BackgroundPesticide exposures are ubiquitous and of substantial public concern. We examined the potential association of congenital heart defects with residential proximity to commercial agricultural pesticide applications in the San Joaquin Valley, California. MethodsStudy subjects included 569 heart defect cases and 785 non-malformed controls born from 1997 to 2006 whose mothers participated in a population-based case-control study. Associations with any versus no exposure to physicochemical groups of pesticides and specific chemicals were assessed using logistic regression adjusted for relevant covariates, for 8 heart defect phenotypes that included ≥50 cases and pesticide exposures with ≥5 exposed cases and controls, which resulted in 235 comparisons. Results38% of cases and controls were classified as exposed to pesticides within a 500m radius of mother׳s address during a 3-month periconceptional window. Adjusted odds ratios (AORs) with 95% CIs excluding 1.0 were observed for 18 comparisons; all were >1 and ranged from 1.9 to 7.1. They included tetralogy of Fallot (n=101 cases) and neonicotinoids; hypoplastic left heart syndrome (n=59) and strobins; coarctation of the aorta (n=74) and pyridazinones; pulmonary valve stenosis (n=53) and bipyridyliums and organophosphates; ventricular septal defects (n=93) and avermectins and pyrethroids; and atrial septal defects (n=132) and dichlorphenoxy acid or esters, organophosphates, organotins, and pyrethroids. No AORs met both of these criteria for d-transposition of the great arteries (n=58) or heterotaxia (n=53). ConclusionsMost pesticides were not associated with increased risk of specific heart defect phenotypes. For the few that were associated, results should be interpreted with caution until replicated in other study populations.