we found no difference in any of the behavior ratings by arsenic quartile (data not shown). Many socioeconomic variables and child char- acteristics were significantly correlated with both urinary arsenic and one or more child development measures (Table 3). We con- trolled for all variables significantly related to any child development variable in multiple regression analyses of each developmental out- come. Current length for age and weight for age were highly related to each other, so we chose length for age because it had slightly higher correlations with the development measures. For similar reasons, we offered birth length and head circumference and not birth weight. In all regression analyses, we entered age (and sex for support) in the first step. We entered fathers’ education; mothers’ education, BMI, and parity; housing; assets; income deficits; and child’s gestational age, birth length, head circumference, and current length Z-score in the second step, and then entered the urinary arsenic concentration in the third step (Table 4). Urinary arsenic was not significant in any of the regressions. Assets, fathers’ educational level, mothers’ BMI, and child’s gestational age, birth length, current height, sex, and age were significant covariates in one or more of the regressions. We exam- ined possible interactions of arsenic with these covariates and sex. None were significant. We conducted analogous multiple regression anal- yses with the five behavior ratings and found no effect of urinary arsenic on any of them. Birth characteristics and current anthro- pometry. We repeated the regressions omit- ting measures of birth size and gestational age because it is possible that arsenic expo- sure affects child development through its effect on birth size and gestation. We also omitted current height for age because not only could arsenic exposure affect growth, but also 234 children had missing anthropometric data. The effect of arsenic exposure remained nonsignificant. Prenatal arsenic exposure and infant development Discussion After controlling for socioeconomic differ- ences, we failed to detect any deficit in prob- lem-solving abilities, motor development, or behavior in tests of 7-month-old infants who were prenatally exposed to a wide range of arsenic concentrations. This was a large pop- ulation-based study, involving 1,799 infants, and we had individual measures of mater- nal urinary arsenic concentrations at two periods in pregnancy. In addition, we mea- sured a large number of variables that could affect child development and took them into account in the analyses. The developmental tests had good test–retest and interobserver reliabilities and appeared to be sensitive. In the multiple regressions, household assets, fathers’ education, maternal nutritional sta- tus, and child’s birth size, gestational age, current nutritional status, sex, and age were significantly independently related to one or more of the child development outcomes. It is therefore reasonable to conclude that the lack of any marked effect of arsenic exposure in pregnancy on infant motor development and problem solving is probably a valid finding. The lack of detectable effect is encour- aging considering the high levels of arsenic exposure. However, we need to be cautious when interpreting the findings because other unmeasured cognitive functions might have been affected. Furthermore, we examined these children at only one age, and it remains possible that effects could appear at a later age when new functions develop. We were unable to find another prospective study that examined the effect of intrauterine exposure of arsenic on infant development. A recent study took a retrospective history of prenatal exposure to arsenic-contaminated drinking water and found no effect on school- age children’s cognition (von Ehrenstein et al. 2007). However, cognitive deficits in school- children currently exposed to arsenic-con- taminated drinking water have been found in different countries (Rosado et al. 2007; Wang et al. 