Janet M. Catov

Introduction: To evaluate the association between the use of antihypertensive medications during the peripartum period among individuals with hypertensive disorders of pregnancy (HDP) and the risk of incident hypertension in the years after pregnancy. Methods: We conducted a secondary analysis of the nuMoM2b‐Heart Health Study (HHS), a multi‐site prospective cohort study that enrolled nulliparous pregnant individuals in their first trimester who were followed during pregnancy and subsequently underwent a cardiovascular screening visit (HHS visit) 2‐7 years after delivery. Individuals without chronic hypertension who developed HDP (gestational hypertension, preeclampsia without severe features, or preeclampsia with severe features) were included. The exposure was treatment with antihypertensive medication (oral or intravenous) during the pregnancy episode (pregnancy through 6 weeks postpartum). The primary outcome was stage 1 (blood pressure [BP] ≥130/80 mmHg) and stage 2 hypertension (BP ≥140/90 mmHg or use of antihypertensive medications) at the HHS visit, which was ascertained following a standardized research protocol. Multinomial logistic regression models estimated the association of antihypertensive medication use with incident hypertension, adjusted for co‐variates. Results: Among 4484 individuals who underwent a follow‐up visit (mean follow‐up: 3.2 ± 1.8 years), 1007 (22.5%) had HDP during the nuMoM2b pregnancy and were included. Of those, 132 (13%) were treated with an antihypertensive medication during the pregnancy episode. Treated individuals had higher systolic (119 ± 13 vs. 114 ± 11 mmHg, p < 0.001) and diastolic (80 ± 12 vs. 74 ± 10 mmHg, p < 0.001) BP at follow‐up. In multivariable regression, those treated with antihypertensive medications had 2.5‐fold (95% confidence interval [CI], 1.6–4.1) greater odds of stage 1 hypertension and 4.3‐fold (95% CI, 2.5–7.3) greater odds of stage 2 hypertension compared to those with HDP who were not treated with antihypertensive medications. Conclusion: Among nulliparous individuals with HDP, treatment with antihypertensive medication during or immediately after pregnancy is associated with a two‐ to fourfold higher odds of incident hypertension in the years postpartum, independent of HDP type. The use of antihypertensive medication in the peripartum period may serve as an easily ascertainable risk marker to identify individuals at heightened risk of persistent hypertension who may benefit from targeted postpartum surveillance and intervention.

Background: How prepregnancy body mass index (BMI) and pregnancy physical activity (PA) jointly shape postpartum cardiovascular risk remains unclear. This study evaluated whether joint trajectories of PA and sedentary behavior during pregnancy mediate the association between prepregnancy BMI and postpartum blood pressure (BP). Methods: Pregnancy 24/7 is a multisite observational cohort enrolling individuals <13 weeks' gestation, aged 18 to 45 years, without chronic hypertension, diabetes, sleep disorders, or severe mobility limitation (n=500). Participants with valid PA/sedentary behavior data for ≥1 trimester and a clinic BP reading 4 to 8 weeks postpartum were analyzed. Prepregnancy BMI was chart‐abstracted; PA/sedentary behavior were measured each trimester via the activPAL3 micro. Hypertensive postpartum BP was defined as systolic BP ≥130 mm Hg or diastolic BP ≥80 mm Hg. Parallel‐process latent growth modeling and K‐means clustering identified PA trajectory groups; mediation analysis tested whether these groups explained the BMI‐BP association. Results: Among 388 participants (aged 30.9±4.5 years), 109 (28.4%) had hypertensive postpartum BP. Each 1‐unit increase in prepregnancy BMI was associated with 6.0% greater risk of hypertensive postpartum BP (risk ratio, 1.06 [95% CI, 1.04–1.09]), adjusting for demographic and pregnancy characteristics. Three trajectory groups emerged: active‐declining (n=142), active‐improving (n=103), and consistently sedentary (n=143). The active‐declining group had 37% lower risk than the consistently sedentary group, but this attenuated after BMI adjustment. Physical activity trajectories did not mediate the BMI‐BP relationship, which was largely explained by prepregnancy BMI alone. Conclusions: Prepregnancy BMI predicted hypertensive postpartum BP independent of activity patterns, underscoring the clinical value of prepregnancy weight optimization and vigilant postpartum monitoring for those entering pregnancy with elevated BMI. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04749849.

