Per- and Polyfluoroalkyl substances exposure levels and maternal-offspring systemic inflammation: A birth cohort study

Per- and polyfluoroalkyl substances (PFAS) are persistent, bioaccumulative chemicals that can cross the placenta, posing potential immunomodulatory risks to offspring. Epidemiological data on PFAS, particularly emerging alternatives (e.g., Cl-PFESA and its isomers) and comprehensive maternal-child inflammation, remain limited. Based on a birth cohort in Wuhan, we quantified 32 PFAS concentrations in cord serum, used as a proxy for late-pregnancy maternal exposure and validated via paired maternal-cord data. We then assessed their associations with multiple inflammatory cytokines measured in maternal serum during pregnancy ( n = 559) and in child serum at 3.05 ± 0.4 years of age ( n = 459). We found that several PFAS were associated with lower IL-17A levels during pregnancy. The significant association was observed for PFHxS (β = −0.19; 95% CI: −0.28, −0.09; P- FDR = 0.003), followed by 6:2 Cl-PFESA (β = −0.13; 95% CI: −0.21, −0.05; P- FDR = 0.015). By applying weighted quantile sum (WQS) regression, we found that the PFAS mixture was significantly associated with lower concentrations of IL-17A during pregnancy (WQS-index: -0.19; 95% CI: −0.29, −0.09, P < 0.001 ). Three main components were determined via principal component analysis. Principal Component 1 (PFOS and its substitutes) was the main component associated with IL-17A during pregnancy. For childhood inflammation, PFAS isomers were associated with lower periostin concentrations, including 5 m-PFOA (β = −0.10; 95% CI: −0.16, −0.04; P- FDR = 0.032), 6 m-PFOA (β = −0.10; 95% CI: −0.17, −0.03; P- FDR = 0.048), and br-PFHxS (β = −0.11; 95% CI: −0.18, −0.04; P- FDR = 0.036). This study suggested that prenatal PFAS exposure might be linked to altered IL-17A during pregnancy and childhood periostin levels, but causality was not established. Future research should evaluate whether these inflammatory signatures translate into clinical immune dysfunction or allergic diseases.