Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and associations with hypertensive disorders of pregnancy in the Atlanta African American Maternal-Child cohort.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are man-made chemicals that are slow to break down in the environment and widely detected in humans. Epidemiological evidence suggests that prenatal exposure to perfluorooctanoic acid (PFOA), a legacy PFAS, is linked to gestational hypertension and preeclampsia. However, the relationship between other PFAS, which are structurally similar, and these outcomes remains largely understudied, despite biologic plausibility. Here, we examined associations between serum PFAS mixtures in relation to hypertensive disorders of pregnancy within a birth cohort of African Americans. METHODS: Participants in the present study were enrolled in the Atlanta African American Maternal-Child cohort between 2014 and 2020 (n = 513). Serum samples collected between 8 and 14 weeks gestation were analyzed for four PFAS. Logistic regression was used to assess associations between individual natural log transformed PFAS and specific hypertensive disorders of pregnancy (preeclampsia, gestational hypertension), while quantile g-computation was used to estimate mixture effects. Preeclampsia and gestational hypertension were treated as separate outcomes in individual models. All models were adjusted for maternal education, maternal age, early pregnancy body mass index, parity, and any alcohol, tobacco, or marijuana use. RESULTS: The geometric mean of PFOS and PFHxS was slightly lower among those with preeclampsia relative to those without a hypertensive disorder (e.g., geometric mean for PFOS was 1.89 and 1.94, respectively). Serum concentrations of PFAS were not strongly associated with gestational hypertension or preeclampsia in single pollutant or mixture models. For example, using quantile g-computation, a simultaneous one quartile increase in all PFAS was not associated with odds of gestational hypertension (odds ratio = 0.86, 95% CI = 0.60, 1.23), relative to those without a hypertensive disorder of pregnancy. CONCLUSIONS: In this birth cohort of African Americans, there was no association between serum PFAS measured in early pregnancy and hypertensive disorders of pregnancy, which may be reflective of the fairly low PFAS levels in our study population.

Reproductive and Social Policies, Sociopolitical Stress, and Implications for Maternal and Child Health Equity.

PURPOSE OF REVIEW: Although many environmental exposures (e.g., air pollution) are geographically patterned and persist as a result of historic economic policies (e.g., redlining), the impact of reproductive and social policies on maternal and child health remains incompletely understood. Reproductive and social policies are increasingly important for maternal and child health equity, particularly following the 2022 US Supreme Court decision in Dobbs v Jackson Women's Health Organization ("Dobbs decision"), which restricted access to abortion. Here, we summarize the literature from original research studies examining influences of reproductive and social policy on maternal and child health, focusing on impacts on adverse birth outcomes and policies as sources of stress. RECENT FINDINGS: Several studies suggest that those most impacted by the Dobbs decision are younger, non-white, socioeconomically disadvantaged, and living in states with less access to government safety net programs, all of which are compounded by environmental injustices. Further, studies conducted in the wake of the Dobbs decision find elevated stress levels among women of reproductive age. This may represent one pathway leading to adverse birth outcomes, as epidemiologic studies demonstrate that preterm birth rates increased following the 2016 election, a period of heightened stress. Reproductive and social policies are understudied contributors to adverse outcomes for reproductive-aged women and their children. This has important implications for maternal and child health equity, as those who will be the most impacted by reproductive and social policies already experience the highest rates of adverse birth outcomes and environmental toxicant exposure.

Phthalate exposure increases interferon-γ during pregnancy: The Atlanta African American Maternal-Child Cohort.

