title: Chlorination disinfection by-products in drinking water and congenital anomalies: review and meta-analyses.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Research in Environmental Epidemiology, Barcelona, Spain. mnieuwenhuijsen@creal.cat
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Nieuwenhuijsen
authors.forename: David
authors.initials: D
authors.lastname: Martinez
authors.forename: James
authors.initials: J
authors.lastname: Grellier
authors.forename: James
authors.initials: J
authors.lastname: Bennett
authors.forename: Nicky
authors.initials: N
authors.lastname: Best
authors.forename: Nina
authors.initials: N
authors.lastname: Iszatt
authors.forename: Martine
authors.initials: M
authors.lastname: Vrijheid
authors.forename: Mireille B
authors.initials: MB
authors.lastname: Toledano
mesh_terms: D000013:Congenital Abnormalities / Q000453:epidemiology* / Q000209:etiology; D004203:Disinfection; D005260:Female; D054879:Halogenation; D006801:Humans; D007231:Infant, Newborn; D011247:Pregnancy; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D014881:Water Supply / Q000032:analysis
chemical_list: D014874:Water Pollutants, Chemical