Intermittent administration of iron and sulfadoxine-pyrimethamine to control anaemia in Kenyan children: A randomised controlled trial

Background: Iron supplementation is recommended for children at high risk of anaemia, but its benefits may not outweigh the associated risk of malaria in areas of seasonal transmission. We investigated the effect on haemoglobin concentrations of intermittent administration of iron supplements and sulfadoxine-pyrimethamine in symptom-free children under intense health surveillance. Methods: In a trial of two by two factorial design, 328 anaemic Kenyan children were randomly assigned either iron or placebo and sulfadoxine-pyrimethamine or placebo (82 to each group). Primary outcomes were haemological indicators of iron status and inflammation at the end of the follow-up, and occurrence of malaria attacks. Morbidity surveillance consisted of medical examinations every 4 weeks, continuous passive case detection, and visits twice a week to community health-workers. Analyses were by intention to treat. Findings: After 12 weeks, the groups assigned iron plus sulfadoxine-pyrimethamine, iron alone, or sulfadoxine-pyrimethamine alone had higher haemoglobin concentrations than the group assigned placebo (treatment effect adjusted for prognostic factors at baseline: 11.1 g/L [95% CI 7.5 to 14.7]; 10.7 g/L [7.1 to 14.3]; and 3.1 g/L [-0.5 to 6.7]). Administration of iron plus sulfadoxine-pyrimethamine also lowered the proportion with anaemia from 100% at baseline to 36% at 12 weeks, and of iron deficiency from 66% at baseline to 8% at 12 weeks. Survival analysis showed no evidence of substantially increased risk of malaria after iron supplementation. Interpretation: Iron supplementation gives substantial health benefits, which may outweigh possible inherent risks caused by malaria. A larger study than ours is needed to assess benefits and risks of intermittent administration of sulfadoxine-pyrimethamine in reducing the incidence of malaria attacks in areas of seasonal malaria transmission.