Improving iron status in children in poor environments

Iron deficiency among children is common, especially in less developed countries, and affects psychomotor development.¹ But the potential risk is that improving iron status may stimulate the development of infection.²,³ Although iron supplements improve cognition and growth⁴,⁵ of deficient children, they can be harmful. Microbial proliferation is influenced by the iron concentration of the culture medium⁶ and iron supplements can produce oxidative stress.⁷ Over the years increased infection rates have been reported after iron intervention.⁸ Bad news always travels faster than good news and clinicians and public health professionals have not given wholehearted support to programmes for prevention of iron deficiency when they are introduced in populations with a high prevalence of infection.

A careful, systematic review in this issue (p 1142) by Gera and Sachdev of a large number of iron intervention trials provides considerable new insights.⁹ Using strict criteria they identified 47 randomised controlled trials and analysed 28—22 published and six unpublished studies. Overall data are from 7892 children who come from a range of environments including Africa,¹⁰ Asia,⁸ the Americas,⁵ Europe,² and Australia and New Zealand.² They found a rate of infection among the iron intervention groups that was no higher than that of the controls. On analysis for individual infections, however, a small but statistically significantly increased risk of diarrhoea was found (11%, P<0.04). In practice this represents only an extra 0.05 diarrhoeal episodes per child per year (95% confidence interval 0.03 to 0.01) and is not striking. Intervention with iron did not have a significant effect on malaria. Is that the end of the story?

Two important infections were not identified during the studies included in this analysis—HIV and hepatitis B. Both are potentially influenced by iron status.^10–12 However, associations between iron status and infection may be bidirectional—viral infection can alter iron metabolism and iron status may alter severity of disease. No trials have been conducted on the effect of iron interventions on viral replication rates or severity of disease in HIV or hepatitis C, and so a possible deleterious effect of iron intervention has not been ruled out.

How should these findings affect current public health nutrition policy, especially for children in less developed countries? The rigorous review supports the safety of iron interventions among anaemic children, even if they live in poor environments where infective agents are common. It is not yet clear whether iron interventions make HIV or hepatitis C worse. Randomised clinical trials among iron deficient patients with these infections would clarify the situation.