Uma M. Reddy

Background: Prenatal stress and social support are associated with adverse birth outcomes, including stillbirth, in the general population. Their relationship to stillbirth among fetuses with birth defects is unclear. Using data from the National Birth Defects Prevention Study and the Birth Defects Study To Evaluate Pregnancy exposureS, we examined associations between maternal stress and social support and the risk of stillbirth among fetuses with birth defects and whether these associations differed by maternal race/ethnicity. Methods: Participants self‐reported exposure to stressors and social supports experienced 3 months before conception through the first trimester. Using log‐binomial models, we estimated relative risks (RR) and 95% confidence intervals (CI) of stillbirth associated with high stress and low social support, adjusting for maternal age and race/ethnicity. We assessed additive and multiplicative effect measure modification by maternal race/ethnicity. Results: Neither stress nor social support was associated with stillbirth among fetuses with birth defects. Although we did not observe interaction, we observed increased risk of stillbirth among non‐Hispanic Black women with low stress (RR = 2.1, 95% CI = 1.3–3.6), Hispanic women with low stress (1.4, 1.0–2.1), and non‐Hispanic Black women with high stress (2.8, 1.4–5.2) compared to non‐Hispanic White women with low stress. We observed a similar pattern of results for low social support. Conclusions: Stress and social support were not associated with stillbirth in fetuses with birth defects. We observed elevated risk of stillbirth among non‐Hispanic Black women regardless of stress and social support levels.

Background: Differences in extracellular vesicles (EVs), bioactive nanoparticles involved in intercellular signaling, have been reported in those with autism. However, little is known about the association between maternal EVs during pregnancy and the likelihood of autism in offspring. This study evaluated the association of the concentration and cargo material of EVs in prenatal maternal plasma with childhood autism likelihood. Methods: Participants in the Nulliparous Pregnancy Outcomes Study provided maternal plasma at 15–23 weeks’ gestational age. EVs were isolated by ultracentrifugation, and concentration, mean size, CD63 levels, and RNA cargo were assessed by nanoparticle tracking analysis, ELISA, and small RNA sequencing. At 4.5–6 years of age, parents completed the Social Communication Questionnaire. Thirty-one children at high-risk for autism were matched to 31 low-risk children on sex, age, and gestational age. Differential RNA transcript analysis and over representation analysis were performed. Results: There were no group differences in CD63 levels, mean particle size, or EV concentration ( p >0.1). Nominal bin-level differences were observed at 280–290 nm and 430–440 nm before multiple-comparison correction. One hundred forty-five RNAs, including protein-coding RNAs, piRNAs, lncRNAs, miRNAs, snoRNAs, snRNAs, and tRNAs, were differentially contained, most of them downregulated in those at high risk of autism. These RNAs mapped to pathways involved in immune/inflammatory signaling, intracellular trafficking, protein turnover, and neurodevelopment. Six of the 62 (9.7%) differentially contained protein-coding RNAs overlapped with genes in the SFARI Gene database. Limitations: Large studies involving individuals diagnosed with autism are needed to evaluate the role of prenatal EVs in the pathogenesis of the condition. Additionally, prenatal sampling of EVs across multiple timepoints and subsequent deconvolution to determine the source of the EVs will strengthen interpretability and veracity of our findings. Conclusions: These findings provide preliminary evidence that maternal prenatal EV RNA cargo is associated with childhood autism likelihood.

Background: In the United States, mental health complications and cardiovascular events are the 2 leading causes of death for birthing parents in the year following delivery. Most of these deaths are preventable, with Black and Latinx individuals experiencing higher rates of these postpartum complications. Current postpartum care has not reduced these disparities. Objective: This randomized controlled trial aims to train nonmedical professionals in a novel intervention to prevent postpartum depressive symptoms and improve cardiovascular health following childbirth in a low-income New York City (NYC) birthing population. Methods: We aim to recruit 600 birthing individuals over 3 sites across NYC. After screening and consent, participants will be randomized to the Living Healthy for Moms intervention (doula-delivered cognitive behavioral therapy and cardiovascular behavioral health intervention) or attention control (a variation of standard postpartum doula care). Daily telephone contacts for the first 7 days immediately after hospital discharge are followed by 12 doula-led video sessions conducted over 6 months. The primary outcomes are postpartum depressive symptoms and cardiovascular health, with secondary outcomes of psychosocial status, health behaviors, health care use, and patient satisfaction. All outcomes are measured via REDCap (Research Electronic Data Capture; Vanderbilt University) surveys administered at baseline, 2 weeks, 6 weeks, 3 months, and 6 months post discharge. Physiological measurements of glycated hemoglobin (hemoglobin A1c), lipids, and blood pressure will be collected at baseline, 3 months, and 6 months. Doulas, hospital staff, and birthing individuals will be recruited to evaluate the implementation of the intervention following the conclusion of recruitment at each site. A mixed methods triangulated approach will be used, including electronic health record data extraction, web-based surveys, key informant interviews, and focus groups. Results: Recruitment and data collection began at the first site in Brooklyn on January 23, 2025. Data collection for participants from each of the 3 recruitment sites will be concluded by November 30, 2027, February 29, 2028, and August 31, 2029, respectively, for Brooklyn, Queens, and upper Manhattan. Thus, all data for the total expected 600 participants will be collected by the end of the grant year 6, August 31, 2029. Trial results will not be analyzed until grant year 7, beginning September 1, 2029. Data will be analyzed on an intention-to-treat basis by study team members blinded to participant conditions. Conclusions: This hybrid type 1 effectiveness-implementation randomized controlled trial will test a novel nonspecialist intervention to prevent mental health and cardiovascular health complications of childbirth, culturally adapted to our local population in NYC. We expect that our findings will contribute to knowledge on the effectiveness and implementation of nonspecialist postpartum interventions in low-resourced settings and the expansion of doula care in the post partum. Trial Registration: ClinicalTrials.gov NCT06666400; https://clinicaltrials.gov/study/NCT06666400 International Registered Report Identifier (IRRID): DERR1-10.2196/76871

