Large-Scale Proteomics in Early Pregnancy and Hypertensive Disorders of Pregnancy.

Importance: There is no consensus regarding the best method for prediction of hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia. Objective: To determine predictive ability in early pregnancy of large-scale proteomics for prediction of HDP. Design, Setting, and Participants: This was a nested case-control study, conducted in 2022 to 2023, using clinical data and plasma samples collected between 2010 and 2013 during the first trimester, with follow-up until pregnancy outcome. This multicenter observational study took place at 8 academic medical centers in the US. Nulliparous individuals during first-trimester clinical visits were included. Participants with HDP were selected as cases; controls were selected from those who delivered at or after 37 weeks without any HDP, preterm birth, or small-for-gestational-age infant. Age, self-reported race and ethnicity, body mass index, diabetes, health insurance, and fetal sex were available covariates. Exposures: Proteomics using an aptamer-based assay that included 6481 unique human proteins was performed on stored plasma. Covariates were used in predictive models. Main Outcomes and Measures: Prediction models were developed using the elastic net, and analyses were performed on a randomly partitioned training dataset comprising 80% of study participants, with the remaining 20% used as an independent testing dataset. Primary measure of predictive performance was area under the receiver operating characteristic curve (AUC). Results: This study included 753 HDP cases and 1097 controls with a mean (SD) age of 26.9 (5.5) years. Maternal race and ethnicity were 51 Asian (2.8%), 275 non-Hispanic Black (14.9%), 275 Hispanic (14.9%), 1161 non-Hispanic White (62.8% ), and 88 recorded as other (4.8%), which included those who did not identify according to these designations. The elastic net model, allowing for forced inclusion of prespecified covariates, was used to adjust protein-based models for clinical and demographic variables. Under this approach, no proteins were selected to augment the clinical and demographic covariates. The predictive performance of the resulting model was modest, with a training set AUC of 0.64 (95% CI, 0.61-0.67) and a test set AUC of 0.62 (95% CI, 0.56-0.68). Further adjustment for study site yielded only minimal changes in AUCs. Conclusions and Relevance: In this case-control study with detailed clinical data and stored plasma samples available in the first trimester, an aptamer-based proteomics panel did not meaningfully add to predictive utility over and above clinical and demographic factors that are routinely available.

Diet quality, community food access, and glycemic control among nulliparous individuals with diabetes.

Better diet quality regardless of community food access was associated with a higher likelihood of glycemic control in early pregnancy among nulliparous individuals with pregestational diabetes. These findings highlight the need for interventions that address nutrition insecurity for pregnant individuals living with diabetes.

Socioeconomic Disadvantage in Pregnancy and Postpartum Risk of Cardiovascular Disease.

BACKGROUND: Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. But the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. OBJECTIVE: To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. METHODS: An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic CVD (ASCVD, composite of fatal and non-fatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2-to-7 years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD >10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. RESULTS: Among 4,309 nulliparous individuals at baseline, the median age was 27 years (IQR: 23-31) and the median ADI was 43 (IQR: 22-74). At 2-to-7 years postpartum (median: 3.1 years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk >10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adj. ß: 0.41; 95% CI: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top two ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (aRR: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). CONCLUSIONS: Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

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.

Prediction of metabolic syndrome following a first pregnancy.

