Abstract Aim Examine cross-sectional associations between mid-pregnancy food intake indicators and prenatal depressive symptomatology. Methods This secondary analysis of the Comparison of Two Screening Strategies for Gestational Diabetes trial (N = 718) examined domains of mid-pregnancy food intake (direct timing, energy timing, meal/snack structure, meal energy distribution, diet quality) derived from 24-hour dietary recalls. Depressive symptoms were measured with the Edinburgh Postnatal Depression Scale (EPDS). Generalized linear models examined associations between food intake indicators, total, and high (EPDS ≥13) depressive symptoms. Results Mean (SD) EPDS score was [6.3 (4.9)]; 12.4% (n = 89) had high depressive symptoms. Eating frequency (B = 0.08 [0.02, 0.14], p = 0.009), snack frequency (B = 0.06 [0.00, 0.12], p = 0.040), nighttime snacking frequency (B = 0.06 [0.00, 0.11], p = 0.041), and total daily energy intake (B = 0.06 [0.01, 0.12], p = 0.031) were positively associated with total depressive symptoms. Energy intake from breakfast (PR = 1.2 [1.0, 1.3], p = 0.017) was associated with a higher prevalence of high depressive symptoms. Energy intake from dinner (PR = 0.81 [0.69, 0.94], p = 0.007), later timing of the first eating episode (PR = 0.83 [0.70, 0.99], p = 0.034) and first energy quartile (PR = 0.84 [0.70, 1.0], p = 0.048), were associated with a lower prevalence of high depressive symptoms. Conclusion These findings extend prior chrononutrition-depression literature to the prenatal period, implicating eating frequency, energy intake, and meal energy timing and distribution in depressive symptomatology during pregnancy, warranting further longitudinal investigation. Key Messages Eating frequency, snacking, nighttime snacking, and longer eating windows were positively associated with increased prevalence of depressive symptomatology within the prenatal period. Each of these results align with previous literature in general adult or postpartum populations and extend to prenatal populations specifically. These results suggest the role of circadian misalignment (potentially via mechanisms including nocturnal cortisol response, serotonin and dopamine dysregulation, systemic inflammation, and delayed melatonin production) in prenatal psychopathology. Importantly, the potential bidirectional nature of food intake and depression cannot be overlooked. Total energy consumed per day, percentage of energy from breakfast and dinner, as well as later timing of initial energy intake and first caloric quartile were positively associated with prenatal depression. Additionally, particular indicators of dietary quality and macronutrient percentages (e.g., percentage of energy obtained from fat), were not significantly associated with prenatal depression. These findings call for future research to explore nuance regarding macronutrient consumption, energy intake percentages, meal timing regularity, and the possible implications of emotionally responsive eating in the relationship between food intake and prenatal depression The current study is exploratory in nature, being the first to explore a robust range of food intake indicators and their relationship to depressive symptomatology in the prenatal period. As prenatal depression is a strong predictor of worsening mental health during postpartum, it is important that future research test a priori hypotheses regarding food intake indicators and prenatal depression longitudinally in order to determine both temporal precedence and validate the associations found within our study. If validated, multiple domains of food intake may potentially provide modifiable behaviors that can protect against depression during the prenatal period.

In this study, a single hepatitis C virus (HCV) RNA at 2-6 months was sensitive and specific (86.7% and 95% confidence interval [CI], 62.1%-96.3% and 100% and 95% CI, 98.8%-100%, respectively) in identifying perinatal transmission of HCV. No cases of perinatal infection requiring treatment were missed.

OBJECTIVE:To examine the intersectionality of three frequently measured neighborhood social determinants during pregnancy-socioeconomic disadvantage, food access, and walkability-and their collective association with nulliparous term, singleton, vertex (NTSV) cesarean delivery. METHODS:This was a secondary analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be observational cohort. Home addresses in the first trimester were geocoded at the census-tract level to define three adverse neighborhood measures: 1) socioeconomic disadvantage by the Area Deprivation Index (in tertiles), 2) low food access by the U.S. Department of Agriculture Food Access Research Atlas (yes/no), and 3) low walkability by the Environmental Protection Agency National Walkability Score (yes/no). The exposure was the number of neighborhood adverse social determinants and was assessed by number (0, 1, 2 or more) and specific combinations. The outcome was NTSV cesarean delivery. Multivariable modified Poisson regression with robust error variance was used. We secondarily assessed the distribution of clinical indications for cesarean delivery and whether associations between neighborhood social determinants and cesarean delivery varied by self-reported race and ethnicity. RESULTS:Among 8,010 nulliparous individuals with NTSV deliveries, 27.3% lived in a neighborhood in the top tertile of socioeconomic disadvantage, 24.5% with low food access, and 66.4% with low walkability. The risk of NTSV cesarean delivery was higher only among individuals living in neighborhoods with low walkability (adjusted relative risk [RR] 1.17, 95% CI, 1.06-1.28). Individuals exposed to one (adjusted RR 1.14, 95% CI, 1.01-1.27) or two or more (adjusted RR 1.19, 95% CI, 1.06-1.34) compared with no adverse neighborhood social determinants had a higher risk of cesarean delivery. Individuals living in neighborhoods with low walkability and high socioeconomic disadvantage (adjusted RR 1.21, 95% CI, 1.03-1.41) or low walkability and low food access (adjusted RR 1.20, 95% CI, 1.05-1.37) had a higher risk of cesarean delivery. The frequency of all three adverse neighborhood social determinants was higher for non-Hispanic Black and Hispanic individuals compared with non-Hispanic White individuals (P<.05), but the above association between neighborhood social determinants and cesarean delivery did not vary by self-reported race and ethnicity (adjusted interaction P=.6). CONCLUSION:In a prospective U.S. cohort, living in a neighborhood with low walkability, alone and in combination with socioeconomic disadvantage and food access, was associated with an increased risk of NTSV cesarean delivery.

