Maternal exposure to legacy PFAS compounds PFOA and PFOS is associated with disrupted cytokine homeostasis in neonates: the Upstate KIDS Study (2008-2010)

Abstract Background. Numerous studies suggest exposure to the environmentally ubiquitous legacy per/polyfluoroalkyl (PFAS) compounds perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA) may be associated with suppressed immune response, including attenuated vaccine-antibody response in children and greater susceptibility to opportunistic infections in general adult populations. We examined associations between neonatal concentrations of legacy PFAS compounds PFOA and PFOS and neonatal cytokine profiles from a large sample of residual newborn dried blood spots (NBDS) in upstate New York. Methods. We measured 30 common cytokines along with PFOA and PFOS in eluted samples of newborn dried blood spots (NDBS) from 3448 neonates participating in the Upstate KIDs Study (2008-2010), following parental consent. We performed adjusted mixed effects regressions for each cytokine against PFAS species, testing for effect modification by infant sex. We then performed exploratory factor analysis (EFA) on PFAS species-specific cytokine subsets selected via the prior regressions, extracting 4 factor axes for the PFOA cytokine subset and 3 for the PFOS cytokine subset based on results from cluster analysis and parallel analysis. Regressions on each PFAS-specific set of factors followed. All models were adjusted for infant birth weight and gestational age at birth, maternal age, race, and use of fertility treatment, and included a random intercept to account for twins. Results. Significant cytokine profiles were dominated by cytokines negatively associated with the given PFAS (9 of 11 cytokines for PFOA; 8 of 11 for PFOS). Regression by PFAS quartile shows evidence of nonlinearity in dose-response for most cytokines. All significant associations between factor groupings defined by EFA are negative for both PFOA and PFOS. Conclusions. There is strong evidence that PFOA and PFOS exposures are associated with disrupted, typically reduced, cytokine levels, both singly and as functional groups defined by EFA and cluster analysis.