Prenatal Insecticide Exposure and Adverse Birth Outcomes: Evidence for Mediation via Disruptions in Amino Acid and Acylcarnitine Metabolism

= 406 mother-neonate pairs, 2022-2023) elucidates metabolic pathways linking pesticide exposure to birth outcomes. Maternal urine (first/third trimesters) was analyzed for five OP and two pyrethroid metabolites. Neonatal heel blood was assessed for metabolomic biomarkers. Results indicated that third-trimester maternal urinary levels of 3-phenoxybenzoic acid (3-PBA) and diethyl dithiophosphate (DEDTP) were negatively associated with birth weight. Specifically, a one-unit increase in their ln-transformed concentrations was associated with a 1.508% decrease in birth weight for 3-PBA (95% CI: -2.702 to -0.299%) and a 1.366% decrease for DEDTP (95% CI: -2.610 to -0.105%). Conversely, dimethyl thiophosphate (DMTP) was positively associated with gestational age (% change = 0.244%, 95% CI = 0.033%, 0.416%), with stronger associations observed in male infants. OP/pyrethroid exposure was associated with disrupted neonatal amino acids and acylcarnitine profiles, with patterns varying by trimesters and sexes. Mediation analysis showed that linoleoylcarnitine (C18:2), an acylcarnitine vital for cellular energy metabolism, significantly mediated the associations between 3-PBA and lower birth weight. This is the first study linking neonatal metabolomics and OP/pyrethroid exposure to developmental toxicity, suggesting that disruptions in acylcarnitine-mediated energy metabolism may contribute to adverse birth outcomes.