OBJECTIVE:To evaluate the association between latency of expectant management in individuals with preterm onset of a hypertensive disorder of pregnancy (HDP) and markers of cardiovascular risk 2-7 years after a first pregnancy. METHODS:This was a secondary analysis of the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be)-Heart Health Study, a prospective study with adjudicated pregnancy outcomes and follow-up cardiovascular measures 2-7 years after the first birth. Participants were included if HDP was diagnosed before 37 weeks of gestation and they did not have pregestational hypertension or diabetes. Latency, the interval between HDP diagnosis and delivery, was categorized as short (2-7 days) or long (more than 7 days) for univariate analyses and treated as continuous for regression analyses. The primary outcome was the American Heart Association's Life's Essential 8 health factor score 2-7 years after delivery using body mass index (BMI), blood pressure, non-high-density lipoprotein (non-HDL) cholesterol, and hemoglobin A 1C . Secondary outcomes included high-sensitivity C-reactive protein (CRP) and N-terminal probrain natriuretic peptide (NT-proBNP) concentrations 2-7 years after delivery. Multivariable linear regression models were adjusted for prespecified covariates, with sensitivity analyses for early-onset (before 34 weeks of gestation) and severe HDP. RESULTS:Among 142 participants with preterm-onset HDP, 30 had short latency and 112 had long latency (median 17.5 days, interquartile range 9-35 days). In adjusted regression models, longer latency was not associated with the overall Life's Essential 8 health factor score (β=-0.26, 95% CI, -0.94 to 0.41, P =.44) but was associated with lower non-HDL scores (β=-1.36, 95% CI, -2.50 to -0.21, P =.02) and higher high-sensitivity CRP (β=0.05 log[mg/dL], 95% CI, 0.001-0.10, P=.04 ). Other Life's Essential 8 health factor score components and NT-proBNP did not differ between groups. Sensitivity analyses demonstrated that early-onset and severe HDP subtypes did not account for latency-related differences. CONCLUSION:In this prospective cohort of individuals with preterm HDP in first pregnancies, longer latency of expectant management was not associated with differences in overall cardiovascular health 2-7 years after pregnancy but was associated with adverse subclinical inflammatory and lipid measures, suggesting elevated subclinical cardiovascular risk.

OBJECTIVE:We sought to evaluate the association between the timing of new-onset hypertensive disorders of pregnancy (HDP) development (ie, antepartum, intrapartum, or postpartum) and the risk of incident hypertension 2-7 years after delivery in nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be) and nuMoM2b-HHS (the nuMoM2b Heart Health Study). METHODS:This is a secondary analysis of a multisite prospective observational cohort study conducted at eight clinical sites that enrolled nulliparous individuals with singleton pregnancies in their first trimester who were followed during pregnancy and subsequently underwent a cardiovascular screening visit 2-7 years after delivery. For this analysis, we excluded individuals with prepregnancy chronic hypertension in their nuMoM2b pregnancy. We compared rates of stage 1 hypertension (blood pressure 130/80 mm Hg or higher or use of antihypertensive medications) at the 2-7 year postpartum study visit based on the timing of the onset of HDP (categorized as antepartum, intrapartum, postpartum) with no HDP (referent). Multivariable logistic regression models adjusted for baseline covariates (age, insurance, tobacco use, diabetes, and early pregnancy body mass index [BMI]) were used to generate adjusted odds ratios (aOR) and 95% CIs. Interaction analysis was performed to evaluate effect modification by the presence of severe features of HDP. P <.05 was considered statistically significant. RESULTS:Of 4,342 individuals included in this analysis (mean age 27.0 years [SD 5.6 years]), 23.2%% (n=1,007) had new-onset HDP. Among those with HDP, 53.6% (n=540) were diagnosed antepartum, 42.4% (n=427) were diagnosed intrapartum, and 4.0% (n=40) were diagnosed postpartum. At a mean follow-up of 3.2±0.9 years after delivery, the frequency of incident hypertension was elevated regardless of whether HDP occurred antepartum (37.6%, n=203), intrapartum (26.0%, n=111), or postpartum (40.0%, n=16) (compared with no HDP [16.5%, n=550]). After adjustment for maternal age, insurance type, tobacco use, prepregnancy diabetes, and early pregnancy BMI, the risk of chronic hypertension remained elevated regardless of when HDP was diagnosed, although the risk was higher when it developed antepartum (aOR 2.40, 95% CI, 1.95-2.95) or postpartum (aOR 2.90, 95% CI, 1.49-5.64) compared with when it developed intrapartum (aOR 1.55, 95% CI, 1.21-1.97; referent no HDP, P <.01 for all). CONCLUSION:New-onset HDP, regardless of whether it is diagnosed antepartum, intrapartum, or postpartum, is associated with an increased risk of incident hypertension 2-7 years after delivery, compared with individuals without HDP during their first birth. Greater awareness of cardiovascular disease risk after HDP-even when HDP is diagnosed during labor or postpartum-is needed to appropriately risk stratify and help prevent hypertension after delivery. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT02231398.