BACKGROUND: The prevalence of metabolic syndrome is rapidly increasing in the United States. We hypothesized that prediction models using data obtained during pregnancy can accurately predict the future development of metabolic syndrome. OBJECTIVE: This study aimed to develop machine learning models to predict the development of metabolic syndrome using factors ascertained in nulliparous pregnant individuals. STUDY DESIGN: This was a secondary analysis of a prospective cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study [nuMoM2b-HHS]). Data were collected from October 2010 to October 2020, and analyzed from July 2023 to October 2023. Participants had in-person visits 2 to 7 years after their first delivery. The primary outcome was metabolic syndrome, defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, which was measured within 2 to 7 years after delivery. A total of 127 variables that were obtained during pregnancy were evaluated. The data set was randomly split into a training set (70%) and a test set (30%). We developed a random forest model and a lasso regression model using variables obtained during pregnancy. We compared the area under the receiver operating characteristic curve for both models. Using the model with the better area under the receiver operating characteristic curve, we developed models that included fewer variables based on SHAP (SHapley Additive exPlanations) values and compared them with the original model. The final model chosen would have fewer variables and noninferior areas under the receiver operating characteristic curve. RESULTS: A total of 4225 individuals met the inclusion criteria; the mean (standard deviation) age was 27.0 (5.6) years. Of these, 754 (17.8%) developed metabolic syndrome. The area under the receiver operating characteristic curve of the random forest model was 0.878 (95% confidence interval, 0.846-0.909), which was higher than the 0.850 of the lasso model (95% confidence interval, 0.811-0.888; P<.001). Therefore, random forest models using fewer variables were developed. The random forest model with the top 3 variables (high-density lipoprotein, insulin, and high-sensitivity C-reactive protein) was chosen as the final model because it had the area under the receiver operating characteristic curve of 0.867 (95% confidence interval, 0.839-0.895), which was not inferior to the original model (P=.08). The area under the receiver operating characteristic curve of the final model in the test set was 0.847 (95% confidence interval, 0.821-0.873). An online application of the final model was developed (https://kawakita.shinyapps.io/metabolic/). CONCLUSION: We developed a model that can accurately predict the development of metabolic syndrome in 2 to 7 years after delivery.

Associations between individual and structural level racism and gestational age at birth in the Nulliparous Pregnancy Outcomes Study: Monitoring mothers-to-be.

The purpose of this study was to investigate the associations between multilevel racism and gestational age at birth among nulliparous non-Hispanic Black, non-Hispanic White and Hispanic women. We conducted a secondary analysis of data of the nuMoM2b Study (2010-2013) to examine the associations between individual and structural-level experiences of racism and discrimination and gestational age at birth among nulliparous women (n=7,732) at eight sites across the U.S. Measures included the individual Experiences of Discrimination (EOD) scale and the Index of Concentration (ICE) at the Extremes to measure structural racism. After adjustment,we observed a significant individual and structural racism interaction on gestational length (p=0.03). In subgroup analyses, we found that among these with high EOD scores, women who were from households concentrated in the more privileged group had significantly longer gestations (ß = 1.07, 95% CI: 0.24, 1.90). Women who reported higher EOD scores and more economic privilege had longer gestations, demonstrating the moderating effect of ICE as a measure of structural racism. In conclusion, ICE may represent a modifiable factor in the prevention of adverse birth outcomes in nulliparas.

NuMoM2b Study Insights: Primary Exposures, Outcomes, and Directions for Future Research.

OBJECTIVE: To summarize the publications to date from a large obstetric cohort of nulliparous individuals. STUDY DESIGN: We summarized all of the publications from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-be (nuMoM2b). We descriptively summarized the most common outcomes and exposures reported in current publications. RESULTS: Fifty-six publications to date are discussed. The most common primary exposures reported are participant baseline characteristics such as body mass index (24%), sociodemographic characteristics (22%), and sleep factors (16%). These exposures were most commonly measured in the first trimester (77%). The most commonly reported primary outcomes were related to adverse pregnancy outcomes (APOs, 51.6%), with 25% using a composite of multiple APOs as the primary outcome. At least 8,000 participants were used in the analyses of over half of the publications. CONCLUSION: The nuMoM2b study has generated a diverse array of publications and conclusions on factors associated with APOs. The publicly available data set from the nuMoM2b study continues to hold potential for considerable advances, new insights, and future research opportunities to optimize pregnancy and pregnancy-related health. KEY POINTS: · The nuMoM2b pregnancy cohort has generated 56 publications thus far.. · The main findings of these publications are summarized and categorized in this work.. · The data and specimens from this cohort are available and can answer many clinical questions..

Body Mass Index, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk.

BACKGROUND: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors. METHODS: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels. RESULTS: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth. CONCLUSIONS: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.

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.

Genetic Associations with Dynamic Placental Proteins Identify Causal Biomarkers for Hypertension in Pregnancy.