BACKGROUND In the United States, mental health complications and cardiovascular events are the 2 leading causes of death for birthing parents in the year following delivery. Most of these deaths are preventable, with Black and Latinx individuals experiencing higher rates of these postpartum complications. Current postpartum care has not reduced these disparities. OBJECTIVE This randomized controlled trial aims to train nonmedical professionals in a novel intervention to prevent postpartum depressive symptoms and improve cardiovascular health following childbirth in a low-income New York City (NYC) birthing population. METHODS We aim to recruit 600 birthing individuals over 3 sites across NYC. After screening and consent, participants will be randomized to the Living Healthy for Moms intervention (doula-delivered cognitive behavioral therapy and cardiovascular behavioral health intervention) or attention control (a variation of standard postpartum doula care). Daily telephone contacts for the first 7 days immediately after hospital discharge are followed by 12 doula-led video sessions conducted over 6 months. The primary outcomes are postpartum depressive symptoms and cardiovascular health, with secondary outcomes of psychosocial status, health behaviors, health care use, and patient satisfaction. All outcomes are measured via REDCap (Research Electronic Data Capture; Vanderbilt University) surveys administered at baseline, 2 weeks, 6 weeks, 3 months, and 6 months post discharge. Physiological measurements of glycated hemoglobin (hemoglobin A1c), lipids, and blood pressure will be collected at baseline, 3 months, and 6 months. Doulas, hospital staff, and birthing individuals will be recruited to evaluate the implementation of the intervention following the conclusion of recruitment at each site. A mixed methods triangulated approach will be used, including electronic health record data extraction, web-based surveys, key informant interviews, and focus groups. RESULTS Recruitment and data collection began at the first site in Brooklyn on January 23, 2025. Data collection for participants from each of the 3 recruitment sites will be concluded by November 30, 2027, February 29, 2028, and August 31, 2029, respectively, for Brooklyn, Queens, and upper Manhattan. Thus, all data for the total expected 600 participants will be collected by the end of the grant year 6, August 31, 2029. Trial results will not be analyzed until grant year 7, beginning September 1, 2029. Data will be analyzed on an intention-to-treat basis by study team members blinded to participant conditions. CONCLUSIONS This hybrid type 1 effectiveness-implementation randomized controlled trial will test a novel nonspecialist intervention to prevent mental health and cardiovascular health complications of childbirth, culturally adapted to our local population in NYC. We expect that our findings will contribute to knowledge on the effectiveness and implementation of nonspecialist postpartum interventions in low-resourced settings and the expansion of doula care in the post partum. CLINICALTRIAL ClinicalTrials.gov NCT06666400; https://clinicaltrials.gov/study/NCT06666400 INTERNATIONAL REGISTERED REPORT DERR1-10.2196/76871

Objectives: To estimate the association between chronic hypertension and perinatal mortality and to evaluate the extent to which risks are impacted by preterm delivery.Design: Cross‐sectional analysis.Setting: United States, 2015–18.Population: Singleton births (20–44 weeks of gestation).Exposure: Chronic hypertension, defined as elevated blood pressure diagnosed before pregnancy or recognised before 20 weeks of gestation.Main outcomes and measures: We derived the risk of perinatal mortality in relation to chronic hypertension from Poisson models, adjusted for confounders. The impacts of misclassification and unmeasured confounding were assessed. Causal mediation analysis was performed to quantify the impact of preterm delivery on the association.Results: Of the 15 090 678 singleton births, perinatal mortality rates were 22.5 and 8.2 per 1000 births in chronic hypertensive and normotensive pregnancies, respectively (adjusted risk ratio 2.05, 95% CI 2.00–2.10). Corrections for exposure misclassification and unmeasured confounding biases substantially increased the risk estimate. Although causal mediation analysis revealed that most of the association of chronic hypertension on perinatal mortality was mediated through preterm delivery, the perinatal mortality rates were highest at early term, term and late term gestations, suggesting that a planned early term delivery at 37–38^6/7 weeks may optimally balance risk in these pregnancies. Additionally, 87% (95% CI 84–90%) of perinatal deaths could be eliminated if preterm deliveries, as a result of chronic hypertension, were preventable.Conclusions: Chronic hypertension is associated with increased risk for perinatal mortality. Planned early term delivery and targeting modifiable risk factors for chronic hypertension may reduce perinatal mortality rates.Tweetable Maternal chronic hypertension is associated with increased risk for perinatal mortality, largely driven by preterm birth.