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

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          Abstract

          (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 I 2 and τ 2 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.

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          Most cited references20

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          Maternal and child undernutrition and overweight in low-income and middle-income countries

          The Lancet, 382(9890), 427-451
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            Long-term consequences of stunting in early life.

            This review summarizes the impact of stunting, highlights recent research findings, discusses policy and programme implications and identifies research priorities. There is growing evidence of the connections between slow growth in height early in life and impaired health and educational and economic performance later in life. Recent research findings, including follow-up of an intervention trial in Guatemala, indicate that stunting can have long-term effects on cognitive development, school achievement, economic productivity in adulthood and maternal reproductive outcomes. This evidence has contributed to the growing scientific consensus that tackling childhood stunting is a high priority for reducing the global burden of disease and for fostering economic development. Follow-up of randomized intervention trials is needed in other regions to add to the findings of the Guatemala trial. Further research is also needed to: understand the pathways by which prevention of stunting can have long-term effects; identify the pathways through which the non-genetic transmission of nutritional effects is mediated in future generations; and determine the impact of interventions focused on linear growth in early life on chronic disease risk in adulthood. © 2011 Blackwell Publishing Ltd.
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              The role of zinc in growth and cell proliferation.

              The inhibition of growth is a cardinal symptom of zinc deficiency. In animals fed a zinc-inadequate diet, both food intake and growth are reduced within 4-5 d. Despite the concomitant reduction in food intake and growth, reduced energy intake is not the limiting factor in growth, because force-feeding a zinc-inadequate diet to animals fails to maintain growth. Hence, food intake and growth appear to be regulated by zinc through independent, although well coordinated, mechanisms. Despite the long-term study of zinc metabolism, the first limiting role of zinc in cell proliferation remains undefined. Zinc participates in the regulation of cell proliferation in several ways; it is essential to enzyme systems that influence cell division and proliferation. Removing zinc from the extracellular milieu results in decreased activity of deoxythymidine kinase and reduced levels of adenosine(5')tetraphosphate(5')-adenosine. Hence, zinc may directly regulate DNA synthesis through these systems. Zinc also influences hormonal regulation of cell division. Specifically, the pituitary growth hormone (GH)-insulin-like growth factor-I (IGF-I) axis is responsive to zinc status. Both increased and decreased circulating concentrations of GH have been observed in zinc deficiency, although circulating IGF-I concentrations are consistently decreased. However, growth failure is not reversed by maintaining either GH or IGF-I levels through exogenous administration, which suggests the defect occurs in hormone signaling. Zinc appears to be essential for IGF-I induction of cell proliferation; the site of regulation is postreceptor binding. Overall, the evidence suggests that reduced zinc availability affects membrane signaling systems and intracellular second messengers that coordinate cell proliferation in response to IGF-I.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                20 March 2018
                March 2018
                : 10
                : 3
                : 377
                Affiliations
                [1 ]Institutional Centers of Clinical and Translational Research, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115, USA
                [2 ]Division of Gastroenterology, Hepatology and Nutrition, Boston Children’s Hospital, 300 Longwood Ave, Boston, MA 02115, USA; christopher.duggan@ 123456childrens.harvard.edu
                [3 ]Friedman School of Nutrition Science and Policy, Tufts University, 150 Harrison Ave, Boston, MA 02111, USA; laura.pimpin@ 123456gmail.com (L.P.); shulkinm@ 123456gmail.com (M.S.); Sarah.Kranz@ 123456tufts.edu (S.K.); Dariush.Mozaffarian@ 123456tufts.edu (D.M.)
                [4 ]Department of Nutrition, Harvard T.H. Chan School of Public Health, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA
                [5 ]Department of Global Health and Population, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA; mina@ 123456hsph.harvard.edu
                [6 ]Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA
                Author notes
                [* ]Correspondence: Enju.Liu@ 123456childrens.harvard.edu ; Tel.: +857-218-3822
                Article
                nutrients-10-00377
                10.3390/nu10030377
                5872795
                29558383
                07ca1a35-7e9f-4b00-bb30-07a3f8b06df3
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 27 February 2018
                : 14 March 2018
                Categories
                Review

                Nutrition & Dietetics
                zinc supplementation,child growth,randomized controlled trial,meta-analysis,systematic review

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