Preeclampsia (PE), a gestational hypertensive disorder, ranks as the second leading cause of maternal mortality worldwide. While PE is considered a multifactorial disease, placental insufficiency is believed to drive its progression. To noninvasively study placental physiology related to adverse pregnancy outcomes (APOs) and predict these outcomes before symptom onset, we measured nine placental protein levels in first- and second-trimester serum samples from 2,352 nulliparous pregnant women in the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers- to-Be (nuMoM2b) study. The proteins analyzed include VEGF, PlGF, ENG, sFlt-1, ADAM-12, PAPP-A, fßHCG, INHA, and AFP. Currently, little is known about the genetic variants contributing to the heritability of these proteins during pregnancy, and no studies have explored the causal relationships between early pregnancy proteins and gestational hypertensive disorders. Our study has three objectives. First, we conducted genome-wide association study (GWAS) of nine placental proteins in maternal serum during the first and second trimesters and the difference between time points to understand how genetics may influence placental proteins in early pregnancy. Second, we examined whether early pregnancy placental proteins are causal factors for PE and gestational hypertension (gHTN). Lastly, we investigated the causal relationship between PE/gHTN and long-term HTN. In conclusion, our study discovered significant genetic associations with placental proteins ADAM-12, VEGF, and sFlt-1, offering insights into their regulation during pregnancy. Mendelian randomization (MR) analyses demonstrated evidence of causal relationships between placental proteins, particularly ADAM-12, and gHTN, potentially informing prevention and treatment strategies. Our findings suggest that placental proteins like ADAM-12 could serve as biomarkers for postpartum HTN risk.

Adverse Pregnancy Outcomes and Future Metabolic Syndrome.

Background: Metabolic syndrome (MetS) is associated with a history of gestational diabetes (GDM), hypertensive disorders of pregnancy (HDP), and preterm birth (PTB), but it is unclear whether this association is due to the pregnancy complication(s) or prepregnancy/early pregnancy confounders. The study examines the association of GDM, HDP, and PTB with MetS 2-7 years later, independent of early pregnancy factors. Materials and Methods: Large, diverse cohort of nulliparous pregnant people with singleton gestations enrolled during their first trimester and who attended a follow-up study visit 2-7 years after delivery. The longitudinal cohort was recruited from eight medical centers across the United States. Using standardized protocols, anthropometry, biospecimens, and surveys were collected at study visits and pregnancy outcomes were abstracted from medical records. We estimated the relative risk of prevalent MetS at the follow-up study visit for participants with GDM, HDP, or PTB (vs. no complications), adjusting for early pregnancy age, body mass index, self-reported race/ethnicity, insurance type, and smoking status. Results: Of 4,402 participants, 738 (16.8%) had MetS at follow-up: 13.1% (441/3,365) among those with no complications, and 27.9% (290/1,002) among those with complications. MetS occurred in 39.0% of GDM (73/187, adjusted relative risk [aRR] = 1.75; 95% confidence interval [CI] 1.42-2.16); 29.2% of HDP (176/603, aRR = 1.49; 95% CI 1.27-1.75); and 29.7% of PTB (113/380, aRR = 1.78; 95% CI 1.49-2.12). Those who had both HDP and PTB (n = 113) had an aRR = 1.95 (95% CI 1.50-2.54). Conclusions: People whose pregnancies were complicated by GDM, HDP, or PTB are at a higher risk of MetS within 2-7 years after delivery, independent of early pregnancy risk factors. The highest MetS risk follows pregnancies complicated by both HDP and PTB.

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..

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..

Association of a Mediterranean Diet Pattern With Adverse Pregnancy Outcomes Among US Women.