Objective:Adverse social determinants of health are known to be associated with adverse pregnancy outcomes. The objective of this analysis was to assess the association between adverse community-level social determinants of health, measured with the Centers for Disease Control and Prevention/Agency for Toxic Substances and Disease Registry Social Vulnerability Index (CDC/ATSDR SVI), and acute presentation to obstetric triage. We hypothesized that adverse community-level social determinants of health would be associated with greater clinical acuity at time of presentation. Study Design:This was a secondary analysis of an observational, multi-site cohort study of all triage visits from 200/7 to 346/7 weeks' gestation occurring from January 1, 2019, to March 31, 2019. Individuals enrolled with geocode and CDC SVI data available were included. The primary exposure was the overall CDC SVI. The primary outcome was presentation to obstetric triage with greater acuity. Secondary outcomes included adverse maternal and neonatal outcomes. Outcomes were compared between groups based on overall SVI and by the four SVI themes. Baseline characteristics were compared. Logistic and quantile regressions were used with the lowest SVI quartile (Q1) group as referent, adjusting for hospital, parity, maternal age, tobacco use, body mass index (BMI) at delivery, drug use, and existing comorbidity. Results:A total of 2,659 individuals were eligible for analysis. Individuals with higher overall SVI scores were younger and had higher BMI, and were more likely to be multiparous, use tobacco or illicit drugs, and live with co-morbidities. Higher SVI quartiles were not associated with acuity of presentation to triage (Q1 reference; Q2 adjusted odds ratio [aOR]: 0.97, 95% confidence interval [CI]: 0.68-1.38; Q3 aOR: 1.10, 95% CI: 0.76-1.57; Q4 aOR: 1.04, 95% CI: 0.72-1.50). Conclusion:We found no consistent association between the CDC SVI and acuity of presentation to obstetrical triage. Further research is needed to understand the relationships between adverse community-level social determinants of health and adverse perinatal outcomes. Key Points:· There was no association between the CDC SVI and acuity of presentation to obstetric triage, whether SVI was assessed as an overall score or by subtheme.. · This analysis adds to the understanding of the association between adverse community-level social determinants of health and conditions related to preterm delivery.. · This study indicates a need for ongoing research to better understand the mechanisms through which social vulnerability affects pregnancy outcomes..

Objective:Perinatal and maternal morbidity in the setting of preterm birth may differ by delivery indication. We compared perinatal and maternal outcomes of second-trimester (240/7-276/7 weeks of gestation) deliveries indicated for preeclampsia with severe features (PE-SF), with those following preterm premature rupture of membranes (PPROM). Study Design:Secondary analysis of an observational cohort study of singleton and twin preterm deliveries before 35 weeks' gestation at 33 hospitals across the United States. Singletons without congenital anomalies who were delivered due to PE-SF or PPROM from 240/7 to 276/7 weeks of gestation were included. The primary outcome was a composite of perinatal morbidity or death, defined as fetal or neonatal death, severe bronchopulmonary dysplasia (BPD) grade III, intraventricular hemorrhage (IVH) grade III to IV, necrotizing enterocolitis (NEC) stage IIA or greater, periventricular leukomalacia (PVL), retinopathy of prematurity (ROP) stage III to IV, or culture-proven sepsis. Secondary outcomes included components of the primary outcome, small-for-gestational-age (SGA) birth, and a composite of maternal morbidity. Adjusted odds ratios (aORs) with 95% confidence intervals (CIs) were calculated. Results:Among the 7,515 in the original cohort, 164 deliveries for PE-SF and 119 deliveries following PPROM were included. Individuals with PE-SF were more likely to have a BMI of ≥30 kg/m2, hypertensive disorder of pregnancy in a prior pregnancy, chronic hypertension, and cesarean birth (p < 0.05) compared with those who delivered following PPROM. Composite perinatal morbidity or death did not differ between groups (aOR = 1.60, 95% CI: 0.89, 2.85, p = 0.11), but fetal death was significantly higher in the PE-SF group (aOR = 6.04, 95% CI: 1.42, 25.71). Neonates delivered for PE-SF were more likely to be SGA (aOR = 13.45, 95% CI: 2.92, 61.94). Composite maternal morbidity did not differ between groups (aOR = 1.18, 95% CI: 0.62, 2.26). Conclusion:Second-trimester preterm birth indicated for PE-SF was associated with a higher rate of fetal death than birth for PPROM. Composite neonatal and maternal morbidity did not differ by indication. Key Points:· Fetal death occurred more frequently in individuals with PE-SF compared with PPROM in the second trimester.. · Composite perinatal and maternal outcomes were similar between groups.. · Our findings can be used for risk stratification and survival prediction rates..

