Effect of preventive zinc supplementation on linear growth in children under 5 years of age in developing countries: a meta-analysis of studies for input to the lives saved tool

Introduction: Zinc plays an important role in cellular growth, cellular differentiation and metabolism. The results of previous meta-analyses evaluating effect of zinc supplementation on linear growth are inconsistent. We have updated and evaluated the available evidence according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria and tried to explain the difference in results of the previous reviews. Methods: A literature search was done on PubMed, Cochrane Library, IZiNCG database and WHO regional data bases using different terms for zinc and linear growth (height). Data were abstracted in a standardized form. Data were analyzed in two ways i.e. weighted mean difference (effect size) and pooled mean difference for absolute increment in length in centimeters. Random effect models were used for these pooled estimates. We have given our recommendations for effectiveness of zinc supplementation in the form of absolute increment in length (cm) in zinc supplemented group compared to control for input to Live Saves Tool (LiST). Results: There were thirty six studies assessing the effect of zinc supplementation on linear growth in children < 5 years from developing countries. In eleven of these studies, zinc was given in combination with other micronutrients (iron, vitamin A, etc). The final effect size after pooling all the data sets (zinc +/- iron etc) showed a significant positive effect of zinc supplementation on linear growth [Effect size: 0.13 (95% CI 0.04, 0.21), random model] in the developing countries. A subgroup analysis by excluding those data sets where zinc was supplemented in combination with iron showed a more pronounced effect of zinc supplementation on linear growth [Weighed mean difference 0.19 (95 % CI 0.08, 0.30), random model]. A subgroup analysis from studies that reported actual increase in length (cm) showed that a dose of 10 mg zinc/day for duration of 24 weeks led to a net a gain of 0.37 (+/- 0.25) cm in zinc supplemented group compared to placebo. This estimate is recommended for inclusion in Lives Saved Tool (LiST) model. Conclusions: Zinc supplementation has a significant positive effect on linear growth, especially when administered alone, and should be included in national strategies to reduce stunting in children < 5 years of age in developing countries.