Abstract
BackgroundThe impact of iron supplements and iron fortification on diarrhea in children is controversial, with some studies reporting an increase and others reporting no effect. ObjectiveThe aim of the study was systematically assess the published literature on oral iron supplementation and fortification to evaluate its impact on diarrhea incidence among children aged 4–59 mo. MethodsRandomized controlled trials of oral iron supplementation or iron fortification that reported diarrheal outcomes in children aged 4–59 mo were identified from a systematic search of 5 databases. ResultsOf the 906 records identified, 19 studies were found to fit the inclusion criteria for this systematic review. However, variable case definitions for diarrhea made meta-analysis impossible. Of the 19 studies, 7 (37%) studies showed a significant increase, either in overall diarrhea incidence or within a specific subgroup of the population, between iron-supplemented and control groups. Subgroups included children who were iron-replete and children undergoing their first month of iron intervention. Two studies reported an increase in bloody diarrhea. The remaining 12 (63%) studies showed no difference between iron-supplemented and control groups. ConclusionsStudies on iron supplementation and fortification use divergent case definitions for diarrhea. A number of studies (37%) showed an increase in overall diarrhea incidence or within a specific subgroup of the population, between iron-supplemented and control groups, but the majority (63%) did not. In addition, there was no clear relation between diarrhea and type of intervention or amount of iron administered observed. In future studies, we recommend that diarrhea be clearly defined and consistently recorded as a secondary outcome. Antibiotic status of participants receiving iron should also be collected to help assess possible drug interactions resulting in a “red stool effect.” Finally, further microbiome research is required to better understand the effects of oral iron on specific bacterial species in the colon.
Highlights
Iron is required for many essential metabolic processes [1]
There was no clear relation between diarrhea and type of intervention or amount of iron administered observed
Antibiotic status of participants receiving iron should be collected to help assess possible drug interactions resulting in a “red stool effect.”
Summary
Iron is required for many essential metabolic processes [1]. Pathogens and humans require iron and have developed complex ways to acquire, transport, and store it [2]. Bacteria have developed multiple mechanisms for chelating iron and heme directly and for acquiring iron attached to various human iron chaperone molecules [3]. Humans tightly regulate free iron at a molar concentration of less than 1024, and bind it with proteins such as ferritin, transferrin, and lactoferrin [4]. Iron deficiency anemia occurs when both intake and total body iron are insufficient to meet the needs of erythropoiesis. A 2011 WHO report estimated a prevalence of 43% of anemia. The impact of iron supplements and iron fortification on diarrhea in children is controversial, with some studies reporting an increase and others reporting no effect
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