WITHDRAWN: The impact of folic acid supplementation in early to mid-pregnancy on the risk of hypertensive disorders of pregnancy: The Japan Environment and Children’s Study

doi:10.21203/rs.3.rs-8170068/v1

WITHDRAWN: The impact of folic acid supplementation in early to mid-pregnancy on the risk of hypertensive disorders of pregnancy: The Japan Environment and Children’s Study

2025 · doi:10.21203/rs.3.rs-8170068/v1

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Abstract

Abstract Background Hypertensive disorders of pregnancy (HDP) are potentially life-threatening conditions for both the pregnant woman and fetus with long-term effects on maternal health, and while folic acid supplementation has been suggested to reduce the risk of HDP, current epidemiological evidence remains inconclusive. This study evaluated the impact of folic acid supplementation on the risk of HDP and postpartum hypertension in a large-scale prospective cohort study within the Japanese population. Methods Data were obtained from the national birth cohort of the Japan Environment and Children's Study (JECS), collected between 2011 and 2014. Crude and adjusted binomial logistic regression analyses were performed to assess the association between maternal folic acid supplementation during pregnancy and HDP as well as postpartum hypertension. HDP was further classified according to onset timing as early-onset (Eo) or late-onset (Lo), and multinomial logistic regression was applied to examine these subtypes. Results A total of 89,683 pregnant women were included in the analysis. Compared with the non-supplementation group, participants who took folic acid supplements from early to mid-pregnancy exhibited a significantly lower incidence of HDP (adjusted odds ratio [aOR]: 0.87, 95% confidence interval [CI]: 0.79–0.96). Furthermore, the incidence of postpartum hypertension was significantly lower in the supplementation group (aOR: 0.86, 95% CI: 0.80–0.93). In additional analysis where HDP was classified into Eo and Lo, a reduced risk was observed for Lo HDP (aOR: 0.88, 95% CI: 0.80–0.96), whereas no significant association was identified for Eo HDP (aOR: 0.89, 95% CI: 0.76–1.05). Conclusions Folic acid supplementation during pregnancy was inversely associated with the incidence of HDP, particularly Lo HDP. Furthermore, it may contribute to the prevention of postpartum hypertension. In addition to its established role in preventing neural tube defects, continuous folic acid supplementation before conception may be beneficial for maintaining maternal health throughout pregnancy and the postpartum period.

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WITHDRAWN: The impact of folic acid supplementation in early to mid-pregnancy on the risk of hypertensive disorders of pregnancy: The Japan Environment and Children’s Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article WITHDRAWN: The impact of folic acid supplementation in early to mid-pregnancy on the risk of hypertensive disorders of pregnancy: The Japan Environment and Children’s Study Akira Oku, Yoshihiro Saito, Hiroyoshi Iwata, Sachiko Itoh, Ami Hosokawa, and 8 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8170068/v2 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 06 Mar, 2026 Read the published version in BMC Pregnancy and Childbirth → Version 2 posted You are reading this latest preprint version Show more versions Editorial Note The full text of this preprint has been withdrawn by the authors in order to comply with an institutional policy on preprints. Therefore, the authors do not wish this work to be cited as a reference. Editorial notes are used to provide important context regarding the topic of a preprint or to alert readers to potential issues concerning that preprint or a downstream publication associated with it. For more information on editorial notes, see our Editorial Policies . Abstract The full text of this preprint has been withdrawn by the authors in order to comply with an institutional policy on preprints. Therefore, the authors do not wish this work to be cited as a reference. Full Text The authors have withdrawn this preprint from Research Square. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 06 Mar, 2026 Read the published version in BMC Pregnancy and Childbirth → Version 2 posted You are reading this latest preprint version Show more versions Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. 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