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Maternal occupational exposure to organic solvents during early pregnancy and risks of neural tube defects and orofacial clefts
  1. Tania A Desrosiers1,2,
  2. Christina C Lawson3,
  3. Robert E Meyer2,
  4. David B Richardson1,
  5. Julie L Daniels1,
  6. Martha A Waters3,
  7. Edwin van Wijngaarden4,
  8. Peter H Langlois5,
  9. Paul A Romitti6,
  10. Adolfo Correa7,
  11. A Olshan1,
  12. and the National Birth Defects Prevention Study
  1. 1Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, USA
  2. 2Birth Defects Monitoring Program, State Center for Health Statistics, North Carolina Division of Public Health, Raleigh, North Carolina, USA
  3. 3National Institute for Occupational Safety and Health, Centers for Disease Control and Prevention, Cincinnati, Ohio, USA
  4. 4Department of Community and Preventative Medicine, University of Rochester Medical Center, Rochester, New York, USA
  5. 5Birth Defects Epidemiology and Surveillance Branch, Texas Department of State Health Services, Austin, Texas, USA
  6. 6Department of Epidemiology, University of Iowa College of Public Health, Iowa City, Iowa, USA
  7. 7National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, Georgia, USA
  1. Correspondence to Dr Tania A Desrosiers, Department of Epidemiology, Campus Box 7435, University of North Carolina, Chapel Hill, NC 27599, USA; ta_desrosiers{at}


Objectives Though toxicological experiments demonstrate the teratogenicity of organic solvents in animal models, epidemiologic studies have reported inconsistent results. Using data from the population-based National Birth Defects Prevention Study, the authors examined the relation between maternal occupational exposure to aromatic solvents, chlorinated solvents and Stoddard solvent during early pregnancy and neural tube defects (NTDs) and orofacial clefts (OFCs).

Methods Cases of NTDs (anencephaly, spina bifida and encephalocoele) and OFCs (cleft lip ± cleft palate and cleft palate alone) delivered between 1997 and 2002 were identified by birth defect surveillance registries in eight states; non-malformed control infants were selected using birth certificates or hospital records. Maternal solvent exposure was estimated by industrial hygienist review of self-reported occupational histories in combination with a literature-derived exposure database. ORs and 95% CIs for the association between solvent class and each birth defect group and component phenotype were estimated using multivariable logistic regression, adjusting for maternal age, race/ethnicity, education, pre-pregnancy body mass index, folic acid supplement use and smoking.

Results The prevalence of exposure to any solvent among mothers of NTD cases (n=511), OFC cases (n=1163) and controls (n=2977) was 13.1%, 9.6% and 8.2%, respectively. Exposure to chlorinated solvents was associated with increased odds of NTDs (OR=1.96, CI 1.34 to 2.87), especially spina bifida (OR=2.26, CI 1.44 to 3.53). No solvent class was strongly associated with OFCs in these data.

Conclusions The findings suggest that maternal occupational exposure to chlorinated solvents during early pregnancy is positively associated with the prevalence of NTDs in offspring.

  • Congenital abnormalities
  • occupational exposure
  • solvents
  • epidemiology
  • congenital anomalies
  • female reproductive effects and adverse pregnancy outcomes
  • solvents
  • cancer
  • mortality studies
  • longitudinal studies
  • radiation
  • hygiene/occupational hygiene
  • aviation medicine
  • exposure assessment
  • retrospective exposure assessment
  • risk assessment
  • mental health
  • materials
  • exposures and occupational groups
  • polymorphisms
  • male reproduction
  • genetic susceptibility
  • environment

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  • The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention or the National Institute for Occupational Safety and Health.

  • Funding This work was supported by a cooperative agreement from the Centers for Disease Control and Prevention (U50CCU422096) and in part by a grant from the National Institute of Environmental Health Sciences (P30ES10126).

  • Competing interests None.

  • Ethics approval Ethics approval was provided by UNC Institutional Review Board.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data sharing statement This manuscript has been approved for submission to Occupational and Environmental Medicine by the National Institute for Occupational Safety and Health, the National Center for Birth Defects and Developmental Disabilities and the National Birth Defects Prevention Study.