Comparison of Effects of Iron and Multiple Micronutrient Supplementation on Hematological and Growth Indicators among Older Children, Adolescents, and Young Adults in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Context Middle childhood, adolescence, and young adulthood are characterized by high nutritional demands and vulnerability to anemia. Limited efforts have been made to synthesize the evidence comparing the effects of iron and multiple micronutrient (MMN) supplementation in these populations. Objective In this study we sought to examine the effects of iron and MMN on anemia and anthropometric variables among people aged 5 to 24 years in low- and middle-income countries. Data Sources The PubMed, Embase, Cochrane Library, and CINAHL databases were searched from inception to July 2024 to identify 50 randomized controlled trials (RCTs) of iron or MMN supplementation with outcomes. Data Extraction Only RCTs that used iron or MMN were included in this analysis. Data Analysis Compared to placebo, supplementation with iron and MMN was associated with 5.81 g/L (95% CI: 4.19-7.44 g/L) and 4.82 g/L (95% CI: 2.32-7.32 g/L) incremental increases in hemoglobin levels, respectively. The therapeutic effects of MMN (hemoglobin: 9.3 g/L, 95% CI: 1.52-17.09 g/L) and iron (10.24 g/L, 95% CI: 5.10-15.39 g/L) were both observed in populations of older children, adolescents, and young adults with anemia. Stratified analysis showed that with either MMN or iron supplementation, higher iron content (> 30 mg/d) could lead to a higher increment of hemoglobin, while a shorter intervention duration (< 3 months) showed more benefits in improving hemoglobin. For ferritin, the significant benefit of supplementation was observed only with iron and not with MMN. Iron was also found to decrease serum transferrin receptor and zinc protoporphyrin, but there was no effect on C-reactive protein. For growth indicators, iron was found to increase weight (0.52 kg, 95% CI: 0.12-0.93 kg), while MMN was found to increase height (0.87 cm, 95% CI: 0.16-1.59 cm). Conclusions Overall, supplementation with iron compared with MMN had similarly beneficial effects on improving the hemoglobin level in older children, adolescents, and young adults, but there was some indication that there may be differential effects on growth indicators.