尿道下裂之母體、胎兒及環境風險因素：系統性回顧與統合分析

楊宏祥¹、楊宇祥^1,2

¹臺北市立萬芳醫院泌尿科－委託財團法人臺北醫學大學辦理

²臺北醫學大學泌尿學科

Maternal, Fetal, and Environmental Risk Factors for Hypospadias in Offspring: A Systematic Review and Meta-analysis

Hung-Hsiang Yang¹, Yu-Hsiang Yang^1,2

¹Department of Urology, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

²Department of Urology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

Background: Hypospadias is a common congenital anomaly in males, affecting approximately 1 in 150–300 live births. Its etiology is multifactorial, involving genetic and environmental factors. We aimed to evaluate maternal, fetal, and environmental risk factors associated with hypospadias.

Methods: We conducted a systematic review and meta-analysis of observational studies identified through PubMed, Embase, and the Cochrane Library up to May 2025. Cohort and case–control studies reporting odds ratios (ORs) were included. Adjusted odds ratios (aORs) were pooled using random-effects models and presented with 95% confidence intervals (CIs). Statistical significance was defined as p<0.05.

Results: A total of 174 studies, comprising 72,895 pregnancies, were analysed. Fetal growth restriction was associated with increased risk of hypospadias, including low birth weight (OR 1.68, 95% CI 1.45–1.94), prematurity (OR 1.44, 95% CI 1.28–1.63), and small for gestational age (OR 1.89, 95% CI 1.60–2.23). Maternal comorbidities, including pre-eclampsia (OR 1.62, 95% CI 1.35–1.94), hypertension (OR 1.51, 95% CI 1.28–1.79), diabetes (OR 1.47, 95% CI 1.25–1.73), and obesity (OR 1.36, 95% CI 1.18–1.57), were also associated with increased risk. Multiple gestations (OR 1.32, 95% CI 1.12–1.55) and advanced maternal age (>30 years; OR 1.20, 95% CI 1.08–1.34) were significant. Maternal alcohol use, proton pump inhibitors, and phenytoin exposure were associated with increased risk, whereas family history, in vitro fertilization, and gestational diabetes were not.

Conclusions: Hypospadias is associated with fetal growth restriction, maternal metabolic and hypertensive disorders, and selected environmental exposures. These findings support a multifactorial etiology involving placental dysfunction and endocrine disruption and may inform preventive strategies and targeted modification of modifiable maternal risk factors.