Opler et al. employment status, maternal education, maternal race/ethnicity, and paternal educa- tion. A change of ±10% in the point estimate corresponding to the Pb exposure variable provided justiﬁcation for including a variable in the model. Because we included maternal race/ethnicity in the matching criteria for the NE-NCPP sample, we used an indicator vari- able that coded for this covariate only in the PDS study. Results These cohorts have previously been reported to differ in terms of several variables, including ethnicity, maternal age, and education (Strauss and Dietz 1999). The samples that were obtained for this study reﬂect these differences (Table 1). The NE-NCPP cohort was younger, was less ethnically diverse, and had a higher proportion of mothers who did not complete high school. By contrast, the PDS sample was more ethnically diverse, and most of the moth- ers in the sample had graduated high school and/or received further education. δ-ALA concentrations. As previously reported, retention times for δ-ALA occurred within a limited range, consistently near the mean (± SD) of 9.2 ± 0.36 min. Similar to previous findings, detectable δ-ALA peaks were very clear, and chromatograms were consistently characterized by low baselines and high signal-to-noise ratios. No other detectable compounds had retention times or signals that caused interference with the δ-ALA peak. In subjects from the NE-NCPP sample, δ-ALA levels ranged up to 70.5 ng/mL Table 1. Demographic variables in the PDS and NE-NCPP samples. PDS (%)a NE-NCPP (%)a Measure Case status (no.) SSDb cases Matched controls Maternal age (years) 0–19 20–29 30–39 ≥ 40 Race White Black Other Paternal age (years) 20–29 30–39 ≥ 40 Mother’s education < High school ≥ High school Unknown 44 75 11.4 47.1 37 4.2 47.9 40.3 10.1 33.6 37.8 16.8 11.8 79 8.4 27 54 16 67.9 14.8 1.2 74.1 25.9 0 51.9 27.2 7.4 43.2 54. 2.5 aAll values are percentages except for case status. bSchizophrenia spectrum disorder, defined in the PDS study as schizophrenia, schizoaffective disorder, delu- sional disorder, schizoid personality disorder, or psychosis not otherwise speciﬁed, and in NE-NCPP as schizophrenia and schizoaffective disorder. 1588 (Figure 2A), with a mean (± SD) of 11.6 ± 15.2 ng/mL; the mean concentration in the PDS study was 9.0 ± 9.8 ng/mL. Despite some differences in the distribution of δ-ALA concentrations, a similar proportion of sub- jects within each sample met the study deﬁni- tion for Pb exposure (Figure 2B). We classiﬁed 42% of subjects (n = 34) as exposed in the NE-NCPP sample and 45% of subjects as exposed (n = 53) in the PDS sample. Distribution of covariates by exposure and case status. We noted differences in distribu- tions of covariates between sites (Table 1). Although the NE-NCPP sample demon- strated no difference in maternal age in exposed versus unexposed subjects, in the PDS sample mothers of unexposed subjects were on average 1 year older than those classified as exposed. Mean maternal age was higher in cases than in controls at both sites, but this was not associated with risk of disease in either the NE-NCPP sample [OR = 1.01; 95% con- ﬁdence interval (CI), 0.62–1.64; p = 0.97] or the PDS sample (OR = 1.1; 95% CI, 0.54–2.4; p = 0.8). Higher maternal age appears to be associated with lower exposure levels, although this association is not statisti- cally significant for either the NE-NCPP sample (OR = 0.744; 95% CI, 0.25–2.23; p = 0.6) or the PDS sample (OR = 0.78; 95% CI, 0.43–1.41; p = 0.4). Higher maternal edu- cation (i.e., graduation from high school or equivalent) had a nonsignificant protective association with case status in the NE-NCPP sample (OR = 0.49; 95% CI, 0.17–1.38; p = 0.17) and PDS sample (OR = 0.49; 95% CI, 0.19–1.22; p = 0.12). Conversely, the risk of exposure appears to be higher among subjects whose mothers completed high school for both the NE-NCPP sample (OR = 2.08; 95% CI, 0.84–5.16; p = 0.11) and the PDS sample (OR = 1.43; 95% CI, 0.57–3.6; p = 0.43). Estimates of effect size. Table 2 presents the conditional results from independent and combined analyses, as both unadjusted and adjusted effect estimates. With conditional logistic regression, the unadjusted estimated OR for schizophrenia in subjects classified as exposed in the NE-NCPP cohort was 1.58 (95% CI, 0.55–4.51). As previously reported, a similar unadjusted measure in the PDS study yields an OR = 1.89 (95% CI, 0.86–4.11). After we combined both samples into a multilevel, random-intercept logistic regression model, the estimate of the unad- justed OR was 1.72 (95% CI, 0.96–3.09). When adjusted for maternal age and educa- tion, the estimated OR was 1.92 (95% CI, 1.05–3.52). We tested several other covariates in the model including paternal age, paternal employment status, and maternal race/ethnic- ity. None of the additional variables tested had any appreciable impact, deﬁned as a change of ±10% or more on the coefﬁcient of the expo- sure variable when added to or removed from the model. In the saturated model, including all available covariates, the estimated OR for exposure was 1.96 (95% CI, 1.04–3.69). Discussion We have attempted to build on our earlier study by ﬁrst replicating our previous results in the NE-NCPP sample and then pooling sub- jects from two separate cohorts to increase our sample size. This new study expands on our preliminary work, further demonstrating a pos- sible association between Pb exposure during NE-NCPP cohort n = 17,741 pregnancies Screened positive (potential cases) n = 241 Other diagnosis n = 131 Face-to-face assessment n = 167 Chart diagnosis n = 74 Schz and SchzA n = 36 Schz and SchzA n = 15 Total Schz and SchzA cases n = 51 Total cases with available serum n = 27 Other diagnosis n = 59 Figure 2. Case ascertainment in the NE-NCPP. Abbreviations: Schz, schizophrenia; SchzA, schizoaffective disorder. VOLUME 116 | NUMBER 11 | November 2008 • Environmental Health Perspectives