{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T09:19:05Z","timestamp":1778750345135,"version":"3.51.4"},"reference-count":51,"publisher":"The Royal Society","issue":"1950","license":[{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:00:00Z","timestamp":1778716800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001655","name":"Deutscher Akademischer Austauschdienst","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001655","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007886","name":"Fondation Nestl\u00e9","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007886","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Iron deficiency, with or without anemia, remains a major public health concern among young children in Myanmar. While iron supplementation is widely recommended, its potential adverse effects on growth and gut microbiota warrant investigation, particularly in contexts of poor complementary feeding. To assess the effects of iron supplementation, with or without complementary feeding recommendations (CFRs), on micronutrient status, linear growth and gut microbiota composition among Myanmar children aged 12\u201323 months, a 24-week randomized controlled trial was conducted in Ayeyarwady Region of Myanmar. Fourteen clusters (villages\/wards) were randomized to receive CFRs or not, and children within the clusters were randomized to receive daily aqueous iron or placebo, creating four arms: Placebo (n = 104), CFR (n = 112), Fe (n = 105) and CFRFe (n = 112) totalling 433 children. All intervention groups (CFR, Fe, CFRFe) improved haemoglobin and reduced anaemia risk compared with Placebo (AOR = 0.31 (0.15\u20130.62), 0.15 (0.07\u20130.32), 0.14 (0.07\u20130.31), respectively). CFR and CFRFe also improved zinc status. However, iron-alone (Fe) increased the stunting risk (AOR= 2.74 (1.04\u20137.23)), while CFRFe did not. No significant effects were observed on gut microbiota composition. Aqueous iron supplementation may impair linear growth when diets are not optimized; combining supplements with optimized complementary feeding may support healthier outcomes.<\/jats:p>\n                  <jats:p>This article is part of the theme issue \u2018Biological, biomedical and environmental drivers of stunting\u2019.<\/jats:p>","DOI":"10.1098\/rstb.2025.0042","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:52:58Z","timestamp":1778748778000},"source":"Crossref","is-referenced-by-count":0,"title":["Is iron supplementation likely to impair linear growth and gut microbiota composition of Myanmar young children when complementary feeding is not optimized? A randomized controlled trial"],"prefix":"10.1098","volume":"381","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7944-2009","authenticated-orcid":false,"given":"Lwin Mar","family":"Hlaing","sequence":"first","affiliation":[{"name":"Ministry of Health and Sports 1 , ,","place":["Naypyidaw, Myanmar, 100604"],"department":["National Nutrition Centre, Department of Public Health"]},{"name":"Universitas Indonesia 2 , ,","place":["Jakarta, Indonesia, 10430"],"department":["Southeast Asian Ministers of Education Organization Regional Centre for Food and Nutrition (SEAMEO RECFON) - Pusat Kajian Gizi Regional (PKGR)"]},{"name":"The University of Sydney 3 , , ,","place":["Sydney, New South Wales, Australia, 2006"],"department":["Sydney School of Public Health"]},{"name":"Kai Ming Head Start Inc. 4 , , ,","place":["San Francisco, CA, USA, 94103"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6417-2942","authenticated-orcid":false,"given":"Min Kyaw","family":"Htet","sequence":"additional","affiliation":[{"name":"Universitas Indonesia 2 , ,","place":["Jakarta, Indonesia, 10430"],"department":["Southeast Asian Ministers of Education Organization Regional Centre for Food and Nutrition (SEAMEO RECFON) - Pusat Kajian Gizi Regional (PKGR)"]},{"name":"The University of Sydney 3 , , ,","place":["Sydney, New South Wales, Australia, 2006"],"department":["Sydney School of Public Health"]},{"name":"Sinergi Qalbu Fikri, Depok 5 , ,","place":["Depok, Jawa Barat 16952, Indonesia"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosalind","family":"Gibson","sequence":"additional","affiliation":[{"name":"University of Otago 6 , ,","place":["Dunedin, New Zealand, 9016"],"department":["Department of Human Nutrition"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Budi","family":"Utomo","sequence":"additional","affiliation":[{"name":"Universitas Indonesia 7 , , ,","place":["Depok, West Java, Indonesia, 16424"],"department":["Center for Health Research, and Department of Population and Biostatistics, Faculty of Public Health"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agus","family":"Firmansyah","sequence":"additional","affiliation":[{"name":"Universitas Indonesia 8 , ,","place":["Jakarta, Indonesia, 10430"],"department":["Division of Pediatric Gastro-hepatology, Department of Child Health, Faculty of Medicine"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1403-6242","authenticated-orcid":false,"given":"Umi","family":"Fahmida","sequence":"additional","affiliation":[{"name":"Universitas Indonesia 2 , ,","place":["Jakarta, Indonesia, 10430"],"department":["Southeast Asian Ministers of Education Organization Regional Centre for Food and Nutrition (SEAMEO RECFON) - Pusat Kajian Gizi Regional (PKGR)"]},{"name":"Universitas Indonesia\u2014Dr. Cipto Mangunkusumo General Hospital 9 , ,","place":["Jakarta, Indonesia, 10430"],"department":["Department of Nutrition Science, Faculty of Medicine"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"175","published-online":{"date-parts":[[2026,5,14]]},"reference":[{"key":"2026051404525430100_R1","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1093\/jn\/nxab088","article-title":"Complementary feeding practices in 80 low- and middle-income countries: prevalence of and socioeconomic inequalities in dietary diversity, meal frequency, and dietary adequacy","volume":"151","author":"Gatica-Dom\u00ednguez","year":"2021","journal-title":"J. Nutr."