{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T04:23:20Z","timestamp":1783571000018,"version":"3.55.0"},"reference-count":64,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Intl J of Devlp Neuroscience"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Neural tube defects (NTDs) are birth defects that arise during embryogenesis when normal neural tube closure fails to occur. According to the World Health Organization, NTDs are detected annually in approximately 300,000 neonates worldwide. The exact etiology of NTDs remains complex and poorly understood. It is generally agreed that most NTD cases are of multifactorial origin, having a combination of multiple genes and a number of environmental risk factors. The role of folic acid, vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs, has also been extensively studied. This knowledge synthesis brings together different types of evidence to update the role of vitamin B12 deficiency, genetics and other risk factors, in the etiology of NTDs. Following a PubMed search and screening for relevant articles, we included 40 studies in our review (30 case\u2013control studies, 3 cross\u2010sectional studies, 5 cohort studies, and 2 case reports). The available data showed that vitamin B12 levels were decreased in mothers and infants in NTD groups compared with control groups. Holo\u2010transcobalamin, the active form of vitamin B12, was also found in lower levels in mothers with NTD\u2010affected infants. Several studies reported elevated homocysteine levels in mothers and infants in NTD groups. Additionally, numerous studies reported links between genetic variants and increased NTD risk. These genes include GIF, LRP2, CUBN, TCb1R, MTHFR, and others. Several maternal factors have also been linked with significant NTD risk such as BMI, maternal diet, air pollutants, low maternal age, and many others. The majority of studies on NTDs have focused on the role of folic acid, hence there is a need for well\u2010designed studies on the role of other risk factors like vitamin B12 deficiency in the etiology of NTDs.<\/jats:p>","DOI":"10.1002\/jdn.10113","type":"journal-article","created":{"date-parts":[[2021,4,14]],"date-time":"2021-04-14T10:15:12Z","timestamp":1618395312000},"page":"386-406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The role of Vitamin B12 and genetic risk factors in the etiology of neural tube defects: A systematic review"],"prefix":"10.1002","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5853-8987","authenticated-orcid":false,"given":"Farah","family":"Wahbeh","sequence":"first","affiliation":[{"name":"Division of Medical Education Weill Cornell Medicine \u2013 Qatar  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5905-0027","authenticated-orcid":false,"given":"Mange","family":"Manyama","sequence":"additional","affiliation":[{"name":"Division of Medical Education Weill Cornell Medicine \u2013 Qatar  Doha Qatar"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1515\/jomb-2017-0051"},{"issue":"22","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1080\/14767058.2019.1623778","article-title":"Neural tube defects in eastern Turkey; Is low folate status or vitamin B12 deficiency or both associated with a high rate of NTDs?","volume":"33","author":"Ayaz R.","year":"2019","journal-title":"Journal of Maternal\u2010Fetal & Neonatal Medicine"},{"issue":"22","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"3835","DOI":"10.1080\/14767058.2019.1623778","article-title":"Neural tube defects in eastern Turkey; Is low folate status or vitamin B12 deficiency or both associated with a high rate of NTDs?","volume":"33","author":"Ayaz R.","year":"2019","journal-title":"Journal of Maternal\u2010Fetal & Neonatal Medicine"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3906\/sag-1502-128"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.3109\/09513590.2012.730571"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/aje\/kwr254"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/ppe.12123"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1001\/archpediatrics.2011.185"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.3109\/09513591003632183"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2013.01.022"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.2643"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1373"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1159\/000348463"},{"issue":"2","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1159\/000350393","article-title":"Maternal obesity and pre\u2010pregnancy folic acid supplementation","volume":"6","author":"Farah N.","year":"2013","journal-title":"Obesity Facts"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/ajcn\/nqy340"},{"issue":"2","key":"e_1_2_11_17_1","first-page":"211","article-title":"Magnitude of neural tube defects and associated risk factors at three teaching hospitals in Addis Ababa","volume":"6","author":"Gedefaw A.","year":"2018","journal-title":"Ethiopia. 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