Engel et al. associations were not heterogeneous by race/ ethnicity. However, for the combined popu- lation, we again found effect heterogeneity according to the PON1 Q192R polymor- phism for the associations between ΣDAP and ΣDMP biomarkers and perceptual rea- soning domain. In contrast to the 12-month BSID-II MDI, children of mothers with the slow-catalytic-activity genotype (QQ) experi- enced a substantial decrement in the overall perceptual reasoning score with each log10 increment increase in exposure, whereas we found no effect of ΣDAP and ΣDMP bio- markers on the perceptual reasoning score of children with mothers who carried the QR/RR genotypes (Table 5). Comparing bio- marker tertiles according to genotype, increas- ing tertiles of ΣDAP, ΣDEP, and ΣDMP among the children of mothers with the PON1 192QQ genotype were generally asso- ciated with monotonically declining adjusted means in FSIQ and perceptual reasoning, whereas we found no consistent pattern in the QR/RR group (Figure 1). For perceptual Combined populations (6–9 years) FSIQ 140 –1.39 Perceptual Reasoning –2.36 Verbal Comprehension –0.42 WISC-IV (7–9 years) FSIQ 114 –1.10 Perceptual Reasoning –2.39 Verbal Comprehension 0.56 Processing Speed –1.05 Working Memory –0.53 WPPSI-III (6 years) FSIQ 96 –1.14 Perceptual Reasoning –2.07 Verbal Comprehension –1.16 Processing Speed –1.22 –6.04 to 1.31 –3.45 to 2.62 –6.97 to 2.19 –3.11 to 4.23 –5.57 to 3.46 –4.24 to 3.18 –4.55 to 2.28 –5.66 to 1.52 –4.59 to 2.27 –5.12 to 2.67 FSIQ Log10 ΣDAP Log10 ΣDEP Log10 ΣDMP Log10 ΣDAP Log10 ΣDEP Log10 ΣDMP Log10 ΣDAP Log10 ΣDEP Log10 ΣDMP Perceptual Reasoning Verbal Comprehension WPPSI-III instrument. 1186 Table 4. Prenatal organophosphate biomarker levels and psychometric intelligence at 6–9 years in the Mount Sinai Children’s Environmental Health Study. n Log10 ΣDAP β 95% CI n Log10 ΣDEP β 95% CI Log10 ΣDMP n β 95% CI –4.54 to 1.77 140 –2.89 –6.15 to 0.36 142 –0.46 –5.01 to 2.81 114 –3.15 –7.19 to 0.89 115 –0.39 Data are for a generalized linear models adjusted for sex, race/ethnicity, maternal education, language in the home, maternal PON1 enzymatic activity, alcohol use in pregnancy, batch season of urine collection, and urinary creatinine. Combined population models additionally adjusted for whether the score came from the WISC-IV or WPPSI-III instrument. Table 5. Joint prenatal organophosphate biomarker and PON1 Q192R effect on combined IQ domains at 6–9 years in the Mount Sinai Children’s Environmental Health Study. PON1 192 QR/RR (fast; n = 101) PON1 192 QQ (slow; n = 39) β –0.66 –2.32 0.28 –0.56 –3.24 0.71 –0.33 –0.45 0.12 95% CI –4.33 to 3.00 –6.49 to 1.86 –2.89 to 3.44 –4.80 to 3.68 –8.11 to 1.62 –2.96 to 4.38 –3.87 to 3.20 –4.51 to 3.60 –2.93 to 3.16 β –2.33 –3.13 –1.79 –7.52 –4.80 –6.15 0.73 –1.20 0.24 95% CI –8.40 to 3.74 –8.21 to 1.96 –6.83 to 3.25 –14.53 to –0.51 –10.73 to 1.13 –11.99 to –0.31 –5.12 to 6.59 –6.13 to 3.74 –4.60 to 5.09 reasoning, the first- versus third-tertile con- trasts for ΣDAP and ΣDMP were statistically significant (p < 0.05). Maternal third-trimester blood PCB concentration was inversely associated with mental development at 12 months (loge β = –7.18; 95% CI, –14.47 to 0.11) but not at 24 months (loge β = 1.60; 95% CI, –6.57 to 9.77) and was not associated with IQ [see Supplemental Material, Table 4 (doi:10.1289/ ehp.1003183)]. However, although the effect estimates for PCBs were sometimes quite large, they were also measured with extreme imprecision, as indicated by the very large CIs. Maternal third-trimester blood DDE was not associated with any of the outcome measures. Discussion We report an association between prenatal increasing ΣDAP and ΣDMP urinary metabo- lite concentrations and poorer scores on the BSID-II MDI at 12 months among