},{"key":"2026051404525430100_R2","unstructured":"WHO\n          . 1998Complementary feeding of young children in developing countries. A review of current scientific knowledge. Geneva, Switzerland: WHO."},{"key":"2026051404525430100_R3","doi-asserted-by":"crossref","DOI":"10.1159\/000371618","article-title":"The epidemiology of global micronutrient deficiencies","volume":"66","author":"Bailey","year":"2015","journal-title":"Ann. Nutr. Metab."},{"key":"2026051404525430100_R4","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1016\/S0140-6736(13)60937-X","article-title":"Maternal and child undernutrition and overweight in low-income and middle-income countries","volume":"382","author":"Black","year":"2013","journal-title":"Lancet"},{"key":"2026051404525430100_R5","volume-title":"Guidelines for the use of iron supplements to prevent and treat iron deficiency anemia","author":"Stoltzfus","year":"1998"},{"key":"2026051404525430100_R6","volume-title":"Vitamin and mineral requirements in human nutrition","author":"WHO & FAO","year":"2004","edition":"2nd"},{"key":"2026051404525430100_R7","volume-title":"Iron supplementation of young children in regions where malaria transmission is intense and infectious disease highly prevalent","author":"WHO","year":"2006"},{"key":"2026051404525430100_R8","doi-asserted-by":"crossref","first-page":"133","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":"Sazawal","year":"2006","journal-title":"Lancet"},{"key":"2026051404525430100_R9","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1093\/ajcn\/84.6.1261","article-title":"Iron supplementation in early childhood: health benefits and risks","volume":"84","author":"Iannotti","year":"2006","journal-title":"Am. 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Nay Pyi Taw, Myanmar: MICS."},{"key":"2026051404525430100_R24","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1038\/cmi.2010.67","article-title":"The role of gut microbiota (commensal bacteria) and the mucosal barrier in the pathogenesis of inflammatory and autoimmune diseases and cancer: contribution of germ-free and gnotobiotic animal models of human diseases","volume":"8","author":"Tlaskalov\u00e1-Hogenov\u00e1","year":"2011","journal-title":"Cell. Mol. Immunol."},{"key":"2026051404525430100_R25","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1038\/sj.ejcn.1600888","article-title":"Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6-36 month old Togolese children","volume":"54","author":"Berger","year":"2000","journal-title":"Eur. J. Clin. Nutr."},{"key":"2026051404525430100_R26","doi-asserted-by":"crossref","first-page":"1169","DOI":"10.1017\/S0007114508012208","article-title":"Effect of sodium iron ethylenediaminetetra-acetate (NaFeEDTA) on haemoglobin and serum ferritin in iron-deficient populations: a systematic review and meta-analysis of randomised and quasi-randomised controlled trials","volume":"100","author":"Wang","year":"2008","journal-title":"Br. J. Nutr."},{"key":"2026051404525430100_R27","unstructured":"Bickel\n              G\n            , NordM, PriceC. 2000Global Forum on Food Security and Nutrition: Guide to measuring household food security. Seehttps:\/\/www.fao.org\/fsnforum\/index.php\/resources\/trainings-tools-and-databases\/guide-measuring-household-food-security."},{"key":"2026051404525430100_R28","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1093\/ajcn\/nqz304","article-title":"Adjusting plasma or serum zinc concentrations for inflammation: biomarkers reflecting inflammation and nutritional determinants of anemia (BRINDA) project","volume":"111","author":"McDonald","year":"2020","journal-title":"Am. J. Clin. Nutr."},{"key":"2026051404525430100_R29","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.3748\/wjg.v10.i12.1802","article-title":"Intestinal microecology and quality of life in irritable bowel syndrome patients","volume":"10","author":"Si","year":"2004","journal-title":"World J. 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Karger."},{"key":"2026051404525430100_R33","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1006\/jfca.2000.0922","article-title":"Guidelines for recipe information and calculation of nutrient composition of prepared foods (dishes)","volume":"13","author":"Bogn\u00e1r","year":"2000","journal-title":"J. Food Compos. Anal."},{"key":"2026051404525430100_R34","volume-title":"User\u2019s guide to the operation of the Worldfood Dietary Assessment system, version 2.0","author":"Bunch","year":"1997"},{"key":"2026051404525430100_R35","unstructured":"WHO\n              FAO\n            \n          . 2006Guidelines on food fortification with micronutrients. Geneva, Switzerland: World Health Organisation."