Efficacy and Safety of Daily Iron Supplementation in Children: Lessons from Three Systematic Reviews and Meta-analyses of Randomized Controlled Trials.

ABSTRACT

Objectives: 47% of pre-school children and 25% of school-aged children are anaemic. Daily iron supplementation remains a key anaemia control intervention, but benefits and safety in children are debated. We systematically reviewed evidence for daily iron supplementation in 4–23m, 2-5y and 5-12y children. Methods: Separate searches and systematic-reviews/meta-analyses were performed for each age-group. Electronic databases and other sources were searched for randomized controlled trials comparing daily iron supplementation with control. Random-effects meta-analysis was used. Risk-of-bias was estimated using the Cochrane tool. Results: For children 4-23m, 2-5y and 5-12y respectively we identified 9533, 9169 and 16501 citations, from which 35, 15 and 32 eligible studies were identified, of which 9, 0 and 4 were at low overall risk-of-bias. Iron improved haemoglobin and ferritin and, in 4-23 m and 5-12y, reduced anaemia and iron deficiency. In 5-12y, iron improved global cognitive scores (SMD 0.50 [0.11, 0.90], p = 0.01) and in anaemic children, IQ (MD 4.55 [0.16, 8.94], p = 0.04). In 2-5y, limited data suggested a small improvement from iron in cognitive performance. No benefit was evident in 4-23 m (Bayley’s mental development index MD 1·65 [–0·63, 3·94]) overall but was seen in iron deficient children (MD 5.90 [1.91, 10.00], p=0.005). Iron did not benefit growth in 4-23 m or 2-5y, but did improve growth in 5-12y. Vomiting and fever were increased in 4-23m receiving iron. Conclusions: Although supplementation iron improves cognition in older children or children with ID, evidence of non-haematologic benefit in pre-school children is inadequate. Further research is needed to enable guideline development.