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Marginalized populations experience disproportionate rates of preterm birth and early term birth. Exposure to per- and polyfluoroalkyl substances (PFAS) has been reported to reduce length of gestation, but the underlying mechanisms are unknown. In the present study, we characterized the molecular signatures of prenatal PFAS exposure and gestational age at birth outcomes in the newborn dried blood spot metabolome among 267 African American dyads in Atlanta, Georgia between 2016 and 2020. Pregnant people with higher serum perfluorooctanoic acid and perfluorohexane sulfonic acid concentrations had increased odds of an early birth. After false discovery rate correction, the effect of prenatal PFAS exposure on reduced length of gestation was associated with 8 metabolomic pathways and 52 metabolites in newborn dried blood spots, which suggested perturbed tissue neogenesis, neuroendocrine function, and redox homeostasis. These mechanisms explain how prenatal PFAS exposure gives rise to the leading cause of infant death in the United States. Mechanisms of the impact of PFAS (also known as forever chemicals) on adverse birth outcomes remain largely unknown. Here, authors identified tissue neogenesis, neuroendocrine function, and redox homeostasis as imprints of prenatal PFAS exposures and reduced gestational age in the newborn metabolome.

Background The extent to which past preterm or early term births are risk factors for recurrent shortened gestational age at delivery in the US is unclear. The underlying causes of shortened gestational age and the role of maternal health can vary over time and across the 50 US states. Objectives To estimate differences in the probability of a second live birth being full term (> 38 weeks’ gestation), early term (37–38 weeks’) or preterm (< 37 weeks’) conditional on the gestational age of the first live birth. Study design We used linked birth and hospital discharge records from the state of Georgia to construct a retrospective cohort of individuals whose first and second births resulted in a singleton live birth (2011–2020). Multinomial models were used to estimate the difference in the probability of the second live birth gestational age category (< 32, 32–36, 37–38, ≥ 39 weeks) conditional on the first birth gestational age category. Baseline models were only adjusted for year fixed effects. Subsequent models were adjusted for birthing individual characteristics: race, age at first birth, ethnicity, country of birth, and education at first birth; second birth health, behavioral and socioeconomic risk factors; and, for interpregnancy birth interval and change in paternal characteristics between first and second births. All analyses were completed in Stata 17. Results Individuals whose first live birth was preterm or early term were significantly less likely to have a second full term live birth, compared to individuals who had a first full term live birth. The probability of a full term second live birth following a first preterm live birth at < 32 weeks or 32–36 weeks decreased by 27.7% points (pp) (95% CI -30.0, -25.2) and 22.1 pp (95% CI-23.3, -21.0) respectively. Similarly, the probability of a full term second birth following a first early term birth decreased by 14.9 pp (95% CI − 15.7, -14.2). Individuals who had early term or preterm first births were more likely to have early term and preterm second births, with higher risk for recurrent preterm birth among birthing individuals with earlier preterm first births. For example, following a first birth that is early term, the probability of a second birth at 32–36 weeks increased by 4.7 pp (95% CI 4.2, 5.1), whereas following a first birth at < 32 weeks the probability of a second birth at 32–36 weeks increased by 13.6 pp (95% CI 11.5, 15.6). Conclusions A first live birth that is early term or preterm predicts a higher probability of a second early term or preterm birth. Health information systems that flag these early birth outcomes on the problem list may help clinicians address known risk factors interconceptionally and prenatally in a subsequent pregnancy.

