Ciesielski et al. the reference person had lower educational achievement (Table 1). Children with LD and children who participated in special educa- tion had higher median urinary cadmium lev- els, whereas children with ADHD had lower median urinary cadmium levels (Table 2). Children in the two highest quartiles of urinary cadmium concentration had higher odds of LD and special education in both the creatinine-adjusted and fully adjusted analyses (Table 3). In contrast, children in the three highest quartiles of urinary cadmium concentration had lower odds of ADHD in the both the creatinine-adjusted and fully adjusted analyses (Table 3). When we com- pared children in the highest quartile of urine cadmium concentration with those in the lowest quartile, the fully adjusted odds ratios (ORs) were 3.21 (95% CI: 1.43, 7.17) for LD, 3.00 (95% CI: 1.12, 8.01) for special education, and 0.67 (95% CI: 0.28, 1.61) for ADHD. Adding a term for low hemoglobin level to the fully adjusted models had little effect on these ORs and did not change the significance conclusions (data not shown). ORs from core models adjusted only for uri- nary creatinine, age, sex, blood lead, smoker in the home, serum cotinine, prenatal smoke exposure (mother smoked while pregnant), and poverty income ratio were similar: 3.50 (95% CI: 1.56, 7.88) for LD, 2.66 (95% CI: 1.07, 6.63) for special education, and 0.65 (95% CI: 0.28, 1.51) for ADHD. When urinary cadmium was modeled with an ordinal tend variable (coded as 0, 1, 2, or 3 based on the quartile of exposure), the fully adjusted ORs for a one-quartile increase in urinary cadmium were 1.51 (95% CI: 1.14, n = 78 n = 14 ADHD n = 39 n = 64 n = 98 LD n = 70 Special education n = 49 No diagnosis n = 1,771 Total with complete diagnosis information 760 n = 2,183 (99% of the 2,199 participants) Figure 1. The co-occurrence of neurodevelopmen- tal outcomes in the study population among the 2,183 participants with information on all three out- comes (99% of the 2,199 participants). 2.00) for LD, 1.44 (95% CI: 1.03, 2.01) for special education, and 0.84 (95% CI: 0.61, 1.16) for ADHD (Table 4). In sex-stratified analyses, the corresponding ORs for LD and special education were somewhat larger among males than among females [for LD, 1.75 (95% CI: 1.24, 2.46) vs. 1.24 (95% CI: 0.75, 2.04) and for special education, 1.73 (95% CI: 1.02, 2.92) vs. 1.31 (95% CI: 0.81, 2.13)]. In blood lead–stratified analyses, the corresponding OR for ADHD was 1.11 (95% CI: 0.65, 1.91) for those with lead levels below the median and 0.73 (95% CI: 0.52, 1.03) for those with lead above the median. However, these interactions were not significant (p = 0.71 for cadmium–sex in the LD analysis, p = 0.43 for cadmium–sex in the special education analy- sis, and p = 0.43 for cadmium–lead in the ADHD analysis), and none of the remaining cadmium–sex or cadmium–lead interaction terms were significant. Discussion LD and special education. We observed that children in the highest quartile of urinary cad- mium had significantly higher odds of both LD and special education when compared with those in the lowest quartile. A few prior studies have linked cadmium exposure with Variable Age (years) 6–7 8–9 10–11 12–13 14–15 Urinary creatinine (mg/dL) 8–78 79–117 118–174 175–614 Poverty income ratio 0.00–0.82 0.83–1.51 1.52–2.99 3.00–5.00 Missing Blood lead (μg/dL) 0.2–0.8 0.9–1.2 1.3–1.9 2.0–57.1 Missing Hemoglobinb