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Exposure During Pregnancy to Glycol Ethers and Chlorinated Solvents and the Risk of Congenital Malformations

Cordier, Sylvainea; Garlantézec, Ronana,b; Labat, Laurencec; Rouget, Florencea,d; Monfort, Christinea; Bonvallot, Nathaliea,b; Roig, Benoite; Pulkkinen, Juhaf; Chevrier, Cécilea; Multigner, Luca

doi: 10.1097/EDE.0b013e31826c2bd8

Background: Exposure to solvents during pregnancy has long been suspected of increasing the risk of congenital malformations, but the lack of prospective assessment of specific solvent exposures has prevented definitive conclusions.

Methods: In a cohort of 3421 pregnant women in Brittany (2002–2006), occupational solvent exposure was assessed from self-report during pregnancy and from a job-exposure matrix. Congenital malformations were diagnosed among live births, stillbirths, and medical pregnancy terminations. In a nested case–control sample, urinary concentrations of 10 metabolites of glycol ethers and chlorinated solvents were measured in maternal samples collected during early pregnancy (n = 79 cases, 580 controls).

Results: Dose–response trends linked occupational solvent exposure (both self-reported and based on a job-exposure matrix) to the risk of major congenital malformations––especially oral clefts, urinary tract malformations, and male genital malformations. Detection of some glycol ether metabolites and trichloroacetic acid in urine was associated with increased risks of oral clefts and of urinary tract and limb defects.

Conclusions: This prospective study, using three independent methods of exposure assessment, suggests several specific associations between solvent exposure during early pregnancy and congenital malformations. Results based on urinary biomarkers, although limited by small numbers, identify work situations that require further investigation.

Supplemental Digital Content is available in the text.

From the aIRSET Inserm U1085; Univ Rennes I; IFR-140, Rennes, France; bDepartment of Environmental and Occupational Health, EHESP, Rennes, France; cLaboratory of Toxicology and Genopathy, CHRU Lille, Lille, France; dPerinatality Network, Rennes; Department of Pediatrics, CHU Rennes, Rennes, France; eLERES, EHESP, Rennes, France; and fSchool of Pharmacy, University of Eastern Finland, Kuopio, Finland.

Submitted 22 November 2011; accepted 11 May 2012; posted 21 September 2012.

Supported by grants from the National Institute for Public Health Surveillance (InVS) and the French Ministry of Labor.

Supplemental digital content is available through direct URL citations in the HTML and PDF versions of this article ( This content is not peer-reviewed or copy-edited; it is the sole responsibility of the author.

Correspondence: Sylvaine Cordier, INSERM U1085, IRSET, Univ Rennes I, Campus de Beaulieu, Rennes, F-35042, France. E-mail:

© 2012 Lippincott Williams & Wilkins, Inc.