Effect of Zinc Supplementation on Growth Outcomes in Children under 5 Years of Age

(1) Background: The effects of zinc supplementation on child growth, and prior reviews of these studies, have shown mixed results. We aim to systematically review and meta-analyze randomized controlled trials evaluating effects of preventive zinc supplementation for 3 months or longer during pregnancy or in children up to age 5 years on pregnancy outcomes and child growth; (2) Methods: We searched PubMed, EMBASE, Cochrane Library, Web of Science, and trial registries for eligible trials up to October 10, 2017. Inclusion selection and data extractions were performed independently and in duplicate. Study quality was evaluated by the Cochrane Risk of Bias tool. Findings were pooled using random effects meta-analysis, with heterogeneity assessed by I² and τ² statistic, stratified analyses, and meta-regression, and publication bias by Egger's and Begg's tests; (3) Results: Seventy-eight trials with 34,352 unique participants were identified, including 24 during pregnancy and 54 in infancy/childhood. Maternal zinc supplementation did not significantly increase birth weight (weighted mean difference (WMD) = 0.08 kg, 95%CI: -0.05, 0.22) or decrease the risk of low birth weight (RR = 0.76, 95%CI: 0.52-1.11). Zinc supplementation after birth increased height (WMD = 0.23 cm, 95%CI: 0.09-0.38), weight (WMD = 0.14 kg, 95%CI: 0.07-0.21), and weight-for-age Z-score (WMD = 0.04, 95%CI: 0.001-0.087), but not height-for-age Z-score (WMD = 0.02, 95%CI: -0.01-0.06) or weight-for-height Z score (WMD = 0.02, 95%CI: -0.03-0.06). Child age at zinc supplementation appeared to modify the effects on height (P-interaction = 0.002) and HAZ (P-interaction = 0.06), with larger effects of supplementation starting at age ≥2 years (WMD for height = 1.37 cm, 95%CI: 0.50-2.25; WMD for HAZ = 0.12, 95%CI: 0.05-0.19). No significant effects of supplementation were found on the risk of stunting, underweight or wasting; (4) Conclusion: Although the possibility of publication bias and small study effect could not be excluded, the current meta-analysis indicates that zinc supplementation in infants and early childhood, but not pregnancy, increases specific growth outcomes, with evidence for a potentially stronger effect after 2 years of age. These findings inform recommendation and policy development for zinc supplementation to improve growth among young children.