A multifactorial assessment of the maternal status and the risk of down syndrome

A possible association of an impaired maternal micronutrient (especially folate/homocysteine/vitamin B12) metabolism to down syndrome (DS) risk and associated birth defects as suggested by several studies, together with the combined presence of two or more mutant alleles in the genome and the interaction of several factors of environmental, epigenetic and stochastic origin might affect disorder/associated birth defects risk. In order to shed light on the potential role if any, of micronutrients including folate, vitamin B12, Homocysteine metabolism to the non-disjunction of chromosome 21/DS risk and associated birth defects, we in this review have paralleled epidemiological studies by invitro and invivo studies. Literature survey was conducted using five databases: Pubmed, GoogleScholar, SCOPUS, Cochrane Library and Science Direct. Relevant studies conducted in different parts of the world have been included in the review article, which mostly focus on the role of micronutrients especially folic acid, vitamin B12 on the maternal health and its effect on the development of down syndrome and associated birth defects alongwith the combined interplay of maternal genetic and exposure status. Although, some putative DS/associated birth defect risk factors have been identified from the studies conducted so far, but it is now time to design and conduct studies large enough to split trisomy 21 and associated birth defects into their component parts and to test for the contribution of folate/Homocysteine gene polymorphisms to each of them. The article reviews studies demonstrating how parental particularly maternal micronutrient levels, genetic factors and environmental exposures can be used to estimate the risk of Down syndrome in a population. It emphasizes the role of micronutrients, specifically folate and vitamin B12, which are key components of the folate metabolism pathway, crucial for proper chromosomal segregation. Additionally, the article highlights the influence of environmental factors, such as parental smoking, alcohol consumption, oral contraceptive use and radiation exposure on the likelihood of Down syndrome births.