BACKGROUND: The United States suffers from an increasing rate of severe maternal morbidity, paired with a wide disparity in maternal health by race. Doulas are posited to be a useful resource to increase positive outcomes and to decrease this disparity. OBJECTIVE: This study aimed to evaluate the association between doula care and a broad range of maternal and neonatal outcomes in various subpopulations. STUDY DESIGN: This was a retrospective cohort study of deliveries that were recorded from January 2021 to December 2022 at a single institution where they received prenatal care. The exposure was receipt of doula care prenatally and at delivery. We evaluated both the maternal (cesarean delivery, cesarean delivery of nulliparous, term, singleton, vertex infant, vaginal birth after cesarean, gestational hypertension, preeclampsia, postpartum emergency department visit, readmission, and attendance of postpartum office visit) and neonatal (neonatal intensive care unit admission, unexpected complications in term newborns, breastfeeding, preterm delivery, and intrauterine growth restriction) outcomes. Because our institution previously employed targeted outreach by offering doula services to patients at highest risk, we used multiple methods to generate an appropriate comparison population. We conducted a multivariate logistic regression and conditional regressions using propensity scores to model the likelihood of doula care to generate adjusted risk differences associated with doula care. Analyses were repeated in populations stratified by race (White vs Black) and then by payor status (public vs commercial). RESULTS: Our cohort included 17,831 deliveries; 486 of those received doula care and 17,345 did not. Patients who received doula care were more likely to self-report Black race, be publicly insured, and to live in a more disadvantaged neighborhood. Regardless of the analytical approach, for every 100 patients who received doula care, there were 15 to 34 more vaginal births after cesarean (adjusted risk difference, 15.6; 95% confidence interval, 3.8-27.4; adjusted risk difference, 34.2; 95% confidence interval, 0.046-68.0) and 5 to 6 more patients who attended a postpartum office visit (adjusted risk difference, 5.4; 95% confidence interval, 1.4-9.5; adjusted risk difference, 6.8; 95% confidence interval, 3.7-9.9) when compared with those who did not receive doula services. Infants born to these patients were 20% more like likely to be exclusively breastfed (adjusted risk ratio, 1.22; 95% confidence interval, 1.07-1.38), and doula care was associated with 3 to 4 fewer preterm births (adjusted risk difference,-3.8; 95% confidence interval,-6.1 to-1.5;-4.0; 95% confidence interval,-6.2 to-1.8) for every 100 deliveries that received doula care. Results were consistent regardless of race or insurance. Results were also consistent when doula care was redefined as having at least 3 prenatal encounters with a doula. CONCLUSION: Doula care was associated with more vaginal births after cesarean delivery, improved attendance of postpartum office visits, improved breastfeeding rates, and fewer preterm deliveries. The effect of doula care was consistent across race and insurance status.

BACKGROUND:We evaluated whether neighborhood-level socioeconomic disadvantage was associated with mid-pregnancy antenatal depressive symptoms. METHODS:We conducted a secondary analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be, a prospective cohort of nulliparous pregnant individuals. The exposure was socioeconomic disadvantage by the Area Deprivation Index (ADI) categorized by tertile, with the least deprived tertile (T1) as the reference. The ADI was calculated per participant residential address in early pregnancy geocoded at the block group level. The outcome was depressive symptoms assessed between 22 and 29 weeks as a score ≥ 10 on the Edinburgh Postnatal Depression Scale (EPDS), and secondarily as a score ≥ 13. Multivariable modified Poisson regression was used and adjusted for age, individual-level social determinants of health, and the EPDS score in early pregnancy. RESULTS:Of 8678 nulliparous individuals, the median ADI score was 38.0 (interquartile range [IQR]: 18.0, 69.0). A total of 16.1 % of individuals had an EPDS score ≥ 10, and 6.5 % had an EPDS score ≥ 13 at a median gestational age of 26.9 weeks. Individuals who lived in a neighborhood with the highest tertile of ADI were more likely to have a score ≥ 10 compared with those in the lowest tertile (21.6 % vs. 11.7 %; adjusted risk ratio [aRR]: 1.29; 95 % CI: 1.12, 1.50). The association was similar at the higher EPDS screening threshold ≥13 (9.9 % vs. 3.8 %; aRR: 1.60; 95 % CI: 1.23, 2.09). These results held in sensitivity analyses, including without adjusting for the EPDS in early pregnancy, when adjusting for additional clinical characteristics, when analyzing the ADI in declines and as a continuous variable, and when analyzing the ADI per national tertile cutoffs. CONCLUSIONS:Neighborhood-level socioeconomic disadvantage was associated with an increased risk of screening positive for elevated antenatal depressive symptoms in mid-pregnancy.

