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Methods Major online databases, namely PubMed, Scopus, and Web of Science, were searched up to April 24, 2015 using the following terms: folate, polymorphisms, gene variant, genetic variant, homocysteine, congenital heart defects, and Down syndrome. Only peer-reviewed case-control studies showing demographic data of case and control mothers, and tabular data of allele and genotype frequencies, have been considered for this review and included in Tables 1, 3, 4

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No consistent serious adverse events have emerged in limited case series

Glossary of Key Terms All reference links valid and accessible on 30 June 2026 5