were black smoke, nitric oxide (NO), nitro- gen oxides (NOx), and particulate matter with aerodynamic diameter ≤ 2.5 mμ (PM 2.5). Pollutant concentration distributions showed different patterns across studies (Table 1); for example, average CO concentrations were highest in the California study (Ritz et al. 2002), but O3 concentrations were highest in the Taiwan study (Hwang and Jaakkola 2008). In most studies where this informa- tion was provided, pollutant concentra- tions did not increase by more than a factor of 2 between the 25th and 75th percentile (Table 1). Cardiac anomalies. Cardiac anomalies were analyzed in seven studies. Each study included at least six separate cardiac anomaly groups [see Supplemental Material, Table 1 (doi:10.1289/ehp.1002946)] and tested these against three to six pollutant groups. Each study reported only one or a few statistically significantly increased risks with increased exposure among the multiple associations Table 1. continued tested; few of these occurred in more than one study: CO was related to higher risk of VSD in two studies, with ORs for fourth- versus first-quartile exposure of 2.95 [95% confidence interval (CI), 1.44–6.05 (Ritz et al. 2002)] and 1.66 [95% CI, 1.37–2.02 (Dadvand et al. 2011b)]. The studies in California and Australia both reported raised risks of pulmonary artery and valve defects in association with O3 exposure [OR quartile 4 vs. quartile 1 = 2.94; 95% CI, 1.00–6.05 (Ritz et al. 2002); OR per 5 ppb = 2.96; 95% CI, 1.34–7.52 (Hansen et al. 2009)]. Various inverse associations (decreasing risks with increasing exposure) were also observed. We conducted meta-analyses for 18 com- binations of pollutants and cardiac anomaly groups for which four or more studies pub- lished results [for summary results, see Table 2; for full results, see Supplemental Material, Table 2 (doi:10.1289/ehp.1002946)]. The summary risk estimates from these meta- analyses were generally close to one, with a Air pollution and congenital anomalies range of summary ORs for continuous expo- sure from 0.87 to 1.20, and for high versus low exposure from 0.80 to 1.23. Heterogeneity tests showed evidence for heterogeneity among studies (p < 0.10) in fewer than half of the analyses conducted, most consistently related to analyses of VSDs. Egger test p-values were statistically significant for only 3 of the 68 meta-analyses we conducted (see Supplemental Material, Table 2), indicating that wide-scale publication bias is unlikely. We found statisti- cally significantly increased summary risk esti- mates for continuous NO2 exposure and risk of coarctation of the aorta (OR per 10 ppb = 1.17; 95% CI, 1.01–1.36) and tetralogy of Fallot (OR per 10 ppb = 1.20; 95% CI, 1.02–1.42), for continuous PM10 exposure and atrial septal defect (ASD; OR per 10 gμ/m 3 = 1.14; 95% CI, 1.01–1.28), and for continu- ous SO2 exposure and risk of coarctation of the aorta (OR per 1 ppb = 1.07; 95% CI, 1.01–1.13) and tetralogy of Fallot (OR per 1 ppb = 1.03; 95% CI, 1.01–1.05) (Table 2, Reference Hansen et al. 2009 Dolk et al. 2010 Marshall et al. 2010 Dadvand et al. 2011a Dadvand et al. 2011b Setting Brisbane (Australia), 1997–2004; 150,308 births Four regions of England, 1991–1999; 759,993 births New Jersey (USA), 1998–2003; 690,000 births Northern region (UK), 1985–1996; 449,355 births Northern region (UK), 1993–2003; 356,767 births Design Case and control definition Exposure assessment Case–control Cases with cardiac defects and clefts, stillbirths and live births; five matched controls per case Average of daily measurements of CO, NO2, O3, PM10, and SO2 at the monitoring site nearest to the center of small area of residence Exposure range in second month of gestation IQR, mean: CO, 0.6, 1.1 ppm NO2, 4.0, 8.2 ppb O3, 0.5, 2.6 pphm PM10, 4.0, 18.0 μg/m3 SO2, 0.6, 1.5 ppb Cohort 9,085 cases with chromosomal and nonchromosomal anomalies, live births and fetal deaths ≥ 20 weeks; all live and stillbirths Case–control 717 cases with cleft lip and/or palate, live births; random sample of eligible nonmalformed births Case–control 2,713 cases with cardiac defects, live births and fetal deaths ≥ 20 weeks gestation; 9,975 controls, live and stillbirths Case–control 2,140 cases with cardiac defects, live births and fetal deaths > 20 weeks gestation; 14,256 controls, live and stillbirths Annual mean p10–p90: concentrations in 1996 NO2, 21.5–47.8 μg/m3 of NO2, PM10, and PM10, 18.8–26.4 μg/m3 SO2 for 1 × 1 km grids; SO2, 3.9–15.0 μg/m3 population-weighted average assigned to census ward of residence Average of measurements p25–p75: of CO, NO2, O3, PM10, CO, 0.65–1.02 ppm PM2.5, and SO2 at NO2, 18–30 ppb nearest monitor O3, 1.5–3.3 pphm (maximum, 40 km; PM10, 22–33.5 μg/m3 median, 13–20 km) SO2, 3–7 ppb Two-stage spatiotemporal p25–p75: modeling of weekly Black smoke, 5.93– averages of black smoke 14.57 μg/m3 and SO2 levels (from SO2, 17.6–31.2 μg/m3 56 monitors) at maternal residence using traffic data, land cover data, and other predictors Weekly average p25–p75: measurements of CO, CO, 0.39–0.64 mg/m3 NO, NO2, O3, PM10, and NO2, 29.2–38.4 μg/m3 SO2, at nearest of six NO, 13.3–32.5 μg/m3 monitoring stations in O3, 33.2–42.4 μg/m3 the region (maximum, PM10, 20.5–30.2 μg/m3 56–83 km; median, SO2, 6.8–15.0 μg/m3 8–12 km) Gestational period Weeks 3–8 1996 average Weeks 3–8 Weeks 3–8 Weeks 3–8 Abbreviations: p10, 10th percentile; p25, 25th percentile; p75, 75th percentile; p90, 90th percentile. Environmental Health Perspectives • volume 119 | number 5 | May 2011 Adjustment variables Infant sex; matching variables: maternal age, marital status, indigenous status, parity, month of last menstrual period, area-level socioeconomic status, and distance to monitor Maternal age, deprivation index, region, and hospital catchment Maternal race, age, education, gravidity, alcohol use, smoking, season of conception, and infant sex Year of birth, socioeconomic status, infant sex, season of conception, and degree of urbanity Year of birth, socioeconomic status, infant sex, season of conception, and degree of urbanity 601