neurodevelopmental deficits persisting into the early school years, when more refined neuropsychological tests are available to iden- tify particular functional impairments. Materials and Methods Participants and recruitment. The subjects for this report are participants in an ongoing prospective cohort study (Columbia Center for Children’s Environmental Health) of inner-city mothers and their newborn infants (Perera et al. 2002). The cohort study was initiated in 1997 to evaluate the effects of prenatal exposures to ambient pollutants on birth outcomes and neurocognitive develop- ment in a cohort of mothers and newborns from low-income communities in New York City. Nonsmoking women (classified by self- report and validated by blood cotinine levels < 15 ng/mL), 18–35 years of age, who self- identified as African American or Dominican and who registered at New York Presbyterian Medical Center or Harlem Hospital prenatal clinics by the 20th week of pregnancy, were approached for consent. Eligible women were free of diabetes, hypertension, known HIV, and documented drug abuse and had resided in the area for at least 1 year. The study was approved by the Institutional Review Board of Columbia University. Informed consent was obtained from all participating mothers, and informed assent was obtained from all children as well, starting at 7 years of age. Of 725 consenting women, 535 were active participants in the ongoing cohort study at the time of this report, and 265 of their children had reached the age of 7 years with complete data on the following: a) prenatal maternal interview data, b) biomarkers of prenatal CPF exposure level from maternal and/or cord blood samples at delivery, c) postnatal covari- ates, and d) neurodevelopmental outcomes. Maternal interview and assessment. A 45-min questionnaire was administered to each woman in her home by a trained bilingual interviewer during the third tri- mester of pregnancy and annually thereafter. From the interviews and medical records, the following sociodemographic and biomedi- cal variables, among others, were available: race/ethnicity, infant sex, household income, maternal age, maternal completed years of education at child’s age 7 years, birth weight, gestational age, and self-reported maternal exposure to environmental tobacco smoke (ETS) during pregnancy. We measured maternal nonverbal intelli- gence by the Test of Nonverbal Intelligence, 3rd edition (TONI-3) (Brown et al. 1997), a 15-min language-free measure of general intelli- gence, administered when the child was 3 years of age. The quality of the care-taking environ- ment was measured by the Home Observation for Measurement of the Environment (HOME) inventory when the child was 3 years of age (Caldwell and Bradley 1979) to assess physi- cal and interactive home characteristics. The mother report version of the Child Behavior Checklist for ages 6–18 years, a well-validated measure of child behavior problems occurring in the preceding 2 months (Achenbach and Rescorla 2001), was administered at 7 years as part of the larger cohort study. Biological samples and pesticide exposure. A sample of umbilical cord blood (30–60 mL) was collected at delivery, and a sample of maternal blood (30–35 mL) was collected within 2 days postpartum by hospital staff. Portions were sent to the Centers for Disease Control and Prevention (Atlanta, GA) for analysis of CPF in plasma, as well as lead and cotinine, described in detail elsewhere (Perera et al. 2002; Whyatt et al. 2003). Methods for the laboratory assay for CPF, including quality control, reproducibility, and limits of detec- tion (LODs), have also been previously pub- lished (Barr et al. 2002). In cases where the umbilical cord blood sample was not collected (12% of subjects), mothers’ values were sub- stituted, using a formula previously derived from regression analyses (Whyatt et al. 2005). As previously reported, maternal and umbilical cord blood CPF concentrations were similar (arithmetic means ± SDs of 3.9 ± 4.8 pg/g for maternal blood and 3.7 ± 5.7 pg/g for cord blood) (Whyatt et al. 2005), and CPF levels in paired maternal and umbilical cord plasma samples were highly correlated (r = 0.76; p < 0.001, Spearman’s rank), indicating that CPF was readily transferred from mother to fetus during pregnancy. Prenatal blood lead levels were available for a subset of children (n = 89). ETS exposure, measured by maternal self-report, was validated by cotinine levels in umbilical cord blood, as described in detail elsewhere (Rauh et al. 2004). We measured polycyclic aromatic hydrocarbon (PAH) expo- sure by personal air monitoring during the third trimester, using a previously described method, and excluding poor-quality samples (Perera et al. 2003). As previously described (Perera et al. 2003), we computed a composite log-transformed PAH variable from the eight correlated PAH air concentration measures (r-values ranging from 0.34 to 0.94; all p-values < 0.001 by Spearman’s rank). In the larger cohort study, > 40% of CPF exposure values for combined mater- nal and umbilical cord blood samples were below the LOD. Using a method suggested by Richardson and Ciampi (2003), we made a distributional assumption for the exposure variable (log-normal CPF), computed the expected value of the exposure (E) for all non- detects [E(X/X < LOD)], and assigned this value to all nondetects. Measures of neurodevelopment. For the 7-year assessment, we selected the Wechsler Environmental Health Perspectives • volume 119 | number 8 | August 2011 Neurodevelopment and chlorpyrifos Intelligence Scale for Children, 4th edition (WISC-IV), because of its revised structure based on the latest research in neurocognitive models of information processing (Wechsler 2003). The WISC-IV is sensitive to low- dose neurotoxic exposures, as demonstrated by studies of lead toxicity in 6- to 7.5-year- old children (Chiodo et al. 2004; Jusko et al. 2008; Rothenberg and Rothenberg 2005). The instrument measures four areas of mental functioning that are associated with, but dis- tinct from, overall intelligence quotient (IQ) and is sensitive to cognitive deficits related to learning and working memory, which have been linked to CPF exposure in rodent stud- ies (e.g., Levin et al. 2002). Each standardized scale has a mean of 100 and SD of 15. The Verbal Comprehension Index is a measure of verbal concept formation, a good predic- tor of school readiness (Hecht et al. 2000; Wechsler 2003); the Perceptual Reasoning Index measures nonverbal and fluid reason- ing; the Working Memory Index assesses chil- dren’s ability to memorize new information, hold it in short-term memory, concentrate, and manipulate information; the Processing Speed Index assesses ability to focus attention and quickly scan, discriminate, and sequen- tially order visual information; and the Full- Scale IQ score combines the four composite indices. The General Ability Index score is a summary score of general intelligence, simi- lar to Full-Scale IQ, but excludes contribu- tions from both Working Memory Index and Processing Speed Index (Wechsler 2003). WISC-IV scores may be influenced by socio- economic background and/or child behavior problems particularly those related to anxiety (Wechsler 2003). D a t a a n a l y s i s . W e c o n d u c t e d a l l analyses using the statistical program R (R Development Core Team 2010). We treated CPF exposure level (picograms per gram) as a continuous variable. We natural log (ln) transformed the WISC-IV Composite Index scores to stabilize the variance and to improve the linear model fit, based on regres- sion diagnostics. Unadjusted correlation analy- ses were used to explore associations between CPF exposure and WISC-IV scores. We con- structed smoothed cubic splines to explore the shape of the functional relationships between CPF exposure and each of the log-transformed WISC-IV indices. We compared the mod- els in which CPF is entered as a single con- tinuous outcome with those in which CPF is modeled using B-splines, using the Davidson– MacKinnon J-test for comparing nonnested models (Davidson and MacKinnon 1981). Demographic, biomedical, and chemi- cal exposure variables collected for the larger cohort study were available for possible inclu- sion in the present analysis. We used two dif- ferent approaches for covariate selection and 1197