contrasts with that between sodium intake and hypertension in the nonpregnant state and may reflect differences in the pathophysiology underlying pregnancy- vs non-pregnancy-related hypertensive disorders.

Risk factors and perinatal outcomes for persistent placenta previa in nulliparas.

BACKGROUND: Placenta previa diagnosed on midtrimester ultrasound often resolves by the third trimester. Multiparity and previous cesarean delivery have been associated with persistence of placenta previa at delivery. Risk factors for persistent placenta previa in nulliparas are not well characterized. OBJECTIVE: This study aimed to identify risk factors for persistent placenta previa in the nulliparous population, and evaluate differences in outcomes between persistent and resolved placenta previa. STUDY DESIGN: This was a secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b), a prospective cohort study that observed 10,037 nulliparous individuals throughout pregnancy. Nulliparas diagnosed with placenta previa on midtrimester ultrasound were included in this analysis. Baseline characteristics and delivery outcomes of nulliparas with persistent placenta previa were compared with those of nulliparas with resolved placenta previa. Multivariate logistic regression with stepwise model selection was used for adjusted analyses. RESULTS: A total of 171 nulliparas (1.7%) in the nuMoM2b study were diagnosed with placenta previa on midtrimester ultrasound, of whom 17% (n=29) had persistent placenta previa at delivery. When compared with those with resolved placenta previa, nulliparas with persistent placenta previa were more likely to be older (median, 32 years [interquartile range, 30-37] vs 29 years [interquartile range, 25-31]; P<.01), have a previous pregnancy of <20 weeks (48.3% vs 22.5%; P=.01), have a previous dilation and curettage/evacuation procedure (27.6% vs 10.6%; P=.03), or have a pregnancy that resulted from assisted reproductive technology (31% vs 4.9%; P=.01). After adjusting for potential confounders, maternal age (adjusted odds ratio, 1.11; 95% confidence interval, 1.02-1.21), in vitro fertilization (adjusted odds ratio, 9.00; 95% confidence interval, 1.97-41.14), and previous pregnancy of <20 weeks (adjusted odds ratio, 2.77; 95% confidence interval, 1.10-6.95) remained statistically significant risk factors for persistent placenta previa. Persistent placenta previa was also associated with higher likelihood of antepartum admission (10.3% vs 0%; P<.01), preterm delivery (34.5% vs 12%; P<.01), lower neonatal birthweight (median, 2847 g [interquartile range, 2655-3310] vs 3263 g [interquartile range, 2855-3560]), and cesarean delivery (100% vs 20.4%; P<.001), but there were no differences in overall pregnancy or neonatal outcomes. CONCLUSION: In nulliparous individuals diagnosed with placenta previa on midtrimester ultrasound, older maternal age, previous pregnancy of <20 weeks, and in vitro fertilization are associated with persistent placenta previa at delivery.

Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b.

Adverse pregnancy outcomes (APOs) are major risk factors for women's health during pregnancy and even in the years after pregnancy. Due to the heterogeneity of APOs, only few genetic associations have been identified. In this report, we conducted genome-wide association studies (GWASs) of 479 traits that are possibly related to APOs using a large and racially diverse study, Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). To display extensive results, we developed a web-based tool GnuMoM2b (https://gnumom2b.cumcobgyn.org/) for searching, visualizing, and sharing results from a GWAS of 479 pregnancy traits as well as phenome-wide association studies of more than 17 million single nucleotide polymorphisms. The genetic results from 3 ancestries (Europeans, Africans, and Admixed Americans) and meta-analyses are populated in GnuMoM2b. In conclusion, GnuMoM2b is a valuable resource for extraction of pregnancy-related genetic results and shows the potential to facilitate meaningful discoveries.

Searching and visualizing genetic associations of pregnancy traits by using GnuMoM2b.

Adverse pregnancy outcomes (APOs) are major risk factors for women's health during pregnancy and even in the years after pregnancy. Due to the heterogeneity of APOs, only few genetic associations have been identified. In this report, we conducted genome-wide association studies (GWAS) of 479 traits that are possibly related to APOs using a large and racially diverse study, Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be (nuMoM2b). To display the extensive results, we developed a web-based tool GnuMoM2b ( https://gnumom2b.cumcobgyn.org/ ) for searching, visualizing, and sharing results from GWAS of 479 pregnancy traits as well as phenome-wide association studies (PheWAS) of more than 17 million single nucleotide polymorphisms (SNPs). The genetic results from three ancestries (Europeans, Africans, and Admixed Americans) and meta-analyses are populated in GnuMoM2b. In conclusion, GnuMoM2b is a valuable resource for extraction of pregnancy-related genetic results and shows the potential to facilitate meaningful discoveries.