blacks and Hispanics. At some ages, these associations were modified by maternal PON1 Q192R genotype, although the interaction effects across exam years were not entirely consistent. For the 12-month exam, the strongest negative associations with organophosphate exposure was found in the QR/RR group, whereas for the psychometric exams the strongest negative associations were found in the QQ group. An explanation for a switch in the enhanced-risk genotype is not readily apparent; however, PON1 is a complex gene involved in multiple physiological processes, including organophos- phate metabolism but also lipid peroxidation and oxidative stress (Li et al. 2003), which may impact neurodevelopment independently (Eskenazi et al. 2010) and/or jointly with organophosphate exposure. Heterogeneity according to maternal race/ ethnicity may indicate differences in exposure sources rather than any underlying susceptibil- ity. As previously described, overall, 46.4% of our mothers reported that pesticides were applied in their home either by themselves or by a family member during their pregnancy, although there was a profound racial dispar- ity in this behavior (Berkowitz et al. 2003). Among the women who returned for the 12-month BSID-II exam in the present study, 70.5% of the blacks and Hispanics reported buying pesticides, applying pesticides, or fumi- gating their house during their pregnancy, compared with only 31.6% of the whites, and yet we did not detect significant differences in their exposure distributions [see Supplemental Material, Table 1 (doi:10.1289/ehp.1003183)]. In our population, race/ethnicity was strongly associated with whether a subject lived in pub- lic or private housing. And indeed, we found similar trends in the effect estimates when we stratified by housing type (public vs. private) rather than race/ethnicity, although the mag- nitude of the interaction was not as strong. This indicates that whites, or people living in private or owner-occupied housing, may have experienced a different source of exposure to pesticides or their metabolites that contributed substantially to their urinary concentrations; one possibility is that pesticide residues from fresh fruit and vegetable consumption account for a large fraction of the urinary metabo- lite levels among whites. Unfortunately, this presents serious complications for exposure reconstruction using urinary metabolites. A recent examination of dialkylphosphate resi- dues on fruits and vegetables found that more than half of the samples tested contained more preformed dialkylphosphate residues than par- ent organophosphate pesticides (Zhang et al. 2008). These dialkylphosphate residues were produced by abiotic hydrolysis, photolysis, or plant metabolism (Zhang et al. 2008). Direct intake of the metabolite (i.e., pesticide residue) without the active oxon, rather than the parent pesticide, does not inhibit cholinesterase activ- ity. Thus, for subjects for whom the primary –1.15 –0.05 –1.24 0.39 –0.79 0.29 –1.46 –0.52 –0.84 –3.17 to 2.26 –4.31 to 2.02 –2.64 to 2.54 –3.64 to 2.86 –5.05 to 2.57 –2.65 to 3.42 –4.52 to 2.94 –2.81 to 3.38 –3.68 to 2.56 –4.74 to 1.83 –3.67 to 2.62 –4.35 to 2.67 Interaction p-value 0.64 0.80 0.49 0.09 0.68 0.05 0.76 0.81 0.97 –3.51 –1.20 –4.37 –0.08 –2.11 –3.48 –1.59 –2.27 –1.85 –7.31 to 0.30 –4.35 to 1.96 –9.10 to 0.36 –3.91 to 3.76 –6.81 to 2.59 –7.29 to 0.34 –5.27 to 2.47 –5.68 to 2.50 –6.14 to 1.60 –6.25 to 2.56 96 –1.40 98 –0.56 Generalized linear models adjusted for sex, race/ethnicity, maternal education, language in the home, alcohol use in pregnancy, batch season of urine collection, urinary creatinine, and an indicator variable to designate the WISC-IV or ovlume 119 | number 8 | August 2011 • Environmental Health Perspectives