Importance: The Mediterranean diet pattern is inversely associated with the leading causes of morbidity and mortality, including metabolic diseases and cardiovascular disease, but there are limited data on its association with adverse pregnancy outcomes (APOs) among US women. Objective: To evaluate whether concordance to a Mediterranean diet pattern around the time of conception is associated with lower risk of developing any APO and individual APOs. Design, Setting, and Participants: This prospective, multicenter, cohort study, the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be, enrolled 10 038 women between October 1, 2010, and September 30, 2013, with a final analytic sample of 7798 racially, ethnically, and geographically diverse women with singleton pregnancies who had complete diet data. Data analyses were completed between June 3, 2021, and April 7, 2022. Exposures: An Alternate Mediterranean Diet (aMed) score (range, 0-9; low, 0-3; moderate, 4-5; and high, 6-9) was computed from data on habitual diet in the 3 months around conception, assessed using a semiquantitative food frequency questionnaire. Main Outcomes and Measures: Adverse pregnancy outcomes were prospectively ascertained and defined as developing 1 or more of the following: preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, delivery of a small-for-gestational-age infant, or stillbirth. Results: Of 7798 participants (mean [SD] age, 27.4 [5.5] years), 754 (9.7%) were aged 35 years or older, 816 (10.5%) were non-Hispanic Black, 1294 (16.6%) were Hispanic, and 1522 (19.5%) had obesity at baseline. The mean (SD) aMed score was 4.3 (2.1), and the prevalence of high, moderate, and low concordance to a Mediterranean diet pattern around the time of conception was 30.6% (n=2388), 31.2% (n=2430), and 38.2% (n=2980), respectively. In multivariable models, a high vs low aMed score was associated with 21% lower odds of any APO (adjusted odds ratio [aOR], 0.79 [95% CI, 0.68-0.92]), 28% lower odds of preeclampsia or eclampsia (aOR, 0.72 [95% CI, 0.55-0.93]), and 37% lower odds of gestational diabetes (aOR, 0.63 [95% CI, 0.44-0.90]). There were no differences by race, ethnicity, and prepregnancy body mass index, but associations were stronger among women aged 35 years or older (aOR, 0.54 [95% CI, 0.34-0.84]; P = .02 for interaction). When aMed score quintiles were evaluated, similar associations were observed, with higher scores being inversely associated with the incidence of any APO. Conclusions and Relevance: This cohort study suggests that greater adherence to a Mediterranean diet pattern is associated with lower risk of APOs, with evidence of a dose-response association. Intervention studies are needed to assess whether dietary modification around the time of conception can reduce risk of APOs and their downstream associations with future development of cardiovascular disease risk factors and overt disease.

Association between aspirin use during pregnancy and cardiovascular risk factors 2-7 years after delivery: The nuMoM2b Heart Health Study.

OBJECTIVES: To evaluate the association between aspirin use during first pregnancy and later maternal cardiovascular risk. STUDY DESIGN: In this secondary analysis of a prospective cohort, we included participants who carried their first pregnancy to 20 + weeks, had data regarding aspirin use, and attended a study visit 2-7 years following delivery. The exposure was aspirin use during the first pregnancy. We calculated aspirin use propensity scores from logistic regression models including baseline variables associated with aspirin use in pregnancy and cardiovascular risk. Outcomes of interest were incident cardiovascular-related diagnoses 2-7 years following delivery. Robust Poisson regression calculated the risk of outcomes by aspirin exposure, adjusting for the aspirin use propensity score. MAIN OUTCOME MEASURES: The primary outcome was a composite of incident cardiovascular diagnoses at the time of the study visit: cardiovascular events, chronic hypertension, metabolic syndrome, prediabetes or type 2 diabetes, dyslipidemia, and chronic kidney disease. RESULTS: Of 4,480 women included, 84 (1.9%) reported taking aspirin during their first pregnancy. 52.6% of participants in the aspirin-exposed group and 43.0% in the unexposed group had the primary outcome. After adjusting for the aspirin use propensity scores, aspirin use during the first pregnancy was not associated with any of the outcomes. CONCLUSION: We did not detect an association between aspirin use during the first pregnancy and cardiovascular-related diagnoses 2-7 years later. Our study was only powered to detect a large difference in relative risk, so we cannot rule out a smaller difference that may be clinically meaningful.

Association of N-Terminal Pro-Brain Natriuretic Peptide Concentration in Early Pregnancy With Development of Hypertensive Disorders of Pregnancy and Future Hypertension.

