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However, the potential for reversibility with iron supplementation remains debatable. Therefore, we aimed in this double-blind placebo-controlled clinical trial to investigate the effect of the novel iron preparation, Liposomal Iron (LI), on the development and growth of iron-deficient children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For iron deficiency anemia (IDA) and non-anemic iron deficiency (NAID), 433 children aged 6 to 59 months underwent screening. The NAID group was divided into two groups: one group received a placebo, while the interventional group received liposomal iron for four months, as in the IDA group. Then, compared to baseline, efficacy, development, and growth were reevaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The NAID interventional group showed significant improvement in developmental total scores compared to the NAID placebo group with a mean difference of +29.57 versus +0.96 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001). Furthermore, the final score was notably superior in the NAID interventional group 181.5, compared to the IDA group, 175.0 (\n                      <jats:italic>P<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Liposomal iron showed, in addition to good efficacy and tolerability, a favorable impact on the development and growth of iron-deficient children. However, the best results were obtained from early management prior to the onset of anemia (NAID).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Impact<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>NAID, though common, is still underappreciated, and evidence about the benefits of giving iron to children before IDA progression is limited.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The Ages and Stages Questionnaires is a reliable screening tool for development during the critical first five years of life.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Through an interventional clinical trial, LI demonstrated an effective and tolerable alternative for ID treatment, while overcoming the usual adverse effects of conventional iron therapies.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Growth and developmental outcomes improved significantly with early detection and treatment of ID with LI during the NAID stage than when the supplement was used after anemia emergence. Conversely, children with NAID who received a placebo showed further deterioration.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1038\/s41390-025-04204-9","type":"journal-article","created":{"date-parts":[[2025,6,20]],"date-time":"2025-06-20T07:22:14Z","timestamp":1750404134000},"page":"2228-2239","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Interventional impact of liposomal iron on iron-deficient children developmental outcome: randomized, double-blind, placebo-controlled trial"],"prefix":"10.1038","volume":"98","author":[{"given":"Wael A.","family":"Bahbah","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zein A.","family":"Omar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali M.","family":"El-Shafie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kerollos S.","family":"Mahrous","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9202-0495","authenticated-orcid":false,"given":"Heba M. 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Our participants completed the study after written consent from their parents\/guardians.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"Informed consent was obtained from all the legally authorized representatives of participants included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}