Zinc supplementation in pediatric practice
Scientific Knowledge about the essentiality of zinc in human health and diseases is emerging. Children are more prone to infectious diseases like diarrhoea, pneumonia, common cold and sepsis that lead to enormous deaths in the developing world. Zinc is mainly required for the maturation of B and T cells and its deficiency adversely affects the growth and functions of immune cells leading to impaired immune functions and increased susceptibility to infection. This review makes a summary of the effects of zinc supplementation in diarrhoea, common cold focusing more on the future perspective of zinc in sepsis.
awareness towards zinc supplementation: A review. Int J Nutr Metab. 2012;4:45–50. 2
Collipp PJ, Nichols BL, Roy C, et al. Vitamin and mineral supplement needs in normal children in the United States. Pediatr. 1980;66:1015–21. 3
(http://www.naturalhealthyconcepts.com/zinc- benefits.html). healthy concepts 4
Counting the zinc proteins encoded in the human genome. J Proteome Res. 2006;5:196–201. 5
function: The biological basis of altered resistance to infection. Am J Clin Nutr. 1998;68:447–63. 6
supplementation for the treatment or prevention of disease: Current status and future perspectives. Exp Gerontol. 2008;43:394–408. 7
duration of exclusive breastfeeding:Report of an expert consultation. Geneva: WHO 2001. 8
J, Lemmonier D. Zinc supplements in breastfed infants. Lancet. 1992;340:683–85. 9
The trace element of major importance in human nutrition and health. Int J Med Sci Public Health. 2013;2:1–6. National Institutes of
Yanagisawa H. Clinical aspects of zinc deficiency. J Japan Med Assoc. 2002;127:261–68. 13
and Th2 cytokine shifts. J Infect Dis. 2000;182:62– 68. 15
Brewer GJ, Bach JF, et al. Serum thymulin in human zinc deficiency. J Clin Invest. 1988;82:1202–10. 16
Lefrancier P, Derrien M, Choay J, et al. Contribution of zinc and other metals to the biological activity of the serum thymic factor. Proc Natl Acad Sci USA. 1982;79:5370–73. 17
Specific receptor for the serum thymic factor (FTS) in lymphoblastoid cultured cell lines. Proc Natl Acad Sci USA. 1980;77:2861–65. zinc
association. Prasad AS. Effects of zinc deficiency on Th1 Prasad AS, Meftah S, Abdallah J, Kaplan J, Dardenne M, Pleau JM, Nabarra B, Pleau JM, Fuentes V, Morgat JL, Bach JF. Mosmann TR, Coffman RL. Th1 and Th2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu Rev Immunol. 1989;7:145–73.
Romagnani S. Lymphokine production by human T cells in disease stats. Annu Rev Immunol. Clerici M, Shearer GM. A Th1 vs Th2 switch is a critical step in the etiology of HIV infection. Immunol Today. 1993;14:107–11. 21
zinc on immune cells. Mol Med. 2008;14:353–57.
Prasad AS, Boa B, Beck FW, Sarkar FH. Zinc activates NF-κB in HUT-78 cells. J Lab Clin Med. 2001;138:250–56.
Van Wouwe JP. Clinical and laboratory diagnosis of acrodermatitis enteropathica. Eur J Pediatr.1989;149:2–8. 24
assessment of zinc deficiency in Dutch children. A review. Biol Trace Elem Res. 1995;49:211–25. 25
Tamja S, Adiguma T, et al. The influence of zinc supplementation on morbidity due to Plasmodium falciparum: A randomized trial in preschool children in Papua New Guinea. Am J Trop Med Hyg. 2000;62:663–69.
Bates CJ, Evans PH, Dardenne M,Prentice A, Lunn PG, Northrop-Clewes CA, et al. A trial of zinc supplementation in young rural Gambian children. Br J Nutr. 1993;69:243–55.
Abdallah JM, Kukuruga M, Nakeff A, Prasad AS. Cell cycle distribution defect in PHA-stimulated T lymphocytes of sickle cell disease patients. Am J Hematol. 1988;28:279–81.
Bobat R, Coovadia H, Stephen C, Naidoo KL, McKerrow N, Black RE, et al. Safety and efficacy of zinc supplementation for children with HIV-1 infection in South Africa: a randomized double-blind 2005;366:1862–67. trial.
Lancet. Green JA, Lewin SR, Wightman F, Lee M, Ravindran TS, Paton NI. A randomised controlled trial of oral zinc on the immune response to tuberculosis in HIV- infected patients. Int J Tuberc Lung Dis. 2005;9:1378–84.
