A cross-sectional retrospective passive epidemiological study for pediatric population aged 0–17 was performed using stratified random sampling. Children with hemodynamically significant congenital heart disease (CHD) in the period from 2005 to 2012 were identified using the official statistical database of the Department of Public Health in the Kemerovo region. In addition, a prospective study of 188 children with hemodynamically significant CHD admitted to the Department of Pediatric Cardiology at the Kemerovo Cardiology Dispensary was conducted. The average incidence of hemodynamically significant CHD in the large cities with 137Cs contaminated soil surface layers was significantly higher compared to that rate in the cities of the Kemerovo region, where the surface layers of intact soils are not contaminated with radioactive cesium (Tgr (av.) = +13.24 %; 95 % CI [9.25, 17.23] vs. Tgr (av.) = +5.31 %; 95 % CI [1.54, 9.07]; p < 0.05). Positive associations have been found between the risk of CHD in the next generation and the HLA- DRB1*11 and HLA-DRB1*03 allele in the female, the HLA-DRB1*07 allele in the male and a combination of HLA-DRB1*11 in the female and HLA-DRB1*01 in the male.