{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:11:17Z","timestamp":1772169077707,"version":"3.50.1"},"reference-count":30,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2022,1,18]],"date-time":"2022-01-18T00:00:00Z","timestamp":1642464000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004440","name":"Wellcome","doi-asserted-by":"publisher","award":["220225\/Z\/20\/Z"],"award-info":[{"award-number":["220225\/Z\/20\/Z"]}],"id":[{"id":"10.13039\/100004440","id-type":"DOI","asserted-by":"publisher"}]},{"name":"MRC Unit The Gambia"},{"name":"Joint Global Health Trials","award":["MRT003960\/1"],"award-info":[{"award-number":["MRT003960\/1"]}]}],"content-domain":{"domain":["wellcomeopenresearch.org"],"crossmark-restriction":false},"short-container-title":["Wellcome Open Res"],"abstract":"<ns3:p>\n                    <ns3:bold>Background:<\/ns3:bold>\n                    A recent analysis showed that plasma iron concentrations decline rapidly from birth in Gambian infants, irrespective of sex or birthweight, to concentrations well below normal expected values for iron-replete children older than two months of age (typically &gt;10 \u03bcmol\/L). The development and function of neural and immune cells may thus be compromised before the minimum age at which children should receive iron supplementation as per World Health Organisation recommendations.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Methods:<\/ns3:bold>\n                    This study is a two-arm, double-blind, placebo-controlled, randomised superiority trial. Infants will be randomised to receive iron drops (7.5mg\/day of iron as ferrous sulphate) or placebo daily for 98 days, to test the impact on serum iron concentrations in healthy, breastfed infants (n = 100) aged 6-10 weeks at enrolment. Participants will be visited daily and supplemented by the field team. Daily health and weekly breastfeeding questionnaires will be administered. Anthropometry, and venous blood and faecal samples will be collected at enrolment and after 98 days of supplementation with serum iron as the primary endpoint. Low birthweight (less than 2.5kg at birth) and infants born prematurely (&lt; 37 weeks) will not be excluded. Formula-fed and infants with any illness will be excluded. An additional study exploring maternal stakeholder perspectives of the intervention will be conducted by means of maternal interviews and four focus group discussions with local stakeholders.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Discussion:<\/ns3:bold>\n                    Most breast-fed Gambian infants have very low circulating iron levels by five months of age. This study will introduce iron supplements much earlier in infancy than has previously been attempted in a low-income setting with the primary aim of increasing serum iron concentration.\n                  <\/ns3:p>\n                  <ns3:p>\n                    <ns3:bold>Trial registration:<\/ns3:bold>\n                    Clincaltrials.gov (\n                    <ns3:ext-link xmlns:ns4=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" ns4:href=\"https:\/\/clinicaltrials.gov\/ct2\/show\/NCT04751994\">NCT04751994<\/ns3:ext-link>\n                    ); 12\n                    <ns3:sup>th<\/ns3:sup>\n                    February 2021\n                  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A.","family":"Silverio","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hans","family":"Verhoef","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ebrima","family":"Comma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew M.","family":"Prentice","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1650-3238","authenticated-orcid":false,"given":"Sophie 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Cusick","year":"2018","journal-title":"Nutrients."},{"key":"ref-3","doi-asserted-by":"publisher","first-page":"89-106","DOI":"10.1111\/nyas.12314","article-title":"Issues in the timing of integrated early interventions: contributions from nutrition, neuroscience, and psychological research.","volume":"1308","author":"T Wachs","year":"2014","journal-title":"Ann N Y Acad Sci."},{"key":"ref-4","doi-asserted-by":"publisher","first-page":"e336-45","DOI":"10.1542\/peds.2006-2525","article-title":"An event-related potential study of attention and recognition memory in infants with iron-deficiency anemia.","volume":"120","author":"M Burden","year":"2007","journal-title":"Pediatrics."},{"key":"ref-5","doi-asserted-by":"publisher","first-page":"1588s-93s","DOI":"10.3945\/ajcn.117.155846","article-title":"Iron assessment to protect the developing brain.","volume":"106","author":"M Georgieff","year":"2017","journal-title":"Am J Clin 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A methodological study of sample-size reporting in focus group studies.","volume":"11","author":"B Carlsen","year":"2011","journal-title":"BMC Med Res Methodol."