A Cochrane systematic review (17) was conducted to assess the effects and safety of intermittent iron supplementation alone or in combination with other micronutrients inchildren under 12 years of age with regard to health and nutrition outcomes. The review compared the provision of iron supplements on an intermittent basis versus no intervention or placebo, and versus daily use of iron supplements, among children living in a variety of settings, including malaria-endemic areas.
The outcomes considered to be critical for decision-making by the Nutrition Guidance Expert Advisory Group (NUGAG) were anaemia, haemoglobin concentration, iron status and mortality. The potential modifying effects of the baseline anaemia prevalence, total iron dose per week, the intermittent regimen scheme, duration of the intervention, supplement formulation and sex were also assessed.
The review included 33 randomized controlled trials involving 13 144 children from 20 countries in Latin America, Africa and Asia where anaemia prevalence was moderate to high. Most of the trials used ferrous sulfate as the iron source, with doses ranging from 7.5 mg to 200 mg of elemental iron per week. In five studies, iron was given in combination with folic acid, in doses that ranged from 100 μg (0.1 mg) to 500 μg (0.5 mg) per week.
Compared with placebo or no intervention, intermittent iron supplementation (alone or in combination with other nutrients) in children younger than 12 years of age significantly increased the concentration of haemoglobin (mean difference (MD) 5.20 g/l, 95% confidence interval (CI) 2.51–7.88, 19 studies) and ferritin (MD 14.17 μg/l, 95% CI 3.53–24.81, five studies), and reduced the risk of presenting anaemia at the end of the intervention (relative risk (RR) 0.51, 95% CI 0.37–0.72, 10 studies).
On the other hand, compared with children receiving daily iron supplements, those receiving iron supplements intermittently were more likely to be anaemic at the end of the intervention (RR 1.23, 95% CI 1.04–1.47, six studies) but the mean difference in the haemoglobin and ferritin concentrations between the two groups was not significant (MD −0.60, g/l 95% CI −1.54 to 0.35, 19 studies, and −4.19 μg/l, 95% CI −9.42 to 1.05, 10 studies, respectively). Adherence tended to be higher among children receiving intermittent supplementation compared with those receiving daily supplementation, although this result was not statistically significant.
The micronutrient composition of the supplements (iron alone, iron plus folic acid, or iron plus other micronutrients) did not impact on the above findings, although most of the evidence was derived from trials using supplements containing only iron. In addition, the intervention seemed efficacious in settings with different baseline prevalence of anaemia, in both sexes, across trials lasting either less or more than 3 months and with all intermittent regimens.
No deaths were reported in the trials. Although limited data were available on outcomes related to morbidity, neurocognitive outcomes, other indicators of vitamin and mineral status, and side-effects, no evidence was found of increased morbidity or side-effects, including in malaria-endemic settings.
In comparison with a placebo or no intervention, the overall quality of the available evidence was found to be moderate for anaemia, low for haemoglobin and ferritin concentrations and very low for iron deficiency. When compared with daily supplementation, the quality of the available evidence for intermittent supplementation with regard to anaemia and haemoglobin and ferritin concentrations was found to be low and for iron deficiency it was very low (Annex 1).
