Previous studies have demonstrated that early delivery and low birth weight are strong predictors of 2 urogenital anomalies, cryptorchidism (undescended testis) and hypospadias. Several questions regarding the association of fetal growth restriction with urogenital anomalies remain unanswered. It is unclear whether growth restriction might predict urogenital anomalies independently of absolute birth weight. Small for gestational age as a measure of poor fetal growth has limited usefulness because of the unknown growth potential of each fetus. It is unknown whether there are causal factors shared by fetal growth restriction and urogenital anomalies that create the associations. Few studies have investigated the possible interactions between gestational age and birth weight or small for gestational age on the risk of urogenital anomalies.
The aim of this study was to evaluate the prevailing hypotheses on the role of fetal growth restriction as a risk factor for cryptorchidism and hypospadias. The possible associations of birth weight, gestational age, body dimensions, and fetal growth on the risks of cryptorchidism and hypospadias were studied in a large population-based cohort. The study population was composed of 934,538 Danish boys born alive between 1980 and 2008. Risks of urogenital anomalies according to birth weight were evaluated in both singletons and twins; when possible, relative birth weight of male singletons in a family was compared with other singleton brothers, and that of twins was compared with their male cotwins.
The data showed an association of low weight for gestational age with both cryptorchidism and hypospadias. This association was strengthened by early delivery. Attaining lower birth weight than one’s singleton brother or cotwin was associated with higher risk of urogenital anomalies, indicating an effect of relative fetal growth restriction within families. In contrast to previous studies, newborns’ body proportions, when assessed independently of birth weight, had no significant effect on the risk of urogenital anomalies. Comparison of urogenital anomaly risks in singletons and twins and co-occurrence patterns in individuals with cryptorchidism and hypospadias supported the hypothesis that shared factors cause both fetal growth restriction and urogenital anomalies.
These findings suggest that identifying shared causal factors may provide new important information on the biology and prenatal etiology of urogenital anomalies and other male reproductive conditions, including testicular cancer and poor semen quality.
Perinatal Epidemiology Research Unit, Department of Pediatrics, Aarhus University Hospital, Aarhus, Denmark