Cryptorchidism and Hypospadias in a Cohort of 934,538 Danish Boys: The Role of Birth Weight, Gestational Age, Body Dimensions, and Fetal Growth

Early delivery and low birth weight are strong predictors of the urogenital anomalies cryptorchidism (undescended testis) and hypospadias. Understanding these associations may lead to important etiologic clues. Therefore, the authors revisited the prevailing hypotheses regarding fetal growth restriction as a risk factor for urogenital anomalies. They studied a population of 934,538 Danish boys born alive between January 1, 1980, and December 31, 2008. Cryptorchidism and hypospadias were associated with low weight-for-gestational-age, an indicator of fetal growth restriction, and furthermore the authors observed strong interaction with early delivery. Low birth weight in a singleton compared with the mean birth weight of all singleton brothers in the family or in a twin compared with the male co-twin was associated with higher risk of urogenital anomalies, suggesting an effect of relative fetal growth restriction within families. Contrary to previous reports, newborns' body dimensions assessed independently of birth weight were not associated with urogenital anomalies. The hypothesis that shared factors cause both fetal growth restriction and urogenital anomalies was supported by comparison of urogenital anomaly risks in singletons and twins and by patterns of cryptorchidism and hypospadias co-occurrence in individuals. These novel insights might also extend to other male reproductive conditions with prenatal etiology.