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.

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.

Association of per- and polyfluoroalkyl substances with the antioxidant bilirubin across pregnancy.

BACKGROUND: In mechanistic and preliminary human studies, prenatal exposure to per- and polyfluoroalkyl substances (PFAS) is associated with oxidative stress, a potential contributor to maternal liver disease. Bilirubin is an endogenous antioxidant abundant in the liver that may serve as a physiological modulator of oxidative stress in pregnant people. Hence, our objective was to estimate the association between repeated measures of PFAS and bilirubin during pregnancy. METHODS: The study population included 332 participants in the Atlanta African American Maternal-Child Cohort between 2014 and 2020. Serum samples were collected up to two times (early pregnancy: 6-18 gestational weeks; late pregnancy: 21-36 gestational weeks) for the measurement of perfluorohexane sulfonate (PFHxS), perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), and total bilirubin. We analyzed single PFAS with linear mixed effect regression and a mixture of the four PFAS with quantile g-computation. Models were repeated with a multiplicative interaction term to explore effect modification by study visit. RESULTS: Overall, PFHxS was positively associated with bilirubin (ß = 0.08, 95 % CI = 0.01, 0.15). We also found during late pregnancy, there was a positive association of PFHxS and the PFAS mixture with bilirubin (ß = 0.12, 95 % CI = 0.02, 0.22; ψ = 0.19, 95 % CI = 0.03, 0.34, respectively). Finally, study visit modified the PFOA-bilirubin association (interaction p-value = 0.09), which was greater during early pregnancy (ß = 0.08, 95 % CI = 0.01, 0.15). CONCLUSION: In a prospective cohort of pregnant African Americans, an increase in PFOA, PFHxS, and the PFAS mixture was associated with an increase in bilirubin. Our results suggest that, depending on pregnancy stage, prenatal PFAS exposure disrupts the maternal liver antioxidant capacity.