Guts, Germs, and Iron: A Systematic Review on Iron Supplementation, Iron Fortification, and Diarrhea in Children Aged 4-59 Months.

BACKGROUND: 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. OBJECTIVE: The 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. METHODS: Randomized 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. RESULTS: Of 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. CONCLUSIONS: Studies 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.