Background: Poor prenatal sleep health is associated with greater gestational weight gain, but the contributions to longer-term maternal weight retention remain unclear. Purpose: To examine associations between prenatal sleep health across multiple domains and maternal weight retention 2 to 7 years after a first birth. Methods: Participants were from the nuMoM2b-Heart Health Study. Self-reported sleep was assessed during early (6 to 13 6/7 weeks) and mid-pregnancy (22 to 28 6/7 weeks) across six domains: regularity, quality, sleepiness, timing, efficiency, and duration. A multidimensional sleep health (MSH) score reflected the number of domains meeting healthy thresholds. Outcomes included maternal weight retention, total and substantial (>11 lbs.), from pre-pregnancy to 2 to 7 years after a first birth. Associations were estimated using adjusted linear regression for total weight retention and Poisson regression with robust variance for substantial weight retention. Results: The sample included 3,661 individuals with data in early (n = 2,962) and mid-pregnancy (n = 3,210). In early pregnancy, healthy sleep duration was associated with lower total weight retention, whereas healthy sleep regularity was unexpectedly associated with greater retention. In contrast, during mid-pregnancy, a higher MSH score was associated with a lower risk of substantial weight retention (RR = 0.96, 95% CI: 0.93 to 0.99). Healthy sleep duration and quality were the two individual domains associated with lower weight retention (2 to 3 lbs.). Conclusions: In a prospective cohort of pregnant nulliparous individuals, healthy prenatal sleep, particularly during mid-pregnancy, was associated with less maternal weight retention 2 to 7 years after delivery. Future studies should estimate the causal effects of sleep health on long-term maternal weight retention.

Background: Adverse pregnancy outcomes (APOs) are associated with increased hypertension risk. Black women experience higher rates of APOs and hypertension compared with White women, but whether APOs contribute to Black‐White hypertension disparities remains unknown. Methods: The nuMoM2b‐HHS (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers‐To‐Be–Heart Health Study) prospectively recruited nulliparous pregnant people at 8 US centers (2010–2013) with follow‐up 2 to 7 years postpartum (2014–2017). Race, which represents a social construct, was self‐identified. The primary outcome was incident hypertension at follow‐up. APOs included hypertensive disorders of pregnancy, preterm birth, and small‐for‐gestational age birth. Potential confounders (psychological health, social factors, and health behaviors) were assessed via validated questionnaires. We used targeted maximum likelihood‐based estimation to estimate Black‐White hypertension differences that would remain if racial disparities in APOs were eliminated. Results: Among 3335 participants (17% Black; 83% White; mean [SD] age, 27.6 [5.1] years), APO incidence was higher in Black versus White individuals (rate differences [RDs] per 1000 births: hypertensive disorders of pregnancy: 52.5 [95% CI, 20.0–85.1]; preterm birth: 45.4 [95% CI, 20.8–70.1]; small‐for‐gestational age: 102.4 [95% CI, 75.8–129.1]). Incident hypertension at median 3 years postpartum was higher in Black versus White individuals (RD, 107.1 [95% CI, 69.6–144.4]). APOs mediated the racial disparity in hypertension; eliminating Black‐White disparities in APOs would decrease the Black‐White disparity in hypertension by 18.2% for hypertensive disorders of pregnancy (RD, 87.6 [95% CI, 36.1–139.2]), 16.3% for preterm birth (RD, 89.6 [95% CI, 41.7–137.6]), and 13.9% for small‐for‐gestational age (RD, 92.2 [95% CI, 41.6–142.9]). Conclusions: Black‐White differences in hypertension were partially mediated by APOs. APOs may represent a pregnancy‐specific pathway contributing to racial disparities in hypertension.

Background: Hypertensive disorders of pregnancy (HDP) may first be diagnosed antepartum, during labor, or postpartum. We utilized untargeted large-scale proteomics to identify pathways associated with HDP based on timing of onset. Methods: We performed a nested case-control study comparing differential protein expression, from the SomaScan 7K platform, based on timing of onset of HDP versus controls (referent) using first-trimester samples from the NuMoM2b-Heart Health Study, a multi-site cohort that followed nulliparous individuals from the first trimester. Associations of proteins with timing of onset of HDP, adjusted for co-variates, were assessed using logistic regression q value-based false discovery rates and pathway enrichment and differential expression analysis were conducted. Results: Of 1628 individuals included, 678 had HDP, of which 67% manifested antepartum (AP), 29% intrapartum (IP), and 3% postpartum (PP). After adjusting for co-variates, compared to controls, 698 proteins, 39 proteins, and 144 proteins were differentially expressed in those with HDP according to AP, IP, PP onset, respectively. There was little overlap in individual protein expression based on timing of HDP. Pathway enrichment and graphical summary analyses suggested distinct processes. Specifically, there was downregulation of angiogenic proteins in AP HDP, downregulation of immune-related proteins in IP HDP, and upregulation of complement activation promoting fibrotic changes leading to cardiac dysfunction in PP HDP. Conclusion: There are differences in first-trimester protein expression based on whether HDP first manifests AP, IP or PP. This raises the possibility that there may be distinct mechanistic phenotypes that could uniquely inform diagnostic and therapeutic targets for HDP.

