Maternal occupational exposures and risk of specific birth defects

Occupational Medicine 2006; 56: 532-543.

Thulstrup Ane Marie and Bonde Jens Peter

Five specific birth defects were identified:

1. Neural tube defects
2. Cleft lip and cleft palate
3. Congenital heart defects
4. Urinary tract defects
5. Limb defects

Birth defects or congenital malformations (at time of birth): 3,5% of all live births.

Data on spontaneous abortion may be important for the detection of teratogenic factors.

In nearly 70% of all birth defects, there is still no known risk factor.

Close to 30% of all pregnancies end in a foetal loss or spontaneous abortion.

Neural tube defects

Prevalence in Europe +/- 1 per 1000 births

Protective factor: Folic acid intake

Non-occupational risk factor: hight vitamin A (retinol) intake

Occupational risk: 10 studies (2 cohort & 8 case-control studies)

Possible risks among women working in health care, agriculture and cleaning.

Risk seems to be following exposure to glycol ethers or lead

Caution: Limited evidence !!!

Holmberg et al. / Ericson et al. / Matte et al. / Bianchi et al. / Cordier et al. / Blatter et al. / Lin et al. / Irgens et al. / Blaasaas et al. / Brender et al.

Cleft lip and Cleft palate

Prevalence in Europe:

+/- 1.5 per 1000 births for cleft lip

+/- 0.8 per 1000 births for cleft palate

Well accepted that genetic factors contribute to the aetiology

Protective factor: folic acid intake

Non-occupational risk factors: Maternal smoking - High vitamin A intake

Occupational risk: 11 studies (2 registry-based & 9 case-control studies)

Employment during pregnancy in the leather industry or as a hairdresser has been suggested to be associated with increased risk of cleft lip or cleft palate.

Exposures like organic solvents, glycol ethers and pesticides have been suggested in a number of studies.

Caution: Limited evidence !!!

Holmberg et al. / Matte et al. / Nurminen / Bianchi et al. / Cordier et al. / Lin et al. / Lorente et al. / Blaasaas et al. / Shaw et al. / Carmichael et al. / Chia et al.

Heart abnormality

Prevalence is +/- 4-6 per 1000 births

Prevalence increased simultaneously with the increasing survival of premature infants.

Possible non-occupational risk factors: alcohol consumption during first trimester, maternal diabetes mellitus, high body mass index & use of antiepileptics

Occupational risk: 7 studies (2 registry-based & 5 case-control studies)

Evidence is inconclusive !!!

Tikkanen et al. / Matte et al. / Bianchi et al. / Cordier et al. / Cedergren et al. / Carmichael et al. / Chia et al.

Urogenital abnormality

Prevalence of hypospadias: 2-4 per 1000 births

Prevalence of cryptorchidism: <>

Genetic defects play a role in hypospadias

Occupational risk factors: 8 case-control studies

Few studies do not allow any conclusions on occupational risk for cryptorchidism or for hypospadias !!!

Bianchi et al. / Cordier et al. / Garcia / Matte et al. /Weidner et al. / Vrijheid et al. / Pierik et al.

Limb defects

Prevalence: +/- 0.5-1% per 1000 births

Genetic interaction of teratogenic effects of smoking ?

Non-occupational risk factors: Maternal smoking

Occupational risk: 6 studies

Limited number of studies focusing on limb defects are insufficient to assess the risk !!!

Bianchi et al. / Cordier et al. / Garcia / Matte et al. / Weidner et al. / Vrijheid et al. / Pierik et al.

Discussion & Remarks:

Original literature does not provide clear evidence for causal associations between maternal occupational exposures and specific birth defects.

It seems that little progress has been made since Sever published a review (1994).

There is a strong interaction between age, lifestyle factors (smoking, alcohol, social class, nutrition) and occupational exposures during pregnancy, which complicates the proper interpretation of associations.

Final conclusions:

Epidemiological research has not convincingly demonstrated any workplace exposure as a specific teratogen but sevral concerns implying possible teratogenic effects of volatile organic solvents, glycol ethers, some pesticides and some heavy metals call for additional research.

It seems to be difficult or impossible to establish exposure-response relationships. Such studies will probably require very large source populations and call for international research cooperation.