George R. Saade

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.

Purpose: Postpartum Depression (PPD) is the most common mental health complication of childbirth, and has short-term and long-term consequences for mother, child, and the entire family. PPD is a function of several factors. Prenatal exposure to nicotine (PEN) by Active Tobacco Smoking (ATS), Secondhand Smoking (SHS), or Electronic Nicotine Products (ENPs) is a major potential risk factor. This systematic review and meta-analysis aim to summarize and evaluate all evidence regarding the association between PEN and PPD. Methods: We searched the following databases, PubMed, Medline, Cochrane, EMBASE, and CINHAL, for studies published between Jan.1st ,2000&Sep.19th ,2024, with the outcome PPD. Studies quality was assessed using the Newcastle–Ottawa Scale. Pooled Prevalence (PP) was calculated using the Freeman-Tukey Double Arcsine Transformation method. Pooled Odds Ratio (pooled-OR) was estimated using a random-effects model. Sensitivity analysis was conducted using the leave-one-out technique. Results: Of 29 studies in the systematic review, 26 included in the meta-analysis. PP of PPD was 0.15,(95% CI[0.12–0.17]; I ² = 99.80%, p < 0.001). Pooled-OR for ATS 1.96,(95%CI[1.59–2.41]; Z = 6.46, p < 0.001), 1.22,(95%CI[0.69–2.18], Z = 0.69, p = 0.49) for SHS, and 1.14,(95%CI[0.82–1.58,Z = 0.78, p = 0.43) for ENPs. While the overall Pooled-OR for all PEN was 1.74,(95%CI[1.44–2.12]; Z = 5.59, p < 0.001), funnel plots and Egger test showed no evidence of publication bias. Sensitivity analysis confirmed the robustness of the findings. Conclusion: This meta-analysis reveals that the accumulated evidence shows a significant association between prenatal PEN and PPD; though this final finding should be interpreted cautiously due to the high heterogeneity. Therefore, the exposure-stratified estimates represent the principal findings of this meta-analysis. The findings indicates a significant association between prenatal ATS and PPD, but no clear conclusion could be drawn about prenatal SHS or ENPs use due to the limited number of studies. There is a need for future studies that prospectively assess the impact of SHS and ENP on PPD.

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.

Background/Objectives: Prior spontaneous preterm birth (sPTB) and short cervical length predict the occurrence of sPTB with low sensitivity, highlighting the need for better detectors of at-risk pregnancies. PreTRM^® is a validated, biomarker-based sPTB predictor that we aimed to improve in this study by developing models that incorporate parity and key risk factors. Methods: A Model was developed and validated through retrospective analysis of a cohort of singleton pregnancies that resulted in a live term or preterm birth (PTB) (n = 976). The Model’s ability to predict sPTB and PTB was assessed and its clinical utility compared to PreTRM. Results: The Model predicted sPTB with 77.1% sensitivity, 74.4% specificity, 21.4% positive predictive value (PPV) and 97.3% negative predictive value (NPV), an improvement over PreTRM’s sensitivity (75.0%) and PPV (14.6%), and a higher PPV than short cervix (16.2%). PTB was predicted by the Model with 76.8% sensitivity, 74.6% specificity, 31.6% PPV and 95.5% NPV. Relative to PreTRM, the Model achieved significantly higher area under the receiver operating characteristic curve (AUC) results when predicting whether a PTB or sPTB would be associated with a neonatal hospital stay ≥5 days (p = 0.001 for PTB; p = 0.044 for sPTB). The Model also achieved significantly higher sensitivity than PreTRM in predicting a ≥5 day hospital stay associated with PTB (p = 0.009) and higher sensitivity for a ≥5 day hospital stay associated with sPTB, showing improved clinical utility over PreTRM. Conclusions: The Model achieved substantially higher performance than standard of care risk predictors, and an improvement in clinical utility over PreTRM, demonstrating the robustness of the Model as a sPTB and PTB predictor.

BACKGROUND: Adverse pregnancy outcomes (APOs) are associated with a higher risk of developing chronic hypertension. The objectives of this study were to determine whether patterns of perceived stress during and after pregnancy were associated with blood pressure and incident hypertension 2 to 7 years after delivery, and whether having an APO modified this association. METHODS: Analyses utilized data from the prospective nuMoM2b-HHS cohort (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study). Perceived stress was assessed using the Perceived Stress Scale in the first and third trimester and 2 to 7 years after delivery. Latent class trajectory analysis characterized subgroups with similar patterns of perceived stress over time. APOs were abstracted from medical charts and included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age, and stillbirth. Multivariable regression models evaluated the independent effects of perceived stress on systolic and diastolic blood pressure and incident hypertension and 2 to 7 years after delivery. RESULTS: Three distinct stress trajectory groups emerged, delineated by persistently low, moderate, and high stress levels. No associations between stress trajectory group and blood pressure or incident hypertension were observed after adjustment for covariates. However, there was a significant interaction between stress trajectory group and APO on blood pressure ( P for interaction=0.04). Stress trajectory group was associated with higher blood pressure only among those with APO ( β =1.991±0.819 mm Hg; P =0.02) but not without APO ( β =0.040±0.471 mm Hg, P =0.93). CONCLUSIONS: These findings suggest that elevated perceived stress may contribute to higher blood pressure, specifically among women who had an APO.