MTHFR and folate deficiency: Several factors have been identified as potential contributors to the prevalence of NTDs, encompassing parental history of NTDs, prior occurrence of such defects in a sibling, folic acid deficiency, genetic predispositions such as MTHFR gene defects and homocysteinemia, low socioeconomic status, and maternal use of certain medications, including antiepileptics like carbamazepine and valproate as well as drugs such as isotretinoin, aminopterin, thalidomide, and methotrexate.