Research | Children’s Health Seven-Year Neurodevelopmental Scores and Prenatal Exposure to Chlorpyrifos, a Com mon Agricultural Pesticide Virginia Rauh,1 Srikesh Arunajadai,2 Megan Horton,3,4 Frederica Perera,4 Lori Hoepner,4 Dana B. Barr,5 and Robin Whyatt 4 1Heilbrunn Center for Population and Family Health, Mailman School of Public Health, 2Department of Biostatistics, Mailman School of Public Health, 3Sergievsky Center, and 4Columbia Center for Children’s Environmental Health, Mailman School of Public Health, Columbia University, New York, New York, USA; 5Emory University, Atlanta, Georgia, USA Background : In a longitudinal birth cohort study of inner-city mothers and children (Columbia Center for Children’s Environmental Health), we have previously reported that prenatal exposure to chlorpyrifos (CPF) was associated with neurodevelopmental problems at 3 years of age. o Bjectiv : The goal of the study was to estimate the relationship between prenatal CPF exposure and neurodevelopment among cohort children at 7 years of age. Methods : In a sample of 265 children, participants in a prospective study of air pollution, we measured prenatal CPF exposure using umbilical cord blood plasma (picograms/gram plasma) and 7-year neurodevelopment using the Wechsler Intelligence Scale for Children, 4th edition (WISC-IV). Linear regression models were used to estimate associations, with covariate selection based on two alternate approaches. r esult : On average, for each standard deviation increase in CPF exposure (4.61 pg/g), Full-Scale intelligence quotient (IQ) declined by 1.4% and Working Memory declined by 2.8%. Final covari- ates included maternal educational level, maternal IQ, and quality of the home environment. We found no significant interactions between CPF and any covariates, including the other chemical exposures measured during the prenatal period (environmental tobacco smoke and polycyclic aro- matic hydrocarbons). c onclusi : We report evidence of deficits in Working Memory Index and Full-Scale IQ as a function of prenatal CPF exposure at 7 years of age. hTese findings are important in light of con - tinued widespread use of CPF in agricultural settings and possible longer-term educational implica- tions of early cognitive deficits. k ey words : chlorpyrifos, neurodevelopment, pesticides. Environ Health Perspect 119:1196–1201 (2011). doi:10.1289/ehp.1003160 [Online 21 April 2011] Each year, thousands of new chemicals are released in the United States, with very little documentation about potential long-term human health risks (Landrigan et al. 2002). First registered in 1965 for agricultural and pest control purposes, chlorpyrifos (CPF; 0,0-diethyl-0-3,5,6-trichloro-2-pyridyl phos- phorothioate) is a broad-spectrum, chlorinated organophosphate (OP) insecticide. Before regulatory action by the U.S. Environmental Protection Agency (EPA) to phase out resi- dential use beginning in 2000, CPF applica- tions were particularly heavy in urban areas, where the exposed populations included preg- nant women (Berkowitz et al. 2003; Whyatt et al. 2002, 2003). In a sample of pregnant women in New York City (Perera et al. 2002) detectable levels of CPF were found in 99.7% of personal air samples, 100% of indoor air samples, and 64–70% of blood samples col- lected from umbilical cord plasma at delivery (Whyatt et al. 2002). Early concerns about the possible neuro- toxicity of OP insecticides for humans derived from rodent studies showing that prenatal and early postnatal exposures to CPF were associated with neurodevelopmental deficits, and these effects have been seen at exposure levels well below the threshold for systemic toxicity caused by cholinesterase inhibition 1196 in the brain (e.g., Slotkin and Seidler 2005). Evidence has accumulated over the past decade showing that noncholinergic mechanisms may play a role in the neurotoxic effects of CPF exposure in rodents, involving disruption of neural cell development, neurotransmitter sys- tems (Aldridge et al. 2005; Slotkin 2004), and synaptic formation in different brain regions (Qiao et al. 2003). Such developmental dis- ruptions have been associated with later func- tional impairments in learning, short-term working memory, and long-term reference memory (Levin et al. 2002). In humans, OPs have been detected in amnionic fluid (Bradman et al. 2003) and are known to cross the placenta (Richardson 1995; Whyatt et al. 2005), posing a threat to the unborn child during a period of rapid brain development. Using urinary metabo- lites as the biomarker of exposure, several different birth cohort studies have reported that prenatal maternal nonspecific OP expo- sure was associated with abnormal neonatal reflexes (Engel et al. 2007; Young et al. 2005), mental deficits and pervasive develop- ment disorder at 2 years (Eskenazi et al. 2007), and attention problem behaviors and a composite attention-deficit/hyperactivity disorder indicator at 5 years of age (Marks et al. 2010). Using a different biomarker of exposure (the parent compound of CPF in umbilical cord plasma), we have previously reported (in the same cohort as the present study) significant associations between prenatal exposure to CPF (> 6.17 pg/g) and reduced birth weight and birth length (Whyatt et al. 2004), increased risk of small size for ges- tational age (Rauh V, Whyatt R, Perera F, unpublished data), increased risk of mental and motor delay (< 80 points) and 3.5- to 6-point adjusted mean decrements on the 3-year Bayley Scales of Infant Development (Rauh et al. 2006), and evidence of increased problems related to attention, attention deficit hyperactivity disorder, and pervasive developmental disorder as measured by the Child Behavior Checklist at 2–3 years (Rauh et al. 2006). Taken together, these prospective cohort studies show a consistent pattern of early cognitive and behavioral deficits related to prenatal OP exposure, across both agricul- tural and urban populations, using different biomarkers of prenatal exposure. We undertook the present study to iden- tify the developmental consequences of pre- natal exposure to CPF in a sample of New York City children at 7 years of age. Given the mechanisms proposed in the rodent literature, and early findings from prospec- tive human studies involving nonspecific OP exposures, we hypothesized that prenatal exposure to CPF would be associated with Address correspondence to V.A. Rauh, Heilbrunn Center for Population and Family Health, Mailman School of Public Health, 60 Haven Ave., B-2, New York, NY 10032 USA. Telephone: (212) 304-7438. Fax: (212) 305-7024. E-mail: var1@columbia.edu Supplemental Material is available online (doi:10. 1289/ehp.1003160 via http://dx.doi.org/). We are grateful to the families of northern Manhattan who have so generously contributed their time and effort to the study. This study was supported by the National Institute of Environmental Health Sciences (grants 5P01ES09600, P50ES015905, and 5R01ES08977), the U.S. Environmental Protection Agency (grants R827027, 8260901, and RR00645), the Educational Foundation of America, the John and Wendy Neu Family Foundation, the New York Community Trust, and the Trustees of the Blanchette Hooker Rockefeller Fund. The authors declare they have no actual or poten- tial competing financial interests. Received 2 November 2010; accepted 12 April 2011. ovlume 119 | number 8 | August 2011 • Environmental Health Perspectives