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

Ambreen Asim,Deepika Delsa Dean,Sarita Agarwal

doi:10.3390/pediatric14010015

Ambreen Asim, Deepika Delsa Dean + Show 1 more

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https://doi.org/10.3390/pediatric14010015

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Abstract

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

Highlights

Down syndrome (DS), called as trisomy 21, is caused due to maternal nondisjunction of chromosome 21
Maternal methylenetetrahydrofolate reductase (MTHFR) and methyltransferase reductase (MTRR) polymorphisms are involved in the occurrence of congenital heart defects (CHD) and DS in Indian population when controlling for periconceptional folic acid supplementation
In Group healthy control mothers (III), highest frequency was observed in participants taking folic acid supplementation compared to Group I (52%) and mothers of DS without CHD (II) (65%), which suggests that folic acid is associated with the occurrence of CHD in DS fetuses. (Table 2)

Summary

Introduction

Down syndrome (DS), called as trisomy 21, is caused due to maternal nondisjunction of chromosome 21. The maternal age and previous history of miscarriages are well-defined risk factors for DS. Few reports have showed the association of maternal age and previous history of miscarriages with CHD as well, respectively [5–10]. The same finding was reported in a study conducted in 2016 and 2018, respectively, where the authors reported that advanced maternal age is one of the important risk factors for developing CHD in DS [6,7]. Feng et al examined a relationship with maternal reproductive history and risk of developing CHD in DS. The authors identified previous history of miscarriages as one of the potential risk factors for developing CHD. Its association in combination with CHD and DS remains unexplored and speculative in the Indian population

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