Characteristics of included studies.

Background
Iron and folic acid (IFA) are essential nutrients, with deficiencies associated not only with anemia but also with other significant health consequences, including impaired cognitive development, increased susceptibility to infections, and adverse pregnancy outcomes. Despite the widespread use of IFA for management, a notable percentage of individuals failed to respond resulting in persistent anemia. This systematic review investigates the management of non-responders to oral iron and folic acid (IFA) treatment, among children under five. Non-responders are anemic individuals who do not recover after the standard IFA treatment. A comprehensive search was conducted across multiple databases including Medline, Cochrane, Embase, and Google Scholar, covering the period from January 1, 2000, to May 31, 2024. From the initial search of 14,242 studies, we conducted title and abstract screening, and 27 articles were selected for full text screening. After further exclusion, a total of 8 studies were identified, including randomized controlled trials, cohort studies, and case series. The review found that intravenous management, particularly ferric carboxymaltose, was found to be effective in cases of iron non-responsiveness. However, the causes of poor/non-responders to oral iron are less explored, indicating a need for further research. The review also identified a lack of high-quality studies on this topic. The review highlights the limited evidence on managing anemia unresponsive to oral iron, especially in low- and middle-income countries. While intravenous iron shows promise, more data is required to draw solid conclusions. Developing personalized treatment strategies is crucial to improving outcomes and addressing the global burden of anemia.