Gestational organophosphate pesticide exposure and childhood cardiovascular outcomes

Introduction: The general population is chronically exposed to organophosphate pesticides through various routes including ingestion, hand-to-mouth contact, inhalation, and dermal contact. Exposure to organophosphate pesticides during pregnancy impairs fetal development, but the potential long-term effects of gestational organophosphate pesticide exposure are less well understood. Methods: We investigated associations between gestational organophosphate pesticide exposure and cardiovascular outcomes in 643 children in the Generation R Study, a prospective pregnancy cohort based in Rotterdam, The Netherlands. Urinary organophosphate pesticide metabolites (dimethyl [Sigma DMAP], diethyl [Sigma DEAP], and total dialkyl phosphate [Sigma DAP] metabolites) were quantified in three urine samples collected from pregnant participants, and their children were followed until age 10 years at which time cardiac magnetic resonance imaging, ultrasonography, blood pressure, and serum biomarkers assessed cardiovascular health. Linear regression models estimated associations ((3 and 95 % confidence interval [CI]) between a one-interquartile range (IQR) increase in averaged gestational exposure biomarker concentrations and z-scored pediatric cardiovascular outcomes. We investigated effect modification of associations by PON1 genotype. Results: Carotid intima-media thickness z-score was lower ((3: -0.14 [95 % CI: -0.25, -0.02]) and HDL cholesterol z-score was higher ((3: 0.14 [95 % CI: 0.02, 0.25]) for increases in Sigma DEAP concentrations. Carotid intima-media distensibility z-score was lower ((3: -0.08 [95 % CI: -0.19, 0.03]) for increases in Sigma DMAP concentrations, and systolic blood pressure z-score was higher ((3: 0.10 [95 % CI: -0.01, 0.21]) for increases in Sigma DMAP and Sigma DAP. Among those with PON1-161CC and PON1-L55MTT genotypes, higher organophosphate pesticide concentrations conferred an excess risk of adverse vascular and glycemic outcomes, respectively. Conclusions: We observed heterogenous associations between gestational organophosphate pesticide exposure and pediatric cardiovascular health: an anti-atherogenic profile was observed for increases in Sigma DEAP concentrations, and impairments in multiple aspects of cardiovascular health was observed for increases in Sigma DMAP concentrations. PON1-161 and PON1-L55M single nucleotide polymorphisms modified associations for vascular and glycemic outcomes, respectively.