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

Abstract

To study the effect of zinc supplementation in children under 5 years of age rom low- and middle-income countries (LMICs) on anthropometry and prevalence of malnutrition. Systematic review of randomized controlled trials and cluster randomized trials. Low- and middle-income countries. 63 trials with zinc supplementation, incorporating data on 27372 children. Trials conducted exclusively in specifically diseased participants and in children with severe acute malnutrition were excluded. Zinc supplementation, provided either as medicinal supplementation or through food fortification. (i) Anthropometry: weight, height, weight-for-height, mid-arm circumference, head circumference; (ii) Prevalence of malnutrition. 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 dose and duration of zinc between trials. There was little or no effect on change in height-for-age Z score (13 trials; 8852 participants; MD= 0.11 Z; 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 a little positive effect on change in length (19 trials; 10783 participants; MD= 0.43 cm; 95% CI 0.16, 0.70, P=0.002; moderate quality evidence; considerable heterogeneity, I²=93%). There was no evidence of effect on weight-for-age Z score or change in weight-for-age Z score 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; considerable heterogeneity, 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 the end of supplementation period, but there was a little positive effect on change in MUAC from baseline (8 trials; 1724 participants; MD = 0.09 cm; 95% CI 0.01, 0.16; P=0.03; no heterogeneity, I²=0%). Head circumference in zinc supplemented group was marginally 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; Moderate Quality 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%). Available evidence suggests that zinc supplementation probably leads to little or no improvement in anthropometric indices and malnutrition (stunting, underweight and wasting) in children under five years of age in LMICs. Advocating zinc supplementation as a public health measure to improve growth, therefore appears unjustified in these settings with scarce resources.