10 Prenatal exposure to phthalates, parabens, and phenols disrupts the neonatal metabolome measured in umbilical cord plasma

Objectives/Goals: Prenatal exposure to phthalates, parabens, and phenols (EDCs) may be risk factors for adverse birth outcomes, but the biological mechanisms driving these relationships are not well understood. This study aims to explore the associations between prenatal EDC exposure – individually and as a mixture – and the neonatal metabolome. Methods/Study Population: This study included 180 pregnant people from a Columbia Center for Children’s Environmental Health cohort in New York City (1998-2002). Eleven phthalates, 1 phthalate replacement, 5 phenols, and 3 parabens were quantified in umbilical cord plasma samples using gas chromatography-tandem mass spectrometry. Metabolomic features in cord plasma were characterized via liquid chromatography coupled with high-resolution mass spectrometry. Metabolome-wide association studies using linear regression and quantile g-computation were used to identify features associated with exposure to the individual and mixture of EDCs, respectively. Correlated metabolites were grouped into modules using weighted gene co-expression network analysis (WGCNA) to identify associations with EDC exposure at a systemic resolution. Results/Anticipated Results: We observed metabolome-wide associations between 18 individual EDCs and 64 unique features in the umbilical cord plasma (p-value <0.05). For example, 9 different phthalates were significantly negatively associated with methionine, creatinine, and 2-methylcitrate. The overall EDC mixture was negatively associated with 2-methylcitrate, arginine, and creatinine (p-value <0.05). In the WGCNA analyses, 13 individual EDCs and the overall EDC mixture were significantly associated with at least 1 of the modules. Pathway enrichment analyses revealed that these metabolites were related to energy, amino acid, and lipid metabolism. Discussion/Significance of Impact: Prenatal EDC exposure, individually and as a mixture, is associated with levels of metabolites measured in umbilical cord plasma at delivery. The identified EDC-responsive metabolites and associated pathways offer insight into the biological processes that could underpin the relationship between prenatal EDC exposure and adverse birth outcomes.