Adherence to home fortification with micronutrient powders in Kenyan pre-school children: self-reporting and sachet counts compared to an electronic monitoring device.

BACKGROUND: The efficacy of home fortification with iron-containing micronutrient powders varies between trials, perhaps in part due to population differences in adherence. We aimed to assess to what extent adherence measured by sachet count or self-reporting forms is in agreement with adherence measured by electronic device. In addition, we explored how each method of adherence assessment (electronic device, sachet count, self-reporting forms) is associated with haemoglobin concentration measured at the end of intervention; and to what extent baseline factors were associated with adherence as measured by electronic device. METHODS: Three hundred thirty-eight rural Kenyan children aged 12-36 months were randomly allocated to three treatment arms (home fortification with two different iron formulations or placebo). Home fortificants were administered daily by parents or guardians over a 30 day-intervention period. We assessed adherence using an electronic device that stores and provides information of the time and day of opening of the container that was used to store the fortificants sachets in each child's residence. In addition, we assessed adherence by self-reporting and sachet counts. We also measured haemoglobin concentration at the end of intervention. RESULTS: Adherence, defined as having received at least 24 sachets (≥ 80%), during the 30-day intervention period was attained by only 60.6% of children as assessed by the electronic device. The corresponding values were higher when adherence was assessed by self-report (83.9%; difference: 23.3%, 95% CI: 18.8% to 27.8%) or sachet count (86.3%; difference: 25.7%, 95% CI: 21.0% to 30.4%). Among children who received iron, each 10 openings of the electronic cap of the sachet storage container were associated with an increase in haemoglobin concentration at the end of intervention by 1.2 g/L (95% CI: 0.0 to 1.9 g/L). Adherence was associated with the age of the parent but not with intervention group; with age, sex or anthropometric indices of the child; or with age or sex of the parent or guardian. CONCLUSIONS: The use of self -reporting and sachet count may lead to overestimates of adherence to home fortification. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov ( NCT02073149 ) on 25 February 2014.

Daily home fortification with iron as ferrous fumarate versus NaFeEDTA: a randomised, placebo-controlled, non-inferiority trial in Kenyan children.

BACKGROUND: We aimed to show the non-inferiority of home fortification with a daily dose of 3 mg iron in the form of iron as ferric sodium ethylenediaminetetraacetate (NaFeEDTA) compared with 12.5 mg iron as encapsulated ferrous fumarate in Kenyan children aged 12-36 months. In addition, we updated a recent meta-analysis to assess the efficacy of home fortification with iron-containing powders, with a view to examining diversity in trial results. 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, 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate. We assessed haemoglobin concentration (primary outcome), plasma iron markers, plasma inflammation markers and Plasmodium infection in samples collected at baseline and after 30 days of intervention. We conducted a meta-analysis of randomised controlled trials in pre-school children to assess the effect of home fortification with iron-containing powders on anaemia and haemoglobin concentration at end of intervention. RESULTS: A total of 315 children completed the 30-day intervention period. At baseline, 66.9% of children had inflammation (plasma C-reactive protein concentration >5 mg/L or plasma α 1-acid glycoprotein concentration >1.0 g/L); in those without inflammation, 42.5% were iron deficient. There was no evidence, either in per protocol analysis or intention-to-treat analysis, that home fortification with either of the iron interventions improved haemoglobin concentration, plasma ferritin concentration, plasma transferrin receptor concentration or erythrocyte zinc protoporphyrin-haem ratio. We also found no evidence of effect modification by iron status, anaemia status and inflammation status at baseline. In the meta-analysis, the effect on haemoglobin concentration was highly heterogeneous between trials (I 2: 84.1%; p value for test of heterogeneity: <0.0001). CONCLUSIONS: In this population, home fortification with either 3 mg iron as NaFeEDTA or 12.5 mg iron as encapsulated ferrous fumarate was insufficiently efficacious to assess non-inferiority of 3 mg iron as NaFeEDTA compared to 12.5 mg iron as encapsulated ferrous fumarate. Our finding of heterogeneity between trial results should stimulate subgroup analysis or meta-regression to identify population-specific factors that determine efficacy. TRIAL REGISTRATION: The trial was registered with ClinicalTrials.gov ( NCT02073149 ) on 25 February 2014.

Comparison of home fortification with two iron formulations among Kenyan children: Rationale and design of a placebo-controlled non-inferiority trial.

INTRODUCTION: Home fortification powders containing iron and other micronutrients have been recommended by World Health Organisation to prevent iron deficiency anaemia in areas of high prevalence. There is evidence, however, that home fortification at this iron dose may cause gastrointestinal adverse events including diarrhoea. Providing a low dose of highly absorbable iron (3 mg iron as NaFeEDTA) may be safer because the decreased amount of iron in the gut lumen can possibly reduce the burden of these adverse effects whilst resulting in similar or higher amounts of absorbed iron. OBJECTIVE: To show non-inferiority of home fortification with 3 mg iron as NaFeEDTA compared with 12.5 mg iron as encapsulated ferrous fumarate, with haemoglobin response as the primary outcome. DESIGN: 338 Kenyan children aged 12-36 months will be randomly allocated to daily home fortification with either: a) 3 mg iron as NaFeEDTA (experimental treatment), b) 12.5 mg iron as encapsulated ferrous fumarate (reference), or c) placebo. At baseline, after 30 days of intervention and within 100 days post-intervention, blood samples will be assessed for primary outcome (haemoglobin concentration), iron status markers, Plasmodium parasitaemia and inflammation markers. Urine and stool samples will be assessed for hepcidin concentrations and inflammation, respectively. Adherence will be assessed by self-reporting, sachet counts and by an electronic monitoring device. CONCLUSION: If daily home fortification with a low dose of iron (3 mg NaFeEDTA) has similar or superior efficacy to a high dose (12.5 mg ferrous fumarate) then it would be the preferred choice for treatment of iron deficiency anaemia in children.