Universal iron with malaria chemoprevention did not improve cognition in Malawian infants

Design

Randomised, placebo-controlled four-arm trial (IRMA), four centres, southern Malawi

Population

2,168 infants aged about 6 months, 71% anaemic, in a malaria-endemic area

Primary outcome

Bayley-III cognitive composite score after 6 months of intervention

Effect

Iron syrup vs chemoprevention alone: MD -0.52 (95% CI -2.52 to 1.48); micronutrient powder: MD -0.85 (95% CI -2.80 to 1.09)

IRMA randomised 2,168 infants aged about 6 months in rural, malaria-endemic southern Malawi (71% anaemic) to four arms for six months: iron syrup plus malaria chemoprevention, iron-containing micronutrient powder plus chemoprevention, chemoprevention alone, or placebo. The primary outcome was the Bayley-III cognitive composite score at the end of the intervention.

Compared with chemoprevention alone, iron syrup made no difference (mean difference -0.52, 95% CI -2.52 to 1.48), nor did micronutrient powder (-0.85, -2.80 to 1.09). Both raised ferritin but neither reduced anaemia prevalence. Neither iron arm increased malaria risk, which addresses a long-standing concern; chemoprevention alone reduced malaria compared with placebo.

This challenges the assumed functional benefit of universal infant iron in this setting, but it does not say that iron is useless for iron-deficiency anaemia. The WHO recommendation has not changed on the basis of this single trial, and findings may not carry to settings without malaria or with a different iron-deficiency pattern, including India.

• Iron with malaria chemoprevention did not improve the Bayley-III cognitive score (syrup MD -0.52, 95% CI -2.52 to 1.48).
• Neither iron arm reduced anaemia prevalence, though ferritin rose.
• Iron did not increase the risk of malaria in this trial.
• Malaria chemoprevention alone reduced malaria compared with placebo.
• Keep treating confirmed iron deficiency, and note that guidance has not changed.

Why it matters

It tests a widely recommended universal intervention against a functional outcome and finds no gain.

Don't overread it

One trial in rural Malawi does not overturn a WHO recommendation or show that iron is unnecessary for children with iron-deficiency anaemia.

The statistics, in plain English

The cognitive score differences are small relative to the interval (about 2.5 points either side), so the data are compatible with no effect or a small effect in either direction. A null result in a large trial is informative; it is not the same as a trial that was too small to tell.

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