Hypospadias and Early Gestation Growth Restriction in Infants

Objective: There has been a major increase in the incidence of hypospadias in infants in the 1990s, but the risk factors are not known. Although there are scattered reports in the literature regarding the association of low birth weight and hypospadias, this has not been systematically studied. The objective of this study was to determine the association between early gestation intrauterine growth and hypospadias.

Methods: A retrospective review of 13 years of admissions to 2 tertiary care neonatal intensive care units (NICUs) in Connecticut (1987--2000) showed that 112 (1.66%) of 6746 male infants had any degree of hypospadias. Of these, 8 were part of a genetic syndrome and were excluded. A retrospective cohort analysis of these 6738 infants was performed. Infant growth parameters at birth (weight, head circumference, and length) were analyzed along with maternal risk factors known to be associated with changes in fetal growth, including maternal age, race, diagnosis of preeclampsia, gestational diabetes, and maternal use of alcohol or tobacco or substance abuse during pregnancy.

Results: The incidence of hypospadias in the NICU population increased 10-fold from 0.4% in 1987 to 4% in the first quarter of 2000. Hypospadias was significantly more common in infants who had uniformly poor intrauterine growth (<10th percentiles) in the various parameters measured: birth weight, length, or head circumference. There were no significant differences in maternal age or race, nor were there differences in the use of alcohol, tobacco, or street drugs by the mother. There were no differences between singletons and multiple-gestation births. However, the frequency of occurrence was significantly higher among first-born infants (1.9%) compared with all other infants (0.9%).

Conclusions: The incidence of hypospadias in our NICU population has increased 10-fold during the 13-year period of study. There was a significant association of hypospadias with poor intrauterine growth. The growth restriction was probably of early gestational cause as there was proportionate involvement of somatic (weight and length) and brain growth (head circumference). The increasing frequency of hypospadias and its association with poor intrauterine growth originating in early gestation suggests that common environmental factor(s) that have an impact on both conditions may be involved.