OBJECTIVE:To describe the development of the EMBRACE Center, which seeks to advance Black maternal health in Allegheny County through research and capacity building. DESIGN:The EMBRACE Center is a multidisciplinary community-academic research partnership at the University of Pittsburgh. Researchers and community collaborators-many of them Black-led organisations-share power in ways that value diverse forms of knowledge. SETTING:Allegheny County, Pennsylvania. POPULATION OR SAMPLE:Birthing people in Allegheny County, Pennsylvania, and surrounding regions. METHODS:The EMBRACE Center's Research Project seeks to enhance postpartum (4th Trimester) and interconception care that improves pregnancy outcomes and reduces rates of severe maternal morbidity among Black individuals. EMBRACE's community and training components facilitate community partnerships throughout research, implementation, training, and capacity building for reproductive justice and equity. Working groups focus on shared decision-making, communication, and dissemination processes that enhance data collection and sharing with the community. A multi-disciplinary advisory board and a community advisory board provide feedback to the Center. MAIN OUTCOME MEASURES:Research outcomes of interest include reducing maternal morbidity and mortality. Center outcome measures include development of a regional maternal health equity workforce. RESULTS:Center activities include education in maternal health and reproductive justice, data justice community trainings, development of measures for structural and social determinants of maternal health, and convening community advocates, researchers and practitioners for black maternal health and reproductive justice. CONCLUSIONS:The work of EMBRACE will result in sustainable approaches to advance maternal and reproductive health equity and improve well-being for black birthing People.

Background Preeclampsia is a complex syndrome that accounts for considerable maternal and perinatal morbidity and mortality. Despite its prevalence, no effective disease-modifying therapies are available. Maternal serum placenta-derived proteins have been in longstanding use as markers of risk for aneuploidy and placental dysfunction, but whether they have a causal contribution to preeclampsia is unknown. Objective We aimed to investigate the genetic regulation of serum placental proteins in early pregnancy and their potential causal links with preeclampsia and gestational hypertension. Study design This study used a nested case-control design with nulliparous women enrolled in the nuMoM2b study from eight clinical sites across the United States between 2010 and 2013. The first- and second-trimester serum samples were collected, and nine proteins were measured, including vascular endothelial growth factor (VEGF), placental growth factor, endoglin, soluble fms-like tyrosine kinase-1 (sFlt-1), a disintegrin and metalloproteinase domain-containing protein 12 (ADAM-12), pregnancy-associated plasma protein A, free beta-human chorionic gonadotropin, inhibin A, and alpha-fetoprotein. This study used genome-wide association studies to discern genetic influences on these protein levels, treating proteins as outcomes. Furthermore, Mendelian randomization was used to evaluate the causal effects of these proteins on preeclampsia and gestational hypertension, and their further causal relationship with long-term hypertension, treating proteins as exposures. Results A total of 2,352 participants were analyzed. We discovered significant associations between the pregnancy zone protein locus and concentrations of ADAM-12 (rs6487735, P= 3.03×10 -22 ), as well as between the vascular endothelial growth factor A locus and concentrations of both VEGF (rs6921438, P= 7.94×10 -30 ) and sFlt-1 (rs4349809, P= 2.89×10 -12 ). Our Mendelian randomization analyses suggested a potential causal association between first-trimester ADAM-12 levels and gestational hypertension (odds ratio=0.78, P= 8.6×10 -4 ). We also found evidence for a potential causal effect of preeclampsia (odds ratio=1.75, P =8.3×10 -3 ) and gestational hypertension (odds ratio=1.84, P =4.7×10 -3 ) during the index pregnancy on the onset of hypertension 2-7 years later. The additional mediation analysis indicated that the impact of ADAM-12 on postpartum hypertension could be explained in part by its indirect effect through gestational hypertension (mediated effect=-0.15, P= 0.03). Conclusions Our study discovered significant genetic associations with placental proteins ADAM-12, VEGF, and sFlt-1, offering insights into their regulation during pregnancy. Mendelian randomization analyses demonstrated evidence of potential causal relationships between the serum levels of placental proteins, particularly ADAM-12, and gestational hypertension, potentially informing future prevention and treatment investigations.

