{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T08:42:51Z","timestamp":1788424971024,"version":"build-2803163510"},"reference-count":83,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T00:00:00Z","timestamp":1750291200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Key Project of the Regional Innovation and Development Joint Fund of the National Natural Science Foundation of China","award":["U23A20420"],"award-info":[{"award-number":["U23A20420"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Folic acid (FA) supplementation can effectively reduce the occurrence of neural tube defects (NTDs). Vitamin B12 is involved in folate metabolism; however, studies have not reached a definitive conclusion on the association between vitamin B12 and NTDs independent of folate levels. A systematic review and meta-analysis were performed to summarize existing research and investigate the effect of vitamin B12 on NTDs. Methods: Studies were systematically searched in PubMed, Web of Science, Embase, and Cochrane, published before 1 March 2024. Standardized mean difference (SMD) with 95% confidence interval (CI) was employed to assess the association between maternal vitamin B12 in blood and NTDs. Results: A total of 38 studies were included, with a total of 2316 NTDs and 4298 controls, covering 14 countries worldwide. Compared with the non-NTD group, the NTD group exhibited a lower vitamin B12 level [SMD = \u22120.23, 95% CI (\u22120.32, \u22120.14), p &lt; 0.001, I2 = 58.3%] with a statistically significant difference. Additionally, there was a significant association between maternal vitamin B12 concentration and NTDs when there was no significant difference in folate between the NTD and control groups [SMD: \u22120.19, 95% CI (\u22120.28, \u22120.10)]. Conclusions: Vitamin B12 supplement is also essential for the prevention of NTDs besides folic acid. Monitoring vitamin B12 concentration among pregnant women and considering appropriate supplementation with a combination of vitamin B12 and folic acid could be explored.<\/jats:p>","DOI":"10.3390\/nu17122040","type":"journal-article","created":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T05:08:39Z","timestamp":1750309719000},"page":"2040","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Beyond Folate: The Emerging Role of Maternal Vitamin B12 in Neural Tube Development"],"prefix":"10.3390","volume":"17","author":[{"given":"Lirong","family":"Nie","sequence":"first","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinru","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Public Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxue","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Health Education, Cangzhou City Center for Disease Prevention and Control, Cangzhou 061000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyang","family":"Ren","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-5511-1961","authenticated-orcid":false,"given":"Xiao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuwei","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7570-3809","authenticated-orcid":false,"given":"Zhiwen","family":"Li","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5844-8973","authenticated-orcid":false,"given":"Jufen","family":"Liu","sequence":"additional","affiliation":[{"name":"Institute of Reproductive and Child Health, National Health Commission Key Laboratory of Reproductive Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"},{"name":"Department of Epidemiology and Biostatistics, School of Public Health, Peking University, No 38 College Rd, Haidian District, Beijing 100191, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1485","DOI":"10.1056\/NEJM199911113412001","article-title":"Prevention of neural-tube defects with folic acid in China. 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