To evaluate the association between the early pregnancy vaginal microbiome and spontaneous preterm birth (sPTB) and early term birth (sETB) among African American women. Vaginal samples collected in early pregnancy (8-14 weeks' gestation) from 436 women enrolled in the Emory University African American Vaginal, Oral, and Gut Microbiome in Pregnancy Study underwent 16S rRNA gene sequencing of the V3-V4 region, taxonomic classification, and community state type (CST) assignment. We compared vaginal CST and abundance of taxa for women whose pregnancy ended in sPTB (N = 44) or sETB (N= 84) to those who delivered full term (N = 231). Nearly half of the women had a vaginal microbiome classified as CST IV (Diverse CST), while one-third had CST III ( dominated) and just 16% had CST I, II, or V (non-iners dominated). Compared to vaginal CST I, II, or V (non-iners dominated), both CST III ( dominated) and CST IV (Diverse) were associated with sPTB with an adjusted odds ratio (95% confidence interval) of 4.1 (1.1, infinity) and 7.7 (2.2, infinity), respectively, in multivariate logistic regression. In contrast, no vaginal CST was associated with sETB. The linear decomposition model (LDM) based on amplicon sequence variant (ASV) relative abundance found a significant overall effect of the vaginal microbiome on sPTB (p=0.034) but not sETB (p=0.320), whereas the LDM based on presence/absence of ASV found no overall effect on sPTB (p=0.328) but a significant effect on sETB (p=0.030). In testing for ASV-specific effects, the LDM found that no ASV was significantly associated with sPTB considering either relative abundance or presence/absence data after controlling for multiple comparisons (FDR 10%), although in marginal analysis the relative abundance of (p=0.011), non-iners (p=0.016), and (p=0.035) and the presence of (p=0.049), BVAB2 (p=0.024), (p=0.011), and (p=0.044) were associated with sPTB. The LDM identified the higher abundance of 7 ASVs and the presence of 13 ASVs, all commonly residents of the gut, as associated with sETB at FDR < 10%. In this cohort of African American women, an early pregnancy vaginal CST III or IV was associated with an increased risk of sPTB but not sETB. The relative abundance and presence of distinct taxa within the early pregnancy vaginal microbiome was associated with either sPTB or sETB.

Background Differential exposure to chronic stressors by race/ethnicity may help explain Black-White inequalities in rates of preterm birth. However, researchers have not investigated the cumulative, interactive, and population-specific nature of chronic stressor exposures and their possible nonlinear associations with preterm birth. Models capable of computing such high-dimensional associations that could differ by race/ethnicity are needed. We developed machine learning models of chronic stressors to both predict preterm birth more accurately and identify chronic stressors and other risk factors driving preterm birth risk among non-Hispanic Black and non-Hispanic White pregnant women. Methods Multivariate Adaptive Regression Splines (MARS) models were developed for preterm birth prediction for non-Hispanic Black, non-Hispanic White, and combined study samples derived from the CDC’s Pregnancy Risk Assessment Monitoring System data (2012–2017). For each sample population, MARS models were trained and tested using 5-fold cross-validation. For each population, the Area Under the ROC Curve (AUC) was used to evaluate model performance, and variable importance for preterm birth prediction was computed. Results Among 81,892 non-Hispanic Black and 277,963 non-Hispanic White live births (weighted sample), the best-performing MARS models showed high accuracy (AUC: 0.754–0.765) and similar-or-better performance for race/ethnicity-specific models compared to the combined model. The number of prenatal care visits, premature rupture of membrane, and medical conditions were more important than other variables in predicting preterm birth across the populations. Chronic stressors (e.g., low maternal education and intimate partner violence) and their correlates predicted preterm birth only for non-Hispanic Black women. Conclusions Our study findings reinforce that such mid or upstream determinants of health as chronic stressors should be targeted to reduce excess preterm birth risk among non-Hispanic Black women and ultimately narrow the persistent Black-White gap in preterm birth in the U.S.

Background Adverse birth and neonatal outcomes disproportionately affect African American women and infants compared to those of other races/ethnicities. While significant research has sought to identify underlying factors contributing to these disparities, current understanding remains limited, constraining prevention, early diagnosis, and treatment. With the development of next generation sequencing techniques, the contribution of the vaginal microbiome to adverse maternal and neonatal outcomes has come under consideration. However, most microbiome in pregnancy studies include few African American women, do not consider the potential contribution of non-vaginal microbiome sites, and do not consider the effects of sociodemographic or behavioral factors on the microbiome. Methods We conceived our on-going, 5-year longitudinal study, Biobehavioral Determinants of the Microbiome and Preterm Birth in Black Women, as an intra-race study to enable the investigation of risk and protective factors within the disparate group. We aim to recruit over 500 pregnant African American women, enrolling them into the study at 8–14 weeks of pregnancy. Participants will be asked to complete questionnaires and provide oral, vaginal, and gut microbiome samples at enrollment and again at 24–30 weeks. Chart review will be used to identify pregnancy outcomes, infections, treatments, and complications. DNA will be extracted from the microbiome samples and sequencing of the V3 and V4 regions of the 16S rRNA gene will be conducted. Processing and mapping will be completed with QIIME and operational taxonomic units (OTUs) will be mapped to Greengenes version 13_8. Community state types (CSTs) and diversity measures at each site and time will be identified and considered in light of demographic, psychosocial, clinical, and biobehavioral variables. Discussion This rich data set will allow future consideration of risk and protective factors, between and within groups of women, providing the opportunity to uncover the roots of the persistent health disparity experienced by African American families.