2007; Wasserman et al. 2004), although the specific cognitive functions affected Table 4. Significant regression coefficients (B), standard error (SE), and 95% confidence interval (CI) from multiple regressions of Support and Cover PSTs (n = 1,467) and PDI (n = 1,465). Cover Variable Age (months) 0.03 ± 0.03 (–0.02 to 0.09) Sex — Assets — Father’s education 0.2 ± 0.04 (0.2–0.3)** Gestational age (weeks) 0.5 ± 0.1 (0.2–0.7)** Length at birth (cm) 0.3 ± 0.1 (0.2–0.7)** Length at 7 months (Z-scores) — Mothers’ BMI (kg/m2) — Mothers’ urinary arsenic (mean 0.4 ± 0.4 (–0.4 to 1.3) of weeks 8 and 30, µg/L) R2 0.05 B ± SE (95% CI) Support 0.05 ± 0.03 (–0.01 to 0.1) –1.1 ± 0.4 (–1.6 to –0.2)* 0.2 ± 0.09 (–1.6 to –0.2)* 0.1 ± 0.04 (0.03–0.2)** 0.6 ± 0.1 (0.2–0.7)** — 0.4 ± 0.2 (0.05–0.8)* 0.1 ± 0.1 (0.005–0.3)* –0.6 ± 0.5 (–1.5 to 0.4) 0.04 PDI –0.5 ± 0.05 (–0.6 to –0.4)** — — — 2.2 ± 0.5 (1.7–2.7)** — 1.3 ± 0.4 (0.6–2.1)* 0.4 ± 0.1 (0.1–0.7)* 0.9 ± 0.9 (–0.9 to 2.7) 0.12 The model was as follows: step 1, age (and sex for support) entered; step 2, mothers’ and fathers’ education (years com- pleted), housing, assets, income, mothers’ BMI and parity, and child’s birth length and head circumference, gestational age, and length in Z-scores at 7 months offered; step 3, mean of mothers’ urinary arsenic (log) entered. The PSTs are raw scores. The regression coefficients (B) of the PSTs indicate the amount of change in raw scores per unit of the indepen- dent variable (one standard score for Cover is 7 and for Support is 7.6). *p < 0.05; **p < 0.001. Table 3. Correlations among maternal urinary arsenic concentration, infant developmental outcomes, socioeconomic variables, and child characteristics.a Variable Mothers’ BMI on enrollment (log) Parity Mother’s education (years in school) Father’s education (years in school) Income/expenditure deficit Assets Housing Birth weight (g) Length at birth (cm) Gestational age (weeks) Head circumference at birth (cm) Length for age (Z-score at 7 months)d Weight for age (Z-score at 7 months)d Weight for length (Z-score at 7 months)d 8 weeks (log) –0.08** (n = 1,791) 0.04 (n = 1,797) –0.12** (n = 1,799) –0.12** (n = 1,786) –0.02 (n = 1,799) –0.14** (n = 1,799) –0.20** (n = 1,799) –0.02 (n = 1,730) –0.02 (n = 1,728) –0.02 (n = 1,798) –0.05* (n = 1,736) –0.03 (n = 1,542) –0.04 (n = 1,542) –0.03 (n = 1,542) Mothers’ urinary arsenicb 30 weeks (log) –0.09** (n = 1,791) –0.01 (n = 1,797) –0.12** (n = 1,799) –0.10** (n = 1,786) 0.01 (n = 1,799) –0.08** (n = 1,799) –0.17** (n = 1,799) –0.04 (n = 1,730) –0.05* (n = 1,728) –0.06* (n = 1,798) –0.05* (n = 1,736) –0.06* (n = 1,542) –0.06* (n = 1,542) –0.03 (n = 1,542) Mean of 8 and 30 weeks (log) –0.09** (n = 1,791) –0.02 (n = 1,797) –0.13** (n = 1,799) –0.12** (n = 1,786) –0.01 (n = 1,799) –0.12** (n = 1,799) –0.21** (n = 1,799) –0.04 (n = 1,730) –0.04 (n = 1,728) –0.05* (n = 1,798) 0.07* (n = 1,736) –0.05* (n = 1,542) –0.05 (n = 1,542) –0.02 (n = 1,542) Coverc 0.06* (n = 1,787) –0.04 (n = 1,793) 0.08** (n = 1,795) 0.12** (n = 1,782) 0.07* (n = 1,795) 0.08* (n = 1,795) 0.07** (n = 1,795) 0.13** (n = 1,726) 0.15** (n = 1,724) 0.17** (n = 1,794) 0.09** (n = 1,732) 0.13** (n = 1,540) 0.12** (n = 1,538) 0.04* (n = 1,538) Developmental outcome Supportd 0.06* (n = 1,787) –0.05* (n = 1,793) 0.06** (n = 1,795) 0.08* (n = 1,782) 0.06* (n = 1,795) 0.07* (n = 1,795) 0.05* (n = 1,795) 0.11** (n = 1,726) 0.11** (n = 1,724) 0.17** (n = 1,794) 0.10** (n = 1,731) 0.12** (n = 1,539) 0.11** (n = 1,537) 0.03* (n = 1,537) PDIc 0.08** (n = 1,787) 0.06* (n = 1,793) 0.03 (n = 1,795) 0.05* (n = 1,782) 0.04 (n = 1,795) 0.02 (n = 1,793) 0.03 (n = 1,795) 0.22** (n = 1,726) 0.17** (n = 1,724) 0.26** (n = 1,794) 0.13** (n = 1,732) 0.16** (n = 1,540) 0.15** (n = 1,538) 0.04* (n = 1,538) an = 1,799–1,724, depending on available data (see Table 1), except n = 1,542–1,537 for anthropometry at 7 months. bPearson’s correlations. cControlling for age. dControlling for age and sex. *p < 0.05; **p < 0.001. Environmental Health Perspectives • volume 117 | number 2 | February 2009 291