BACKGROUND: The immune system undergoes unique adaptations during pregnancy and is particularly sensitive to environmental chemicals, such as phthalates, which are associated with acute and chronic inflammatory medical conditions. However, current knowledge of how phthalate exposures are associated with systemic inflammation in pregnant people is limited by cross-sectional study designs and single chemical models. Our objective was to estimate the association between repeated measures of prenatal phthalate exposures, examined individually and collectively, and a panel of clinical inflammatory biomarkers. METHODS: In the Atlanta African American Maternal-Child Cohort, biospecimens were collected at mean 11 and 26 weeks gestation (N = 126). Concentrations of eight urinary phthalate metabolites and five serum inflammatory biomarkers, including CRP, IFN-γ, IL-6, IL-10, and TNF-α, were measured. Linear mixed effect regression and quantile g-computation models were used to estimate the associations for single phthalates and their exposure mixture, respectively. RESULTS: Participants who self-reported any use of alcohol, tobacco, or marijuana in the month prior to pregnancy had increased MEP, MBP, MiBP, and CRP, relative to those with no substance use. IFN-γ was elevated in response to MECPP (% change = 17.35, 95 % confidence interval [CI] = 0.32, 32.27), MEHHP (% change = 12.75, 95 % CI = 2.22, 24.36), MEOHP (% change = 11.63, 95 % CI = 1.21, 23.12), and their parent phthalate, ΣDEHP (% change = 15.03, 95 % CI = 0.28, 31.94). The phthalate mixture was also associated with an increase in IFN-γ (% change = 15.03, 95 % CI = 6.18, 24.61). CONCLUSIONS: Our findings suggest DEHP metabolites induce systemic inflammation during pregnancy. The pro-inflammatory cytokine IFN-γ may play an important role in the relationship between prenatal phthalate exposures and adverse pregnancy outcomes.

Delivering Diversity and Inducing Inclusion: Evidence-Based Perspectives on Charting a Future of Equity in Obstetrics and Gynecology Residency Programs.

An active implementation of principles encompassed by the terms diversity, equity, and inclusion (DEI) is critical to the success of obstetrics and gynecology (OB/GYN) residency programs. The patients served by our specialty come from a vast array of backgrounds, identities, and experiences. Preparing OB/GYN providers for the reality of this practice requires commitment to DEI principles in training programs nationwide through evidence-based policies and practices while empowering the next generation to chart the path forward to equity.

Association between a Mixture of Per- and Polyfluoroalkyl Substances (PFAS) and Inflammatory Biomarkers in the Atlanta African American Maternal-Child Cohort.

Per- and polyfluoroalkyl substances (PFAS) have been identified as environmental contributors to adverse birth outcomes. One potential mechanistic pathway could be through PFAS-related inflammation and cytokine production. Here, we examined associations between a PFAS mixture and inflammatory biomarkers during early and late pregnancy from participants enrolled in the Atlanta African American Maternal-Child Cohort (N = 425). Serum concentrations of multiple PFAS were detected in >90% samples at 8-14 weeks gestation. Serum concentrations of interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at up to two time points (8-14 weeks and 24-30 weeks gestation). The effect of the PFAS mixture on each inflammatory biomarker was examined using quantile g-computation, Bayesian kernel machine regression (BKMR), Bayesian Weighted Sums (BWS), and weighted quantile sum (WQS) regression. Across all models, the PFAS mixture was associated with increased IFN-γ, IL-10, and TNF-α at both time points, with the strongest effects being observed at 24-30 weeks. Using quantile g-computation, increasing concentrations of a PFAS mixture were associated with a 29% (95% confidence interval = 18.0%, 40.7%) increase in TNF-α at 24-30 weeks. Similarly, using BWS, the PFAS mixture was associated with increased TNF-α at 24-30 weeks (summed effect = 0.29, 95% highest posterior density = 0.17, 0.41). The PFAS mixture was also positively associated with TNF-α at 24-30 weeks using BKMR [75th vs 50th percentile: 17.1% (95% credible interval = 7.7%, 27.4%)]. Meanwhile, PFOS was consistently the main drivers of overall mixture effect across four methods. Our findings indicated an increase in prenatal PFAS exposure is associated with an increase in multiple pro-inflammatory cytokines, potentially contributing to adverse pregnancy outcomes.

Exposure to phthalate metabolites, bisphenol A, and psychosocial stress mixtures and pregnancy outcomes in the Atlanta African American maternal-child cohort.

