{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T15:25:35Z","timestamp":1791300335097,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T00:00:00Z","timestamp":1706745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To investigate the validity of the conclusion from Cochrane reviews and meta\u2010analyses that treatment with calcium supplementation during pregnancy reduces the risk for pre\u2010eclampsia by 55%, which has been influential in international guidelines and future research.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Sensitivity analysis of data from Cochrane reviews of trials evaluating high\u2010dose calcium supplementation (of at least 1\u2009g\/day) for reduction of pre\u2010eclampsia risk.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Systematic review and meta\u2010analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>The Cochrane reviews and meta\u2010analyses included 13 trials enrolling a total of 15\u2009730 women. Random\u2010effects meta\u2010analysis of these studies resulted in a mean risk ratio (RR, calcium\/placebo) of 0.45 (95% confidence interval [CI] 0.31\u20130.65; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We carried out a sensitivity analysis of evidence from the relevant Cochrane review, to examine the impact of study size.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main outcome measures<\/jats:title><jats:p>pre\u2010eclampsia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the three largest studies, accounting for 13\u2009815 (88%) of total recruitment, mean RR was 0.92 (95% CI 0.80\u20131.06) and there was no evidence of heterogeneity between studies (<jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090). With inclusion of the smaller studies, mean RR decreased to 0.45 and <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup> increased to 70%.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In assessment of the effect of calcium supplementation on pre\u2010eclampsia risk, the naive focus on the mean of the random\u2010effects meta\u2010analysis in the presence of substantial heterogeneity is highly misleading.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.17769","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T04:19:30Z","timestamp":1706847570000},"page":"1524-1529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Calcium supplementation for the prevention of pre\u2010eclampsia: Challenging the evidence from meta\u2010analyses"],"prefix":"10.1111","volume":"131","author":[{"given":"David","family":"Wright","sequence":"first","affiliation":[{"name":"Institute of Health Research University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Wright","sequence":"additional","affiliation":[{"name":"Institute of Health Research University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1355-610X","authenticated-orcid":false,"given":"Laura A.","family":"Magee","sequence":"additional","affiliation":[{"name":"School of Life Course and Population Sciences, Institute of Women and Children's Health King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4136-3070","authenticated-orcid":false,"given":"Peter","family":"Von\u00a0Dadelszen","sequence":"additional","affiliation":[{"name":"School of Life Course and Population Sciences, Institute of Women and Children's Health King's College London  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-0711","authenticated-orcid":false,"given":"Kypros H.","family":"Nicolaides","sequence":"additional","affiliation":[{"name":"Fetal Medicine Research Institute King's College Hospital  London 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