Intrauterine growth restriction and hypospadias: is there a connection?

Abstract

Hypospadias is one of the most common congenital malformations of the genitourinary tract in males. It is an incomplete fusion of urethral folds early in fetal development and may be associated with other malformations of the genital tract. The etiology is poorly understood and may be hormonal, genetic, or environmental, but most often is idiopathic or multifactorial. Among many possible risk factors identified, of particular importance is low birth weight, which is defined in various ways in the literature. No mechanism has been identified for the association of low birth weight and hypospadias, but some authors propose placental insufficiency as a common inciting factor. Currently, there is no standardized approach for evaluating children with hypospadias in the setting of intrauterine growth restriction. We reviewed the available published literature on the association of hypospadias and growth restriction to determine whether it should be considered a separate entity within the category of disorders of sexual differentiation.

The role of genetic variation in DGKK on moderate and severe hypospadias

“…Within this classification, hypospadias severity is stratified in ascending categories based on the severity of this disease. However, studies of hypospadias may use different classifications to describe severity and often fail to characterize additional features of hypospadias such as the presence of chordee (Chen et al, ).…”

Maternal vegetarian diet in pregnancy, a predisposition to hypospadias?

“…10,11 A particular factor responsible has been shown to be intake of phytoestrogens and its deleterious effect on the development of male genital system. 4,5,8,9,12 We have attempted to supplement this hypothesis by correlating an increased maternal gestational vegetarian diet with increased prevalence of hypospadias n male babies. Similar studies done back in 2000 have shown that phytoestrogen intake does cause ill effects on the development of male genital system which may cause hypospadias.…”

“…The prevalence varies worldwide and different rising trends have been seen in different population groups. 3,4 Both genetic and environmental factors are believed to be responsible. [3][4][5] There has been a recent interest in understanding its relation to the maternal gestational factors.…”

Hypospadias: One Defect, Multiple Causes, Acting Through Shared Pathways

“…Additionally, placental dysfunction may reduce nutrient transfer to the fetus, consequently contributing to restricted growth [56]. However, placental insufficiency after the critical developmental window that results in growth restriction would not cause hypospadias [53]. In Fig.…”

“…Placental dysfunction and androgen deficiency in early pregnancy have been proposed as shared causes of intrauterine growth restriction and hypospadias [46••, 49, 50]. Specifically, placental dysfunction may lead to inadequate production or transport of human chorionic gonadotropin, or other placenta-derived factors, which fail to stimulate appropriate fetal androgen production necessary for normal urethral closure [49][50][51][52][53] and potentially involved in somatic growth [54,55]. Additionally, placental dysfunction may reduce nutrient transfer to the fetus, consequently contributing to restricted growth [56].…”