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

Abstract

IntroductionWHO guidelines on iron supplementation among children call for further research to identify the optimal schedule, duration, dose and cosupplementation regimen.MethodsA 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.Results129 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).ConclusionsWeekly and shorter duration iron supplementation at moderate or high doses might be optimal approaches for children and adolescents at risk of deficiency.Trial registration numberCRD42016039948.

Oral iron therapy: Current concepts and future prospects for improving efficacy and outcomes

“…Although this meta‐analysis did not find an increased incidence of adverse outcomes associated with oral iron supplementation, negative side effects associated with oral iron supplementation have been described in other human trials 14 . In sum, weekly and more frequent iron supplementation at moderate to high doses was most effective at restoring iron balance while still avoiding adverse GI side effects 14,77 …”

“…A recent systematic review of published iron supplementation studies done in children and adolescents <20 years of age over the past 50 years considered the effect of dose, schedule and duration on the efficacy of oral iron therapy. 77 Most of these clinical trials (70%) utilized iron salts, including FeSO 4 (most frequently) and ferrous fumarate. Iron supplementation 1-2 times per week had similar efficacy in mitigating IDA compared to supplementation 3-7 times per week, while higher doses were more effective at improving anaemia compared to lower doses.…”

“…14 In sum, weekly and more frequent iron supplementation at moderate to high doses was most effective at restoring iron balance while still avoiding adverse GI side effects. 14,77 Recent studies, again mainly using oral iron salts, demonstrated that fractional iron absorption is higher at lower iron doses and when supplements are taken on alternate days. [29][30][31]78,79 Oral iron doses ≥60 mg in iron-deficient women triggered an increase in circulating hepcidin that persisted up to 24 h after dosing, thereby decreasing absorption of supplemental iron administered the following day by 35%-45%.…”

“…A recent systematic review of published iron supplementation studies done in children and adolescents <20 years of age over the past 50 years considered the effect of dose, schedule and duration on the efficacy of oral iron therapy 77 . Most of these clinical trials (70%) utilized iron salts, including FeSO 4 (most frequently) and ferrous fumarate.…”

Safety and efficacy of East Asian herbal medicine for iron deficiency anemia in children and adolescents: a systematic review and meta-analysis

“…The symptoms reported as AEs in both groups were mostly gastrointestinal symptoms, such as vomiting, abdominal pain, diarrhea, and constipation. As gastrointestinal AEs are one of the main factors that reduce adherence to oral iron treatment in children with IDA ( Andersen et al, 2023 ), it is important to evaluate whether HM is significantly safer than oral iron. Although the meta-ANOVA revealed no significant difference between the HM monotherapy and combination groups ( p = 0.07), significantly fewer AEs were reported in both the HM alone and HM plus oral iron treatment groups compared to those reported in the oral iron groups.…”