IMPORTANCE: Hypertensive disorders of pregnancy are associated with future cardiovascular disease, perhaps because of subclinical cardiac dysfunction before pregnancy leading to impaired adaptation to pregnancy. Natriuretic peptides are promising biomarkers for detecting subclinical cardiac dysfunction outside of pregnancy. OBJECTIVE: To investigate whether higher concentrations of N-terminal pro-brain natriuretic peptide (NT-proBNP) in early pregnancy would be associated with hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used data from the The Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study, a prospective multicenter observational study. A total of 4103 nulliparous women with complete data and no prepregnancy hypertension or diabetes who were treated at 8 clinical sites were included. Women were followed up with for 2 to 7 years after pregnancy. Data were collected from October 2010 to October 2017, and data were analyzed from August 2020 to November 2021. EXPOSURES: NT-proBNP concentration, measured using an electrochemiluminescence immunoassay from a first-trimester blood sample. MAIN OUTCOMES AND MEASURES: Hypertensive disorders of pregnancy and incident hypertension (systolic blood pressure of 130 mm Hg or diastolic blood pressure of 80 mm Hg or use of antihypertensive agents) at follow-up visit. RESULTS: A total of 4103 women met inclusion criteria; the mean (SD) age was 27.0 (5.6) years. Among these women, 909 (22.2%) had an adverse pregnancy outcome, and 817 (19.9%) had hypertension at the follow-up visit. Higher NT-proBNP concentrations were associated with a lower risk of hypertensive disorders of pregnancy (adjusted odds ratio per doubling, 0.81; 95% CI, 0.73-0.91), which persisted after adjustment for age, self-reported race and ethnicity, early-pregnancy body mass index, smoking, and aspirin use. Similarly, higher NT-proBNP concentration in early pregnancy was also associated with a lower risk of incident hypertension 2 to 7 years after delivery (adjusted odds ratio per doubling, 0.84; 95% CI, 0.77-0.93), an association that persisted after controlling for confounders, including hypertensive disorders of pregnancy. CONCLUSIONS AND RELEVANCE: In this cohort study, higher NT-proBNP concentrations in early pregnancy were associated with a lower risk of hypertensive disorders of pregnancy and hypertension 2 to 7 years post partum. These findings suggest that normal early-pregnancy cardiovascular physiology, as assessed by NT-proBNP concentration, may provide biologic insights into both pregnancy outcome and cardiovascular disease risk.

A common language for Gulf War Illness (GWI) research studies: GWI common data elements.

AIMS: The Gulf War Illness programs (GWI) of the United States Department of Veteran Affairs and the Department of Defense Congressionally Directed Medical Research Program collaborated with experts to develop Common Data Elements (CDEs) to standardize and systematically collect, analyze, and share data across the (GWI) research community. MAIN METHODS: A collective working group of GWI advocates, Veterans, clinicians, and researchers convened to provide consensus on instruments, case report forms, and guidelines for GWI research. A similar initiative, supported by the National Institute of Neurologic Disorders and Stroke (NINDS) was completed for a comparative illness, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), and provided the foundation for this undertaking. The GWI working group divided into two sub-groups (symptoms and systems assessment). Both groups reviewed the applicability of instruments and forms recommended by the NINDS ME/CFS CDE to GWI research within specific domains and selected assessments of deployment exposures. The GWI CDE recommendations were finalized in March 2018 after soliciting public comments. KEY FINDINGS: GWI CDE recommendations are organized in 12 domains that include instruments, case report forms, and guidelines. Recommendations were categorized as core (essential), supplemental-highly recommended (essential for specified conditions, study types, or designs), supplemental (commonly collected, but not required), and exploratory (reasonable to use, but require further validation). Recommendations will continually be updated as GWI research progresses. SIGNIFICANCE: The GWI CDEs reflect the consensus recommendations of GWI research community stakeholders and will allow studies to standardize data collection, enhance data quality, and facilitate data sharing.

Does brain size affect mate choice? An experimental examination in pygmy halfbeaks.

Choosing a mate is one of the most important decisions in an animal's lifetime. Female mate choice is often guided by the presence or intensity of male sexual ornaments, which must be integrated and compared among potential mates. Individuals with greater cognitive abilities may be better at evaluating and comparing sexual ornaments, even when the difference in ornaments is small. While brain size is often used as a proxy for cognitive ability, its effect on mate choice has rarely been investigated. Here, we investigate the effect of brain size on mate preferences in the pygmy halfbeak Dermogenys collettei, a small freshwater fish that forms mixed-sex shoals where mating takes place. Pygmy halfbeaks are ideal models as their semi-transparent heads allow for external brain measurements. After validating the use of external measurements as a proxy for internal brain size, we presented females with large or small brains (relative to body length) with two males that had either a large or small difference in sexual ornamentation (measured by the total area of red coloration). Unexpectedly, neither total relative brain size nor relative telencephalon size affected any measured aspect of mate preference. However, the difference in male sexual ornamentation did affect preference, with females preferring males with a smaller area of red coloration when the difference in ornaments was large. This study highlights the complexities of mate choice and the importance of considering a range of stimuli when examining mate preferences.