Abstract: We included 33 trials, involving 13,114 children (˜49% females) from 20 countries in Latin America, Africa and Asia. The methodological quality of the trials was mixed. Nineteen trials evaluated intermittent iron supplementation versus no intervention or a placebo and 21 studies evaluated intermittent versus daily iron supplementation. Some of these trials contributed data to both comparisons. Iron alone was provided in most of the trials. Fifteen studies included children younger than 60 months; 11 trials included children 60 months and older, and seven studies included children in both age categories. One trial included exclusively females. Seven trials included only anaemic children; three studies assessed only non-anaemic children, and in the rest the baseline prevalence of anaemia ranged from 15% to 90%. In comparison with receiving no intervention or a placebo, children receiving iron supplements intermittently have a lower risk of anaemia (average risk ratio (RR) 0.51, 95% confidence interval (CI) 0.37 to 0.72, ten studies) and iron deficiency (RR 0.24, 95% CI 0.06 to 0.91, three studies) and have higher haemoglobin (mean difference (MD) 5.20 g/L, 95% CI 2.51 to 7.88, 19 studies) and ferritin concentrations (MD 14.17 µg/L, 95% CI 3.53 to 24.81, five studies). Intermittent supplementation was as effective as daily supplementation in improving haemoglobin (MD –0.60 g/L, 95% CI –1.54 to 0.35, 19 studies) and ferritin concentrations (MD –4.19 µg/L, 95% CI –9.42 to 1.05, 10 studies), but increased the risk of anaemia in comparison with daily iron supplementation (RR 1.23, 95% CI 1.04 to1.47, six studies). Data on adherence were scarce and it tended to be higher among those children receiving intermittent supplementation, although this result was not statistically significant. We did not identify any differential effect of the type of intermittent supplementation regimen (one, two or three times a week), the total weekly dose of elemental iron, the nutrient composition, whether recipients were male or female or the length of the intervention. Intermittent iron supplementation is efficacious to improve haemoglobin concentrations and reduce the risk of having anaemia or iron deficiency in children younger than 12 years of age when compared with a placebo or no intervention, but it is less effective than daily supplementation to prevent or control anaemia. Intermittent supplementation may be a viable public health intervention in settings where daily supplementation has failed or has not been implemented. Information on mortality, morbidity, developmental outcomes and side effects, however, is still lacking.

Plain-language summary: The studies were of mixed quality. Overall, the results of this review show that giving children supplements with iron alone or in combination with other vitamins and minerals one, two or three times a week approximately halves their risk of having anaemia in comparison with receiving no iron supplements or a placebo. Giving children supplements on a intermittent basis was as effective as daily supplementation for improving haemoglobin and ferritin concentrations, although, children receiving iron supplements intermittently were at higher risk of having anaemia. We aimed to examine the effects of intermittent supplementation on illness, death, and school and physical performance, as well as on other side effects, but there was insufficient information to draw firm conclusions. In summary, intermittent iron supplementation is efficacious to improve haemoglobin concentrations and reduce the risk of having anaemia or iron deficiency in children younger than 12 years of age when compared with a placebo or no intervention, but it is less effective than daily supplementation to prevent or control anaemia. Intermittent supplementation may be a viable public health intervention in settings where daily supplementation has failed or has not been implemented. Information on mortality, morbidity, developmental outcomes and side effects, however, is still lacking.