Maternal and fetal risk factors for hypospadias: a hospital-based case-control study in Southern China

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 factors independently associated with hypospadias, yet existing epidemiological studies report mixed and sometimes conflicting results. In this context, the present study aims to systematically evaluate maternal and fetal risk factors for hypospadias to help resolve these uncertainties. From 2019 to 2021, a retrospective hospital-based case-control study was carried out in Hainan, China. Women delivering newborns with hypospadias were enrolled as cases, while women delivering normal newborns were randomly selected as controls. The study included 96 infants with hypospadias and 480 male controls from Hainan Maternal and Child Health Hospital. Maternal demographic and clinical characteristics were extracted from archived clinical records; the relevant information was originally collected via face-to-face or telephone communication as part of routine clinical care. Clinical data pertaining to birth outcomes and maternal complications were verified from medical records. We compared maternal and fetal characteristics between offspring with and without hypospadias. Multivariable conditional logistic regression was performed to identify factors independently associated with hypospadias. No associations of maternal weight before pregnancy, maternal body weight gain during pregnancy, BMI at delivery, maternal age, and Hepatitis B Virus (HBV) infection with hypospadias in offspring were observed. Maternal education (aOR 0.35, 95% CI 0.18-0.68 and aOR 0.18, 95% CI 0.07-0.50), gestational hypertension (aOR 6.27, 95% CI 2.44-16.13), intrahepatic cholestasis of pregnancy (aOR 13.86, 95% CI 3.00-64.03), hypothyroidism (aOR 16.63, 95% CI 5.01- 55.20), birth weight (aOR 19.07, 95% CI 6.58- 55.25) and multiple gestation (aOR 7.89, 95% CI 1.05-59.48) were independently associated with hypospadias in offspring. These findings may help generate hypotheses regarding maternal and fetal characteristics associated with hypospadias and warrant confirmation in larger prospective studies.