Maternal Risk Factors Triggering Congenital Heart Defects in Down Syndrome: A Case-Control Study

Objectives: Maternal MTHFR and MTRR polymorphisms as a risk of CHD in DS fetus were studied along with maternal folic acid supplementation, which could influence the folate metabolism along with other risk factors. Material and Methods: A case-control study comprising of mothers of DS with and without CHD along with controls were recruited from a tertiary care center since 2018–2019. Genomic DNA was isolated followed by PCR-RFLP. Results: Mothers with age ≥35 years and having history of miscarriages have a higher risk of giving birth to DS with CHD (n = 35% and 42%, respectively). Mothers who carried the MTHFR 677CT/TT and MTRR 524CT/TT genotypes combination in the folic acid nonusers group during pregnancies had six-fold (OR = 6.909, p-value = 0.027; 95% CI—1.23 ± 38.51) and four-fold (OR = 4.75, p-value = 0.040; 95% CI—1.067 ± 21.44) increased odds of having a DS child with CHD, respectively, as compared to folic acid users. Conclusion: Maternal age, folic acid supplementation, and previous history of miscarriages is involved in the etiology of CHD in DS fetus in Indian population. Maternal MTHFR and MTRR polymorphisms are also involved in the occurrence of CHD and DS in Indian population when controlling for periconceptional folic acid supplementation. Limitations: Single-Centered Study