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Gillian Ormond,^1,2 Mark J. Nieuwenhuijsen,^2,3 Paul Nelson,⁴ Mireille B. Toledano,² Nina Iszatt,² Sara Geneletti,² and Paul Elliott²

¹Department of Epidemiology and Public Health, University College Cork, Cork, Ireland; ²Department of Epidemiology and Public Health, Imperial College London, London, United Kingdom; ³Center for Research in Environmental Epidemiology (CREAL), Municipal Institute of Medical Research (IMIM), CIBER Epidemiologia y Salud Pública (CIBERESP), Barcelona, Spain; ⁴Independent Public Health Consultant, Phrisk Ltd, London, United Kingdom

Abstract
Background: Hypospadias is one of the most common urogenital congenital anomalies affecting baby boys. Prevalence estimates in Europe range from 4 to 24 per 10,000 births, depending on definition, with higher rates reported from the United States. Relatively little is known about potential risk factors, but a role for endocrine-disrupting chemicals (EDCs) has been proposed.

Objective: Our goal was to elucidate the risk of hypospadias associated with occupational exposure of the mother to endocrine-disruptor chemicals, use of folate supplementation during pregnancy, and vegetarianism.

Design: We designed a case–control study of 471 hypospadias cases referred to surgeons and 490 randomly selected birth controls, born 1 January 1997–30 September 1998 in southeast England. Telephone interviews of mothers elicited information on folate supplementation during pregnancy and vegetarianism. We used a job exposure matrix to classify occupational exposure.

Results: In multiple logistic regression analysis, there were increased risks for self-reported occupational exposure to hair spray [exposed vs. nonexposed, odds ratio (OR) = 2.39 ; 95% confidence interval (CI) , 1.40–4.17] and phthalate exposure obtained by a job exposure matrix (OR = 3.12 ; 95% CI, 1.04–11.46) . There was a significantly reduced risk of hypospadias associated with of folate use during the first 3 months of pregnancy (OR = 0.64 ; 95% CI, 0.44–0.93) . Vegetarianism was not associated with hypospadias risk.

Conclusions: Excess risks of hypospadias associated with occupational exposures to phthalates and hair spray suggest that antiandrogenic EDCs may play a role in hypospadias. Folate supplementation in early pregnancy may be protective.

Key words: endocrine disruptors, hair spray, folate supplementation, hypospadias, occupation. Environ Health Perspect 117:303–307 (2009) . doi:10.1289/ehp.11933 available via http://dx.doi.org/ [Online 20 November 2008]

Address correspondence to P. Elliott, MRC Centre for Environment and Health, Department of Epidemiology and Public Health, Imperial College London, St. Mary’s Campus, Norfolk Place, London, U.K. Telephone: 44 20 7594 3328. Fax: 44 20 7262 1034. E-mail: p.elliott@imperial.ac.uk

We thank M-L. Dudley and C. Brown for conducting the interviews, J. Stewart-Evans for database cleaning, Office for National Statistics (P. Goldblatt, G. Brackett, J. Gallagher, J. Gilmore, K. Bond) for providing names and contact details of subjects, and the surgeons, general practitioners, and mothers who participated in the study. We are grateful to I. Hughes, P. Mouriquand, and D. Wilcox for invaluable clinical input.

The study was funded by a grant from the U.K. Health and Safety Executive/Department of Health/Department of the Environment, Transport and The Regions/European Chemical Industry Council (CEFIC) . P.N. was supported by a Wellcome Trust Research Training Fellowship in Clinical Epidemiology and also in part by the North Thames Training Programme in Public Health Medicine. The study sponsors had no role in the study design, data collection, analysis and interpretation, or writing of the paper.

The authors declare they have no competing financial interests.

Received 14 July 2008 ; accepted 5 November 2008.