In this large European study, with more than 5.8 million births covered by 23 EUROCAT registries, we found a total hypospadias prevalence of 18.61 per 10,000 births that was stable from 2001 to 2010. Hypospadias prevalence and trends are influenced by the registration policies of the individual registries, as is apparent from the large variations in prevalence and trends per registry (Table 1). This could explain the stable prevalence over time found in this study compared to a previous EUROCAT study reporting an increasing trend over the years 1999–2008 using data from partly overlapping registries [14]. Whether glandular hypospadias is registered or not will have a large effect on total hypospadias prevalence because anterior hypospadias is by far the most common [10, 13]. Ascertainment of hypospadias is incomplete in some registries, and this has a large effect on the prevalence of hypospadias, thus hindering the evaluation of trends. Ascertainment depends on the sources of information that registries can access (e.g., if only surgical data are available, mild cases can be missed), how cases are notified to the registry (active versus passive notification), jurisdiction (data protection issues), differences in diagnostic methods, screening or treatment per country (mild cases might not be diagnosed), and variation in the follow-up period of cases (when follow-up is short, mild hypospadias may not yet have been diagnosed, or a preputial anomaly can be misdiagnosed as hypospadias) [7, 16, 24, 25]. The low hypospadias prevalence in South Portugal (5.10/10,000 births) is largely due to incomplete ascertainment, as ascertainment of all congenital anomalies is low in this registry [26]. The lack of an increasing trend in hypospadias prevalence over all EUROCAT registries combined, as well as in the four EUROCAT registries with the highest prevalence, and therefore probably the best ascertainment, is reassuring.
More reliable prevalence rates and trends can be ascertained by systematically performing standardized examination of complete birth cohorts, as was done in Rotterdam for hypospadias [25] and is routinely done by the Mainz registry. In Rotterdam, a hypospadias prevalence of 38 per 10,000 live births was seen from 1998 to 2000 [25], very similar to the total prevalence of 36.83 per 10,000 births found in Mainz from 2001 to 2010. The main drawbacks of this approach are that the population size is invariably small, only a very limited region is covered, and it is more expensive to conduct.
Although environmental factors are known to contribute to the etiology of hypospadias [4, 5], their role in isolated or MCA hypospadias is largely unknown [18]. In this study, no trends over time were seen in isolated or MCA hypospadias.
Hypospadias cases were also classified according to severity: anterior, middle, or posterior hypospadias. Unfortunately, the severity was known in less than half of hypospadias cases, making interpretation of trends difficult. It is possible that the increasing trends in anterior and posterior subtypes found in this study could be explained by the decreasing trend in hypospadias NOS, as EUROCAT efforts to improve and standardize coding led to better specification of hypospadias by some registries over time.
Increased maternal age has been found to be associated with higher risk of hypospadias in some studies [17, 27, 28], but not in others [15, 29, 30]. In this study, hypospadias prevalence did not differ significantly between the maternal age groups after adjustment for registry, but the highest hypospadias prevalence was seen in teenage mothers and not in older mothers.
This study shows both the advantages and disadvantages of using birth defect registry data to investigate prevalence and trends in hypospadias. While the introduction of new EUROCAT coding guidelines in 2005 was intended to standardize registration, further efforts are needed to implement guidelines locally. We recommend better specification of cases and increased ascertainment where possible. Combining data from birth defects registries with smaller studies that can guarantee complete case ascertainment and classification will provide optimal information about prevalence and trends of hypospadias.