{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:45:10Z","timestamp":1789591510063,"version":"build-2803163510"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>To determine whether the reported 0%\u201370% prevalence of vitamin B12 deficiency in sickle cell disease (SCD) reflects true population variation or diagnostic misclassification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a PRISMA 2020\u2010compliant systematic review of observational studies (January 1, 2000\u2013May 13, 2026; PROSPERO CRD420251087800) assessing B12 status in SCD. PubMed, AJOL, and Google Scholar were searched with citation tracking and dual screening. Diagnostic validity was assessed across biomarker strategy, analytical platform, thresholds, and confounder control using a proposed context\u2010integrated framework to classify methodological robustness and discordance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Fourteen studies were included (57% high\u2010income; 43% LMIC). The evidence base was dominated by limited diagnostic approaches: 71% used immunoassays, over one\u2010third relied on circulating B12 alone, and functional biomarkers were inconsistently applied without systematic confounder adjustment. Prevalence estimates were strongly influenced by diagnostic methods rather than underlying population biology, ranging from 0% to 70% in single\u2010marker studies (mostly 0%\u20137.1%, with outliers ~50%\u201370%) and 6.9%\u201353% in multi\u2010marker studies. Discordance was substantial and greater in LMIC settings than HIC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Current diagnostic approaches in SCD appear method\u2010dependent, generating heterogeneous prevalence estimates with uncertain clinical validity. These findings challenge existing estimates and have implications for clinical practice, research design, and diagnostic equity.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>Trial Registration:<\/jats:bold>\n                      ClinicalTrials.gov identifier: CRD420251087800\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ejh.70256","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T01:36:58Z","timestamp":1782437818000},"page":"880-891","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Vitamin\n                    <scp>B12<\/scp>\n                    Deficiency in Sickle Cell Disease: Method\u2010Driven Estimates and Systematic Diagnostic Misclassification"],"prefix":"10.1111","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-4126","authenticated-orcid":false,"given":"Tarimoboere","family":"Agbalalah","sequence":"first","affiliation":[{"name":"Medical Biotechnology Department National Biotechnology Development Agency  Abuja Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8773-5944","authenticated-orcid":false,"given":"Adekunle","family":"Rowaiye","sequence":"additional","affiliation":[{"name":"Agricultural Biotechnology Department National Biotechnology Development Agency  Abuja Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances","family":"Iseghohi","sequence":"additional","affiliation":[{"name":"Medical Biotechnology Department National Biotechnology Development Agency  Abuja 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