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

TLDR

Prenatal exposure to organophosphate pesticides has been shown to impair child neurobehavioral development, and the enzyme paraoxonase 1 (PON1) plays a key role in metabolizing these compounds. The study aimed to examine the relationship between biomarkers of organophosphate exposure, PON1 activity and genotype, and cognitive development at 12 and 24 months and at 6–9 years of age. Researchers enrolled 404 pregnant women in a multiethnic cohort, collected third‑trimester maternal urine for organophosphate metabolites, and analyzed maternal blood for PON1 activity and genotype. Higher prenatal organophosphate metabolite levels were associated with lower mental development at 12 months in black and Hispanic children and with reduced perceptual reasoning in later childhood, with stronger effects observed in children whose mothers carried the PON1 Q192R QR/RR or QQ genotypes, indicating that PON1 genotype modifies the neurodevelopmental impact of prenatal exposure.

Abstract

Background: Prenatal exposure to organophosphate pesticides has been shown to negatively affect child neurobehavioral development. Paraoxonase 1 (PON1) is a key enzyme in the metabolism of organophosphates.Objective: We examined the relationship between biomarkers of organophosphate exposure, PON1, and cognitive development at ages 12 and 24 months and 6–9 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 urine samples were collected and analyzed for organophosphate metabolites (n = 360). Prenatal maternal blood was analyzed for PON1 activity and genotype. Children returned for neurodevelopment assessments ages 12 months (n = 200), 24 months (n = 276), and 6–9 (n = 169) years of age.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 QR/RR genotype. In later childhood, increasing prenatal total dialkyl- and dimethylphosphate metabolites were associated with decrements in perceptual reasoning in the maternal PON1 Q192R QQ genotype, which imparts slow catalytic activity for chlorpyrifos oxon, with a monotonic trend consistent with greater decrements with increasing prenatal exposure.Conclusion: Our findings suggest that prenatal exposure to organophosphates is negatively associated with 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.