BACKGROUND:Pregnant people are vulnerable to more severe outcomes of COVID-19 compared with their non-pregnant counterparts. Research is needed to systematically test the degree to which COVID-19 during pregnancy increases the risk for adverse maternal, perinatal, and infant health and development outcomes and whether social determinants of health or psychological/psychosocial health outcomes confound or intensify the risk. This protocol paper describes a prospective cohort study using electronic health record (EHR) and patient-reported data from four large health systems in Pennsylvania to examine neighborhood, social, and health factors predicting COVID-19 and its severity, birth weight, gestational age, and vaccination among pregnant people to 12 months postpartum. METHODS:Our study will be conducted with two aims. Aim 1 will combine maternal and infant clinical data and neighborhood data from four health systems in Pennsylvania participating in a PCORI-supported clinical research network. The cohort will include all people who were pregnant between June 2019 and May 2025, along with linkage to their newborn delivery records. In Aim 2, a subset of pregnant people from the Aim 1 cohort will be recruited to participate in a series of surveys from pregnancy to one year postpartum. Survey instruments will be developed to collect patient-reported health and social information as well as patient-centered outcomes depicting whether and how the COVID-19 pandemic is impacting pregnant people and their newborns. Survey data will be collected during pregnancy and at one, six, and 12 months postpartum. Survey data will be linked with data from Aim 1 for analysis. RESULTS:Ethical approval has been obtained at all sites. Subcontracts and data use agreements have been established. EHR data across health systems are being collected and curated. Surveys have been developed and recruitment and retention procedures implemented. Recruitment for the survey aim of the study began in July 2023 and is ongoing. DISCUSSION:This study will advance multi-site research involving pregnant people across diverse communities in a time of public health crisis. Data from this study will provide additional evidence of the impact of the COVID-19 pandemic on pregnant people and their infants. Findings will help guide future clinical and public health practices in pandemics for pregnant people.

OBJECTIVE: To evaluate whether cannabis use during pregnancy was associated with depressive symptoms and whether ongoing use beyond the first trimester and higher amounts of cannabis use were associated with increased depressive symptoms.METHODS: This was a secondary analysis of the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers to Be) study with participants enrolled from October 2010 to September 2013 at eight academic centers. Individuals with pregnancy outcome data who completed the EPDS (Edinburgh Postnatal Depression Scale) in the first and third trimesters and had available frozen stored urine samples were included. Cannabis exposure was ascertained by urine immunoassay for THC-COOH (11-nor-9-carboxy-delta-9-tetrahydrocannabinol); positive results were confirmed with liquid chromatography tandem mass spectrometry. Cannabis exposure groups for the primary analysis were classified as any exposure (positive urine assay at any of the three time points: 6 0/7-13 6/7 weeks of gestation, 16 0/7-21 6/7 weeks, and 22 0/7-29 6/7 weeks) or no exposure. In a secondary analysis, cannabis exposure was classified as no, only first trimester, or ongoing exposure beyond the first trimester. The primary outcome was depressive symptoms (EPDS score higher than 10) at 22-29 weeks of gestation. The association between cannabis exposure and later depressive symptoms was assessed with multivariable logistic. In an exploratory analysis, first-trimester urine THC-COOH was quantified to determine whether heavier use was associated with greater odds of depressive symptoms later in pregnancy.RESULTS: Of 10,038 nuMoM2b participants, 8,424 met the inclusion criteria, and 6.4% (n=535) were exposed to cannabis. Of those exposed, 32.1% (n=172) had only first-trimester exposure, and 67.9% (n=363) had ongoing exposure. Any cannabis use was not significantly associated with later depressive symptoms (adjusted odds ratio [aOR] 1.3, 95% CI, 0.97-1.6) compared with no exposure. However, ongoing exposure beyond the first trimester was associated with later depressive symptoms (aOR 1.6, 95% CI, 1.2-2.2). Higher levels of urine THC-COOH in the first trimester and across pregnancy were associated with increased odds of subsequent depressive symptoms.CONCLUSION: Any cannabis exposure was not associated with later-pregnancy increased depressive symptoms. However, ongoing use beyond the first trimester and higher levels of cannabis metabolite in first-trimester urine were associated with greater odds of depressive symptoms in later pregnancy. Directionality of this association cannot be determined given the study design.

