Maternal and Fetal Risk Factors for Hypospadias: A Nested Case-Control Study in Southern China

Background Hypospadias is a frequent congenital anomaly in male infants, defined by the urethral meatus opening on the ventral surface of the penis. Although its causes have been examined for many years, the underlying aetiology in most affected children remains unclear. Maternal factors such as pre-pregnancy body mass index (BMI), gestational weight gain, BMI at delivery and gestational diabetes mellitus (GDM) have been suggested as modifiable determinants, yet existing epidemiological studies report mixed and sometimes conflicting results. In this context, the present study aims to systematically evaluate maternal and foetal risk factors for hypospadias in order to clarify these uncertainties. Methods From 2019 to 2021, we carried out a nested case-control study in Hainan, China. The study included 96 infants with hypospadias and 480 male controls from Hainan Maternal and Child Health Hospital. We collected the demographic information and characteristics of mothers through face-to-face interviews and telephone interviews. Clinical data including childbirth outcomes and maternal complications were confirmed by consulting medical records. We compared the risk factors of the mother and the foetus in the offspring with and without hypospadias. Multi-factor logistic regression analysis is used to determine the independent risk factors of hypospadias. Results No associations of maternal weight before pregnancy, maternal body weight gain during pregnancy, BMI at delivery, maternal age, and HBV infection with hypospadias in offspring were observed. Maternal education, gestational hypertension, intrahepatic cholestasis of pregnancy, hypothyroidism, birth weight, and multiple pregnancies were independent risk factors for hypospadias in offspring. Conclusions Our findings indicate that maternal education,gestational hypertension, intrahepatic cholestasis of pregnancy, hypothyroidism, birth weight, and multiple pregnancies were associated with posterior hypospadias. Our findings may provide helpful guidance on developing targeted and effective hypospadias prevention programs and highlight potential differences in the genesis of hypospadias in the future.