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. Highexposure 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.brain structure | neurotoxicity

An Observational Study to Evaluate Associations Between Low-Level Gestational Exposure to Organophosphate Pesticides and Cognition During Early Childhood

“…Although postnatal exposures to organophosphate pesticides have also been examined, when taken together, studies have demonstrated more frequent and/or stronger associations between prenatal exposures and adverse outcomes than with postnatal exposures (4,6,9). However, to date, studies examining these associations have focused primarily on cohorts that were likely exposed to higher-than-national-average levels of organophosphate pesticides, either through heavy use of pesticides for inner-city pest control or as members of farming communities (4)(5)(6)(7)(8)(9)(10).…”

“…The purpose of the current study was to examine the association of prenatal exposure to organophosphate pesticides with early childhood cognition in a sample of children whose mothers' exposures during pregnancy are similar to reported US levels. This study was initiated after the ban of residential use of chlorpyrifos in 2001, whereas previously published studies included mostly subjects exposed prior to the residential ban (4)(5)(6)(7)(8)(9)(10).…”

“…These include delays in cognitive abilities (4)(5)(6)(7)(8), impairments in motor skills (8), and child behaviors characteristic of attentional disorders (4,9). Infants exposed prenatally to a common agricultural organophosphate pesticide (chlorpyrifos) have been shown to demonstrate abnormal structural changes in areas of the brain related to attention and receptive language, social cognition, reward, emotion, and inhibitory control (10). Although postnatal exposures to organophosphate pesticides have also been examined, when taken together, studies have demonstrated more frequent and/or stronger associations between prenatal exposures and adverse outcomes than with postnatal exposures (4,6,9).…”

Developmental Neurotoxicology: History and Outline of Developmental Neurotoxicity Study Guidelines

“…Children's exposures to developmental neurotoxicants also occur via both inhalation and dermal exposures to environmental contaminants. Other well-known or suspected developmental neurotoxicants include ethanol, antidepressant or anticonvulsant pharmaceuticals, arsenic, lead, toluene, polychlorinated biphenyls (PCBs), organophosphate or organochlorine pesticides and a variety of industrial chemicals 3,[9][10][11][12][13][14][15] . The number of chemicals known to be developmentally neurotoxic in humans is limited at present.…”

Reply to Juberg: Using the biologically based dose response to compare exposures across species

“…In his Letter to the Editor (1), Juberg conflates two sequential statements in our paper (2). The references cited in his letter pertain to the sentence preceding the one in question and relate to the "direct neurotoxic effects of early CPF exposure in animals" (ref.…”