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Maternal exposure to water disinfection by-products during gestation and risk of hypospadias
  1. T J Luben1,
  2. J R Nuckols2,
  3. B S Mosley3,
  4. C Hobbs3,
  5. J S Reif2
  1. 1
    National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, Research Triangle Park, North Carolina, USA
  2. 2
    Department of Environmental and Radiological Health Sciences, Colorado State University, Fort Collins, Colorado, USA
  3. 3
    Arkansas Center for Birth Defects Research and Prevention, University of Arkansas for Medical Sciences and Arkansas Children’s Hospital Research Institute, Little Rock, Arkansas, USA
  1. T J Luben, National Center for Environmental Assessment, Office of Research and Development, US Environmental Protection Agency, MC B-243-01, Research Triangle Park, North Carolina 27711, USA; luben.tom{at}


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 tertile 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.

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  • Funding: This study was funded in part by the Battelle Memorial Institute (PO 182124 Mod 02). The funding source had no involvement in study design, data collection, analyses or interpretation of the data, in writing the report or in the decision to submit the paper for publication.

  • Competing interests: None.

  • Although the research in this article has been reviewed by the US EPA, it does not necessarily reflect the views of the agency, and no official endorsement should be inferred. Mention of trade names or commercial products does not constitute endorsement or recommendation for use.