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Evidence for Action: Does iron supplementation increase the risk of infectious diseases in children?
Best Practices: Issue 14 | 2003-05-01
contributed by: Global Health Council
region: Global
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Evidence for Action is a series of articles that present key findings from systematic reviews of health care interventions. It is designed to help decision-makers cope with the ever-increasing volume of health literature through targeted summaries of reviews that evaluate the effects of health care interventions. Monthly additions to the series will be posted on http://www.globalhealth.org
Does iron supplementation increase the risk of infectious diseases in children?
KEY POINTS
- Iron deficiency is a significant health concern, most notably in children living in low-income communities.
- Iron fortified foods and supplements aim to reduce iron deficiency anemia and its associated health risks.
- Some research suggests that iron supplementation may promote infections in children.
- This systematic review found that iron supplementation produced no harmful effects on the overall incidence of infectious disease in children. However, it slightly increased the risk of diarrhea.
BACKGROUND
Iron deficiency is the most common form of malnutrition, affecting an estimated 4 to 5 million people globally. According to WHO, nearly 50 percent of children under five in developing countries may be iron deficient, often due to diets low in this micronutrient. In tropical environments the problem may be exacerbated by malaria and worm infestations.
Iron Deficiency Anemia (IDA), a condition in which the body contains inadequate amounts of iron to meet its demands, is common and often severe in poor communities. IDA can impair both physical and mental development in children, with even mild anemia negatively affecting normal development in infants and young children. With early intervention, these effects can be reversed.
As iron-rich foods may not be available or accessible in low- and middle-income countries, programs aimed at providing iron through supplementation or fortification of basic food are widely advocated. However, data on the effect of iron supplementation are conflicting, especially in populations with a high infectious disease burden. Some research indicates that iron deficiency may prevent bacterial growth that in turn may offer an important defense mechanism against infection. Other studies suggest that iron deficiency may weaken the immune system, thus increasing susceptibility to infection. The evidence from prospective research of iron supplementation has been inconsistent, with studies showing either lower infection rates, no effect or higher infection rates. As children in developing countries are at substantial risk of illness and death due to infectious disease, it is vital to clearly establish the safety of iron supplementation.
REVIEW OBJECTIVES
To evaluate the effect of iron supplementation on the incidence of infections in children.
REVIEW MAIN FINDINGS
Of the 47 trials identified, 28 met the review inclusion criteria.
Iron supplementation in children has no apparent harmful effect on the overall incidence of infectious illnesses.
Iron supplementation is associated with a small increase in the risk of diarrhea.
REVIEW IMPLICATIONS FOR PRACTICE
There appears to be no increase in infections in children receiving iron supplements or foods fortified with iron. While there was an increased risk for developing diarrhea, the risk equates to an incidence rate difference of only 0.05 episodes per child per year. It cannot be determined from this study whether diarrhea resulted from infection (dysentery) or from the known irritating effect of iron on the stomach and intestine. Further analysis showed there was no increased incidence of diarrhea among those receiving fortified foods. This suggests that foods fortified with iron may provide a safer and more beneficial route when administering iron supplementation.
REVIEW IMPLICATIONS FOR RESEARCH
While clinical and methodological variations (heterogeneity) were present, the main findings remained constant when sensitivity analyses were performed. Uniform definitions and active disease surveillance would have provided greater weight to findings.
Due to a potential protective effect against respiratory tract infections, further research evaluating the effect of iron-fortified foods on iron levels in the blood and their relationship to infection is suggested.
It will be difficult to ascertain the safety of iron in people with anemia, most notably in malaria-endemic regions, due to the ethical problem of withholding treatment in the placebo group of a controlled clinical trial.
KEY REVIEW COMPONENTS
Search strategy for studies.
Cochrane controlled trials register, MEDLINE, EMBASE, IBIDS and Healthstar Reference lists of identified articles
Handsearching of reviews, book bibliographies, international conference abstracts and proceedings
Donor agencies, "experts" and authors of recent iron supplementation trials contacted
Selection criteria for studies.
Randomized controlled trials comparing iron supplementation (oral route or parenterali) or fortification (formula milk or cereal) with placeboii
Trials evaluating one or more infectious illnesses as an outcome
Studies reviewed.
Twenty-eight trials (22 published and 6 unpublished) including 7,892 children followed up for 5,650 child years
Trials were conducted in Africa (11), Asia (8), the Americas (5), Europe (2), and Australasia (2)
20 trials used oral supplementation; 3 trials used parenteral administration; and 5 trials used fortified foods.
Outcomes.
Incidence rate ratios (IRR) for:
All recorded illnesses (26 trialsiii)
1.02, 95% CIiv 0.96 to 1.08
Diarrhea (17 trials)
1.11, 95% CI 1.01 to 1.23
Non-diarrheal infections (24 trials)
0.97, 95% CI 0.95 to 1.06
Dysentery (2 trials)
1.00, 95% CI 0.87 to 1.15
Malaria (5 trials)
1.07, 95% CI 0.94 to 1.24
Respiratory tract infections (17 trials)
0.98, 95% CI 0.90 to 1.06
Lower respiratory tract infections (8 trials)
0.97, 95% CI 0.83 to 1.23
Other infections (13 trials)v
1.04, 95% CI 0.98 to 1.11
iAdministered in a manner other than through the digestive tract.
iiTrials could not be placebo controlled if iron was given parenterally as administering a similar placebo would be difficult.
iiiThree trials were treated as 6 in analysis due to two arms in the study.
ivConfidence interval (random effects model). Random effects model used due to statistical heterogeneity.
vIncluded septicemia, urinary tract infection, tuberculosis, unspecified fever, pyoderma and infectious illnesses not classifiable under RTI, diarrhea or malaria.
Evidence for Action review summaries are produced by the Global Health Council. We have made every effort to provide an accurate summary of the review article profiled here. If further information is required, we encourage you to read the original review article: Source: Gera T, Sachdev HPS. Effect of iron supplementation on incidence of infectious illness in children: systematic review. BMJ 2002; 325:1142
Evidence for Action review summary is written by Colleen Murphy, Research Associate, Research and Analysis Department, Global Health Council, 1701 K Street, NW, Suite 600, Washington, DC 20006, USA; cmurphy@globalhealth.org ; http://www.globalhealth.org
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