Chlorination Disinfection By-Products in Drinking Water and Congenital Anomalies: Review and Meta-Analyses
Nieuwenhuijsen, Mark J., Martinez, David, Grellier, James, Bennett, James, Best, Nicky, Iszatt, Nina, Vrijheid, Martine, Toledano, Mireille B., Environmental Health Perspectives
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 [micro]g/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.
KEY WORDS: birth defects, congenital anomalies, disinfection by-products, fetal development, reproductive health, trihalomethanes. Environ Health Perspect 117:1486-1493 (2009). doi:10.1289/ ehp.0900677 available via http://dx.doi.org/ [Online 15 June 2209]
Disinfection of drinking water has led to a major improvement in public health since it was first applied in the 20th century. It has now been > 30 years since it was discovered that by-products can be formed in small quantities as part of the chlorination process (Rook 1974). Chlorination disinfection byproducts (DBPs) are formed when water is chlorinated and organic matter in the water reacts with chlorine. Their formation and occurrence depends on many factors, including the chlorine dose, type of treatment, pH, temperature, residence time, and bromine levels [International Programme on Chemical Safety (IPCS) 2000; Nieuwenhuijsen et al. 2000a]; up to 600 DBPs have been identified (Richardson 1998; Richardson et al. 2008). Different mixtures of by-products may exist in different locations, depending on the various factors mentioned above, making it more difficult to assess any health effects of DBPs, particularly in epidemiologic studies.
Ingestion of water is thought to be the main route of exposure for nonvolatile DBPs such as haloacetic acids (HAAs). Exposure to volatile DBPs such as trihalomethanes (THMs) may occur through inhalation and absorption during activities such as showering, bathing, and swimming (Nieuwenhuijsen et al. 2000a). Modeling of THM uptake has suggested that swimming may lead to the highest levels of THMs in the blood (Whitaker et al. 2003).
Various reviews have been conducted on the epidemiology of chlorination by-products and reproductive outcomes. These have concluded that there are still many problems to overcome and that the results are inconsistent and inconclusive, except perhaps for small-for-gestational-age/intrauterine growth retardation (Bove et al. 2002; Gevecker Graves et al. 2001; IPCS 2000; Nieuwenhuijsen et al. …