Maternal and gestational risk factors for hypospadias

Background: An increase in the prevalence of hypospadias has been reported, but the environmental causes remain virtually unknown. Objectives: Our goal was to assess the association between risk of hypospadias and indicators of placental function and endogenous hormone levels, exposure to exogenous hormones, maternal diet during pregnancy, and other environmental factors. Methods: We conducted a case-control study in Sweden and Denmark from 2000 through 2005 using self-administered questionnaires completed by mothers of hypospadias cases and matched controls. The response rate was 88% and 81% among mothers of cases and controls, respectively. The analyses included 292 cases and 427 controls. Results: A diet during pregnancy lacking both fish and meat was associated with a more than 4-fold increased risk of hypospadias [odds ratio (OR) = 4.6; 95% confidence interval (CI), 1.6-13.3]. Boys born to obese [body mass index (BMI) = 30] women had a more than 2-fold increased risk of hypospadias (OR = 2.6; 95% CI, 1.2-5.7) compared with boys born to mothers with a normal weight (BMI = 20-24). Maternal hypertension during pregnancy and absence of maternal nausea increased a boy's risk of hypospadias 2.0-fold (95% CI, 1.1-3.7) and 1.8-fold (95% CI, 1.2-2.8), respectively. Nausea in late pregnancy also appeared to be positively associated with hypospadias risk (OR = 7.6; 95% CI, 1.1-53). Conclusions: A pregnancy diet lacking meat and fish appears to increase the risk of hypospadias in the offspring. Other risk associations were compatible with a role for placental insufficiency in the etiology of hypospadias.