Prenatal Exposure to Organophosphates, Paraoxonase 1, and Cognitive Development in Childhood

Abstract

Background: Prenatal exposure to organophosphate pesticides has been shown to negatively impact child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates. Objective: To examine the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months, and 6 to 9 years. Methods: The Mount Sinai Children’s Environmental Health Study enrolled a multiethnic prenatal population in New York City between 1998 and 2002 (n= 404). Third trimester maternal urines were collected and analyzed for organophosphate metabolites (n = 360). Prenatal maternal blood was analyzed for PON1 activity and genotype. Children returned for neurodevelopment assessments at ages 12 months (n = 200), 24 months (n = 276), 6 to 9 (n = 169) years. Results: Prenatal total dialkylphosphate metabolite level was associated with a decrement in mental development at 12 months among blacks and Hispanics. These associations appeared to be enhanced among children of mothers who carried the PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon. In later childhood, increasing prenatal total dialkyl- and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, with a monotonic trend consistent with greater decrements with increasing prenatal exposure. Conclusion: Our findings suggest that prenatal exposure to organophosphates negatively impacts cognitive development, particularly perceptual reasoning, with evidence of effects beginning at 12 months and continuing through early childhood. PON1 may be an important susceptibility factor for these deleterious effects.