},{"key":"ref-15","doi-asserted-by":"publisher","first-page":"623-30","DOI":"10.1046\/j.1365-2648.1997.t01-25-00999.x","article-title":"Sampling in qualitative research. Purposeful and theoretical sampling; merging or clear boundaries?","volume":"26","author":"I Coyne","year":"1997","journal-title":"J Adv Nurs."},{"key":"ref-16","doi-asserted-by":"crossref","first-page":"7-19","DOI":"10.7748\/nr2004.07.12.1.7.c5927","article-title":"Sampling issues in qualitative research.","volume":"12","author":"G Higginbottom","year":"2004","journal-title":"Nurse Res."},{"key":"ref-17","doi-asserted-by":"publisher","first-page":"69-71","DOI":"10.1016\/j.earlhumdev.2019.03.016","article-title":"WASP (Write a Scientific Paper): Sampling in qualitative research.","volume":"133","author":"B Farrugia","year":"2019","journal-title":"Early Hum Dev."},{"key":"ref-18","doi-asserted-by":"publisher","first-page":"671-81, vi","DOI":"10.1016\/j.hoc.2014.04.005","article-title":"Anemia of inflammation.","volume":"28","author":"E Nemeth","year":"2014","journal-title":"Hematol Oncol Clin North Am."},{"key":"ref-19","doi-asserted-by":"publisher","first-page":"S5-S11","DOI":"10.1002\/jpen.1468","article-title":"Characterizing Exclusively Breastfed Infant Stool via a Novel Infant Stool Scale.","volume":"42 Suppl 1","author":"J Gustin","year":"2018","journal-title":"JPEN J Parenter Enteral Nutr."},{"key":"ref-20","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1186\/s12913-017-2031-8","article-title":"Acceptability of healthcare interventions: an overview of reviews and development of a theoretical framework.","volume":"17","author":"M Sekhon","year":"2017","journal-title":"BMC Health Serv Res."},{"key":"ref-21","doi-asserted-by":"publisher","first-page":"202-22","DOI":"10.1080\/14780887.2014.955224","article-title":"The Utility of Template Analysis in Qualitative Psychology Research.","volume":"12","author":"J Brooks","year":"2015","journal-title":"Qual Res Psychol."},{"key":"ref-22","doi-asserted-by":"crossref","DOI":"10.4135\/9781473983304","article-title":"Template analysis for business and management students.","author":"N King","year":"2017"},{"key":"ref-23","article-title":"Nutritional anaemias: tools for effective prevention and control.","year":"2017"},{"key":"ref-24","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3390\/ph12020059","article-title":"The Importance of Iron Status for Young Children in Low- and Middle-Income Countries: A Narrative Review.","volume":"12","author":"A Armitage","year":"2019","journal-title":"Pharmaceuticals (Basel)."},{"key":"ref-25","doi-asserted-by":"publisher","first-page":"e732-e43","DOI":"10.1016\/S2352-3026(21)00193-9","article-title":"Iron deficiency anaemia in sub-Saharan Africa: a review of current evidence and primary care recommendations for high-risk groups.","volume":"8","author":"M Mwangi","year":"2021","journal-title":"Lancet Haematol."},{"key":"ref-26","doi-asserted-by":"publisher","first-page":"133-43","DOI":"10.1016\/S0140-6736(06)67962-2","article-title":"Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial.","volume":"367","author":"S Sazawal","year":"2006","journal-title":"Lancet."},{"key":"ref-27","doi-asserted-by":"publisher","first-page":"1114-21","DOI":"10.3201\/eid2107.142036","article-title":"Malaria Prevalence among Young Infants in Different Transmission Settings, Africa.","volume":"21","author":"S Ceesay","year":"2015","journal-title":"Emerg Infect Dis."},{"key":"ref-28","doi-asserted-by":"publisher","first-page":"238","DOI":"10.12688\/wellcomeopenres.16282.1","article-title":"Acknowledging the gap: a systematic review of micronutrient supplementation in infants under six months of age [version 1; 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Strand, Innlandet Hospital Trust, Department of Research, Norway and the Centre for International Health, University of Bergen, Bergen, 18 May 2022, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/7-16\/v1#referee-response-50161","order":0,"name":"referee-response-50161","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.21956\/wellcomeopenres.19357.r53882, Vicky Fallon, Institute of Population Health, University of Liverpool, Liverpool, 19 Jan 2023, version 1, indexed","URL":"https:\/\/wellcomeopenresearch.org\/articles\/7-16\/v1#referee-response-53882","order":1,"name":"referee-response-53882","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This work was supported by funding to from DFID\/NIHR\/MRC\/Wellcome Joint Global Health Trials \u2013 Call 9 [MRT003960\/1]. This trial is Sponsor is MRCG@LSHTM. SEM is funded by a Wellcome Trust Senior Research Fellowship [220225]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":2,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}