Maternal exposure to water disinfection by-products during gestation and risk of hypospadias

Background: The use of chlorine for water disinfection results in the formation of numerous contaminants called disinfection by-products (DBPs), which may be associated with birth defects, including urinary tract defects. Methods: We used Arkansas birth records (1998-2002) to conduct a population-based case-control study investigating the relationship between hypospadias and two classes of DBPs, trihalomethanes (THM) and haloacetic acids (HAA). We utilised monitoring data, spline regression and geographical information systems (GIS) to link daily concentrations of these DBPs from 263 water utilities to 320 cases and 614 controls. We calculated ORs for hypospadias and exposure to DBPs between 6 and 16 weeks' gestation, and conducted subset analyses for exposure from ingestion, and metrics incorporating consumption, showering and bathing. Results: We found no increase in risk when women in the highest tertiles of exposure were compared to those in the lowest for any DBP. When ingestion alone was used to assess exposure among a subset of 40 cases and 243 controls, the intermediate tertiles of exposure to total THM and the five most common HAA had ORs of 2.11 (95% CI 0.89 to 5.00) and 2.45 (95% CI 1.06 to 5.67), respectively, compared to women with no exposure. When exposure to total THM from consumption, showering and bathing exposures was evaluated, we found an OR of 1.96 (95% CI 0.65 to 6.42) for the highest tertiles of exposure and weak evidence of a dose-response relationship. Conclusions: Our results provide little evidence for a positive relationship between DBP exposure during gestation and an increased risk of hypospadias but emphasise the necessity of including individual-level data when assessing exposure to DBPs.