Routine Infant Iron Supplementation Fails to Improve Cognitive Outcomes in Malaria-Endemic Areas: JAMA
Malawi: In children from a malaria-endemic region of Malawi, routine iron supplementation from 6 to 12 months of age, combined with malaria chemoprevention, did not improve short- or medium-term cognitive outcomes. These findings do not support universal iron supplementation solely to enhance cognitive development in this setting.
The conclusion comes from the IRMA randomized clinical trial, published in JAMA by Kamija S. Phiri of the Training and Research Unit of Excellence, Blantyre, Malawi, and colleagues. The study examined whether preventive iron supplementation, delivered alongside malaria chemoprevention, could improve developmental outcomes in infants living in rural southern Malawi, where anemia and malaria are both common.
The trial enrolled 2,168 infants at approximately six months of age between April 2020 and October 2021. About 71% of the children were anemic at enrollment, and 49% were girls. Participants were randomly assigned to one of four groups for six months: iron syrup plus malaria chemoprevention, iron-containing multiple micronutrient powder plus malaria chemoprevention, malaria chemoprevention alone, or placebo alone. Children were evaluated at 1 year of age, immediately after the intervention period, and again at 18 months, after an additional 6 months of follow-up.
Researchers assessed cognitive development using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III). The primary outcome was the cognitive composite score at one year of age.
The trial revealed the following findings:
- Neither iron syrup nor iron-containing micronutrient powder improved cognitive outcomes compared with malaria chemoprevention alone at either 12 or 18 months of age.
- Malaria chemoprevention alone did not provide a significant cognitive benefit compared with placebo.
- No significant differences were observed in language or motor development across the intervention groups.
- Both iron interventions increased ferritin levels, indicating improved iron stores.
- Despite improving iron status, neither iron intervention significantly reduced anemia prevalence compared with malaria chemoprevention alone.
- Improvements in iron stores did not translate into better developmental outcomes during the study period.
- Neither iron syrup nor iron-containing micronutrient powder increased the risk of malaria or other infections when administered alongside malaria chemoprevention.
- Malaria chemoprevention alone significantly reduced malaria incidence compared with placebo, confirming its protective effect.
The findings challenge the assumption that universal iron supplementation in infancy necessarily improves neurodevelopmental outcomes in populations with a high burden of anemia. While iron remains essential for health, the researchers noted that the functional benefits of routine preventive supplementation have not been consistently demonstrated in randomized trials.
The IRMA trial indicates that, in this rural Malawian setting, six months of iron supplementation from six to 12 months of age did not confer cognitive benefits despite improving iron stores, highlighting the need for further research to identify which children are most likely to benefit from iron interventions.
Reference:
Phiri KS, Mzembe G, Vokhiwa M, et al. Iron or Multiple Micronutrient Powder Supplements With Malaria Chemoprevention in Rural Malawian Children: The IRMA Randomized Clinical Trial. JAMA. Published online August 06, 2026. doi:10.1001/jama.2026.12242
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