source of pesticide exposure is fresh fruit and vegetable consumption, use of urinary metabo- lite concentrations as an indication of parent compound exposure may result in significant misclassification of exposure. Prenatal ΣDEP urinary metabolite concen- trations were associated with slight decrements in FSIQ, Perceptual Reasoning, and Working Memory between the ages of 6 and 9 years. Furthermore, among children of QQ mothers, ΣDAP and ΣDMP urinary metabolite concen- trations were associated with poorer scores on Perceptual Reasoning and FSIQ in a mono- tonically decreasing manner. In both cases, we observed stronger Q192R interactions for ΣDAP and ΣDMP urinary metabolites, rather than ΣDEP metabolites. The reasons for this are unclear. PON1 Q192R exhibits substrate specificity (Richter et al. 2009), but our stron- gest interactions were for dimethylphosphates, not diethylphosphates (into which chlorpyrifos and diazinon both metabolize). An alternative explanation is that our dimethylphosphate metabolite concentrations were simply higher (Engel et al. 2007), indicating more available substrate. Unfortunately, the relevant parent compounds cannot be deduced on the basis of nonspecific urinary dialkylphosphates; how- ever, one well-publicized source of dimethyl- phosphate exposure during the period of enrollment was malathion spraying for mos- quitoes carrying West Nile virus (Nash et al. 2001; O’Sullivan et al. 2005). Interestingly, PON1 status may indirectly influence methyl organophosphate metabolism when multi- ple organophosphate exposures are involved (Jansen et al. 2009). The estimated effects we report for the BSID-II MDI are in line with what has recently been reported in the CHAMACOS (Center for the Health Assessment of Mothers and Children of Salinas) study (Eskenazi et al. 2010), a similarly designed prospective birth QR/RR QQ 130 I C%120 5 9 d ane110 r o c s an100 e m d tse 90 u j d A 80 Prenatal pesticides and cognitive development cohort that enrolled members of an agricultural community in the Salinas Valley of California. Eskenazi et al. (2010) reported evidence of negative effects of ΣDAPs on the MDI, but not the PDI, and particularly among children with the QQ genotype, although there did not appear to be strong effect heterogeneity in the dialkylphosphate–MDI relationship according to PON genotype, and in some circumstances the RR and QQ effect estimates were extremely similar. Although we report interactions with maternal PON1 Q192R genotype, we found very similar interactions and effect estimates for child genotype in our cohort (data not shown). In no cases did we detect effect heterogeneity according to PON1 enzyme activity, perhaps because genotype is a more stable, long-term predictor of metabolism potential. Reconciling estimated effects across studies can be compli- cated when only nonspecific urinary metabo- lites are measured because these metabolites can derive from multiple parent compounds (CDC 2010) that may vary in the degree to which they interact with the Q192R genotype and influence neurodevelopment. Ours was a multiethnic study popula- tion recruited at an inner-city tertiary care hospital that serves a lower-income minor- ity population. Thus, attrition resulting from the challenges of maintaining contact with this population may have affected our study findings. Misclassification of parent com- pound exposure according to exposure route is another significant limitation of our study and other studies relying on urinary dialkylphos- phate biomarkers and may explain the hetero- geneity in effects observed according to race/ ethnicity in our population. It may further complicate the comparison of exposure effects across studies where heterogeneity exists in exposure sources. Additionally, we measured dialkylphosphate biomarkers at one time dur- ing pregnancy, approximately the early third trimester. Although we accounted for seasonal variation in exposure levels in our model, other time-related variability may result in additional misclassification of exposure. Finally, residual confounding by unmeas- ured covariates, including postnatal exposure, should be considered when evaluating our results. Our study enrollment and evaluation periods overlapped with important regulatory changes in residential use of chlorpyrifos and diazinon, which occurred approximately mid- way through our study. Therefore, childhood exposure to these compounds may vary sub- stantially pre- versus postban, although we did not observe any significant interaction with study year (data not shown). However, these changes may explain the inconsistency between our 12- and 24-month BSID-II results. The 0- to 12-month exposure window may include less hand-to-mouth childhood exposure (from crawling exposure to house dust, and/or fresh fruit and vegetable consumption) than in the 12- to 24-month window; thus, more child- hood exposure in the 12- to 24-month window may modify the effect of prenatal exposure. Nonetheless, it is likely, overall, that childhood exposure to chlorpyrifos and diazinon was lower postban (Williams et al. 2008). Conclusion We found that prenatal maternal urinary dialkylphosphate metabolite concentrations were negatively associated with aspects of neurodevelopment at 12 and 24 months, and also at 6–9 years of age, in an urban, inner-city population. At the later ages, the evidence was strongest among the children of mothers with the PON1 192QQ genotype, which was pres- ent in approximately 30% of our population overall, although that varies according to racial ancestry. This important potential source of effect heterogeneity should be considered in future studies of organophosphate exposure. FSIQ Perceptual reasoning T1 T2 T3 T1 T2 T3 ΣDAP T1 T2 T3 T1 T2 T3 ΣDEP T1 T2 T3 T1 T2 T3 ΣDMP T1 T2 T3 T1 T2 T3 ΣDAP T1 T2 T3 T1 T2 T3 ΣDEP T1 T2 T3 T1 T2 T3 ΣDMP Figure 1. Multivariate adjusted mean estimates and 95% CIs according to tertiles (T) of exposure and PON1 Q192R genotype. Among the children of mothers with the PON1 192QQ genotype (triangles), increasing tertile of ΣDAP, ΣDEP, and ΣDMP exposure was generally associated with a monotonic decline in the combined WISC-IV/WPPSI-III FSIQ and Perceptual Reasoning domains, adjusted for sex, race/ethnicity, maternal education, language in the home, alcohol use in preg- nancy, batch and season of urine collection, urinary creatinine, and an indicator variable to designate the WISC-IV or WPPSI-III instrument. We found no consis- tent patterns in the QR/RR genotype group (squares). There was considerable imprecision in all estimates. The first- versus third-tertile contrasts for Perceptual Reasoning were significantly different at p < 0.05 for ΣDAP and ΣDMP. Environmental Health Perspectives • volume 119 | number 8 | August 2011 1187