BACKGROUNDPrenatal exposures to endocrinedisrupting chemicals EDCs are suspected risk factors in the etiology of hypospadias. The aim of this casecontrol study was to test the hypothesis of an association between maternal environmental exposures to EDCs and hypospadias in the offspring.METHODSDetailed 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.RESULTSThe risk to bear an hypospadiac infant was associated with perinatal maternal occupational exposures to EDCs evaluated by a jobexposure matrix: jobs with exposure to one class of EDCs odds ratios ORcrude, 2.83; 95 confidence intervals CI, 1.32–6.07; ORadjusted, 2.44; 95 CI, 1.06–5.61 and jobs with exposure to more than one group of EDCs ORcrude, 4.27; 95 CI, 1.43–12.78; ORadjusted, 4.11; 95CI, 1.34–12.59. Increase in risk was also found among mothers consuming a diet rich in fish or shellfish ORcrude, 3.41; 95 CI, 1.42–8.23; ORadjusted, 2.73; 95CI, 1.09–6.82. Serum hexachlorobenzene concentration above the median of all subjects was significantly associated with the risk of hypospadias ORadjusted, 5.50; 95 CI, 1.24–24.31.CONCLUSIONSThis 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. Birth Defects Research Part A, 2010. © 2010 WileyLiss, Inc.