Ambient Air Pollution and Risk of Congenital Anomalies: A Systematic Review and Meta-analysis

OBJECTIVE: We systematically reviewed epidemiologic studies on ambient air pollution and congenital anomalies and conducted meta-analyses for a number of air pollutant–anomaly combinations. DATA SOURCES AND EXTRACTION: From bibliographic searches we extracted 10 original epidemiologic studies that examined the association between congenital anomaly risk and concentrations of air pollutants. Meta-analyses were conducted if at least four studies published risk estimates for the same pollutant and anomaly group. Summary risk estimates were calculated for a) risk at high versus low exposure level in each study and b) risk per unit increase in continuous pollutant concentration. DATA SYNTHESIS: Each individual study reported statistically significantly increased risks for some combinations of air pollutants and congenital anomalies, among many combinations tested. In meta-analyses, nitrogen dioxide (NO(2)) and sulfur dioxide (SO(2)) exposures were related to increases in risk of coarctation of the aorta [odds ratio (OR) per 10 ppb NO(2) = 1.17; 95% confidence interval (CI), 1.00–1.36; OR per 1 ppb SO(2) = 1.07; 95% CI, 1.01–1.13] and tetralogy of Fallot (OR per 10 ppb NO(2) = 1.20; 95% CI, 1.02–1.42; OR per 1 ppb SO(2) = 1.03; 95% CI, 1.01–1.05), and PM(10) (particulate matter ≤ 10 μm) exposure was related to an increased risk of atrial septal defects (OR per 10 μg/m(3) = 1.14; 95% CI, 1.01–1.28). Meta-analyses found no statistically significant increase in risk of other cardiac anomalies and oral clefts. CONCLUSIONS: We found some evidence for an effect of ambient air pollutants on congenital cardiac anomaly risk. Improvements in the areas of exposure assessment, outcome harmonization, assessment of other congenital anomalies, and mechanistic knowledge are needed to advance this field.