| Chlorination Disinfection By-Products and Risk of Congenital Anomalies in England and Wales Mark J. Nieuwenhuijsen,1,2 Mireille B. Toledano,1 James Bennett,1 Nicky Best,1 Peter Hambly,1 Cornelis de Hoogh,1 Diana Wellesley,3 Patricia A. Boyd,4 Lenore Abramsky,3,5 Nirupa Dattani,6 John Fawell,7 David Briggs,1 Lars Jarup,1 and Paul Elliott1 1Small Area Health Statistics Unit, Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, St. Mary's Campus, London, United Kingdom; 2Center for Research in Environmental Epidemiology (CREAL), Barcelona, Spain; 3British Isles Network of Congenital Anomaly Registers, BINOCAR Management Committee, Newcastle-Upon-Tyne, United Kingdom; 4National Perinatal Epidemiology Unit, University of Oxford, Oxford, United Kingdom; 5North Thames Perinatal Public Health Unit, Northwick Park Hospital, Harrow, United Kingdom; 6Office for National Statistics, London, United Kingdom; 7Independent Consultant, High Wycombe, Buckinghamshire, United Kingdom Abstract
Background: Increased risk of various congenital anomalies has been reported to be associated with trihalomethane (THM) exposure in the water supply. Objectives: We conducted a registry-based study to determine the relationship between THM concentrations and the risk of congenital anomalies in England and Wales. Methods: We obtained congenital anomaly data from the National Congenital Anomalies System, regional registries, and the national terminations registry ; THM data were obtained from water companies. Total THM (< 30, 30 to < 60, ≥ 60 µg/L) , total brominated exposure (< 10, 10 to < 20, ≥ 20 µg/L) , and bromoform exposure (< 2, 2 to < 4, ≥ 4 µg/L) were modeled at the place of residence for the first trimester of pregnancy. We included 2,605,226 live births, stillbirths, and terminations with 22,828 cases of congenital anomalies. Analyses using fixed- and random-effects models were performed for broadly defined groups of anomalies (cleft palate/lip, abdominal wall, major cardiac, neural tube, urinary and respiratory defects) , a more restricted set of anomalies with better ascertainment, and for isolated and multiple anomalies. Data were adjusted for sex, maternal age, and socioeconomic status. Results: We found no statistically significant trends across exposure categories for either the broadly defined or more restricted sets of anomalies. For the restricted set of anomalies with isolated defects, there were significant (p < 0.05) excess risks in the high-exposure categories of total THMs for ventricular septal defects [odds ratio (OR) = 1.43 ; 95% confidence interval (CI) , 1.00–2.04] and of bromoform for major cardiovascular defects and gastroschisis (OR = 1.18 ; 95% CI, 1.00–1.39 ; and OR = 1.38 ; 95% CI, 1.00–1.92, respectively) . Conclusion: In this large national study we found little evidence for a relationship between THM concentrations in drinking water and risk of congenital anomalies. Key words: chlorination, congenital anomalies, disinfection by-products, trihalomethanes. Environ Health Perspect 116:216–222 (2008) . doi:10.1289/ehp.10636 available via http://dx.doi.org/ [Online 6 November 2007]
Address correspondence to P. Elliott, Small Area Health Statistics Unit, Department of Epidemiology and Public Health, Faculty of Medicine, Imperial College London, St. Mary's Campus, Norfolk Place, London W2 1PG, U.K. Telephone: 44 (0) 20 7594 3328. Fax: 44 (0) 20 7262 1034. E-mail: p.elliott@imperial.ac.uk We thank K. Konstantinou, A. Gowers, N. Cobley, I. Maitland, S. Cockings, V. Barnard, and S. Fawell for helpful contributions. We are also grateful to water companies for providing trihalomethane data and to the Office for National Statistics and the British Isles Network of Congenital Anomaly Registers (BINOCAR) members for providing health data. The Small Area Health Statistics Unit is funded by a grant from the Department of Health, the Department of the Environment, Food and Rural Affairs, the Environment Agency, the Scottish Executive, the Welsh Assembly Government, and the Northern Ireland Department of Health, Social Services and Public Safety. Funding was provided by the Drinking Water Inspectorate (contract 70/2/161) and HIWATE, a Specific Targeted Research Project funded under the EU (European Union) FP6 Programme for Research and Technological Development (contract Food-CT-2006-036224) . The views expressed in this article are those of the authors and not necessarily those of the funding organizations. The authors declare they have no competing financial interests. Received 6 July 2007 ; accepted 6 November 2007.
Correction In the manuscript originally published online, column titles in Table 4 were incomplete. They have been corrected here.
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