This study aimed to investigate the association between sexual activity during pregnancy and adverse birth outcomes among Black women, and to explore whether vaginal cytokine inflammation mediates this association. Data from 397 Black pregnant women through questionnaires on sexual activity and vaginal biosamples during early (8–14 weeks) and late (24–30 weeks) pregnancy, and birth outcomes were analyzed. Using a data-driven approach, the study found that vaginal sex during late pregnancy was associated with spontaneous early-term birth (sETB, 38–39 completed weeks’ gestation) (OR = 0.39, 95% CI: [0.21, 0.72], p-value = 0.003) but not with spontaneous preterm birth (sPTB) (OR = 1.08, p-value = 0.86) compared to full-term birth. Overall, despite vaginal sex in late pregnancy showing an overall positive effect on sETB (total effect = −0.1580, p-value = 0.015), we observed a negative effect of vaginal sex on sETB (indirect effect = 0.0313, p-value = 0.026) due to the fact that having vaginal sex could lead to elevated IL6 levels, which in turn increased the odds of sETB. In conclusion, the study found an overall positive association between sexual activity on ETB and a negative partial mediation effect via increased vaginal cytokine inflammation induced by vaginal sexual activity. This inconsistent mediation model suggested that vaginal sexual activity is a complex behavior that could have both positive and negative effects on the birth outcome.

Background The microbial population of the human gut (the gut microbiome) is an integral cog in the bidirectional communication axis that exists between the gastrointestinal tract and the central nervous system. African American infants disproportionately experience multiple, overlapping vulnerabilities such as preterm birth and formula rather than breast feeding that may disrupt the development of the infant microbiome. African American infants also are more likely to have mothers affected by chronic stress both pre- and post-natally. Perhaps relatedly, African American offspring are disproportionately affected by neurodevelopmental delays. Taken together, these findings suggest that one important mechanism that may link prenatal and postnatal stress and African American infant brain development is the composition of the infant microbiome. Methods In our ongoing longitudinal study, Maternal Stress and the Gut-Brain Axis in African American Infants (R01MD009746), we investigate associations between maternal prenatal and postnatal stress and the composition of the infant gut microbiome, in relation to cognitive and social-emotional development. We aim to recruit 300 African American mother-infant dyads, contingent on the mother’s previous participation in an associated prenatal cohort study: Biobehavioral Determinants of the Microbiome and Preterm Birth in Black Women (R01NR014800). Following enrollment, we assess infants at 1-week, and 3-, 6-, 12-and 18-months to collect: standardized assessments of infant neurocognitive and social-emotional development; questionnaire measures of infant feeding and health; observational data on maternal-infant interactions; maternal reports of postnatal stress; blood and saliva samples to evaluate maternal and infant psychoneuroimmunologic (PNI) function; and infant stool samples to characterize acquisition and trajectory of gut microbiome composition. Genetic variants of the major histocompatibility complex that may influence gut microbiome composition are also being evaluated. Discussion This rich data set will allow future consideration of risk and protective factors that influence neurodevelopment in African American infants who are exposed to varying levels of prenatal and early life stress. Evidence for a mechanistic role of the microbiome would provide a framework for future clinical evaluations of preventative interventions (e.g. , probiotics, culturally-appropriate breastfeeding campaigns) that could potentially improve the health and development of African American children in infancy and across the lifespan.