BACKGROUND: Isolated diastolic hypertension can precede combined systolic-diastolic hypertension, suggesting isolated diastolic hypertension may be a risk factor for adverse cardiovascular outcomes. Little is known about the prevalence of hypertensive subtypes (isolated diastolic, isolated systolic, or combined systolic-diastolic hypertension) in the years after first pregnancy, and whether these differ after hypertensive disorder of pregnancy. METHODS: This is a secondary analysis (conducted 2023–2024) of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study. Nulliparas were enrolled at 8 US clinical sites from 2010 to 2013; participants who completed the Heart Health Study visit 2 to 7 years after pregnancy were eligible. Blood pressures were elevated at the visit if systolic was ≥130 mm Hg and diastolic ≥80 mm Hg. Multinomial logistic regression relative risk models were adjusted for age, body mass index, race, and time from pregnancy to visit. RESULTS: Four thousand three hundred two participants were included. Mean age at Heart Health Study visit was 30.7 years (SD, 5.6 years); 812 (19%) had elevated blood pressure. Isolated diastolic hypertension was most prevalent (n=627; 15%). Compared with normotensive pregnancy, hypertensive disorders of pregnancy were associated with combined systolic-diastolic (adjusted risk ratio, 3.09 [95% CI, 2.21–4.31]) and isolated diastolic hypertension (adjusted risk ratio, 1.65 [95% CI, 1.36–2.00]). CONCLUSIONS: Isolated diastolic hypertension is the most prevalent hypertensive subtype after first pregnancy. Women with hypertensive disorders of pregnancy had increased risk of combined systolic-diastolic and isolated diastolic hypertension. Given the high prevalence of isolated diastolic hypertension found in this cohort, postpartum women represent a subgroup with opportunity for cardiovascular risk reduction. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02231398.

Background Individuals diagnosed with depression during pregnancy are more likely to develop cardiovascular disease (CVD) later in life. However, it remains unclear whether subclinical depressive symptoms or symptom trajectories across time are associated with indicators of cardiovascular health (CVH). Therefore, the present study evaluated the relationship between longitudinal depressive symptom trajectories beginning in pregnancy and future CVH. Methods This secondary analysis of the multisite prospective nuMoM2b-Heart Health Study and included participants with complete longitudinal data from early pregnancy to 2-7 years post-delivery. Participants self-reported depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) at 6-13 weeks gestation (early pregnancy), 22-29 weeks gestation (mid- to late-pregnancy), and 2-7 years post-delivery. Latent class mixture modeling was conducted to identify longitudinal patterns of depressive symptoms across early pregnancy, mid-late pregnancy, and extended postpartum follow-up. Structural equation modeling was used to test whether EPDS trajectories were associated with latent CVH, adjusted for length of follow-up interval, pre-pregnancy BMI, gravidity, adverse pregnancy outcomes, smoking history, age, education, income, and use of psychiatric medications. Results A total of 3,934 participants (mean (M) ± standard deviation (SD) age=27.6±5.6 years) met inclusion criteria with a mean follow-up interval of 3.2±0.9 years. A 4-class model, which provided the best fit to the EPDS data (mean posterior probability across classes=0.81), produced the following trajectories: (1) stable low (n=2412; 61.1%), (2) increasing severity (n=848; 21.5%), (3) decreasing severity (n=476; 12.1%), and (4) stable high (n=212; 5.4%). Compared to the stable low group, all groups exhibited significantly lower CVH (stable high: β=0.06, pp=0.02; increasing severity: β=0.08 p0.24). Discussion The longitudinal course of depressive symptoms from pregnancy to 2-7 years post-delivery varied across individuals. Compared to those with consistently low depressive symptoms, individuals with higher severity symptoms at any point all exhibited lower CVH, regardless of the specific trajectory of symptoms. These findings support a life-course perspective in which depressive symptom patterns may represent an early indicator of cardiometabolic vulnerability. Clinical Perspective What is New? We examined the longitudinal relationship between differing trajectories of depressive symptoms during pregnancy and throughout the extended postpartum period and future cardiovascular health. We found that individuals with stably elevated, decreasing severity and increasing severity depressive symptoms from pregnancy to 2-7 years post-delivery exhibited lower cardiovascular health 2-7 years post-delivery relative to individuals with stably low depressive symptoms. What are the Clinical Implications? The longitudinal course depressive symptoms from pregnancy through the extended postpartum period varies across individuals, and individuals with consistently elevated, elevated with decreasing severity, and low with increasing severity symptoms exhibit poorer cardiovascular health compared to those with consistently low severity symptoms. This suggests that any elevation of depressive symptoms, regardless of whether they exceed clinical thresholds indicative of a depressive episode, may relate to cardiovascular risk. Routine assessment of depressive symptoms across pregnancy and in the years following delivery may facilitate early detection of individuals who may be at risk of CVD in the future.

