Maternal Hypertension and Hypospadias in Offspring: A Systematic Review and Meta-Analysis

Background: Hypospadias is one of the most common congenital malformations. Hypertension and preeclampsia occur frequently during pregnancy, and several studies have reported an association between maternal hypertensive disorders and hypospadias in offspring. A systematic review and meta-analysis was conducted to comprehensively evaluate the relationship between maternal hypertensive disorders and hypospadias in offspring. Methods: A systematic search of peer-reviewed articles was conducted, and 15 articles meeting the eligibility criteria were included in the analysis. Pooled odds ratio (OR) estimates were calculated separately for hypertension and preeclampsia using meta-analysis. We also conducted several secondary analyses (e.g., studies conducted before versus after January 1, 1998, studies in the U.S. versus other countries, studies that accounted for ≥3 versus fewer or no potential confounders). Results: Significant positive associations were observed between hypospadias and hypertension (OR 1.68; 95% CI 1.46-1.93), as well as preeclampsia and hypospadias (OR 2.18; 95% CI 1.63-2.91). The direction and magnitude of effect was comparable for the majority of secondary analyses conducted. Conclusions: Our results indicate that maternal hypertensive disorders are associated with hypospadias in offspring. Further research is needed to better understand the mechanisms involved, and to ultimately develop public health strategies geared toward prevention of hypospadias