Efficacy and Safety of Daily Iron Supplementation in Children: Lessons from Three Systematic Reviews and Meta-analyses of Randomized Controlled Trials
Sant-Rayn Pasricha *
University of Melbourne, Melbourne, Victoria, Australia and University of Oxford, Oxford, Oxfordshire, UK.
Michael Low
The Alfred Hospital, Melbourne, Victoria, Australia.
Jane Thompson
The University of Adelaide, Adelaide, South Australia, Australia.
Ann Farrell
Monash Health, Clayton, Victoria, Australia.
Emily Hayes
Monash Health, Clayton, Victoria, Australia.
Kongolo Kalumba
Monash Specialists Women’s and Children’s, Clayon, Victoria, Australia.
Beverley-Ann Biggs
University of Melbourne, Melbourne, Victoria, Australia.
*Author to whom correspondence should be addressed.
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.