title: Brain anomalies in children exposed prenatally to a common organophosphate pesticide.
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 × 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.
authors.affiliation: Heilbrunn Center for Population and Family Health, Columbia University, New York, NY 10032, USA. var1@columbia.edu
authors.forename: Virginia A
authors.initials: VA
authors.lastname: Rauh
authors.forename: Frederica P
authors.initials: FP
authors.lastname: Perera
authors.forename: Megan K
authors.initials: MK
authors.lastname: Horton
authors.forename: Robin M
authors.initials: RM
authors.lastname: Whyatt
authors.forename: Ravi
authors.initials: R
authors.lastname: Bansal
authors.forename: Xuejun
authors.initials: X
authors.lastname: Hao
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Dana Boyd
authors.initials: DB
authors.lastname: Barr
authors.forename: Theodore A
authors.initials: TA
authors.lastname: Slotkin
authors.forename: Bradley S
authors.initials: BS
authors.lastname: Peterson
mesh_terms: D000328:Adult; D001921:Brain / Q000002:abnormalities* / Q000473:pathology; D002648:Child; D004390:Chlorpyrifos / Q000633:toxicity*; D003071:Cognition / Q000187:drug effects; D015331:Cohort Studies; D005260:Female; D005312:Fetal Blood / Q000737:chemistry; D006801:Humans; D007361:Intelligence Tests; D008279:Magnetic Resonance Imaging; D009421:Nervous System Malformations / Q000139:chemically induced*; D009519:New York City; D010755:Organophosphates / Q000633:toxicity*; D010575:Pesticides / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011446:Prospective Studies
chemical_list: D010755:Organophosphates; D010575:Pesticides; D004390:Chlorpyrifos