Perinatal phthalate, paraben, and phenol exposure is associated with the neonatal metabolome measured in umbilical cord plasma

BACKGROUND: Perinatal exposure to phthalates, parabens, and phenols-common endocrine disrupting chemicals (EDCs)-has been associated with adverse health outcomes, but the underlying biological mechanisms remain unclear. This study aims to explore the associations between perinatal EDC exposure--individually and as a mixture--and the neonatal metabolome, which provides a readout of metabolic processes and the factors that impact them. METHODS: EDCs and the metabolome were characterized in umbilical cord blood plasma from 175 pregnant participants recruited through the Columbia Center for Children's Environmental Health. Nontargeted screening revealed 15 EDCs using gas chromatography coupled to high resolution mass spectrometry (HRMS) and 5835 metabolic features using liquid chromatography HRMS. Correlated features were grouped into 21 modules using weighted gene co-expression network analysis and into integrative networks using xMWAS. Linear regression and quantile g-computation were used to assess associations between EDC exposures and individual metabolic feature abundance and the modules. RESULTS: We observed 2208 metabolome-wide associations between individual metabolic features and EDCs modeled individually and one association with the EDC mixture. Eight EDCs were individually associated with 7 modules, and the EDC mixture was associated with 1 module. Pathway enrichment analyses revealed phenol and phthalate exposures were associated with fatty acid and energy metabolism. xMWAS networks demonstrated similar EDC-module and EDC-metabolic feature relationships. CONCLUSION: Perinatal EDC exposure, individually and as a mixture, is associated with individual metabolic features and metabolic networks measured in cord plasma. These results could offer insight into the biological processes underpinning relationships between perinatal EDC exposure and adverse health outcomes.