{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T14:46:07Z","timestamp":1767797167364,"version":"3.49.0"},"reference-count":21,"publisher":"BMJ","issue":"12","license":[{"start":{"date-parts":[[2025,12,29]],"date-time":"2025-12-29T00:00:00Z","timestamp":1766966400000},"content-version":"unspecified","delay-in-days":28,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"The Science Foundation of Lanzhou University","award":["071100107"],"award-info":[{"award-number":["071100107"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,11,30]]},"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Folic acid is crucial for fetal development, particularly during early pregnancy. Studies suggest that high folic acid intake (\u2265800\u2009\u00b5g\/day) may be associated with a reduced risk of miscarriage. However, the impact of an 800\u2009\u00b5g dose on pregnancy outcomes in women with prior pregnancy loss currently remains unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>We will conduct a multi-centre randomised controlled study comparing 800\u2009\u00b5g and 400\u2009\u00b5g in women with previous pregnancy loss. The primary outcome is live birth. Secondary outcomes include early pregnancy loss, ongoing pregnancy at 24 gestation weeks, homocysteine (Hcy) reduction, maternal and perinatal outcomes. We plan to recruit 1116\u2009women (558\u2009women per group). Data analysis will follow the intention-to-treat principle and per-protocol. Subgroup analysis will be conducted based on Hcy levels, previous pregnancy losses and body mass index.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>ChiCTR2500100255.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-108858","type":"journal-article","created":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T06:30:28Z","timestamp":1767076228000},"page":"e108858","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of different folic acid supplementation doses on subsequent pregnancy outcomes in women with a history of pregnancy loss: study protocol for a multicentre randomised controlled trial"],"prefix":"10.1136","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-4099-3796","authenticated-orcid":false,"given":"Cai","family":"Liu","sequence":"first","affiliation":[{"name":"Department of Reproductive medicine, Lanzhou University Second Hospital, Lanzhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3566-8697","authenticated-orcid":false,"given":"Zhuhua","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The Third Affiliated Hospital of Wenzhou Medical University, Ruian, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lirong","family":"Du","sequence":"additional","affiliation":[{"name":"Hebei Key Laboratory of Reproductive Medicine, Hebei Reproductive Health Hospital, Shijiazhuang, Hebei, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhou","family":"Fang","sequence":"additional","affiliation":[{"name":"Reproductive Medical Center, Shandong University of Traditional Chinese Medicine, Jinan, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongjun","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Qilu Hospital of Shandong University Dezhou Hospital, Dezhou, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haiyan","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Pingliang Second People\u2019s Hospital, Pingliang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics, Tianshui First People\u2019s Hospital, Tianshui, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aiqin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Zhangye Second People\u2019s Hospital, Zhangye, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynaecology and Obstetrics, Longxi County Hospital of Traditional Chinese Medicine, Dingxi, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ran","family":"An","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiaohua","family":"He","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine, Henan Provincial People\u2019s Hospital, Zhengzhou, 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China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2025,12,29]]},"reference":[{"key":"2026010703491486000_15.12.e108858.1","article-title":"ESHRE guideline: recurrent pregnancy loss: an update in 2022","volume":"2023","author":"Bender Atik","year":"2023","journal-title":"Hum Reprod Open"},{"key":"2026010703491486000_15.12.e108858.2","doi-asserted-by":"crossref","first-page":"830","DOI":"10.1093\/humrep\/dead040","article-title":"Prevalence, causes, and impact of non-visualized pregnancy losses in a recurrent pregnancy loss population","volume":"38","author":"Bedaiwy","year":"2023","journal-title":"Hum Reprod"},{"key":"2026010703491486000_15.12.e108858.3","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)00682-6"},{"key":"2026010703491486000_15.12.e108858.4","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1097\/AOG.0000000000000859","article-title":"A national survey on public perceptions of 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