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Adequate maternal folate supplementation has been widely acknowledged for its pivotal role in promoting cell proliferation and preventing neural tube defects. However, in the post-fortification era, there has been a rising concern regarding an excess maternal intake of folic acid (FA), the synthetic form of folate. In this review, we focused on recent advancements in understanding the influence of excess maternal FA intake on offspring. For human studies, we summarized findings from clinical trials investigating the effects of periconceptional FA intake on neurodevelopment and molecular-level changes in offspring. For studies using mouse models, we compiled the impact of high maternal FA supplementation on gene expression and behavioral changes in offspring. In summary, excessive maternal folate intake could potentially have adverse effects on offspring. Overall, we highlighted concerns regarding elevated maternal folate status in the population, providing a comprehensive perspective on the potential adverse effects of excessive maternal FA supplementation on offspring.<\/jats:p>","DOI":"10.3390\/nu16050755","type":"journal-article","created":{"date-parts":[[2024,3,7]],"date-time":"2024-03-07T11:33:06Z","timestamp":1709811186000},"page":"755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Risk of Excess Maternal Folic Acid Supplementation in Offspring"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6862-7545","authenticated-orcid":false,"given":"Xiguang","family":"Xu","sequence":"first","affiliation":[{"name":"Epigenomics and Computational Biology Lab, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061, USA"},{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Epigenomics and Computational Biology Lab, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061, USA"},{"name":"Department of Human Development and Family Science, College of Liberal Arts and Human Sciences, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Epigenomics and Computational Biology Lab, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061, USA"},{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA"},{"name":"Genetics, Bioinformatics and Computational Biology Program, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5739-1653","authenticated-orcid":false,"given":"Hehuang","family":"Xie","sequence":"additional","affiliation":[{"name":"Epigenomics and Computational Biology Lab, Fralin Life Sciences Institute, Virginia Tech, Blacksburg, VA 24061, USA"},{"name":"Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA 24061, USA"},{"name":"Genetics, Bioinformatics and Computational Biology Program, Virginia Tech, Blacksburg, VA 24061, USA"},{"name":"Translational Biology, Medicine, and Health Program, Virginia Tech, Blacksburg, VA 24061, USA"},{"name":"School of Neuroscience, Virginia Tech, Blacksburg, VA 24061, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S22","DOI":"10.1177\/15648265100311S103","article-title":"Fortification of flour with folic acid","volume":"31","author":"Berry","year":"2010","journal-title":"Food Nutr. 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