Maternal exposures to endocrine disrupting chemicals and hypospadias in offspring

Birth Defects Res A Clin Mol Teratol. 2010 Apr;88(4):241-50. doi: 10.1002/bdra.20657.


Background: Prenatal exposures to endocrine-disrupting chemicals (EDCs) are suspected risk factors in the etiology of hypospadias. The aim of this case-control study was to test the hypothesis of an association between maternal environmental exposures to EDCs and hypospadias in the offspring.

Methods: Detailed questionnaire data on occupational and dietary exposures to EDCs in the perinatal period were collected from 80 mothers with hypospadiac infants and from 80 mothers with healthy controls within 24 months of childbirth. Maternal exposure to selected EDCs was also ascertained by measuring the concentration of dichlorodiphenyldichloroethylene, hexachlorobenzene, and several polychlorinated biphenyl congeners in the serum of primiparous mothers of 37 cases and 21 controls.

Results: The risk to bear an hypospadiac infant was associated with perinatal maternal occupational exposures to EDCs evaluated by a job-exposure matrix: jobs with exposure to one class of EDCs (odds ratios [OR](crude), 2.83; 95% confidence intervals [CI], 1.32-6.07; OR(adjusted), 2.44; 95% CI, 1.06-5.61) and jobs with exposure to more than one group of EDCs (OR(crude), 4.27; 95% CI, 1.43-12.78; OR(adjusted), 4.11; 95%CI, 1.34-12.59). Increase in risk was also found among mothers consuming a diet rich in fish or shellfish (OR(crude), 3.41; 95% CI, 1.42-8.23; OR(adjusted), 2.73; 95%CI, 1.09-6.82). Serum hexachlorobenzene concentration above the median of all subjects was significantly associated with the risk of hypospadias (OR(adjusted), 5.50; 95% CI, 1.24-24.31).

Conclusions: This study, although based on a limited number of cases, for the first time provides evidence of an association between maternal exposure to EDCs, in particular elevated plasma hexachlorobenzene concentration, and the development of hypospadias in the offspring.

MeSH terms

  • Abnormalities, Multiple / epidemiology
  • Adult
  • Case-Control Studies
  • Dichlorodiphenyl Dichloroethylene / adverse effects
  • Dichlorodiphenyl Dichloroethylene / blood
  • Diet / statistics & numerical data
  • Diseases in Twins / epidemiology
  • Endocrine Disruptors / adverse effects*
  • Female
  • Food Contamination*
  • Hexachlorobenzene / adverse effects
  • Hexachlorobenzene / blood
  • Humans
  • Hypospadias / chemically induced*
  • Hypospadias / epidemiology
  • Infant
  • Infant, Newborn
  • Infant, Small for Gestational Age
  • Male
  • Maternal Exposure / adverse effects*
  • Middle Aged
  • Occupational Exposure / adverse effects*
  • Paternal Exposure / adverse effects
  • Pesticides / adverse effects
  • Polychlorinated Biphenyls / adverse effects
  • Polychlorinated Biphenyls / blood
  • Pregnancy
  • Rome / epidemiology
  • Seafood / adverse effects*
  • Surveys and Questionnaires
  • Young Adult


  • Endocrine Disruptors
  • Pesticides
  • Dichlorodiphenyl Dichloroethylene
  • Hexachlorobenzene
  • Polychlorinated Biphenyls