Oral iron supplementation and anaemia in children according to schedule, duration, dose and cosupplementation: a systematic review and meta-analysis of 129 randomised trials

INTRODUCTION: WHO guidelines on iron supplementation among children call for further research to identify the optimal schedule, duration, dose and cosupplementation regimen. METHODS: A systematic review and meta-analysis of randomised controlled trials was undertaken. Randomised controlled trials providing ≥30 days of oral iron supplementation versus placebo or control to children and adolescents aged <20 years were eligible. Random-effects meta-analysis was used to summarise the potential benefits and harms of iron supplementation. Meta-regression was used to estimate iron effect heterogeneity. RESULTS: 129 trials with 201 intervention arms randomised 34 564 children. Frequent (3–7/week) and intermittent (1–2/week) iron regimens were similarly effective at decreasing anaemia, iron deficiency and iron deficiency anaemia (p heterogeneity >0.05), although serum ferritin levels and (after adjustment for baseline anaemia) haemoglobin levels increased more with frequent supplementation. Shorter (1–3 months) versus longer (7+ months) durations of supplementation generally showed similar benefits after controlling for baseline anaemia status, except for ferritin which increased more with longer duration of supplementation (p=0.04). Moderate-dose and high-dose supplements were more effective than low-dose supplements at improving haemoglobin (p=0.004), ferritin (p=0.008) and iron deficiency anaemia (p=0.02), but had similar effects to low-dose supplements for overall anaemia. Iron supplementation provided similar benefits when administered alone or in combination with zinc or vitamin A, except for an attenuated effect on overall anaemia when iron was cosupplemented with zinc (p=0.048). CONCLUSIONS: Weekly and shorter duration iron supplementation at moderate or high doses might be optimal approaches for children and adolescents at risk of deficiency. TRIAL REGISTRATION NUMBER: CRD42016039948.