Association between Sleep Disordered Breathing and Neonatal Outcomes in Nulliparous Individuals.

OBJECTIVE: Our objective was to determine whether objectively measured sleep-disordered breathing (SDB) during pregnancy is associated with an increased risk of adverse neonatal outcomes in a cohort of nulliparous individuals. STUDY DESIGN: Secondary analysis of the nuMom2b sleep disordered breathing substudy was performed. Individuals underwent in-home sleep studies for SDB assessment in early (6-15 weeks' gestation) and mid-pregnancy (22-31 weeks' gestation). SDB was defined as an apnea-hypopnea index ≥5 events/h at either time point. The primary outcome was a composite outcome of respiratory distress syndrome, transient tachypnea of the newborn, or receipt of respiratory support, treated hyperbilirubinemia or hypoglycemia, large-for-gestational age, seizures treated with medications or confirmed by electroencephalography, confirmed sepsis, or neonatal death. Individuals were categorized into (1) early pregnancy SDB (6-15 weeks' gestation), (2) new onset mid-pregnancy SDB (22-31 weeks' gestation), and (3) no SDB. Log-binomial regression was used to calculate adjusted risk ratios (RR) and 95% confidence intervals (CIs) representing the association. RESULTS: Among 2,106 participants, 3% (n = 75) had early pregnancy SDB and 5.7% (n = 119) developed new-onset mid-pregnancy SDB. The incidence of the primary outcome was higher in the offspring of individuals with early (29.3%) and new onset mid-pregnancy SDB (30.3%) compared with individuals with no SDB (17.8%). After adjustment for maternal age, chronic hypertension, pregestational diabetes, and body mass index, new onset mid-pregnancy SDB conferred increased risk (RR = 1.43, 95% CI: 1.05, 1.94), where there was no longer statistically significant association between early pregnancy SDB and the primary outcome. CONCLUSION: New onset, mid-pregnancy SDB is independently associated with neonatal morbidity. KEY POINTS: · Sleep disordered breathing (SDB) is a common condition impacting pregnancy with known maternal risks.. · Objectively defined SDB in pregnancy was associated with a composite of adverse neonatal outcomes.. · New onset SDB in mid pregnancy conferred statistically significant increased risk..

Can allostatic load in pregnancy explain the association between race and subsequent cardiovascular disease risk: A cohort study.

OBJECTIVE: To assess the relationship between allostatic load, a measure of cumulative chronic stress in early pregnancy and cardiovascular disease risk, 2-7 years postpartum, and pathways contributing to racial disparities in cardiovascular disease risk. DESIGN: Secondary analysis of a prospective cohort study. SETTING MULTICENTER POPULATION: Pregnant women. METHODS: Our primary exposure was high allostatic load in the first trimester, defined as at least 4 of 12 biomarkers (systolic blood pressure, diastolic blood pressure, body mass index, cholesterol, low-density lipoprotein, high-density lipoprotein, high-sensitivity C-reactive protein, triglycerides, insulin, glucose, creatinine and albumin) in the unfavourable quartile. Logistic regression was used to test the association between high allostatic load and main outcome adjusted for confounders: time from index pregnancy and follow up, age, education, smoking, gravidity, bleeding in the first trimester, index adverse pregnancy outcomes, and health insurance. Each main outcome component and allostatic load were analysed secondarily. Mediation and moderation analyses assessed the role of high allostatic load in racial disparities of cardiovascular disease risk. MAIN OUTCOME MEASURE: Incident cardiovascular disease risk: hypertension, or metabolic disorders. RESULTS: Cardiovascular disease risk was identified in 1462/4022 individuals (hypertension: 36.6%, metabolic disorder: 15.4%). After adjustment, allostatic load was associated with cardiovascular disease risk (adjusted odds ratio [aOR] 2.0, 95% CI 1.8-2.3), hypertension (aOR 2.1, 95% CI 1.8-2.4) and metabolic disorder (aOR 1.7, 95% CI 1.5-2.1). Allostatic load was a partial mediator between race and cardiovascular disease risk. Race did not significantly moderate this relationship. CONCLUSIONS: High allostatic load during pregnancy is associated with cardiovascular disease risk. The relationships between stress, subsequent cardiovascular risk and race warrant further study.

