Introduction — There are several reported risk factors for undescended testis (UDT) and hypospadias (HYP). Also, a family history of UDT or HYP has not been accounted for in prior studies and doing so may influence these independent risk estimates.
Study Design — We conducted a population-based retrospective cohort study using linked administrative databases in Ontario, Canada to identify all live male newborns born between 1997-2007 and determined whether they underwent an orchidopexy or HYP repair within 5 years of birth. Baseline maternal and fetal risk factors were obtained using appropriate ICD codes. We performed a statistical analysis using a generalized estimating equation with a logit link, adjusting for clustering in mothers with a previous sibling born in the 5 years prior to the proband with UDT or HYP, to evaluate the adjusted risk factors of UDT and HYP.
Results — We followed 709,968 male infants from birth for 5 years, of which 5830 underwent an orchidopexy and 2722 had a HYP repair. On multivariable analysis, factors associated with a higher risk of UDT included prematurity, small for gestational age (SGA), associated HYP, gestational hypertension, use of assisted fertility techniques, increased maternal age, cesarean section, previous sibling with UDT and disorders of sexual differentiation (DSD). After adjusting for clustering in mothers with a previous baby with UDT; DSD, associated HYP (OR 2.0, 95% CI 1.0-4.1) and a previous sibling with UDT (OR 3.6, 95% CI 2.5-5.2) remained significant risk factors. The risk factors on multivariable analysis predicting risk of HYP included SGA, prematurity, higher income families and associated anomalies like UDT. After adjusting for clustering in mothers with a previous sibling with HYP; SGA (OR 1.8, 95% CI 1.0-3.1), higher income families (OR 1.5-1.6) associated UDT (OR 7.1, 95% CI 4.9-10.0) and a previous sibling with HYP (OR 12.8, 95% CI 9.1-18.1) remained significant risk factors.
Discussion — Studies estimating risk factors for UDT and HYP have utilized variable methodology to identify index cases and perform statistical analysis. This study suggests that having an older sibling with UDT or HYP is a significant independent risk factor. Performing an analysis adjusting for clustering in mothers with a previous sibling with UDT or HYP leads to loss of statistical significance for other described risk factors.
Conclusion — Underlying genetic or similar environmental exposures may be a key risk factor for UDT and HYP, which confounds known maternal and fetal risk factors for these anomalies.