Universal iron with malaria chemoprevention did not improve infant development in Malawi

Design

Four-arm randomised clinical trial (IRMA)

Population

2,168 infants aged about 6 months in rural Malawi, 71% anaemic

Primary outcome

Bayley-III Cognitive Scale composite score after six months

Effect

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

The WHO recommends universal preventive iron for young children where anaemia is common, but its benefits for development have not been confirmed in trials, and there has long been concern that iron raises malaria risk. IRMA randomised 2,168 infants aged about 6 months in rural southern Malawi, 71% of them anaemic, to six months of iron syrup plus malaria chemoprevention, iron-containing micronutrient powder plus chemoprevention, chemoprevention alone, or placebo.

At the end of treatment, neither iron intervention improved Bayley-III cognitive scores against chemoprevention alone (mean difference −0.52, 95% CI −2.52 to 1.48 for syrup; −0.85, −2.80 to 1.09 for powder). Iron raised ferritin but did not reduce anaemia prevalence. Reassuringly, iron given with chemoprevention did not increase malaria, and chemoprevention itself reduced malaria against placebo.

Two things follow for those treating children in malaria-endemic settings. Malaria chemoprevention is the intervention that showed a clinical effect here. And universal iron, at least in this form and over this period, did not deliver the developmental benefit it is given for, though it also did no harm on malaria when paired with chemoprevention.

• Prioritise malaria chemoprevention for infants in endemic settings where it is part of the programme.
• Where universal iron is given, pair it with malaria prevention; together they did not increase malaria.
• Do not expect universal iron alone to correct anaemia in malaria-endemic infants; look for other causes.
• Continue to treat diagnosed iron deficiency individually; this trial tested universal supplementation.

Why it matters

It challenges the main justification for universal infant iron programmes in malaria-endemic areas.

Don't overread it

This tested universal supplementation in one setting for six months; it says nothing against treating diagnosed iron deficiency.

The statistics, in plain English

The confidence intervals for cognitive score differences (around −2.5 to +1.5 points on a scale with a mean of 100) are narrow and centred near zero, which makes a meaningful benefit unlikely rather than merely unproven.

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