A population-based study of prevalence trends and geospatial analysis of hypospadias and cryptorchidism compared with non-endocrine mediated congenital anomalies

Abstract

Several reports have suggested an increase in the prevalence of hypospadias and cryptorchidism over the last few decades. Endocrine disruption caused by exposure to environmental chemicals has been postulated as a possible cause. The objectives of our study were: 1) to determine whether the prevalence of hypospadias and cryptorchidism is increasing compared with other congenital anomalies not known to be mediated by endocrine factors; and 2) to perform a geospatial analysis of these congenital malformations looking for clustering that could offer insight into environmental risk factors. Data were obtained from the Nova Scotia ATLEE Perinatal Database containing the perinatal records of all live births in Nova Scotia, Canada since 1988. Records from 1988 to 2013 defined the study cohort. Overall prevalence rates and prevalence trends by year were calculated for hypospadias, cryptorchidism, gastroschisis, and clubfoot. County of residence was collected and spatial autocorrelation testing for clustering was performed for each of the congenital anomalies. There were 258,147 live births during the study period. Overall prevalence rates for the four malformations over the study period were: hypospadias 78 per 10,000 male births, cryptorchidism 75 per 10,000 male births, clubfoot 24 per 10,000 total births, and gastroschisis 4 per 10,000 total births. Incidence rate ratios per year for hypospadias, cryptorchidism, clubfoot, and gastroschisis were 1.00 (0.99-1.01), 0.99 (0.98-1.00), 0.98 (0.97-0.99), and 1.04 (1.04-1.07), respectively. During the study period, the prevalence rates in the region were unchanged for hypospadias, slightly reduced for cryptorchidism and clubfoot, and rising for gastroschisis (Figure). Spatial autocorrelation testing revealed statistically significant clustering for hypospadias (p=0.03) and cryptorchidism (p=0.03), while no spatial autocorrelation was observed for the other malformations. Contrary to previous studies we show that hypospadias and cryptorchidism prevalence rates are not increasing over time in our region. Nonetheless, rates for these conditions in our area are high compared with other regions of the world. Local clustering of these congenital anomalies without clustering of the control, non-endocrine mediated congenital malformations supports a possible unique spatial distribution associated with environmental exposure. The hotspots identified for hypospadias and cryptorchidism are associated with intense agricultural activity. Our study found no increase in hypospadias and cryptorchidism prevalence over a 26-year period compared with other congenital anomalies not known to be associated with endocrine factors. Geospatial analysis supports high clustering for hypospadias and cryptorchidism in areas of intense agricultural activity.