{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T19:35:10Z","timestamp":1775072110622,"version":"3.50.1"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T00:00:00Z","timestamp":1708387200000},"content-version":"vor","delay-in-days":50,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003819","name":"Hubei Provincial Natural Science Foundation","doi-asserted-by":"publisher","award":["2022CFB200"],"award-info":[{"award-number":["2022CFB200"]}],"id":[{"id":"10.13039\/501100003819","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Research & Developmental Program","award":["2022BCA042"],"award-info":[{"award-number":["2022BCA042"]}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2042022gf0007"],"award-info":[{"award-number":["2042022gf0007"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012226","name":"Fundamental Research Funds for the Central Universities","doi-asserted-by":"publisher","award":["2042022kf1210"],"award-info":[{"award-number":["2042022kf1210"]}],"id":[{"id":"10.13039\/501100012226","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Interdisciplinary Innovative Talents Foundation","award":["JCRCWL-2022-001"],"award-info":[{"award-number":["JCRCWL-2022-001"]}]},{"name":"Interdisciplinary Innovative Talents Foundation","award":["JCRCYG-2022-009"],"award-info":[{"award-number":["JCRCYG-2022-009"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Is there a causal relationship between 25-hydroxyvitamin D (25OHD) and miscarriage?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>In this study, little evidence of a causal relationship was found between low serum 25OHD concentration or vitamin D deficiency and the risk of miscarriages.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>Associations between low vitamin D levels and increased risk of miscarriage have been reported, but causality is unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>The latest and largest genome-wide association studies (GWAS) for serum 25OHD concentration (n\u2009=\u2009417\u00a0580), vitamin D deficiency (426 cases and 354\u00a0812 controls), miscarriage (16\u00a0906 cases and 149\u00a0622 controls), and the number of miscarriages (n\u2009=\u200978\u00a0700) were used to explore the causal association between serum vitamin D levels and miscarriage by two-sample Mendelian randomization analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>This study was based on summary GWAS results from the FinnGen database and the UK Biobank. The random-effect inverse-variance weighted method was regarded as the primary analysis; MR-Egger, weighted median, weighted mode, simple mode, and MR-pleiotropy residual sum and outlier (MR-PRESSO) were further employed as complementary methods. MR-Egger intercept analysis and MR-PRESSO were employed to test pleiotropy, and Cochran\u2019s Q statistic and leave-one-out sensitivity analysis were used to determine the heterogeneity and robustness of the overall estimates, respectively.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>There was insufficient evidence of causal associations between serum 25OHD concentration and miscarriage (odds ratio (OR) = 0.995, 95% CI: 0.888 to 1.114, P\u2009=\u20090.927), or the number of miscarriages (\u03b2 = \u20130.004, 95% CI: \u20130.040 to 0.032, P\u2009=\u20090.829). Furthermore, little evidence of causality between genetically determined vitamin D deficiency to miscarriage (OR = 0.993, 95% CI: 0.966 to 1.021, P\u2009=\u20090.624), or the number of miscarriages (\u03b2 = 0.001, 95% CI: \u22120.009 to 0.011, P\u2009=\u20090.828), was observed. The results of the sensitivity analysis were robust, and no significant heterogeneity or horizontal pleiotropy was found.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>This study is limited by the absence of female-specific GWAS data and the limited amount of GWAS data available for this study, as well as the need for caution in generalizing the findings to non-European ethnic groups.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>These findings enhance the current understanding of the intricate association between vitamin D and pregnancy outcomes, challenging prevailing beliefs regarding the strong association with miscarriage. The results provide a special perspective that may prompt further exploration and potentially offer insights for guiding future research and informing clinical guidelines pertaining to the management of miscarriage.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>This project was supported by the Hubei Provincial Natural Science Foundation Program General Surface Project (2022CFB200), the Key Research &amp; Developmental Program of of Hubei Province (2022BCA042), the Fundamental Research Funds for the Central Universities (2042022gf0007, 2042022kf1210), and the Interdisciplinary Innovative Talents Foundation from Renmin Hospital of Wuhan University (JCRCWL-2022-001, JCRCYG-2022-009). All authors have no conflicts of interest to declare.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                  <jats:p>N\/A.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/hropen\/hoae011","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T02:35:32Z","timestamp":1708396532000},"source":"Crossref","is-referenced-by-count":9,"title":["No evidence of a causal relationship between miscarriage and 25-hydroxyvitamin D: a Mendelian randomization study"],"prefix":"10.1093","volume":"2024","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0326-5365","authenticated-orcid":false,"given":"Feng","family":"Zhang","sequence":"first","affiliation":[{"name":"Reproductive Medical Center, Renmin Hospital of Wuhan University , Wuhan, Hubei, 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