Gestational exposure to organophosphate pesticides and maternal urine metabolomic profile in the GENEIDA birth cohort

Abstract

Early developmental exposure to organophosphate (OP) pesticides has been linked to adverse health effects, though the underlying molecular pathways remain unclear. This study examined urinary metabolomic profiles of 387 pregnant women in their first and third trimesters using UPLC-MS/MS to identify metabolic disruptions associated with OPs exposure measured via dialkyl phosphate (DAPs) metabolites, including total, methyl and ethyl forms. Multiple linear regression models, adjusted for covariates and corrected for multiple comparisons revealed that first trimester OP exposure was significantly associated with 4-pyridoxic acid, a vitamin B6 metabolite. In the third trimester, OP exposure was linked to metabolites related to amino acid metabolism, synaptic function, cytochrome P450-mediated detoxification, cancer and immune pathways. These findings suggest that OP exposure may disrupt maternal metabolic processes during pregnancy, potentially affecting foetal development. This study highlights potential targets for future hypothesis-driven studies and potential interventions to mitigate OP pesticide exposure during pregnancy.