Associations of a Prenatal Serum Per- and Polyfluoroalkyl Substance Mixture with the Cord Serum Metabolome in the HOME Study

Per- and polyfluoroalkyl substances (PFAS) are ubiquitous
and persistent
chemicals associated with multiple adverse health outcomes; however,
the biological pathways affected by these chemicals are unknown. To
address this knowledge gap, we used data from 264 mother–infant
dyads in the Health Outcomes and Measures of the Environment (HOME)
Study and employed quantile-based g-computation to estimate covariate-adjusted
associations between a prenatal (∼16 weeks’ gestation)
serum PFAS mixture [perfluorooctanesulfonic acid (PFOS), perfluorooctanoic
acid (PFOA), perfluorohexanesulfonic acid (PFHxS), and perfluorononanoic
acid (PFNA)] and 14,402 features measured in cord serum. The PFAS
mixture was associated with four features: PFOS, PFHxS, a putatively
identified metabolite (3-monoiodo-l-thyronine 4-O-sulfate), and an unidentified feature (590.0020 m/z and 441.4 s retention time; false discovery rate
<0.20). Using pathway enrichment analysis coupled with quantile-based
g-computation, the PFAS mixture was associated with 49 metabolic pathways,
most notably amino acid, carbohydrate, lipid and cofactor and vitamin
metabolism, as well as glycan biosynthesis and metabolism (P(Gamma)
<0.05). Future studies should assess if these pathways mediate
associations of prenatal PFAS exposure with infant or child health
outcomes, such as birthweight or vaccine response.