In‐home fortification with 2.5 mg iron as NaFeEDTA does not reduce anaemia but increases weight gain: a randomised controlled trial in Kenyan infants

Abstract

In-home fortification of infants with micronutrient powders (MNPs) containing 12.5 mg iron may increase morbidity from infections; therefore, an efficacious low-dose iron-containing MNP might be advantageous. Effects of iron-containing MNPs on infant growth are unclear. We assessed the efficacy of a low-iron MNP on iron status and growth and monitored safety in a randomised, controlled, double-blind 1-year trial in 6-monthold infants (n = 287) consuming daily a maize porridge fortified with either a MNP including 2.5 mg iron as NaFeEDTA (MNP + Fe) or the same MNP without iron (MNP − Fe). At baseline, after 6 and 12 months, we determined haemoglobin (Hb), iron status [serum ferritin (SF), soluble transferrin receptor (sTfR) and zinc protoporphyrin (ZPP)], inflammation [C-reactive protein (CRP)] and anthropometrics. We investigated safety using weekly morbidity questionnaires asking for diarrhoea, cough, flu, bloody or mucus-containing stool and dyspnoea, and recorded any other illness. Furthermore, feeding history and compliance were assessed weekly. At baseline, 71% of the infants were anaemic and 22% iron deficient; prevalence of inflammation was high (31% had an elevated CRP). Over the 1 year, Hb increased and SF decreased in both groups, without significant treatment effects of the iron fortification. At end point, the weight of infants consuming MNP + Fe was greater than in the MNP − Fe group (9.9 vs. 9.5 kg, P = 0.038). Mothers of infants in the MNP + Fe group reported more infant days spent with cough (P = 0.003) and dyspnoea (P = 0.0002); there were no significant differences on any other of the weekly morbidity measures. In this study, low-dose iron-containing MNP did not improve infant's iron status or reduce anaemia prevalence, likely because absorption was inadequate due to the high prevalence of infections and the low-iron dose.

The effects of iron fortification and supplementation on the gut microbiome and diarrhea in infants and children: a review

“…There was a treatment effect of the MNP that contained 12.5 mg Fe on body iron, serum ferritin, soluble transferrin receptor, and zinc protoporphyrin. In contrast, there was no treatment effect of the MNP that contained 2.5 mg Fe on any of the iron-status indicators, thereby suggesting that this iron dose was too low for efficacy (21). In accordance with previous studies on the human gut microbiota (40)(41)(42)(43), the 4 dominant phyla in the infants at baseline were Actinobacteria (63%, mainly Bifidobacteriaceae), Firmicutes (22%), Bacteroidetes (9%), and Proteobacteria (4%).…”

“…In the MixMe MNP, NaFeEDTA is combined with ascorbic acid and an exogenous phytase, both of which are enhancers of iron absorption, and this combination results in higher iron absorption from maize porridge (16). This MNP has shown to have weak efficacy in preschool children in Kenya (19) and school-age children in South Africa (20); however, in a 1-y controlled trial in Kenyan infants, the MNP did not reduce IDA (21), possibly because the absorbed iron dose was insufficient as a result of the low dose and the high prevalence of infections increasing serum hepcidin (12). Thus, it is uncertain how far the iron dose in MNPs can be lowered while maintaining efficacy against anemia.…”

The Effect of Low Dose Iron and Zinc Intake on Child Micronutrient Status and Development during the First 1000 Days of Life: A Systematic Review and Meta-Analysis

“…Effect on hemoglobin concentration: We identified 30 RCTs [26,27,28,29,30,31,32,33,34,35,36,37,38,39,40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55], contributing 43 comparisons, for evaluating the effect of up to 15 mg of additional iron daily on hemoglobin levels of children 6–23 months of age. In total, 6569 children contributed to the pooled estimate.…”

“…Effect on diarrhea, fever and respiratory infection: We identified eight eligible studies [27,38,42,44,48,49,57,58], with a total of 11 comparisons, reporting on the impact of iron use on diarrhea, respiratory infection and/or fever. Given the variability of methods and outcome measures in the studies reviewed, it was not possible to conduct a meta-analysis without introducing a selection bias.…”

Dietary strategies for improving iron status: balancing safety and efficacy

“…The Chilenje Infant Growth, Nutrition, and Infection Study (CIGNIS), which provided richly micronutrient-fortified porridge (12.5 mg iron) to 6-month-old Zambian infants, revealed an increase in the incidence of lower respiratory tract infections at scheduled clinic visits ( P = 0.02) 81 . Similarly, a study that administered micronutrient powders with a low iron content (2.5 mg as sodium iron EDTA [NaFeEDTA]) to Kenyan infants has reported that infants in the iron group spent significantly more days with cough and dyspnea 82 . In a recently completed trial of physician-prescribed lipid-based multiple micronutrients in The Gambia, 83 the supplements failed to reduce the frequency of repeat clinic visits and, on secondary analysis, revealed an increase in repeat visits in the first 3 weeks of administration in those receiving the fortified lipid-based nutrient supplements 84 .…”