},{"key":"2026051404525430100_R36","doi-asserted-by":"crossref","first-page":"455","DOI":"10.3945\/ajcn.114.087775","article-title":"Effectiveness in improving knowledge, practices, and intakes of 'key problem nutrients' of a complementary feeding intervention developed by using linear programming: experience in Lombok, Indonesia","volume":"101","author":"Fahmida","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"2026051404525430100_R37","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1017\/S1368980017003883","article-title":"Food choices to meet nutrient recommendations for the adult Brazilian population based on the linear programming approach","volume":"21","author":"Dos Santos","year":"2018","journal-title":"Public Health Nutr."},{"key":"2026051404525430100_R38","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/nyas.15008","article-title":"Could local foods achieve recommended calcium intakes for nutritionally vulnerable populations in Uganda, Guatemala, and Bangladesh?","volume":"1525","author":"Knight","year":"2023","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"2026051404525430100_R39","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.3945\/ajcn.2009.27588","article-title":"Food-based strategies improve iron status in toddlers: a randomized controlled trial","volume":"90","author":"Szymlek-Gay","year":"2009","journal-title":"Am. J. Clin. Nutr."},{"key":"2026051404525430100_R40","doi-asserted-by":"crossref","DOI":"10.1186\/s12970-014-0050-y","article-title":"Dietary iron intervention using a staple food product for improvement of iron status in female runners","volume":"11","author":"Alaunyte","year":"2014","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"2026051404525430100_R41","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1177\/156482650903000103","article-title":"Education and improved iron intakes for treatment of mild iron-deficiency anemia in adolescent girls in southern Benin","volume":"30","author":"Alaof\u00e8","year":"2009","journal-title":"Food Nutr. Bull."},{"key":"2026051404525430100_R42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/j.1469-7793.1999.0001r.x","article-title":"Metal ion transporters in mammals: structure, function and pathological implications","volume":"518","author":"Rolfs","year":"1999","journal-title":"J. Physiol."},{"key":"2026051404525430100_R43","doi-asserted-by":"crossref","first-page":"631S","DOI":"10.1093\/jn\/135.3.631S","article-title":"Efficacy of a foodlet-based multiple micronutrient supplement for preventing growth faltering, anemia, and micronutrient deficiency of infants: the four country IRIS trial pooled data analysis","volume":"135","author":"Smuts","year":"2005","journal-title":"J. Nutr."},{"key":"2026051404525430100_R44","doi-asserted-by":"crossref","first-page":"S16","DOI":"10.1177\/15648265030243S103","article-title":"The foodLET vehicle designed for and used in the IRIS I intervention","volume":"24","author":"Lock","year":"2003","journal-title":"Food Nutr. 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Seehttps:\/\/www.gainhealth.org\/resources\/reports-and-publications\/nutritional-guidelines-complementary-foods-and-complementary-food-supplements-supported-by-gain."},{"key":"2026051404525430100_R47","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.1016\/S0140-6736(05)66426-4","article-title":"Effectiveness of an educational intervention delivered through the health services to improve nutrition in young children: a cluster-randomised controlled trial","volume":"365","author":"Penny","year":"2005","journal-title":"Lancet"},{"key":"2026051404525430100_R48","doi-asserted-by":"crossref","DOI":"10.1136\/bmjopen-2016-011234","article-title":"Effectiveness of complementary food supplements and dietary counselling on anaemia and stunting in children aged 6\u201323 months in poor areas of Qinghai Province, China: a controlled interventional study","volume":"6","author":"Zhang","year":"2016","journal-title":"BMJ Open"},{"key":"2026051404525430100_R49","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.tim.2018.09.008","article-title":"The human microbiome and child growth\u2014first 1000 days and beyond","volume":"27","author":"Robertson","year":"2019","journal-title":"Trends Microbiol."},{"key":"2026051404525430100_R50","doi-asserted-by":"crossref","first-page":"5433","DOI":"10.1128\/IAI.00052-06","article-title":"Major role for FeoB in Campylobacter jejuni ferrous iron acquisition, gut colonization, and intracellular survival","volume":"74","author":"Naikare","year":"2006","journal-title":"Infect. 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Figshare.","author":"Hlaing","year":"2026"}],"container-title":["Philosophical Transactions B"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article-pdf\/doi\/10.1098\/rstb.2025.0042\/6137117\/rstb.2025.0042.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article-pdf\/doi\/10.1098\/rstb.2025.0042\/6137117\/rstb.2025.0042.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T08:53:22Z","timestamp":1778748802000},"score":1,"resource":{"primary":{"URL":"https:\/\/royalsocietypublishing.org\/rstb\/article\/381\/1950\/20250042\/481644\/Is-iron-supplementation-likely-to-impair-linear"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,14]]},"references-count":51,"journal-issue":{"issue":"1950","published-online":{"date-parts":[[2026,5,14]]},"published-print":{"date-parts":[[2026,5,14]]}},"URL":"https:\/\/doi.org\/10.1098\/rstb.2025.0042","relation":{},"ISSN":["0962-8436","1471-2970"],"issn-type":[{"value":"0962-8436","type":"print"},{"value":"1471-2970","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,14]]},"article-number":"20250042"}}