Placental insufficiency in early gestation is associated with hypospadias

The association of growth retardation and hypospadias is well established. Fetal testosterone secretion is under the influence of placental human chorionic gonadotropin during first 14 weeks of gestation. We hypothesized that placental insufficiency may disrupt the supply of nutrients and human chorionic gonadotropin to the fetus leading to both growth retardation and hypospadias. To validate this hypothesis, we analyzed extremely low-birth-weight male infants with or without hypospadias for fetal growth parameters.

One hundred four male newborn infants with birth body weight of less than 1500 g admitted to a neonatal intensive care unit over a 4-year period were retrospectively reviewed, recording the presence and type of hypospadias, fetal growth parameters, infant growth parameters at birth, placental weight, placental histopathology, cord information, and maternal morbidity. These data of patients with hypospadias were compared with those of controls.

Of the 104 extremely to very low-birth-weight male infants, 16 (15.3%) had hypospadias, and 10 (62.5%) of those had severe proximal hypospadias. Sixty-two controls who did not have hypospadias and whose body weight was less than 1500 g were identified. The incidence of hypospadias in full-term male birth in the hospital was 12 (0.30%) in 3959 births. Birth body weight and their SD for gestational age were lower in patients with hypospadias compared with those for controls (824 +/- 160 vs 1255 +/- 145 g). Placenta-to-fetal ratio (0.323 +/- 0.07 vs 0.229 +/- 0.03) and gestational age were significantly higher in the patients with hypospadias. Histopathologic study of the maternal placenta obtained from the patients with hypospadias revealed pronounced degenerative changes, infarction, and calcification, whereas these abnormalities were rare in controls.

The significant association between the occurrence of hypospadias and early growth retardation with higher placenta-to-fetal ratio and placental abnormalities suggest that placental dysfunction in early gestation may play an important role in the development of hypospadias.