Prenatal exposure to per- and polyfluoroalkyl substances (PFAS) and their influence on inflammatory biomarkers in pregnancy: Findings from the LIFECODES cohort

Background: Per- and polyfluoroalkyl substances (PFAS) are fluorinated chemicals linked to adverse pregnancy and birth outcomes. However, the underlying mechanisms, specifically their effects on maternal inflammatory processes, are not well characterized. Objective: We examined associations between prenatal PFAS exposure and repeated measures of inflammatory biomarkers, including C-reactive protein (CRP) and four cytokines [Interleukin-10 (IL-10), IL-1β, IL-6, and tumor necrosis factor-α (TNF-α)]. Methods: We analyzed data from 469 pregnant women in a nested case-control study of preterm birth at Brigham and Women’s Hospital in Boston, Massachusetts (2006–2008). We measured nine PFAS in early pregnancy plasma samples (median gestation: 10 weeks), with inflammatory biomarkers measured at median gestations of 10, 18, 26, and 35 weeks. We used linear mixed models for repeated measures and multivariable regression for visit-specific analysis to examine associations between each PFAS and inflammation biomarker, adjusting for maternal demographics, pre-pregnancy BMI, and parity. We examined the effects of PFAS mixture using sum of all PFAS (∑PFAS) and quantile-based g-computation approaches. Results: We observed consistent inverse associations between most PFAS and cytokines, specifically IL-10, IL-6, and TNF-α, in both single pollutant and mixture analyses. For example, an interquartile range increase in perfluorooctanesulfonic acid was associated with −10.87 (95% CI: −19.75, −0.99), −13.91 (95% CI: −24.11, −2.34), and −8.63 (95% CI: −14.51, −2.35) percent change in IL-10, IL-6, and TNF-α levels, respectively. Fetal sex, maternal race, and visit-specific analyses showed associations between most PFAS and cytokines were generally stronger in mid-pregnancy and among women who delivered males or identified as African American. Conclusions: The observed suppression of both regulatory (IL-10) and pro-inflammatory (TNF-α) cytokines suggests that PFAS may alter maternal inflammatory processes or immune functions during pregnancy. Further research is needed to understand the effects of both legacy and newer PFAS on inflammatory pathways and their broader clinical implications.