Maternal hypertension and hypospadias in offspring: A systematic review and meta-analysis

Background: Several studies have reported an association between maternal hypertensive disorders and hypospadias in offspring; however there is still debate on the role of maternal hypertension and preeclampsia on this relatively common congenital malformation. Therefore, we conducted a systematic review and meta-analysis to comprehensively evaluate the relationship between these frequent maternal conditions and hypospadias in offspring. Methods: Fifteen articles meeting the eligibility criteria were identified in our search and included in the analysis. A meta-analysis was conducted and pooled odds ratio (OR) estimates were calculated separately for hypertension and preeclampsia using meta-analysis. We also conducted several secondary analyses, including (a) studies conducted before versus after January 1, 1998; (b) studies in United States versus other countries; and (c) studies that accounted for ≥3 versus fewer or no potential confounders, among others. Results: Significant positive associations were observed between hypertension and hypospadias (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 positively 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.