{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T17:48:39Z","timestamp":1793468919797,"version":"4.5.0"},"reference-count":85,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2025,10,31]],"date-time":"2025-10-31T00:00:00Z","timestamp":1761868800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention \u201cLong-term health effects of early-life interventions in family cohorts\u201d","award":["20232701"],"award-info":[{"award-number":["20232701"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Objectives: Maternal folic acid supplementation is recommended to prevent neural tube defects (NTDs), yet its influence on offspring neurodevelopmental disorders (NDDs) remains uncertain. This umbrella review aims to evaluate whether maternal folic acid supplementation before and\/or during pregnancy affects the risk of NDDs. Methods: We conducted a systematic search in MEDLINE, Cochrane Library, EMBASE, PubMed, and Web of Science from inception to 30 June 2025, to identify systematic reviews (SRs) and meta-analyses (MAs) that synthesized evidence from non-randomized studies on maternal folic acid supplementation and NDDs. Methodological quality was assessed using the AMSTAR-2 assessment and evidence certainty using the GRADE framework. Results: A total of 23 SRs\/MAs were included, of which 14 did not perform meta-analysis. Most included SRs\/MAs were methodologically limited, with 50.00% rated as very low quality and only 36.37% achieving high or moderate quality. MAs indicated a protective effect of supplementation, with odds ratio (OR) of 0.66 (95% confidence interval (CI): 0.55\u20130.79) for autism spectrum disorder (ASD), 0.86 (95% CI: 0.78\u20130.95) for attention-deficit\/hyperactivity disorder (ADHD), and 0.75 (95% CI: 0.63\u20130.91) for behavioral problems. No significant associations were found for motor, intellectual\/cognitive, or language development. SRs reported inconsistent conclusions across most outcomes. Conclusions: In summary, maternal folic acid supplementation may reduce the risk of ASD, ADHD, and behavioral problems in offspring. Although the current evidence is of low quality, supplementation guidelines are justified by the well-established benefits for NTDs. Further research is required to address remaining uncertainties.<\/jats:p>","DOI":"10.3390\/nu17213443","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T14:00:33Z","timestamp":1762178433000},"page":"3443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Effect of Maternal Folic Acid Supplementation on Neurodevelopmental Disorders in Offspring: An Umbrella Review of Systematic Reviews and Meta-Analyses"],"prefix":"10.3390","volume":"17","author":[{"given":"Miao","family":"Yu","sequence":"first","affiliation":[{"name":"School of Public Health, Inner Mongolia Medical University, Hohhot 010110, China"},{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Hu","sequence":"additional","affiliation":[{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Hou","sequence":"additional","affiliation":[{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaomin","family":"Wu","sequence":"additional","affiliation":[{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangxin","family":"Chen","sequence":"additional","affiliation":[{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China"},{"name":"School of Public Health, Baotou Medical College, Inner Mongolia University of Science & Technology, Baotou 014040, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruohan","family":"Yan","sequence":"additional","affiliation":[{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China"},{"name":"School of Public Health, Tianjin Medical University, Tianjin 300070, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Dong","sequence":"additional","affiliation":[{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China"},{"name":"School of Public Health, China Medical University, Shenyang 110000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[{"name":"National Center for Chronic and Noncommunicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,31]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025, June 08). 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