Placental Weight and Male Genital Anomalies: A Nationwide Danish Cohort Study

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The most consistently reported risk indicators for the male genital anomalies cryptorchidism and hypospadias are prematurity and low birth weight. Placental dysfunction has been hypothesized as a possible underlying cause, and an association between placental weight at birth and hypospadias has been indicated. In a population-based cohort of 388,422 Danish singleton boys born alive (1997–2008), we studied the association between placental weight and cryptorchidism and hypospadias. Missing data were handled with multiple imputation, and we estimated hazard ratios by means of Cox regression models. During follow-up, 1,713 boys were diagnosed with hypospadias and 6,878 with cryptorchidism (3,624 underwent corrective surgery). We observed an association between low placental weight and risk of both genital anomalies. Boys with a placental weight in the lowest decile (<10%) had higher risks of both cryptorchidism (hazard ratio = 1.52, 95% confidence interval: 1.31, 1.76) and hypospadias (hazard ratio = 1.97, 95% confidence interval: 1.59, 2.45) than boys in the reference decile (50.0–59.9%). In conclusion, we found higher risks of both genital malformations in boys born with a low placental weight. The relationship seemed stronger for hypospadias than for cryptorchidism. Taken together, our data support a role for placental dysfunction in the etiology of these anomalies.

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