Effect of combining multiple micronutrients with iron supplementation on Hb response in children: systematic review of randomized controlled trials.

OBJECTIVES To study the effect of combining multiple (two or more) micronutrients with Fe supplementation on Hb response, when compared with placebo and with Fe supplementation, in children. DATA SOURCES Electronic databases, personal files, hand search of reviews, bibliographies of books, and abstracts and proceedings of international conferences. REVIEW METHODS Randomized controlled trials evaluating change in Hb levels with interventions that included Fe and multiple-micronutrient supplementation in comparison to placebo alone or Fe alone were analysed in two systematic reviews. RESULTS Twenty-five trials were included in the review comparing Fe and micronutrient supplementation with placebo. The pooled estimate (random effects model) for change in Hb with Fe and micronutrient supplementation (weighted mean difference) was 0.65 g/dl (95 % CI 0.50, 0.80, P < 0.001). Lower baseline Hb, lower height-for-age Z score, non-intake of 'other micronutrients' and malarial non-hyperendemic region were significant predictors of greater Hb response and heterogeneity. Thirteen trials were included in the review comparing Fe and micronutrient supplementation with Fe alone. The pooled estimate for change in Hb with Fe and micronutrient supplementation (weighted mean difference) was 0.14 g/dl (95 % CI 0.00, 0.28, P = 0.04). None of the variables were found to be significant predictors of Hb response. CONCLUSIONS Synthesized evidence indicates that addition of multiple micronutrients to Fe supplementation may only marginally improve Hb response compared with Fe supplementation alone. However, addition of 'other micronutrients' may have a negative effect. Routine addition of unselected multiple micronutrients to Fe therefore appears unjustified for nutritional anaemia control programmes.