Exposure to trace elements and per- and polyfluoroalkyl substances (PFAS) during pregnancy is linked to adverse reproductive and developmental outcomes. High smoking rates in western Pennsylvania may influence exposure to these chemicals. We characterized PFAS, trace element, and smoking exposure in the second trimester of pregnancy among women in western Pennsylvania. We measured 38 urine trace elements and 11 serum PFAS in 46 pregnant women in 2017–2021 as part of a nested pilot study from the Magee Obstetric Maternal and Infant (MOMI) biobank and database. We statistically compared environmental chemical concentrations between smoking and non-smoking participants in the MOMI pilot study. Additionally, we descriptively compared MOMI concentrations to a nationally representative sample of US women of reproductive age from the National Health and Nutrition Examination Survey (NHANES) and to published studies characterizing exposures among international populations. Two PFAS (PFOA and PFOS) and 16 trace elements were highly detected in the MOMI pilot study sample. Smoking participants had distributions of 10 trace element concentrations that tended to be significantly higher compared to non-smoking participants, but no significant differences in the distributions of serum PFAS concentrations. All participants had summed PFAS concentrations > 2 μg/L—the National Academies of Sciences Engineering and Medicine threshold for recommending additional health screening. MOMI non-smoking participants had higher concentrations of seven trace elements and lower concentrations of both PFAS compared with NHANES non-smoking participants, while MOMI smoking participants had higher concentrations of 12 trace elements and lower concentrations of both PFAS compared with NHANES smoking participants. Further research is necessary to identify the sources of exposure, potential health effects, and effective strategies to reduce exposure to these environmental chemicals.

Background: The period around pregnancy is a critical window in the primordial prevention of cardiovascular disease, but little is known about the role of dietary patterns in cardiometabolic health. Our objective was to determine the association between alignment of periconceptional diet with the 2020 to 2025 Dietary Guidelines for Americans and the risk of metabolic syndrome. Methods and Results: We used data from the Nulliparous Pregnancy Outcomes Study: monitoring mothers‐to‐Be Heart Health Study, a pregnancy cohort study that followed pregnant participants to a median of 3 years postpartum (n=4423). Usual dietary intake in the 3 months around conception was estimated from a Food Frequency Questionnaire. Alignment with the Dietary Guidelines was measured using the Healthy Eating Index‐2020, where higher scores represent greater alignment. Postpartum metabolic syndrome was defined using the American Heart Association/National Heart, Lung, and Blood Institute guideline. The prevalence of metabolic syndrome at 3 years postpartum was 20%. After adjusting for confounders, the prevalence of metabolic syndrome was flat up to a periconceptional Healthy Eating Index‐2020 total score of ≈60, and then declined steeply as scores increased. Compared with a Healthy Eating Index‐2020 score of 60, having scores of 70, 80, and 90 were associated with 2, 4, and 7 fewer cases of metabolic syndrome per 100 individuals, respectively (prevalence differences: −0.02 [95% CI, −0.03, 0]; −0.04 [−0.08, −0.1]; −0.07 [−0.13, −0.02]). Conclusions: Dietary interventions around conception and systems‐level changes to support high diet quality may be important for improving postpartum cardiometabolic health, and helping to reverse or slow the decline in women's cardiometabolic health.