Hypospadias risk associated with chronic hypertension during pregnancy: A systematic review and meta-analysis

Introduction Previous studies have suggested that hypertensive disorders of pregnancy increase risk of hypospadias, but so far none have focused on the influence of maternal chronic hypertension (CH). This study aimed to conduct a systematic review and meta- analysis of currently available observational data to assess the association of maternal CH with hypospadias risk. Methods Literature searches were performed using EMBASE, SCOPUS, Pubmed, and manual methods according to PRISMA 2020 guidelines and MOOSE checklist. Eligible articles were included in the study and assessed for quality using the Newcastle-Ottawa Scale (NOS). Extracted data were presented in review tables. Pooled analysis for unadjusted and adjusted effect sizes was used to determine OR and 95%CI using DerSimonian and Laird model. Heterogeneity was tested using I2 test, and publication bias was examined using funnel plots. Sensitivity analyses are done to address uncertainties. Results Searches yielded a total of 1130 publications with six eligible studies and high NOS quality score (6-9) were selected as depicted in extended summary figure. There were 519 hypospadias patients with maternal CH among those six eligible studies for analysis. After sensitivity analysis, there is one study that is excluded due to different hypospadias definition. Among the 5 remaining studies, it is found that there is an elevated risk of hypospadias in the context of maternal CH as determined by pooled unadjusted and adjusted OR (OR 1.50 95%CI 1.17-1.93; aOR 1.77 95%CI 1.54-2.04 respectively). Heterogeneity was high in unadjusted pooled analysis (I2 = 73% P = 0.005) and low in adjusted analysis (I2 = 0% P = 0.40)). Funnel plots were symmetrical in both analyses indicating a lack of publication bias. Conclusions This meta-analysis indicates that maternal CH increases risk of hypospadias in male offspring. Future studies should weigh in biological mechanisms and pharmacological effects to elaborate the pathogenesis of this association.