Intrauterine Exposure to Endocrine-disrupting Chemicals and Risk of Hypospadias: A Pilot Study

Context: Hypospadias is a common malformation, which can be caused by a disruption of hormone signaling during development. Endocrine disrupting chemicals (EDCs) cross the placenta and can interfere with hormone synthesis and metabolism. Objective: To evaluate whether intrauterine exposure to environmental phenols and/or parabens is associated with hypospadias. Methods: This was a case-control pilot study of term infant males with (n = 6) and without (n = 16) hypospadias. Meconium was tested for bisphenol-A (BPA), bisphenol-S (BPS), bisphenol-F (BPF), methylparaben (MePb), and propylparaben (PrPb) using a novel lab procedure. Results: BPA concentrations were higher in cases vs controls, though this difference was not statistically significant. Higher meconium concentration of BPA was associated with shorter Anogenital distance (AGD); higher BPS and BPA were associated with shorter stretched penile length (SPL). There were no significant differences for BPS, BPF, MePb, or PrPb. Conclusion: This study demonstrated that EDCs were present in meconium samples, supporting the hypothesis that maternal exposure results in fetal exposure during a time of critical fetal urogenital development. Our data suggests a pattern of higher BPA in cases of hypospadias compared to controls while BPA and BPS were inversely related to AGD and SPL. However, the study is limited by small sample size and therefore was underpowered to detect conclusive differences between the 2 groups. Further studies in EDC exposure and genitourinary differences are warranted.