Daily Versus Intermittent Oral Iron Supplementation for the Treatment of Anaemia in Low- and Middle-Income Countries: A Systematic Review and Meta-analysis

Abstract Background: Iron deficiency anaemia remains a major public health problem in low- and middle-income countries (LMICs), particularly among children, adolescents, women of reproductive age, and pregnant women. Although daily oral iron supplementation is the standard treatment, uncertainty remains regarding whether intermittent dosing provides comparable efficacy with better tolerability and acceptability. We conducted a systematic review and meta-analysis to compare the effectiveness and safety of daily versus intermittent oral iron or iron-folic acid supplementation for treating anaemia in LMICs. Methods: Four electronic databases (PubMed/MEDLINE, Embase, Scopus, and Web of Science) were searched from inception to July 2025. Randomised controlled trials, quasi-experimental studies, and prospective cohort studies conducted in LMICs among anaemic children, adolescents, women of reproductive age, and pregnant women were included. Primary outcomes were changes in haemoglobin concentration and serum ferritin from baseline to study end. Secondary outcomes included adherence, adverse effects, anaemia recovery, and maternal and fetal outcomes. Random-effects meta-analysis, subgroup analysis, and GRADE certainty assessment were performed. Results: Fourteen studies met the inclusion criteria, with 13 studies (19 comparisons; 724 participants receiving daily supplementation and 948 receiving intermittent supplementation) included in the meta-analysis. Daily iron supplementation was associated with a small but statistically significant increase in haemoglobin compared with intermittent regimens (MD=0.34 g/dL; 95% CI: 0.08, 0.60; I2=87.8%). Subgroup analysis demonstrated benefits among children (MD=0.44 g/dL; 95% CI: 0.19, 0.68; I2=68.1%) and pregnant women (MD=0.79 g/dL; 95% CI: 0.04, 1.55; I2=87.8%), whereas no significant difference was observed among adolescents. Daily supplementation also resulted in higher serum ferritin concentrations (MD=4.48 ug/L; 95% CI: 0.37, 8.59). Intermittent regimens were associated with higher adherence and fewer gastrointestinal adverse effects. Conclusion: Very low-certainty evidence suggests daily supplementation may produce a small increase in haemoglobin and serum ferritin compared with intermittent regimens, although the magnitude and clinical significance of these differences remain uncertain. Intermittent regimens were associated with fewer gastrointestinal side effects and better adherence. Where adherence or treatment tolerability is a concern, intermittent regimens may represent a pragmatic alternative to daily supplementation, particularly in resource-constrained LMIC settings. Keywords: Anaemia, iron supplementation, daily, intermittent, haemoglobin, serum ferritin.