Maternal age and hypospadias

Abstract

Sir, The proportion of mothers having babies at the age of 35 and over has increased over the last years, and the association between maternal age and the incidence of congenital anomalies has been recognized for many years. Multiple possible risk factors related to the development of isolated hypospadias have been proposed including genetic, endocrine, and environmental factors. A possible relationship with increasing maternal age was suggested (1), but no biological hypothesis was made. We evaluated 415 newborns with isolated hypospadias (study period 1991–98) from Sicilian Registry of Congenital Malformations compared with a random control group of 812 healthy live births matched for geographic origin. Our results (Table I) suggest that women at the extremes of the age distribution have an increased risk for hypospadias relative to women in the middle of the distribution. However, while the association between chromosomal anomalies and advanced maternal age is well-known, the relationship between structural defects and maternal age is less clear even if it has been reported a positive association between advancing maternal age and congenital malformtations, with a possible cumulative effects of environmental exposures over time (2). On the contrary, several birth defects were found to be elevated among the offspring of young mothers (3). It is generally agreed that both genetic and non-genetic factors are involved in the hypospadias etiology that could be correlated with endocrine factors that control the development of the male genital organs. It has been postulated that changes in concentrations of sex hormones during the fetal critical period of genital development (weeks 8–14), caused by endogenous or exogenous factors, may play a role in the development of hypospadias and that it could be associated with early malfunction of the placenta, resulting in a decreased secretion of placental and fetal hormones that could in turn disturb fetal development. Mothers at the extremes of the age distribution may be more susceptible to this hormonal disruption, than the association between maternal age, for younger than for older women, may be explained as a “defect in nature's quality control” with a reduction of defensive maternal mechanisms in the hypospadias' mothers that would be less efficient in the elimination of malformed fetuses. This hypothesis may be explained in older women with a progressively reduction and in younger women with an immaturity of these biological defensive mechanisms that are probably under hormonal influence. Our results, despite the limitation of sample, want to focus the attention on a possible association between maternal age and hypospadias, but further studies are needed to confirm or refute this association and to investigate into possible etiologic factors.