Zinc Supplementation for Promoting Growth in Children Under 5 years of age in Low- and Middle-income Countries: A Systematic Review

ABSTRACT

Objective: To study the effect of zinc supplementation in children under 5 years of age from low- and middle-income countries (LMICs) onanthropometry and prevalence of malnutrition.Design: Systematic review of randomized controlled trials and cluster randomized trials.Setting: Low- and middle-income countries.Participants: 63 trials with zinc supplementation, incorporating data on 27372 children. Trials conducted exclusively in specificallydiseased participants and in children with severe acute malnutrition were excluded.Intervention Zinc supplementation, provided either as medicinal supplementation or through food fortification.Outcome Measures: (i) Anthropometry weight, height, weight-for-height, mid-arm circumference, head circumference; (ii) Prevalenceof malnutrition.Results: There was no evidence of effect on height-for-age Z score at the end of supplementation period (25 trials; 9165 participants;MD= 0.00 Z; 95% CI -0.07, 0.07; P=0.98; moderate quality evidence) with significant heterogeneity (I² = 57%; P<0.001) related to doseand duration of zinc between trials. There was little or no effect on change in height-for-age Z score (13 trials; 8852 participants; MD= 0.11Z; 95% CI -0.00, 0.21; P=0.05), but the heterogeneity was considerable (I²=94%; P<0.001). There was no evidence of effect on length(6303 participants; MD= 1.18 cm; 95% CI -0.63, 2.99 cm, P=0.20; moderate quality evidence; considerable heterogeneity, I²=99%) but alittle positive effect on change in length (19 trials; 10783 participants; MD= 0.43 cm; 95% CI 0.16, 0.70, P=0.002; moderate qualityevidence; considerable heterogeneity, I²=93%). There was no evidence of effect on weight-for-age Z score or change in weight-for-age Zscore but a little positive effect on weight (19 trials; 8851 study participants; MD= 0.23 kg; 95% CI 0.03, 0.42; P=0.02; considerableheterogeneity, I²=91%) and change in weight (kg) (23 trials; 10143 study participants; MD= 0.11 kg; 95% CI 0.05, 0.17, P<0.001,substantial heterogeneity, I²=80%). There was no evidence of effect on weight-for-height Z score, and mid upper arm circumference at theend of supplementation period, but there was a little positive effect on change in mid-arm circumference from baseline (8 trials; 1724participants; MD = 0.09 cm; 95% CI 0.01, 0.16; P=0.03; no heterogeneity, I²=0%). Head circumference in zinc supplemented group wasmarginally higher compared to control (2966 study participants; MD= 0.39 cm; 95% CI 0.03, 0.75; P=0.03; substantial heterogeneity,I²=67%). There was no evidence of benefit in stunting (10 trials; 11838 study participants; RR= 1.0; 95% CI 0.95, 1.06; P=0.89; moderatequality evidence; no significant heterogeneity, I²=11%), wasting (7 trials; 8988 study participants; RR= 0.94; 95% CI 0.82, 1.06; P=0.31;moderate quality evidence; no significant heterogeneity, I²=13%) or underweight (7 trials; 8677 study participants; RR= 1.08; 95% CI 0.96,1.21; P=0.19; moderate quality evidence; substantial heterogeneity, I²=73%).Conclusion: Available evidence suggests that zinc supplementation probably leads to little or no improvement in anthropometric indicesand malnutrition (stunting, underweight and wasting) in children under five years of age in LMICs. Advocating zinc supplementation as apublic health measure to improve growth, therefore, appears unjustified in these settings with scarce resources.