-3 fatty acid consumption during pregnancy is recommended for optimal pregnancy outcomes and offspring health. We examined characteristics associated with self-reported fish or -3 supplement intake. Pooled pregnancy cohort studies. Cohorts participating in the Environmental influences on Child Health Outcomes (ECHO) consortium with births from 1999 to 2020. A total of 10 800 pregnant women in twenty-three cohorts with food frequency data on fish consumption; 12 646 from thirty-five cohorts with information on supplement use. Overall, 24·6 % reported consuming fish never or less than once per month, 40·1 % less than once a week, 22·1 % 1-2 times per week and 13·2 % more than twice per week. The relative risk (RR) of ever ( . never) consuming fish was higher in participants who were older (1·14, 95 % CI 1·10, 1·18 for 35-40 . <29 years), were other than non-Hispanic White (1·13, 95 % CI 1·08, 1·18 for non-Hispanic Black; 1·05, 95 % CI 1·01, 1·10 for non-Hispanic Asian; 1·06, 95 % CI 1·02, 1·10 for Hispanic) or used tobacco (1·04, 95 % CI 1·01, 1·08). The RR was lower in those with overweight . healthy weight (0·97, 95 % CI 0·95, 1·0). Only 16·2 % reported -3 supplement use, which was more common among individuals with a higher age and education, a lower BMI, and fish consumption (RR 1·5, 95 % CI 1·23, 1·82 for twice-weekly . never). One-quarter of participants in this large nationwide dataset rarely or never consumed fish during pregnancy, and -3 supplement use was uncommon, even among those who did not consume fish.

During pregnancy, women experience numerous physiological changes but, to date, there is limited published data that characterize accompanying changes in gene expression over pregnancy. This study sought to characterize the complexity of the transcriptome over the course of pregnancy among women with healthy pregnancies. Subjects provided a venous blood sample during early (6-15 weeks) and late (22-33 weeks) pregnancy, which was used to isolate peripheral blood mononuclear cells prior to RNA extraction. Gene expression was examined for 63 women with uncomplicated, term deliveries. We evaluated the association between weeks gestation at sample collection and expression of each transcript. Of the 16,311 transcripts evaluated, 439 changed over pregnancy after a Bonferroni correction to account for multiple comparisons. Genes whose expression increased over pregnancy were associated with oxygen transport, the immune system, and host response to bacteria. Characterization of changes in the transcriptome over the course of healthy term pregnancies may enable the identification of genes whose expression predicts complications or adverse outcomes of pregnancy.

Background Prior research has demonstrated bidirectional associations between gestational diabetes mellitus (GDM) and perinatal maternal depression. However, the association between GDM, prenatal depression, and postpartum depression (PPD) has not been examined in a prospective cohort longitudinally. Methods Participants in the current analysis included 5,822 women from the National Institutes of Health’s Environmental influences on Child Health Outcomes (ECHO) Research Program: N  = 4,606 with Neither GDM nor Prenatal Maternal Depression ( Reference Category); N  = 416 with GDM only ; N  = 689 with Prenatal Maternal Depression only ; and N  = 111 with Comorbid GDM and Prenatal Maternal Depression . The PROMIS-D scale was used to measure prenatal and postnatal maternal depressive symptoms. Primary analyses consisted of linear regression models to estimate the independent and joint effects of GDM and prenatal maternal depression on maternal postpartum depressive symptoms. Results A higher proportion of women with GDM were classified as having prenatal depression ( N  = 111; 21%) compared to the proportion of women without GDM who were classified as having prenatal depression ( N  = 689; 13%), however this finding was not significant after adjustment for covariates. Women with Comorbid GDM and Prenatal Maternal Depression had significantly increased postpartum depressive symptoms measured by PROMIS-D T-scores compared to women with Neither GDM nor Prenatal Maternal Depression (mean difference 7.02, 95% CI 5.00, 9.05). Comorbid GDM and Prenatal Maternal Depression was associated with an increased likelihood of PPD (OR 7.38, 95% CI 4.05, 12.94). However, women with GDM only did not have increased postpartum PROMIS-D T-scores or increased rates of PPD. Conclusions Our findings underscore the importance of universal depression screening during pregnancy and in the first postpartum year. Due to the joint association of GDM and prenatal maternal depression on risk of PPD, future studies should examine potential mechanisms underlying this relation.