Exposure to legacy and novel perfluoroalkyl substance disturbs the metabolic homeostasis in pregnant women and fetuses: A metabolome-wide association study

Background: Perfluoroalkyl substances (PFASs) exist extensively and several of these have been verified to be toxic. Prenatal exposure to PFASs has attracted much attention. Metabolome-wide association analyses can be used to explore the toxicity mechanisms of PFASs by identifying associated biomarkers. Objectives: To evaluate associations between the metabolites in maternal and cord serum and internal exposure to several common PFASs. Methods: Paired maternal and cord serum samples were collected from 84 pregnant women who gave birth between 2015 and 2016. Seven legacy and two novel PFASs were measured. A nontarget metabolomic method and an iterative metabolite annotation based on metabolic pathways were applied to characterize the metabolic profiles. Linear regression adjusted with the false discovery rate and covariates was used to indicate the associations. Results: A total of 279 features in maternal serum and 338 features in cord serum were identified as metabolites associated with PFAS exposure. Perfluorooctanoic acid (PFOA) and perfluorohexane sulfonic acid (PFHxS) were two PFASs associated with more metabolites, while the two novel chlorinated polyfluorinated ether sulfonic acids (Cl-PFESAs) showed less relevance to the metabolome. With pathway enrichment analysis, we found that three fatty acid metabolisms and retinol metabolism were correlated with PFAS exposure in maternal blood, and that sterol metabolism showed the correlation in both maternal serum and cord serum. Conclusions: We identified metabolites and pathways in pregnant women and fetuses associated with the exposure to several PFAS, indicating a promising application for metabolome-wide association studies. Additional research is needed to confirm causation