INTRODUCTION:The Jada System® is an FDA-cleared vacuum-induced hemorrhage-control device for the control and treatment of abnormal postpartum uterine bleeding or hemorrhage when conservative management is warranted. The instructions for use for Jada contain a warning stating that the safety and effectiveness of the Jada System in delivery at a gestational age less than 34 weeks or, if multiples, uterus judged less than 34 weeks size, have not been established. While the primary analysis of the RUBY registry, an 800 subject post-approval RWE study of the usage of Jada, included 50 individuals who had preterm births less than 34 weeks gestational age (wGA), the safety and outcomes were not evaluated specifically for less than 28 wGA and 28 to less than 34 wGA subgroups. METHODS:We conducted a descriptive subgroup analysis of the real-world RUBY registry to assess the safety and effectiveness of Jada for postpartum hemorrhage management in preterm births less than 34 weeks (less than 28 wGA and 28 to less than 34 wGA). Of the 50 individuals treated, 24 had vaginal births and 26 had cesarean births. RESULTS:Treatment success rates were 85.7% at less than 28 wGA (81.8% vaginal [9/11], 100% cesarean [3/3]) and 88.9% at 28 to less than 34 wGA (100% vaginal [13/13], 82.6% cesarean [19/23]). No maternal deaths, uterine perforations, device expulsions, or serious adverse device effects (ADEs) were reported in either subgroup. Two nonserious ADEs were reported in 1 individual (endometritis and bacterial vaginosis); 2 individuals required hysterectomy (1 vaginal, 1 cesarean). CONCLUSION:Results for the less than 28 wGA and 28 to less than 34 wGA subgroups were consistent with the overall less than 34 wGA subgroup, which was previously shown to be consistent with births ≥34 wGA; however, continued attention to uterine size is warranted before device placement in births less than 34 wGA. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov; NCT04995887.

OBJECTIVE:To examine whether neighbourhood socioeconomic disadvantage, as measured by the Area Deprivation Index (ADI) in early pregnancy, was associated with severe maternal morbidity (SMM) at delivery hospitalisation. DESIGN:A prospective multi-site observational cohort. SETTING:A secondary analysis of the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be study (nuMoM2b) across eight United States (US) sites from 2010 to 2013. STUDY DESIGN:Participant residential address in the first trimester was geocoded at the US census-tract level to calculate the ADI, a standardised metric of neighbourhood socioeconomic disadvantage. We used modified Poisson regression with robust error variance and adjusted for individual-level covariates: age, pre-pregnancy body mass index, chronic hypertension, and pregestational diabetes to examine the association between the ADI [modelled in quartiles from the least (quartile 1, Q1, reference) to the most (Q4) disadvantage] and SMM. Differences in the association between ADI and SMM by self-reported race and ethnicity as a social construct were evaluated with effect modification via an interaction term in the adjusted model. MAIN OUTCOMES:SMM, based on the US Centers for Disease Control and Prevention definition, and secondarily, SMM without transfusion. RESULTS:Among 9588 nulliparas, 2.3% (n = 221) experienced any SMM and 0.5% (n = 48) experienced non-transfusion SMM. Individuals living in the most disadvantaged neighbourhoods (Q4) were more likely to experience SMM compared with those in the least disadvantaged neighbourhoods (Q1) (3.4% vs. 2.1%; aRR 1.73; 95% CI: 1.17, 2.58). This association was also significant for non-transfusion SMM (1.0% vs. 0.3%; aRR: 2.82; 95% CI 1.15, 6.93). Individuals who self-identified as non-Hispanic Black were more likely to experience SMM than non-Hispanic White individuals (3.9% vs. 2.1%; p < 0.001). There was no evidence of effect modification by self-reported race and ethnicity (interaction p > 0.05). CONCLUSION:Nulliparous pregnant individuals who lived in the most disadvantaged US neighbourhoods were at increased risk of experiencing SMM. Known racial and ethnic disparities in SMM may be related to adverse neighbourhood-level social determinants.

Introduction:Individual- and neighborhood-level social determinants of health (SDOH) have been assessed separately in pregnancy, but their relationship to one another remains uncertain. We investigated the intersectionality of three neighborhood-level SDOH measures with three individual-level SDOH measures. This was done to examine the concomitant experiences of multiple SDOH in pregnancy. Methods:A secondary analysis of data from the Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be. We assessed three neighborhood-level SDOH measures using geocoded participant home addresses in the first trimester at the census-tract level: (1) high socioeconomic disadvantage (in tertiles) by the 2015 Area Deprivation Index, (2) inadequate food access by the USDA Food Access Research Atlas, and (3) low walkability by the EPA National Walkability Score. We assessed three individual-level SDOH measures: low household income, lower educational attainment, and Medicaid insurance. We examined the combinations of these three neighborhood SDOH and three individual SDOH measures by graphical visualization and using statistical tests to assess overall differences in the distribution of these measures. Results:Of 9588 nulliparous individuals, adverse neighborhood-level SDOH [high socioeconomic disadvantage (28%), inadequate food access (24%), and low walkability (66%)] and adverse individual-level SDOH [low household income (19%), lower educational attainment (23%), and Medicaid insurance (33%)] were common in early pregnancy. Six percent of individuals lived in a community with all three adverse neighborhood-level SDOH measures. Of those living in a community with at least two neighborhood-level SDOH measures, 23% lived in areas with inadequate food access and low walkability, 19% with high socioeconomic disadvantage and low walkability, and 1% with high socioeconomic disadvantage and inadequate food access. Overall, 23% lived in a community with no adverse neighborhood-level SDOH, and among this group, 88% had no adverse individual-level SDOH. There were significant differences in adverse individual-level SDOH based on whether individuals lived in a community with all three adverse neighborhood-level measures [low household income (39%), lower educational attainment (44%), Medicaid (55%)], any two measures [low household income (22%), lower educational attainment (27%), Medicaid (37%)], or only one measure [low household income (14%), lower educational attainment (17%), Medicaid (27%)] (p < 0.001 for all). Conclusion:Among nulliparous individuals in early pregnancy, the frequency of adverse individual-level SDOH was generally higher when they lived in communities with more adverse neighborhood-level SDOH. Future approaches that identify and classify the multifaceted and multilevel nature of structural determinants as they relate to pregnancy outcomes are needed.