BACKGROUND: Consumer products are common sources of exposure for phthalates and bisphenol A (BPA), which disrupt the endocrine system. Psychosocial stressors have been shown to amplify the toxic effects of endocrine disruptors but, information is limited among African Americans (AAs), who experience the highest rates of adverse pregnancy outcomes and are often exposed to the highest levels of chemical and non-chemical stressors. We examined the association between an exposure mixture of phthalate metabolites, BPA, and psychosocial stressors with gestational age at delivery and birthweight for gestational age z-scores in pregnant AA women. STUDY DESIGN: Participants were enrolled in the Atlanta African American Maternal-Child Cohort (N = 247). Concentrations of eight phthalate metabolites and BPA were measured in urine samples collected at up to two timepoints during pregnancy (8-14 weeks gestation and 20-32 weeks gestation) and were averaged. Psychosocial stressors were measured using self-reported, validated questionnaires that assessed experiences of discrimination, gendered racial stress, depression, and anxiety. Linear regression was used to estimate individual associations between stress exposures (chemical and psychosocial) and birth outcomes. We leveraged quantile g-computation was used to examine joint effects of chemical and stress exposures on gestational age at delivery (in weeks) and birthweight for gestational age z-scores. RESULTS: A simultaneous increase in all phthalate metabolites and BPA was associated with a moderate reduction in birthweight z-scores (mean change per quartile increase = -0.22, 95% CI = -0.45, 0.0). The association between our exposure mixture and birthweight z-scores became stronger when including psychosocial stressors as additional exposures (mean change per quantile increase = -0.35, 95% CI = -0.61, -0.08). Overall, we found null associations between exposure to chemical and non-chemical stressors with gestational age at delivery. CONCLUSIONS: In a prospective cohort of AA mother-newborn dyads, we observed that increased prenatal exposure to phthalates, BPA, and psychosocial stressors were associated with adverse pregnancy outcomes.

Prenatal exposure to persistent and non-persistent chemical mixtures and associations with adverse birth outcomes in the Atlanta African American Maternal-Child Cohort.

BACKGROUND: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. OBJECTIVE: We examined the individual and mixture effects of non-persistent chemicals and persistent organic pollutants (POPs) on gestational age at birth and birthweight for gestational age z-scores within a prospective cohort of pregnant AAs. METHODS: First-trimester serum and urine samples obtained from participants within the Atlanta African American Maternal-Child cohort were analyzed for 43 environmental chemicals, including per-and polyfluoroalkyl substances (PFAS), polybrominated diphenyl ethers (PBDEs), organochlorine pesticides, pyrethroid insecticides, phthalates, bisphenol A, nicotine, and the primary metabolite of delta-9-tetrahydrocannabinol. Linear regression was used to estimate individual associations between chemicals and gestational age and birthweight z-scores (N ranging from 107 to 523). Mixture associations were estimated using quantile g-computation, principal component (PC) analyses, and hierarchical Bayesian kernel machine regression among complete cases (N = 86). RESULTS: Using quantile g-computation, increasing all chemical exposures by one quantile was modestly associated with a reduction in gestational age (mean change per quartile increase = -0.47, 95% CI = -1.56, 0.61) and birthweight z-scores (mean change per quartile increase = -0.49, 95% CI = -1.14, 0.15). All PCs were associated with a reduction in birthweight z-scores; associations were greatest in magnitude for the two PCs reflecting exposure to combined tobacco, insecticides, PBDEs, and phthalates. In single pollutant models, we observed inconsistent and largely non-significant associations. SIGNIFANCE: We conducted multiple targeted exposure assessment methods to quantify levels of environmental chemicals and leveraged mixture methods to quantify their joint effects on gestational age and birthweight z-scores. Our findings suggest that prenatal exposure to multiple classes of persistent and non-persistent chemicals is associated with reduced gestational age and birthweight z-scores in AAs. IMPACT: African Americans (AAs) experience higher rates of preterm birth and fetal growth restriction relative to other pregnant populations. Differential in utero exposure to environmental chemicals may partially explain these health disparities, as AAs are disproportionately exposed to environmental hazards. In the present study, we analyzed serum and urine samples for levels of 43 environmental chemicals. We used quantile g-computation, principal component analysis, and BKMR to assess associations between chemical exposure mixtures and adverse birth outcomes. Our findings suggest that prenatal exposure to multiple classes of chemicals is associated with reduced birthweight z-scores, a proxy for fetal growth, in AAs.