Severe hypospadias and its association with maternal‐placental factors

Abstract

The neonate born small for gestational age (SGA, birth weight <10th centile) with severe hypospadias, and without the presence of other malformations, is a presentation which clinical geneticists are asked to assess. However, this combination is not well addressed in the literature. Epidemiological studies point to an increased incidence and severity of hypospadias in SGA infants, but leave open the possibility that the association is attributable to the population subset who have multiple congenital abnormalities or genetic syndromes. Epidemiological studies unselected for birth weight have also identified an association between hypospadias with some risk factors tied to SGA, including prematurity, preeclampsia, and placental insufficiency. This study was developed after being involved in the care of several boys with SGA and severe hypospadias who were premature, with gestational histories of maternal hypertension and oligohydramnios. No underlying syndromes, hormonal abnormalities, or contributory family histories could be found. We hypothesized that severe hypospadias may in some cases be causally related to maternal-placental factors rather than primary fetal abnormalities. A retrospective study of a cohort of singletons born SGA with unexplained hypospadias was conducted. We compared their gestational histories and hypospadias severities with those born at normal birth weights. The cohort with SGA had an increased ratio of severe to mild hypospadias. Further, within the cohort of SGA boys, there was a higher prevalence of prematurity, maternal hypertension, and oligohydramnios among those with severe vs mild hypospadias. Small sample sizes are limiting.