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Drinking Water Disinfection By-products, Genetic Polymorphisms, and Birth Outcomes in a European Mother–Child Cohort Study

Kogevinas, Manolis; Bustamante, Mariona; Gracia-Lavedán, Esther; Ballester, Ferran; Cordier, Sylvaine; Costet, Nathalie; Espinosa, Ana; Grazuleviciene, Regina; Danileviciute, Asta; Ibarluzea, Jesus; Karadanelli, Maria; Krasner, Stuart; Patelarou, Evridiki; Stephanou, Euripides; Tardón, Adonina; Toledano, Mireille B.; Wright, John; Villanueva, Cristina M.; Nieuwenhuijsen, Mark

doi: 10.1097/EDE.0000000000000544
Perinatal Epidemiology

Background: We examined the association between exposure during pregnancy to trihalomethanes, the most common water disinfection by-products, and birth outcomes in a European cohort study (Health Impacts of Long-Term Exposure to Disinfection By-Products in Drinking Water). We took into account exposure through different water uses, measures of water toxicity, and genetic susceptibility.

Methods: We enrolled 14,005 mothers (2002–2010) and their children from France, Greece, Lithuania, Spain, and the UK. Information on lifestyle- and water-related activities was recorded. We ascertained residential concentrations of trihalomethanes through regulatory records and ad hoc sampling campaigns and estimated route-specific trihalomethane uptake by trimester and for whole pregnancy. We examined single nucleotide polymorphisms and copy number variants in disinfection by-product metabolizing genes in nested case–control studies.

Results: Average levels of trihalomethanes ranged from around 10 μg/L to above the regulatory limits in the EU of 100 μg/L between centers. There was no association between birth weight and total trihalomethane exposure during pregnancy (β = 2.2 g in birth weight per 10 μg/L of trihalomethane, 95% confidence interval = 3.3, 7.6). Birth weight was not associated with exposure through different routes or with specific trihalomethane species. Exposure to trihalomethanes was not associated with low birth weight (odds ratio [OR] per 10 μg/L = 1.02, 95% confidence interval = 0.95, 1.10), small-for-gestational age (OR = 0.99, 0.94, 1.03) and preterm births (OR = 0.98, 0.9, 1.05). We found no gene–environment interactions for mother or child polymorphisms in relation to preterm birth or small-for-gestational age.

Conclusions: In this large European study, we found no association between birth outcomes and trihalomethane exposures during pregnancy in the total population or in potentially genetically susceptible subgroups. (See video abstract at

From the aBarcelona Institute for Global Health (ISGlobal), Barcelona, Spain; bUniversitat Pompeu Fabra (UPF), Barcelona, Spain; cCIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain; dMunicipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain; eCenter for Genomic Regulation (CRG), Barcelona, Spain; fFISABIO-UJI-University of Valencia Unit of Research, Valencia, Spain; gCIBERESP, Madrid, Spain; hINSERM (National Institute of Health and Medical Research) U1085-IRSET, Rennes, France; iUniversity of Rennes I, Rennes, France; jDepartment of Environmental Sciences, Vytauto Didziojo Universitetas, Kaunas, Lithuania; kBiodonostia Health Institute, San Sebastián, Spain; lPublic Health Department of Gipuzkoa, San Sebastian, Spain; mDepartment of Marine Sciences, University of the Aegean, Mytilene, Greece; nMetropolitan Water District of Southern California, La Verne, CA; oFlorence Nightingale Faculty of Nursing and Midwifery, King’s College London, London, United Kingdom; pEnvironmental Chemical Processes Laboratory (ECPL), Department of Chemistry, University of Crete, Heraklion, Greece; qIUOPA, Universidad de Oviedo, Asturias, Spain; rMRC-PHE Centre for Environment and Health, School of Public Health, Faculty of Medicine, Imperial College London, London United Kingdom; and sBradford Institute for Health Research, Bradford Royal Infirmary, Bradford, United Kingdom.

Submitted 25 August 2015; accepted 25 July 2016.

The HIWATE project was funded under the EU Sixth Framework Program for Research and Technological Development by the Research Directorate-Biotechnology, Agriculture and Food Research Unit (Contract No. Food-CT-2006–036224). The Joint Environment & Human Health Programme [NERC UK Grant NE/E008844/1].

The authors report no conflicts of interest.

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Correspondence: Manolis Kogevinas, Barcelona Institute for Global Health (ISGlobal), 88 Dr Aiguader Rd, Barcelona 08003, Spain. E-mail:

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