Serum Cotinine and Adverse Cardiovascular Outcomes: A Cross-sectional Secondary Analysis of the nuMoM2b Heart Health Study.

OBJECTIVE: We aimed to (1) compare serum cotinine with self-report for ascertaining smoking status among reproductive-aged women; (2) estimate the relative odds of adverse cardiovascular (CV) outcomes among women by smoking status; (3) assess whether the association between adverse pregnancy outcomes (APOs) and CV outcomes varies by smoking status. STUDY DESIGN: We conducted a cross-sectional study of the nuMoM2b Heart Health Study. Women attended a study visit 2 to 7 years after their first pregnancy. The exposure was smoking status, determined by self-report and by serum cotinine. Outcomes included incident chronic hypertension (HTN), metabolic syndrome (MetS), and dyslipidemia. Multivariable logistic regression estimated odds ratios (ORs) for each outcome by smoking status. RESULTS: Of 4,392 women with serum cotinine measured, 3,610 were categorized as nonsmokers, 62 as secondhand smoke exposure, and 720 as smokers. Of 3,144 women who denied tobacco smoke exposure, serum cotinine was consistent with secondhand smoke exposure in 48 (1.5%) and current smoking in 131 (4.2%) After adjustment for APOs, smoking defined by serum cotinine was associated with MetS (adjusted OR [aOR] = 1.52, 95% confidence interval [CI]: 1.21, 1.91) and dyslipidemia (aOR = 1.28, 95% CI: 1.01, 1.62). When stratified by nicotine exposure, nonsmokers with an APO in their index pregnancy had higher odds of stage 1 (aOR = 1.64, 95% CI: 1.32, 2.03) and stage 2 HTN (aOR = 2.92, 95% CI: 2.17, 3.93), MetS (aOR = 1.76, 95% CI: 1.42, 2.18), and dyslipidemia (aOR = 1.55, 95% CI: 1.25, 1.91) relative to women with no APO. Results were similar when smoking exposure was defined by self-report. CONCLUSION: Whether determined by serum cotinine or self-report, smoking is associated with subsequent CV outcomes in reproductive-aged women. APOs are also independently associated with CV outcomes in women. KEY POINTS: · Cotinine was detected in 5.7% of reported nonsmokers.. · Smoking and APOs were independently associated with CV health.. · Smoking was associated with MetS and dyslipidemia..

Periconceptional diet quality is associated with gestational diabetes risk and glucose concentrations among nulliparous gravidas.

Background: Gestational diabetes mellitus (GDM) and elevated glucose concentrations below the threshold for GDM diagnosis have been associated with adverse pregnancy and offspring outcomes. Dietary interventions initiated during pregnancy have demonstrated inconsistent beneficial effects. Limited data exist regarding the effects of periconceptional diet on gestational glycemia. Objective: To evaluate independent associations between periconceptional diet quality with GDM frequency and glucose concentrations from GDM screening and diagnostic tests among nulliparous gravidas. Design: This is a secondary analysis of N=7997 participants from the NuMoM2b multicenter, prospective, observational cohort study of first pregnancies. The Alternative Healthy Eating Index (AHEI)-2010 was computed from food frequency questionnaires completed in early pregnancy (6-13 weeks), reporting usual dietary intake over the preceding 3 months. GDM screening was performed either by non-fasting 1-hour 50g glucose load (N=6845), followed by 3-hour 100g glucose tolerance test (GTT) for those with raised glucose concentrations (N=1116; at risk for GDM), or by a single 2-hour 75g GTT (N=569; all GDM risk levels). Logistic and linear regression were used to estimate the associations between the AHEI-2010 score with odds of GDM, having raised blood glucose on the 1-hour screening test, and continuous glucose concentrations on screening and diagnostic tests. All models were adjusted for a priori covariates: maternal age, race/ethnicity, early-pregnancy body mass index, smoking habits, rate of gestational weight gain, energy intake, nausea and vomiting in early pregnancy, study site. Results: Poorer periconceptional diet quality was observed among participants who were younger, with higher BMI, lower income levels, and of non-Hispanic Black or Hispanic ethnicity. The GDM rate was 4%. Each 1-point increase in AHEI-2010 score was associated with a 1% decrease in the odds of being diagnosed with GDM (beta=-0.015, p=0.022, OR=0.986, 95% CI 0.973 to 0.998). Diet quality was inversely associated with each post glucose load concentration on the non-fasting screening test and the 2-hour and 3-hour GTT. Conclusion: Poor periconceptional diet quality is independently associated with an increased risk of GDM and with minor elevations in serum glucose concentrations on GDM screening and diagnostic tests, in a diverse cohort of nulliparas. Periconception intervention studies targeting diet quality are warranted.

