IV Iron Could Bridge Treatment Gaps for Children With Anemia

A systematic review of two decades of research found that tailored treatment strategies have varying effectiveness for children with anemia who do not respond to oral iron or folic acid therapy.1

This review of 7 studies found intravenous (IV) management, including ferric carboxymaltose (FCM), effective for iron non-responsiveness but identified limited research on its causes, particularly a lack of high-quality studies, and scarce evidence on managing anemia in low-and middle-income countries.

“The review highlights the superiority of IV management, particularly FCM, in cases of iron non-responsiveness,” wrote the investigative team, led by Ranadip Chowdhury, MD, PhD, Society for Applied Studies. “However, the lack of a comprehensive understanding of the causes of poor/non-responders to oral iron necessitates further research.

Nutritional deficiencies notably contribute to rates of anemia, characterized by a reduction in hemoglobin in the blood, as well as other consequences, including impaired cognitive development and a raised risk of maternal and child mortality.2 World Health Organization (WHO) estimates suggest approximately 40% of all children aged 6–59 months are impacted by anemia, with many caused by nutritional deficits.3

Oral iron and folic acid supplementation is increasingly used for at-risk populations, particularly children. Still, a critical proportion of individuals do not respond to management, with estimates pointing to up to 60%, depending on the treatment duration.2

As a result, Chowdhury and colleagues pointed to the need for alternative treatment options, ranging from IV iron therapy and blood transfusions to dietary changes and nutritional supplementation. For this systematic review, the team explored treatment strategies among non-responders to oral iron or folic acid among children under 5 years.1

Medical-related literature databases, including Medline, Cochrane, Embase, and Google Scholar, were assessed from January 2000 to May 2024. After an initial yield of 14,242 studies, a total of 27 studies were selected for full-text screening. Overall, 7 relevant studies, including randomized controlled trials (RCTs), cohort studies, and case series, were included for analysis.

Chowdhury and colleagues defined non-response to iron and folic acid as the failure to achieve a meaningful increase in hemoglobin after a standard 8 to 12-week treatment period.

The review of multiple trials showed varying effectiveness of oral iron formulations in managing non-responsiveness to iron and folic acid. A single RCT addressed the underlying H. pylori infection, which did not approve iron absorption.4 In another study, switching to more bioavailable and better-tolerated forms of iron may have improved outcomes in children who failed to respond to traditional formulations.5

Meanwhile, the utilization of IV iron, including FCM, demonstrated promising benefits for anemia. Retrospective cohort data on 72 patients with mild anemia (median age, 14) treated with a single dose of IV FCM (~435 mg) showed a significant increase in hemoglobin from 9.3 to 12.3 g/dL over 12 weeks.6

In another trial, nearly 500 women of reproductive age with mild anemia were randomized to IV FCM (1000 mg over 15 min) or oral iron (65 mg elemental iron thrice daily for 6 weeks). Analysis showed that 82% of the FCM group achieved a hemoglobin rise by ≥2 g/dL within 42 days of treatment, compared with 62% of the oral iron group.7

Chowdhury and colleagues indicated that FCM may be an effective IV iron intervention for treating various types of anemia across differing age groups. They noted this review, focused on the management of non-response to oral iron therapy in vulnerable groups, highlighted the need for precision medicine and new treatment approaches for anemia.1

“A significant strength of this review is that it is the first of its kind to focus on the management of non-responders to oral iron therapy in vulnerable groups, offering valuable insights through a diverse range of studies from various countries and advocating for the effectiveness of tailored treatments based on individual needs and conditions,” they wrote.

References

1. Manapurath R, Taneja S, Bhandari N, Chowdhury R. Treatment strategies for non-responders to oral iron and folic acid treatment in anemic children: A systematic review. PLOS Glob Public Health. 2025;5(3):e0003870. Published 2025 Mar 13. doi:10.1371/journal.pgph.0003870

2. Barua S, Kuizon S, Junaid MA. Folic acid supplementation in pregnancy and implications in health and disease. J Biomed Sci. 2014;21(1):77. Published 2014 Aug 19. doi:10.1186/s12929-014-0077-z

3. Anaemia. World Health Organization. February 10, 2025. Accessed March 20, 2025. https://www.who.int/news-room/fact-sheets/detail/anaemia.

4. Sarker SA, Mahmud H, Davidsson L, et al. Causal relationship of Helicobacter pylori with iron-deficiency anemia or failure of iron supplementation in children. Gastroenterology. 2008;135(5):1534-1542. doi:10.1053/j.gastro.2008.07.030

5. Russo G, Guardabasso V, Romano F, et al. Monitoring oral iron therapy in children with iron deficiency anemia: an observational, prospective, multicenter study of AIEOP patients (Associazione Italiana Emato-Oncologia Pediatrica). Ann Hematol. 2020;99(3):413-420. doi:10.1007/s00277-020-03906-w

6. Powers JM, Shamoun M, McCavit TL, Adix L, Buchanan GR. Intravenous Ferric Carboxymaltose in Children with Iron Deficiency Anemia Who Respond Poorly to Oral Iron. J Pediatr. 2017;180:212-216. doi:10.1016/j.jpeds.2016.09.053

7. Van Wyck DB, Mangione A, Morrison J, Hadley PE, Jehle JA, Goodnough LT. Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial. Transfusion. 2009;49(12):2719-2728. doi:10.1111/j.1537-2995.2009.02327.x