Exposure during pregnancy to glycol ethers and chlorinated solvents and the risk of congenital malformations

Epidemiology. 2012 Nov;23(6):806-12. 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Abnormalities, Drug-Induced / epidemiology*
  • Adult
  • Bacterial Proteins
  • Carrier Proteins
  • Case-Control Studies
  • Dose-Response Relationship, Drug
  • Ethylene Glycols / adverse effects*
  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Halogenation
  • Humans
  • Infant, Newborn
  • Male
  • Maternal Exposure / statistics & numerical data*
  • Occupational Exposure / adverse effects
  • Occupational Exposure / statistics & numerical data*
  • Population Surveillance
  • Pregnancy
  • Prenatal Exposure Delayed Effects / chemically induced*
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Prospective Studies
  • Solvents / adverse effects*
  • Surveys and Questionnaires


  • Bacterial Proteins
  • Carrier Proteins
  • CooT protein, Rhodospirillum rubrum
  • Ethylene Glycols
  • Solvents