Factors associated with duration of breastfeeding in women giving birth for the first time.

OBJECTIVE: To examine maternal, psychosocial, and pregnancy factors associated with breastfeeding for at least 6 months in those giving birth for the first time. METHODS: We performed a planned secondary analysis of an observational cohort study of 5249 women giving birth for the first time. Women were contacted at least 6 months after delivery and provided information regarding breastfeeding initiation, duration, and exclusivity. Maternal demographics, psychosocial measures, and delivery methods were compared by breastfeeding groups. RESULTS: 4712 (89.8%) of the women breastfed at some point, with 2739 (58.2%) breastfeeding for at least 6 months. Of those who breastfed, 1161 (24.7% of the entire cohort), breastfed exclusively for at least 6 months. In the multivariable model among those who ever breastfed, not smoking in the month prior to delivery (adjusted odds ratio [aOR] 2.04, 95%CI 1.19-3.45), having a Master's degree of higher (aOR 1.89, 95%CI 1.51-2.36), having a planned pregnancy (aOR 1.48, 95%CI 1.27-1.73), older age (aOR 1.02, 95% CI, 1.01-1.04), lower BMI (aOR 0.96 95% CI 0.95-0.97), and having less anxiety measured during pregnancy (aOR 0.990, 95%CI 0.983-0.998) were associated with breastfeeding for at least 6 months. Compared to non-Hispanic White women, Hispanic women, while being more likely to breastfeed initially (aOR 1.40, 95%CI 1.02-1.92), were less likely to breastfeed for 6 months (aOR 0.72, 95%CI 0.59-0.88). While non-Hispanic Black women were less likely than non-Hispanic White women to initiate breastfeeding (aOR 0.68, 95%CI 0.51-0.90), the odds of non-Hispanic Black women of continuing to breastfeed for at least 6 months was similar to non-Hispanic White women (aOR 0.92, 95%CI 0.71-1.19). CONCLUSIONS: In this cohort of women giving birth for the first time, duration of breastfeeding was associated with several characteristics which highlight groups at greater risk of not breastfeeding as long as currently recommended. TRIAL REGISTRATION: NCT01322529 (nuMoM2b) and NCT02231398 (nuMoM2b-Heart Health).

Association of Genetic Predisposition and Physical Activity With Risk of Gestational Diabetes in Nulliparous Women.

Importance: Polygenic risk scores (PRS) for type 2 diabetes (T2D) can improve risk prediction for gestational diabetes (GD), yet the strength of the association between genetic and lifestyle risk factors has not been quantified. Objective: To assess the association of PRS and physical activity in existing GD risk models and identify patient subgroups who may receive the most benefits from a PRS or physical activity intervention. Design, Settings, and Participants: The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort was established to study individuals without previous pregnancy lasting at least 20 weeks (nulliparous) and to elucidate factors associated with adverse pregnancy outcomes. A subcohort of 3533 participants with European ancestry was used for risk assessment and performance evaluation. Participants were enrolled from October 5, 2010, to December 3, 2013, and underwent genotyping between February 19, 2019, and February 28, 2020. Data were analyzed from September 15, 2020, to November 10, 2021. Exposures: Self-reported total physical activity in early pregnancy was quantified as metabolic equivalents of task (METs). Polygenic risk scores were calculated for T2D using contributions of 84 single nucleotide variants, weighted by their association in the Diabetes Genetics Replication and Meta-analysis Consortium data. Main Outcomes and Measures: Estimation of the development of GD from clinical, genetic, and environmental variables collected in early pregnancy, assessed using measures of model discrimination. Odds ratios and positive likelihood ratios were used to evaluate the association of PRS and physical activity with GD risk. Results: A total of 3533 women were included in this analysis (mean [SD] age, 28.6 [4.9] years). In high-risk population subgroups (body mass index ≥25 or aged ≥35 years), individuals with high PRS (top 25th percentile) or low activity levels (METs <450) had increased odds of a GD diagnosis of 25% to 75%. Compared with the general population, participants with both high PRS and low activity levels had higher odds of a GD diagnosis (odds ratio, 3.4 [95% CI, 2.3-5.3]), whereas participants with low PRS and high METs had significantly reduced risk of a GD diagnosis (odds ratio, 0.5 [95% CI, 0.3-0.9]; P = .01). Conclusions and Relevance: In this cohort study, the addition of PRS was associated with the stratified risk of GD diagnosis among high-risk patient subgroups, suggesting the benefits of targeted PRS ascertainment to encourage early intervention.

