Brain anomalies in children exposed prenatally to a common organophosphate pesticide

• Authors: Virginia A. Rauh, Columbia University; Frederica P. Perera, Columbia University; Megan K. Horton, Columbia University; Robin M. Whyatt, Columbia University; Ravi Bansal, Columbia University College of Physicians and Surgeons; Xuejun Hao, Columbia University College of Physicians and Surgeons; Jun Liu, Columbia University College of Physicians and Surgeons; Dana Barr, Emory University; Theodore Slotkin, Duke University; Bradley S. Peterson, Columbia University College of Physicians and Surgeons
• Journal Title: Proceedings of the National Academy of Sciences
• Volume: Volume 109, Number 20
• Publisher: National Academy of Sciences | 2012-05-15, Pages 7871-7876
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1073/pnas.1203396109
• Subjects: Health Sciences, General; Health Sciences, Public Health; Health Sciences, Epidemiology
• Keywords: Science & Technology; Multidisciplinary Sciences; Science & Technology - Other Topics; MULTIDISCIPLINARY SCIENCES; brain structure; neurotoxicity; NEONATAL CHLORPYRIFOS EXPOSURE; MEXICAN-AMERICAN CHILDREN; INNER-CITY CHILDREN; DEVELOPMENTAL NEUROTOXICITY; SEROTONERGIC MECHANISMS; INSECTICIDE EXPOSURES; PREGNANCY; COHORT; ATTENTION; TARGETS

Abstract

Prenatal exposure to chlorpyrifos (CPF), an organophosphate insecticide, is associated with neurobehavioral deficits in humans and animal models. We investigated associations between CPF exposure and brain morphology using magnetic resonance imaging in 40 children, 5.9-11.2 y, selected from a nonclinical, representative community-based cohort. Twenty high-exposure children (upper tertile of CPF concentrations in umbilical cord blood) were compared with 20 low-exposure children on cortical surface features; all participants had minimal prenatal exposure to environmental tobacco smoke and polycyclic aromatic hydrocarbons. High CPF exposure was associated with enlargement of superior temporal, posterior middle temporal, and inferior postcentral gyri bilaterally, and enlarged superior frontal gyrus, gyrus rectus, cuneus, and precuneus along the mesial wall of the right hemisphere. Group differences were derived from exposure effects on underlying white matter. A significant exposure x IQ interaction was derived from CPF disruption of normal IQ associations with surface measures in low-exposure children. In preliminary analyses, high-exposure children did not show expected sex differences in the right inferior parietal lobule and superior marginal gyrus, and displayed reversal of sex differences in the right mesial superior frontal gyrus, consistent with disruption by CPF of normal behavioral sexual dimorphisms reported in animal models. High-exposure children also showed frontal and parietal cortical thinning, and an inverse dose-response relationship between CPF and cortical thickness. This study reports significant associations of prenatal exposure to a widely used environmental neurotoxicant, at standard use levels, with structural changes in the developing human brain.