After adjustment for baseline data, the genetic polymorphisms of the maternal MTHFD1 gene at rs1950902 were shown to be significantly associated with a lower risk of VSD in offspring (GA vs. GG: aOR = 0.67, 95%CI: 0.50–0.90; the dominant model: aOR = 0.66, 95%CI: 0.50–0.88; the additive model: aOR = 0.76, 95%CI: 0.62–0.93). The gene discussed is MTHFD1; the disease is ventricular septal defect.