Low Normal/high Missing Race/ethnicity White Black Mexican Other Hispanic Other race n Median urinary Cd [μg/L (IQR)] 339 0.078 (0.038–0.139) 363 0.093 (0.050–0.151) 345 0.107 (0.058–0.180) 582 0.120 (0.062–0.199) 570 0.146 (0.071–0.220) 541 0.052 (0.030–0.090) 551 0.090 (0.050–0.140) 553 0.130 (0.081–0.182) 554 0.201 (0.139–0.300) 514 0.130 (0.068–0.219) 502 0.110 (0.060–0.184) 507 0.105 (0.057–0.160) 507 0.090 (0.042–0.170) 169 0.124 (0.068–0.199) 489 0.095 (0.048–0.169) 469 0.111 (0.061–0.180) 532 0.110 (0.055–0.197) 496 0.122 (0.061–0.201) 213 0.100 (0.057–0.165) 234 0.120 (0.061–0.207) 1,751 0.110 (0.057–0.182) 214 0.100 (0.057–0.165) 578 0.081 (0.040–0.150) 712 0.137 (0.076–0.220) 729 0.110 (0.060–0.172) 90 0.096 (0.051–0.199) 90 0.113 (0.059–0.210) LD, and these studies relied on hair and blood samples to assess cadmium exposure. Two case–control studies demonstrated higher hair cadmium concentrations in children with LD (Capel et al. 1981; Pihl and Parkes 1977). A third study also found higher hair cadmium concentrations in children with LD, but the difference was statistically significant only for males (Ely et al. 1981). In that study, the authors considered the sexes separately but did not present the type of statistical evaluation for interaction that we report here. Interestingly, in our study the sex–cadmium interaction was not significant, but the effect estimate for urinary cadmium was larger among males. A fourth study reported no association between LD and blood cadmium in the 1999–2000 NHANES data (Lee et al. 2007). Cadmium accumulates in the kidney, and urinary cad- mium concentration is considered to be a marker of cumulative exposure/body burden, whereas blood cadmium is thought to be a better indicator of recent exposure (Lauwerys et al. 1994). The different exposure metric used in the Lee et al. (2007) study may help explain the discrepancy in our findings. In addition to higher odds of LD, we found that children in the highest quartile of urinary cadmium also had higher odds of Variable Sex Male Female Serum cotinine (ng/mL) 0.011–0.034 0.035–0.079 0.080–0.503 0.509–402.0 Missing Smoker in the home Yes No Missing Yes No Missing Mother smoked while pregnant n 1,144 1,055 Median urinary Cd [μg/L (IQR)] 0.110 (0.055–0.180) 0.110 (0.060–0.183) 419 0.097 (0.050–0.170) 546 0.111 (0.059–0.188) 484 0.110 (0.053–0.188) 483 0.120 (0.070–0.193) 267 0.100 (0.058–0.165) 477 0.112 (0.062–0.193) 1,697 0.110 (0.056–0.180) 25 0.109 (0.067–0.140) 354 0.100 (0.052–0.169) 1,815 0.110 (0.058–0.185) 30 0.068 (0.063–0.177) Mother’s age at birth (years) 15–20 521 0.128 (0.068–0.210) 21–24 545 0.114 (0.060–0.177) 25–29 528 0.096 (0.049–0.161) 30–44 550 0.103 (0.056–0.185) Missing 55 0.119 (0.063–0.184) Education of household reference person ≤ 9th grade 306 0.125 (0.062–0.197) ≥ 9th no diploma 472 0.120 (0.070–0.200) High school graduate/ 531 0.104 (0.055–0.174) equivalent Some college/associate 519 0.110 (0.054–0.180) arts degree College graduate Missing 295 0.081 (0.039–0.150) 76 0.118 (0.052–0.192) Table 1. Urinary cadmium concentration by demographic and covariate category.a aValues for the study population, not weighted for oversampling. bHemoglobin levels for age and sex based on informa- tion from Ahsan and Noether (2011): low hemoglobin, < 10th percentile; normal/high hemoglobin, ≥10th percentile. ovlume 120 | number 5 | May 2012 • Environmental Health Perspectives