Risk factors for hypospadias in Norwegian boys - association with testicular dysgenesis syndrome?

Abstract

It has been proposed that hypospadias, cryptorchidism and testicular cancer, as well as decreasing sperm quality are symptoms of an underlying entity called testicular dysgenesis syndrome (TDS). We wanted to study the risk factors for hypospadias and compare them with those of the other conditions belonging to TDS. A large case-control study was undertaken on data on all live-born boys registered in the Medical Birth Registry of Norway during the period 1967-1998 (n = 961 396; hypospadias cases = 2382). Logistic regression analysis was used to study the association between potential risk factors and hypospadias, estimated by odds ratio (OR). The risk factors for hypospadias were divided into four categories: (i) maternal characteristics, e.g. low parity [p(trend) < 0.001], hypertension (OR = 1.49) and bleeding (OR = 1.39) during index pregnancy, and (pre)eclampsia (OR = 1.84); (ii) complications during delivery, e.g. retained placenta (OR = 1.67) or Caesarean section (OR = 1.36); (iii) characteristics of the newborn, e.g. low birth weight [p(trend) < 0.001], small for gestational age (OR = 2.16), and presence of congenital malformations other than hypospadias (OR = 2.72), e.g. inguinal hernia (OR = 5.65); (iv) prevalence among relatives of hypospadias cases, e.g. brother with hypospadias (OR = 20.81). The novel finding of retained placenta as a risk factor indicates that early malfunction of placenta could be a causative factor for hypospadias. When comparing with previously published risk factors for hypospadias, cryptorchidism and testicular cancer, we found that the following risk factors were common to all three conditions: low parity, low birth weight, low gestational age, inguinal hernia, bleeding during pregnancy and Caesarean section. In conclusion, our results support the notion that the conditions of TDS share risk factors.