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

Abstract

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 gcomputation, 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.

Metabolic Perturbations Associated with an Exposure Mixture of Per- and Polyfluoroalkyl Substances in the Atlanta African American Maternal-Child Cohort

“…These findings are supported by prior work that has shown exposures to PFOS and other PFAS chemicals interfere with lipid homeostasis in the mother, placenta, and fetus . For example, lipid-derived biomarkers of systemic inflammation, oxidative stress, and hormone function are altered by simultaneous exposure to multiple PFAS chemicals during the perinatal period. ,, The results we present align with previous epidemiologic work and contribute new information about how fatty acid and lipid metabolism are jointly affected by the four most commonly detected and highly concentrated PFAS in Americans.…”