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

Maternal exposure to organophosphate (OP) and pyrethroid insecticides may adversely affect newborn health, yet existing evidence and underlying mechanisms are limited. Utilizing amino acid and acylcarnitine metabolomics, this prospective cohort study (<i>n</i> = 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.