Comparison of home fortification with two iron formulations:A placebo-controlled non-inferiority trial among Kenyan children protected against malaria by a single course of artemisinin-based combination therapy.

Abstract

The objectives of this study were to: 1) show non-inferiority of home-fortification with a daily dose of 3mg iron as NaFeEDTA compared with 12.5 mg iron as encapsulated ferrous fumarate. 2) Assess to what extent adherence measured by sachet count or self-reporting forms agrees with adherence measured by MEMS electronic device. 3) Assess the diagnostic performance of zinc protoporphyrin either alone or combined with haemoglobin concentration in children. Methods: We gave chemoprevention by dihydroartemisinin-piperaquine, albendazole and praziquantel to 338 afebrile children with haemoglobin concentration ≥70 g/L. We randomly allocated them to daily home-fortification for 30 days with either placebo, 3mg iron as NaFeEDTA, or 12.5 mg iron as encapsulated ferrous fumarate. Each child received 30 sachets of micronutrient powders in a MEMS device, a self-reporting form and requested to store empty sachets. At baseline and after 30 days of intervention, haemoglobin concentration, plasma iron markers, plasma inflammation markers, Plasmodium infection in blood samples and adherence to home-fortification were assessed. Results: Home-fortification with either of the iron interventions did not improved haemoglobin concentration, plasma ferritin concentration and plasma transferrin receptor concentration. Both self-reporting and sachet counts confirmed over-estimation in adherence measurements when compared to MEMS device. Addition of whole blood ZPP or erythrocyte ZPP to haemoglobin concentration increased the area-under-the-ROC-curve. Conclusions: Daily home-fortification with either 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate was not efficacious. This failure precluded further assessment of the non-inferiority of 3 mg iron as NaFeEDTA compared to 12.5 mg iron as encapsulated ferrous fumarate. Self-reporting and sachet counts are less accurate in measuring daily home-fortification with micronutrient powders compared to the MEMS device. In children, whole blood ZPP and erythrocyte ZPP combined with haemoglobin concentration have added diagnostic value in detecting iron deficiency compared to haemoglobin concentration alone.