Association of Cannabis Use With Nausea and Vomiting of Pregnancy.

Our objective was to evaluate whether cannabis use was associated with nausea and vomiting in early pregnancy. Participants from nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be) enrolled from October 2010 through September 2013 with a PUQE (Pregnancy-Unique Quantification of Emesis) questionnaire and an available stored urine sample from the first study visit (median gestational age 12 weeks) were included. Cannabis exposure was ascertained by urine immunoassay for 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH); positive results were confirmed with liquid chromatography tandem mass spectrometry. The primary outcome was moderate-to-severe nausea by the PUQE score. Overall, 9,250 participants were included, and 5.8% (95% CI 5.4-6.3%) had detectable urine THC-COOH. In adjusted analyses, higher THC-COOH levels were associated with greater odds of moderate-to-severe nausea (20.7% in the group with THC-COOH detected vs 15.5% in the group with THC-COOH not detected, adjusted odds ratio 1.6, 95% CI 1.1-2.2 for a 500 ng/mg Cr THC-COOH increment).

Placental protein levels in maternal serum are associated with adverse pregnancy outcomes in nulliparous patients.

BACKGROUND: The Eunice Kennedy Shriver National Institute of Child Health and Human Development Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be was established to investigate the underlying causes and pathophysiological pathways associated with adverse pregnancy outcomes in nulliparous gravidas. OBJECTIVE: This study aimed to study placental physiology and identify novel biomarkers concerning adverse pregnancy outcomes, including preterm birth (medically indicated and spontaneous), preeclampsia, small-for-gestational-age neonates, and stillbirth. We measured levels of placental proteins in the maternal circulation in the first 2 trimesters of pregnancy. STUDY DESIGN: Maternal serum samples were collected at 2 study visits (6-13 weeks and 16-21 weeks), and levels of 9 analytes were measured. The analytes we measured were vascular endothelial growth factor, placental growth factor, endoglin, soluble fms-like tyrosine kinase-1, A disintegrin and metalloproteinase domain-containing protein 12, pregnancy-associated plasma protein A, free beta-human chorionic gonadotropin, inhibin A, and alpha-fetoprotein. The primary outcome was preterm birth between 20 0/7 and 36 6/7 weeks of gestation. The secondary outcomes were spontaneous preterm births, medically indicated preterm births, preeclampsia, small-for-gestational-age neonates, and stillbirth. RESULTS: A total of 10,038 eligible gravidas were enrolled in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be cohort, from which a nested case-control study was performed comparing 800 cases with preterm birth (466 spontaneous preterm births, 330 medically indicated preterm births, and 4 unclassified preterm births), 568 with preeclampsia, 406 with small-for-gestational-age birth, and 49 with stillbirth with 911 controls who delivered at term without complications. Although levels of each analyte generally differed between cases and controls at 1 or 2 visits, the odds ratios revealed a <2-fold difference between cases and controls in all comparisons. Receiver operating characteristic curves, generated to determine the relationship between analyte levels and preterm birth and the other adverse pregnancy outcomes, resulted in areas under the receiver operating characteristic curves that were relatively low (range, 0.50-0.64) for each analyte. Logistic regression modeling demonstrated that areas under the receiver operating characteristic curves for predicting adverse pregnancy outcomes were greater using baseline clinical characteristics and combinations of analytes than baseline characteristics alone, but areas under the receiver operating characteristic curves remained relatively low for each outcome (range, 0.65-0.78). CONCLUSION: We have found significant associations between maternal serum levels of analytes evaluated early in pregnancy and subsequent adverse pregnancy outcomes in nulliparous gravidas. However, the test characteristics for these analytes do not support their use as clinical biomarkers to predict adverse pregnancy outcomes, either alone or in combination with maternal clinical characteristics.