Hypospadias in males with intrauterine growth restriction due to placental insufficiency: The placental role in the embryogenesis of male external genitalia

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Abstract
Our aim was to define the association between early onset intra‐uterine growth restriction (IUGR) due to placental insufficiency and hypospadias in males. We prospectively studied a cohort of small‐for‐gestational age (SGA) male infants with hypospadias managed by a multidisciplinary team over a 5‐year period. Thirty SGA male infants were diagnosed with hypospadias/abnormal genitalia after birth, and four of them were diagnosed antenatally. Five cases occurred in the smaller pair of discordant IUGR twins, where the larger co‐twin had normal male genitalia. Serial ultrasounds demonstrated features of early‐onset IUGR in all cases at a median gestational age of 21 weeks (range 14–31weeks). Twenty‐one (70%) pregnancies were subsequently complicated by absent/reversed end‐diastolic flow in the umbilical arteries indicating severe IUGR, and 17 (57%) women developed severe pre‐eclampsia. There were 27 (90%) live births at a median gestational age of 31 weeks (range 27–37); 23 (77%) of the neonates had birth weights P = 0.02). In conclusion, SGA male newborns with hypospadias exhibit a high rate of early‐onset severe IUGR due to placental insufficiency. Early placental development likely influences male external genitalia formation. Careful sonographic evaluation of the genitalia is advised when early‐onset placentally mediated IUGR is found.