Gestational Perfluorooctanoate Exposure and Childhood Metabolome at Age 8 Years

Abstract

BACKGROUND AND AIM: Gestational exposure to perfluorooctanoate (PFOA) is associated with excess adiposity and increased cardiometabolic risk in children. To identify potential mechanisms underlying these associations, we characterized metabolic alterations and pathways associated with gestational PFOA exposure in 8-year-old children using a metabolome-wide association study (MWAS). METHODS: METHODS: We performed untargeted, high-resolution metabolomic profiling of serum samples collected at age 8-years from 106 children enrolled in the HOME study (Cincinnati, OH) using high-resolution liquid chromatography mass spectrometry (LC-MS). During pregnancy, we quantified PFOA concentrations in serum collected from their mothers using LC-MS methods. Associations between maternal PFOA concentrations during pregnancy and annotated metabolites detected in child serum samples were evaluated using multivariable linear regression adjusted for child age, sex, and race with a false discovery rate 20%. Pathway level changes were determined by characterizing metabolite networks; enriched pathways were determined using Mummichog. RESULTS:Maternal PFOA concentrations during pregnancy (median: 5.2 ng/mL, 25th-75th percentile: 3.6-7.3 ng/mL) were associated with alterations in the child metabolome at age 8 years. Associations that met FDR20% included 203 metabolites, of which 144 were negatively associated with PFOA concentrations. Annotation of metabolites included a range of lipids and dietary factors, while pathway enrichment identified alterations in amino acid metabolism, lipid pathways, oxidative stress, de novo fatty acid biosynthesis and catabolism. CONCLUSIONS:This is the first study to examine gestational PFOA in association with childhood metabolome using untargeted approach. In this study, maternal PFOA concentrations at pregnancy were associated with systemic alterations in metabolic pathways related to energy production, oxidative stress and catabolism in serum collected from 8-year-old children. These results highlight the importance of early life exposure, and suggest that PFOA-related metabolic alterations manifest early in life. Future studies should examine how these PFOA-related alterations contribute to increased risk for childhood adiposity and cardiometabolic risk. KEYWORDS: PFAS, Metabolomics, Children's environmental health