Maternal risk factors in the origin of isolated hypospadias: a population-based case-control study.

The birth prevalence of hypospadias increased in Hungary during the last decades, thus the aim of this study was to analyze the possible role of maternal risk factors in the origin of isolated hypospadias (IHS). The incidence/prevalence of acute and chronic maternal diseases with related drug treatments were compared in the mothers of cases with IHS, population controls without defect and malformed controls affected with other isolated abnormalities in the population-based Hungarian Case-Control Surveillance of Congenital Abnormalities including 3038 cases with IHS, 24 814 population male controls without any defects and 11 096 malformed male controls with other isolated defect. Among exposures, prospective medically recorded chronic diseases and medically recorded or retrospective maternal information regarding acute diseases and drug treatments were evaluated in the study groups. Maternal epilepsy due to the treatment of valproate (odds ratio [OR] with 95% confidence interval [CI]: 1.97, 1.07-3.61) and cervical erosion (4.09, 1.84-9.12) were associated with a higher risk of IHS. In addition, there was an association of oral nystatin (1.94, 1.22-3.09), lynestrenol (26.66, 8.69-81.80) and ethynilestradiol (3.51, 1.61-7.67) treatments in the mothers of cases with a higher risk for IHS. In conclusion, maternal cervical erosion, valproate, nystatin, lynestrenol and ethynilestradiol associated with a higher risk for IHS.