Background:Hospital-based obstetrical triage units frequently serve as an extension to outpatient care. Evaluation of the burden of preterm birth (PTB) typically focuses on the delivery and neonatal periods, while antepartum health care utilization related to risk of PTB is seldom reported. Objective:To identify the characteristics and outcomes associated with multiple triage visits among patients with suspected preterm labor (PTL) or preterm premature rupture of membranes (pPROM). Study Design:Secondary analysis of a retrospective cohort study of all triage visits from 20 0/7 through 34 6/7 weeks gestation on randomly selected dates in 2019 at 34 hospitals across the US. Those in whom the reason for the visit was suspected PTL or pPROM and who were subsequently discharged were eligible for this analysis. Patients with ≥3 triage visits were compared with those who had <3 visits in the index pregnancy visits. Data were abstracted by certified research personnel using predefined criteria. The primary outcome was a composite of severe neonatal morbidity or mortality before 120 days. Secondary outcomes included PTB (<37 weeks gestation), a composite of respiratory neonatal morbidities, and maternal outcomes. Multivariable logistic regression analyses were used for the maternal outcomes, and generalized linear and logistic models were used for the neonatal outcomes to account for the correlation among twins. Results:A total of 1764 mother/newborn dyads were included. Patients with more frequent triage visits (≥3) were more likely to self-identify as Black, be younger, not married/living with a partner, unemployed, have government-assisted insurance, or have less than a college degree compared to those individuals with less frequent triage visits (P<.05). Additionally, individuals in the more frequent triage visits group were more likely to be multiparous, have obesity, and pre-existing medical conditions, including kidney or liver disease requiring treatment (P<.05). There were no significant differences between groups for the primary composite neonatal outcome (1.6% in the more frequent group vs 2.4% in the less frequent group, adjusted odds ratios [aOR] 0.69, 95% CI 0.35-1.39) or secondary neonatal outcomes including PTB less than 37 weeks gestation (25.2% vs 23.2%, aOR 0.94, 95% CI 0.68-1.30), composite of respiratory morbidity (11.8% vs 11.0%, aOR 1.01, 95% CI 0.71-1.43), SGA (10.5% vs 10.6%, aOR 0.92, 95% CI 0.66-1.29), or birthweight (3056±639 g vs 3048±678 g, LS mean 27, 95% CI -27, 82). Similarly, there were also no statistically significant differences between groups for the secondary maternal outcomes including composite of severe maternal morbidity (8.1% vs 8.7%, aOR 1.00, 95% CI 0.69-1.44), composite of maternal infection (5.8% vs 5.1%, aOR 1.11, 95% CI 0.72-1.73), or delivery via cesarean section (31.2% vs 35.2%, aOR 0.86, 95% CI 0.69-1.07). Conclusion:In this multisite registry of triage visits with rigorous ascertainment and data collection, multiple visits (≥3) for suspected PTL or pPROM were not associated with differences in maternal or neonatal outcomes.

OBJECTIVE:To develop and internally validate a practical and data-driven risk-scoring system to predict blood transfusion during hospitalization for delivery in a contemporary U.S. cohort. METHODS:This was a secondary analysis of a multicenter cohort of patients who delivered on randomly selected days at 17 U.S. hospitals (2019-2020). Patients with placenta accreta spectrum were excluded. The primary outcome was any blood transfusion during hospitalization for delivery. Candidate risk factors for transfusion were selected based on relevant literature. A multivariable logistic regression model was developed and internally validated using stratified k-fold (k=5) cross validation with stepwise backward elimination that used significance level of 0.05. Each risk factor included in the final model was assigned a point value by dividing the log of the odds ratio (OR) by the log of the OR of the factor with the lowest value. The summed points for an individual generate a numeric risk score predictive of transfusion. Performance of the risk score to predict transfusion was assessed using the area under the receiver operating curve (AUC). RESULTS:Of 21,780 included individuals, 2.5% (n=545) received a blood transfusion. Factors associated with the highest risk for transfusion in the final model included thrombocytopenia, and placental abruption or significant antepartum bleeding. Risk score outputs among patients in the cohort ranged from 0 to 17 (maximum possible 26) with a corresponding predicted risk for transfusion from 1.0% to 84.4%. The AUC for prediction of transfusion in the validation subsample was 0.81 (95% CI, 0.76-0.85). CONCLUSION:We developed a clinically applicable numeric risk score to predict blood transfusion during hospitalization for delivery. Future work should externally validate this risk-scoring system.