Prenatal Exposure to Perfluoroalkyl Substances Associated with Increased Susceptibility to Liver Injury in Children.

BACKGROUND & AIMS Per- and polyfluoroalkyl substances (PFAS) are widespread and persistent pollutants that have been shown to have hepatotoxic effects in animal models. However, human evidence is scarce. We evaluated how prenatal exposure to PFAS associates with established serum biomarkers of liver injury and alterations in serum metabolome in children. APPROACH & RESULTS We used data from 1105 mothers and their children (median age 8.2 years, IQR 6.6-9.1) from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing population-based birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK). We measured concentrations of perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorononanoate (PFNA), perfluorohexane sulfonate (PFHxS), and perfluoroundecanoate (PFUnDA) in maternal blood. We assessed concentrations of alanine aminotransferase, aspartate aminotransferase, and gamma-glutamyltransferase in child serum. Using Bayesian Kernel Machine regression, we found that higher exposure to PFAS during pregnancy was associated with higher liver enzyme levels in children. We also measured child serum metabolomics through a targeted assay and found significant perturbations in amino acid and glycerophospholipid metabolism associated with prenatal PFAS. A latent variable analysis identified a profile of children at high risk of liver injury (OR 1.56, 95% CI 1.21-1.92) that was characterized by high prenatal exposure to PFAS and increased serum levels of branched-chain amino acids (valine, leucine, isoleucine), aromatic amino acids (tryptophan and phenylalanine), and glycerophospholipids (phosphatidylcholine PC aa C36:1 and Lyso-PC a C18:1). CONCLUSIONS Developmental exposure to PFAS can contribute to pediatric liver injury.