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

• Published in: Environmental health perspectives Vol. 119; no. 8; pp. 1182 - 1188
• Main Authors: Engel, Stephanie M., Wetmur, James, Chen, Jia, Zhu, Chenbo, Barr, Dana Boy, Canfield, Richard L., Wolff, Mary S.
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC National Institute of Environmental Health Sciences 01.08.2011; US Department of Health and Human Services
• Subjects: Aryldialkylphosphatase - genetics; Biological and medical sciences; Biological markers; Chemical hazards; Child; Child, Preschool; Children; Children's Health; Cognition - drug effects; Cognition disorders; Environment. Living conditions; Environmental aspects; Environmental health; Enzymes; Female; Genetic aspects; Genotype; Genotypes; Health aspects; Humans; Infant; Medical sciences; Metabolites; Organophosphates - toxicity; Organophosphorus compounds; Perception - drug effects; Pesticides; Pesticides, fertilizers and other agrochemicals toxicology; Phosphoric acid esters; Physiological aspects; Pregnancy; Prenatal exposure; Prenatal Exposure Delayed Effects; Public health. Hygiene; Public health. Hygiene-occupational medicine; Reasoning; Risk factors; Toxicology; United States; Human; Enzyme; Pesticides; IQ; Esterases; Exposure; organophosphates; Prenatal; Phosphoric triester hydrolases; Health and environment; Hydrolases; Environment; Organophosphorus compounds; Aryldialkylphosphatase; Cognitive development; Child; mental development; Public health; environmental exposures
• ISSN: 0091-6765; 1552-9924
• DOI: 10.1289/ehp.1003183

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 (w = 360). Prenatal maternal blood was analyzed for PONI 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 monotonie 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.