OBJECTIVES: The aim of this study was to review epidemiologic evidence, provide summary risk estimates of the association between exposure to chlorination disinfection by-products (DBPs) and congenital anomalies, and provide recommendations for future studies. DATA SOURCES AND EXTRACTION: We included all published epidemiologic studies that evaluated a relationship between an index of DBP exposure (treatment, water source, DBP measurements, and both DBP measurements and personal characteristics) and risk of congenital anomalies. When three or more studies examined the same exposure index and congenital anomaly, we conducted a meta-analysis to obtain a summary risk estimate comparing the highest exposure group with the lowest exposure group. When five or more studies examined total trihalomethane (TTHM) exposure and a specific congenital anomaly, we conducted a meta-analysis to obtain exposure-response risk estimates per 10 microg/L TTHM. DATA SYNTHESIS: For all congenital anomalies combined, the meta-analysis gave a statistically significant excess risk for high versus low exposure to water chlorination or TTHM [17%; 95% confidence interval (CI), 3-34] based on a small number of studies. The meta-analysis also suggested a statistically significant excess risk for ventricular septal defects (58%; 95% CI, 21-107), but this was based on only three studies, and there was little evidence of an exposure-response relationship. We observed no statistically significant relationships in the other meta-analyses. We found little evidence for publication bias, except for urinary tract defects and cleft lip and palate. CONCLUSION: Although some individual studies have suggested an association between chlorination disinfection by-products and congenital anomalies, meta-analyses of all currently available studies demonstrate little evidence of such an association.

This work was conducted without specific allocated funding, but contributions were made by researchers working on the Integrated Assessment of Health Risks of Environmental Stressors in Europe (INTARESE) project, cofunded by the European Commission under the Sixth Framework Programme (2002–2006), and the Health Impacts of Long-term Exposure to Disinfection By-products in Drinking Water in Europe (HIWATE) project, which is a 3.5-year Specific Targeted Research Project funded under the European Union Sixth Framework Programme for Research and Technological Development by the Research Directorate–Biotechnology, Agriculture and Food Research Unit (contract Food-CT-2006-036224)