Birth Prevalence Of Hypospadias Research Articles

Editorial comment: Birth prevalence of hypospadias and hypospadias risk factors in newborn males in the United States from 1997 to 2012

Editorial comment: Birth prevalence of hypospadias and hypospadias risk factors in newborn males in the United States from 1997 to 2012

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

Hypospadias is one of the most common birth defects among males. Although the birth prevalence of hypospadias has been reported as increasing in some geographic regions, inconsistencies in ascertainment of mild cases and variability in reporting standards are likely contributing to these apparent trends. While hypospadias is highly heritable, there is limited knowledge about the specific genetic and epigenetic factors that play a role in its etiology. Risk factors for hypospadias include family history, older maternal age, nulliparity, high maternal prepregnancy body mass index, hypertension or preeclampsia, multiple gestations, reduced birth weight, and small for gestational age. Of the various prenatal exposures to medications that have been studied, the strongest evidence supports valproic acid as a contributor to hypospadias. Studies evaluating the impact of assisted reproductive technologies (ART) on hypospadias are inconclusive because of potential confounding by subfertility. Many causes of hypospadias may act through a few shared pathways, such as placental dysfunction.

Influence of maternal diet on the development of malformation of the external genitalia – Are we ready to make some recommendations?

The influence of our environment on the development of malformation is well known and, again and again, discussed with great enthusiasm. For example, the supplementation of the diet with folic acid has been proven to prevent neural tube defects already in 1991 [1, 6]. However, despite this well–known fact, only 10.6% of women take folic acid at least four weeks before getting pregnant; although 60% know the increased risk. It was interesting to see, that there were no big differences between the social groups [7]. Some epidemiological studies suggest an increasing risk of disorders / malformation of the external genitalia in males. The influence of the hormonal environment, especially of androgens, has been discussed. A recently published review demonstrated, that with the possible exception of testicular cancer there is no strong epidemiological evidence to indicate that prenatal exposure to estrogen are linked to disturbed development of the external genitalia [8]. Skakkebaek and co–workers suggested that hypospadias, undescended testis, testicular cancer and poor semen quality are symptoms of the testicular dysgenesis syndrome, which may be due to adverse environmental influences [9]. If there really is an increasing incidence of hypospadias, as stated in the article of Kowal and Co–Worker [5], is questionable. For example, in New York State there were no statistically significant changes in hypospadias rates between 1992 and 2005 [4]. Also, in Europe there was no increase in the incidence of hypospadias observed [3]. In a Danish study, birth prevalence of hypospadias was significantly higher than in a parallel Finnish study (1.03 vs. 0.27%; P = 0.012). However, at three years of age the prevalence increased to 4.64% because additional mild cases were detected when physiological phimosis dissolved [2]. Therefore, the so–called increase of hypospadias may be only related to higher awareness of small variants of hypospadias. The presented study by Kowal and co–worker is quite interesting. They looked for some signs of vitamin B12 deficiencies in mothers of babies born with hypospadias. High levels of propionylcarnitine (C3) seem to be a sensitive indicator of vitamin B12 deficiency as stated in the literature mentioned in their article. The authors found that in 41 newborns with hypospadias, the mean concentration of propionylcarnitine was higher compared to 90 newborns without congenital anomalies [3.52 (1.50) micromol/L vs. 2.91 (1.13) micromol/L (p = 0.026)]. The mean methionine level in these cases was insignificantly lower than in controls [5]. This seems to suggest the influence of the environment on the development of congenital anomalies. However, like in many other congenital malformations, the cause is multifactorial and to this day we still do not know which factors are important and which are not. It would be interesting if the authors could also determine the vitamin B12 levels in the mothers, ask them for a description of their diet, and compare it to the levels propionylcarnitine in the newborns. Before recommendation about some vitamin supplementation can be made, we need much stronger evidence that vitamin B12 plays a role in the development of hypospadias.

Hypospadias in Washington State: Maternal Risk Factors and Prevalence Trends

Maternal risk factors for hypospadias are poorly defined, and there is debate about temporal trends in hypospadias prevalence. We examined select maternal characteristics as possible risk factors for hypospadias among male offspring and evaluated yearly prevalence rates in Washington State. We performed a population-based, case-control study using linked birth-hospital discharge data from Washington State for 1987-1997 and prevalence data for 1987-2002. All cases of hypospadias were identified on the basis of International Classification of Diseases, Ninth Revision, codes from the birth hospitalization (N = 2155). Five control subjects were randomly selected for each case subject from the remaining singleton births, frequency matched according to year of birth (N = 10775). Maternal and infant characteristics were ascertained from the birth certificate. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Yearly prevalence was determined by dividing the total number of hypospadias cases by the number of male singleton live births for each year. The risk of delivering an affected male infant increased with advancing maternal age; relative to women <20 years of age, those >40 years of age were at greatest risk (OR: 1.70; 95% CI: 1.17-2.48). Infants of nonwhite women were generally at decreased risk. Infants born to women with preexisting diabetes mellitus were at greater risk than those born to women without diabetes (OR: 2.18; 95% CI: 1.03-4.60); however, this was not observed for infants born to women with gestational diabetes. The birth prevalence of hypospadias in 2002 was 5.0 cases per 1000 male births, not significantly different from that in 1987. Older maternal age, white race, and preexisting diabetes were associated with increased risk of hypospadias among male offspring. The prevalence of hypospadias in Washington State did not increase significantly between 1987 and 2002.