PD29-01: Association of Preconception Paternal Health and Male Genital Malformations

Saturday, September 11, 2021 8:00 PM to 10:00 PM


Authors: Kyla Velaer, Chiyuan Zhang, Shufeng Li, Michael Eisenberg

Introduction: The etiologies of hypospadias and cryptorchidism are largely unknown. Prior studies have shown an association between maternal exposures that may disrupt hormone development. Recent studies have demonstrated that increased preconception paternal metabolic syndrome (MetS) may be associated with adverse pregnancy and infant outcomes. The association between paternal health and genital malformations remains unknown.

Methods: We used the IBM Marketscan® Research claims database to identify infants with one male and one female parent at birth with at least one year of observation before conception. We included all infants that had at least one year of enrollment time data. We identified parental comorbidities using diagnosis codes from inpatient and outpatient records. MetS diagnosed components included hypertension, hyperlipidemia, diabetes, and obesity. We used diagnosis and CPT codes to identify infants diagnosed with hypospadias and cryptorchidism and infants that had surgery for these conditions.

Results: We identified 193,275 male infants that met criteria from 2009 to 2016 with the average follow up time of 3.9 years. The mean age at delivery of fathers was 35 years and 33 years for mothers. 21% of sons were sired by men with at least one component of the metabolic syndrome. While 0.86% of sons whose fathers had no components of MetS had surgery for hypospadias, 1.2% of sons whose fathers had two or more MetS diagnoses had hypospadias repair.  Similar findings were found for hypospadias diagnoses alone.  After adjusting for maternal and paternal age, smoking status, neonatal intensive care stay, low birth weight, prematurity, baby region, maternal MetS and follow up in years, infants born to fathers with increased MetS components had increased odds of undergoing surgery for hypospadias (2+ MetS OR 1.37, 95% CI 1.18-1.59). 0.61% of sons whose fathers had no components of MetS had an orchiopexy for undescended testes, and 0.68% of sons whose fathers had two or more MetS diagnoses had hypospadias repair.  On multivariable adjustment, there was no difference in the odds of cryptorchidism or orchiopexy based on preconception paternal MetS (OR 1.08, 0.89-1.31).

Conclusions: Increased preconception paternal comorbidity may be associated with the development of hypospadias. Although the paternal effect remains modest, these findings highlight that paternal health in addition to maternal and environmental exposures may increase risk of hypospadias.

Source of Funding: Translational Science Award (UL1 TR001085) and internal Stanford University funding
Therapeutic Area