Research | Children’s Health Organophosphate Pesticide Exposure and Attention in Young Mexican-American Children: The CHAMACOS Study Amy R. Marks,1 Kim Harley,1 Asa Bradman,1 Katherine Kogut,1 Dana Boyd Barr,2 Caroline Johnson,1 Norma Calderon,3 and Brenda Eskenazi 1 1Center for Children’s Environmental Health Research, School of Public Health, University of California, Berkeley, Berkeley, California, USA; 2Emory University, Rollins School of Public Health, Atlanta, Georgia, USA; 3Center for the Health Assessment of Mothers and Children of Salinas, Clinica de Salud del Valle de Salinas, Salinas, California, USA Background : Exposure to organophosphate (OP) pesticides, wellk‑nown neurotoxicants, has been associated with neurobehavioral deficits in children. o Bjectivs : We investigated whether OP exposure, as measured by urinary dialkyl phosphate (DAP) metabolites in pregnant women and their children, was associated with attention‑related outcomes among MexicanA‑merican children living in an agricultural region of California. Methods : Children were assessed at ages 3.5 years (n = 331) and 5 years (n = 323). Mothers com‑ pleted the Child Behavior Checklist (CBCL). We administered the NEPSYI‑I visual attention sub ‑ test to children at 3.5 years and Conners’ Kiddie Continuous Performance Test (KC‑PT) at 5 years. The K‑ CPT yielded a standardized attention deficit/hyperactivity disorder (ADHD) Confidence Index score. Psychometricians scored behavior of the 5y‑earo‑lds during testing using the Hillside Behavior Rating Scale. r esult : Prenatal DAPs (nanomoles per liter) were nonsignificantly associated with maternal report of attention problems and ADHD at age 3.5 years but were significantly related at age 5 years [CBCL attention problems: β = 0.7 points; 95% confidence interval (CI), 0.2–1.2; ADHD: β = 1.3; 95% CI, 0.4–2.1]. Prenatal DAPs were associated with scores on the KC‑PT ADHD Confidence Index > 70th percentile [odds ratio (OR) = 5.1; 95% CI, 1.7–15.7] and with a composite ADHD indicator of the various measures (OR = 3.5; 95% CI, 1.1–10.7). Some outcomes exhibited evidence of effect modification by sex, with associations found only among boys. There was also limited ev i‑ dence of associations between child DAPs and attention. c onclusi : In utero DAPs and, to a lesser extent, postnatal DAPs were associated adversely with attention as assessed by maternal report, psychometrician observation, and direct assessment. These associations were somewhat stronger at 5 years than at 3.5 years and were stronger in boys. k ey words : ADHD, attention, Child Behavior Checklist, DAPs, farmworker, Mexican Americans, neurobehavior, organophosphates, pesticides. Environ Health Perspect 118:1768–1774 (2010). doi:10.1289/ehp.1002056 [Online 19 August 2010] mothers’ report of symptoms consistent with pervasive developmental disorder (PDD) as well as of attention deficit/hyperactivity disor- der (ADHD) or attention problems. A recent cross-sectional study also reported associations between child OP metabolite concentrations and ADHD in 8- to 15-year-olds representa- tive of the U.S. population (Bouchard et al. 2010). Although we previously reported that prenatal OP metabolite concentrations were associated with mothers’ report of PDD symptoms in 2-year-olds living in the agri- cultural Salinas Valley of California, we did not find an association between maternal or child dialkyl phosphates (DAPs) and meas- ures of attention at 2 years of age (Eskenazi et al. 2007). However, the children in our study were younger—potentially too young at 2 years of age to manifest attention prob- lems or for mothers to detect them. Although ADHD, characterized by inattention, impul- sivity, and/or hyperactivity, is occasionally diagnosed in children as young as 2 or 3 years, it is more apparent after children begin school and is more commonly reported in boys than Address correspondence to B. Eskenazi, Center for Children’s Environmental Health Research, School of Public Health, UC Berkeley, 1995 University Ave., Suite 265, Berkeley, CA 94720 USA. Telephone: (510) 643-1337. Fax: (510) 642-9083. E-mail: eskenazi@berkeley.edu Supplemental Material is available online (doi:10.1289/ehp.1002056 via http://dx.doi.org/). We acknowledge the CHAMACOS staff, students, community partners, and participants and families, without whom this study would not be possible. We would specifically like to thank the CHAMACOS Field Office staff as well as N. Holland for her assis- tance in specimen management and R. Klein for advice on attention measurements. This publication was made possible by research supported by grants RD 83171001 from the U.S. Environmental Protection Agency (EPA), PO1 ES009605 from the National Institute of Environmental Health Sciences (NIEHS), and RO1 OH007400 from the National Institute for Occupational Safety and Health (NIOSH). The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIEHS, NIOSH, National Institutes of Health, or U.S. EPA. Since this paper was written, B.E. worked as an expert witness in a pesticide poisoning case. The authors declare they have no actual or potential com- peting financial interests. Received 12 February 2010; accepted 29 March 2010. ovlume 118 | number 12 | December 2010 • Environmental Health Perspectives Organophosphate (OP) pesticides are potent toxicants that target the nervous systems of insects and other pests (Jokanovic 2009). OPs operate primarily through the inhibition of acetylcholinesterase, an enzyme that degrades the neurotransmitter acetylcholine, resulting in a buildup of acetylcholine in the neuronal junction (Jeyaratnam and Maroni 1994). However, cholinergic inhibition may not be the sole mechanism of effect, particularly in cases of low-level exposure (Costa 2006; Ray and Richards 2001; Timofeeva et al. 2008). Although accounts of human poisoning with these compounds have reported symptoms such as impaired concentration, slowed infor- mation processing and motor function, anxi- ety, confusion, tremors, seizure, and death (Jeyaratnam and Maroni 1994; Levin and Rodnitzky 1976), few studies have investi- gated the health effects in humans of low- level chronic exposure to OP pesticides. The potential effects of such low-level exposures on neurobehavioral functioning are particu- larly relevant for fetuses and young children, who may be especially vulnerable to neuro- toxicants because of their immature nervous systems, their rapid rate of brain growth and 1768 development in utero and during early child- hood, and their low levels of the enzymes involved in the metabolism and detoxifica- tion of OP pesticides (Eskenazi et al. 1999; Huen et al. 2009). Animal studies have found adverse effects of OP exposure during the pre- natal and early postnatal periods (Costa 2006; Eskenazi et al. 1999). Although research is limited, a few recent epidemiologic studies have reported asso- ciations between in utero OP exposure and adverse effects on neurobehavioral devel- opment (Engel et al. 2007; Eskenazi et al. 2007; Rauh et al. 2006; Young et al. 2005). These studies have found that biomarkers of prenatal OP exposure are associated with an increased number of abnormal neonatal reflexes, as measured by the Brazelton Scales of Neonatal Development (Engel et al. 2007; Young et al. 2005), and poorer mental devel- opment in early childhood, as measured on the Bayley Scales of Infant Development (Eskenazi et al. 2007; Rauh et al. 2006). Rauh et al. (2006) also found in a cohort of 3-year-olds living in New York City that con- centrations of the OP pesticide chlorpyrifos in maternal serum were associated with the