Baqui AH, Black RE, Arifeenn SEI, Yunus M, Chakraborty J, Ahmed S, et al. Effect of zinc supplementation
morbidity and mortality in Bangladeshi children: Community 2002;325:1059. during diarrhoea on randomized trial. Brit Med
J. Patel AB, Mamtani M, Badhoniya N, Kulkarni H, et al. What zinc supplementation does and does not achieve in diarrhoea prevention: a systematic review and meta-analysis. BMC Infect Dis. 2011;11:122. 32
supplementation in treatment of acute diarrhoea among 2–59 months children treated in Black Lion Hospital, Addis Ababa, Ethiopia. Ethiop J Health Dev. 2008;22:187–90. 33
treating diarrhoea in children. Cochrane Database Syst
doi: Sazawal S1, Black RE, Bhan MK, Jalla S, Bhandari N, Sinha A, et al. Zinc supplementation reduces the incidence of persistent diarrhoea and dysentery among low socioeconomic children in India. J Nutr. 1996;126:443–50. 35- Sinha
supplementation in reducing the incidence and N.
prevalence of acute diarrhoea--a community-based, double-blind, controlled trial. Am J Clin Nutr. 1997;66:413–18. 36
JM, Gore S, Hidayat A, et al. (Zinc Investigator/ Collaborative Group). Prevention of diarrhoea and pneumonia by zinc supplementation in children in developing countries: Pooled analysis of randomized controlled trials. J Pediatr. 1999;135:689–97.
zinc Bhutta ZA, Black RE, Brown KH, Gardner Penny ME. Zinc Supplementation in public health. Ann Nutr Metab. 2013;62:31–42. 38
treatment of diarrhoea: effect on diarrhoea morbidity, mortality and incidence of future episodes. Int J Epidemiol. 2010;39:63–69. 39
cold viruses: An overview. J Am Pharm Assoc. 2004;44:594–603.
Shah GS, Dutta AK, Shah D, Mishra OP. Role of zinc in severe pneumonia: A randomized double bind placebo controlled study. Ital J Pediatr. 2012;8:36.,
Bhandari N, Bahl R, Taneja S, Strand T, Molbak K, Ulvik RJ, et al. Effect of routine zinc supplementation on pneumonia in children aged 6 months to 3 years: Randomized controlled trial in an urban slum. Br Med J. 2002;324:1358–62. 42
Bhattacharya M, Wahed M, Khaled M. Zinc supplementation as adjunct therapy in children with measles accompanied by pneumonia: A double-blind, randomized controlled trial. Am J Clin Nutr. 2002;76:604–7.
Sazawal S, Black RE, Jalla S, Mazumdar S, Sinha A, Bhan MK. Zinc supplementation reduces the incidence of acute lower respiratory infections in infants and preschool children: a double-blind, controlled trial. Pediatr. 1998;102:1–5. 44
Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother. 1984;25:20–24. 45- Cochrane
1002/14651858.CD001364.pub3. Syst Rev.
2011;doi: Costello A, Francis V, Byrne A, Puddephatt C. State of the world’s newborns: A report from saving newborn lives, Washington, DC:Save the Children and Women and Children First 2001.
Rittirsch D, Flierl MA, Ward PA. Harmful molecular mechanisms in sepsis. Nat Rev Immunol. 2008;8:776–87. 48
multidrug resistant gram negative organisms in a neonatal unit and the therapeutic implications. J Trop Pediatr. 2000;46:86–91. 49
Clinico-bacteriological study of neonatal septicemia in Hubli. Indian J Pediatr. 2000;67:169–74. Karunasekera KA,
preliminary study on neonatal septicaemia in a tertiary referral hospital paediatric unit. Ceylon Med J. 1999;44:81–86. Pathirana D.
A Stoll BJ. The global impact of neonatal infection. Clin Perinatol. 1997;24:1–21. 52
importance of zinc in human nutrition and estimation of the global prevalence of zinc deficiency. Food Nutr Bull. 2001;22:113–25.
Wynn J, Cornell TT, Wong HR, Shanley TP, Wheeler DS. The host response to sepsis and developmental impact. Pediatr. 2010;125:1031–41. 54
DS, Wong HR. Mechanisms and regulation of the geneexpression 2010;125:1248–58. 55
Wong HR. Novel pharmacologic approaches to the management
inflammatory response. Recent Pat Inflamm Allergy Drug Discov. 2009;3:96–112. 56
Masani M Incidence of neonatal sepsis in tertiary care Hospital: An overview. Int J Med Sci Public Health. 2013;2:548–52. 57
Mwansambo C, Neonatal sepsis: An international perspective. Arch Dis Child Fetal Neonatal Ed. 2005;90:220–24. to sepsis.
Pediatr. Wheeler DS, Zingarelli B, Wheeler WJ, of sepsis: targeting the
host Gandhi S, Ranjan KP, Ranjan N, Sapre N, Vergnano S, Sharland M, Kazembe P, Bhatnagar S, Wadhwa N, Aneja S, Lodha R, Kabra SK, Natchu UC, et al. Zinc as adjunct treatment in infants aged between 7 and 120 days with probable serious bacterial infection: A randomised, double-blind, placebo-controlled trial. Lancet. 2012;379:2072–78. 59
MK, Singh RR. Oral zinc supplementation for reducing mortality in probable neonatal sepsis: A double blind randomized placebo controlled trial. Indian Pediatr. 2013;50:390–93.
Knoell DL, Julian MW, Bao S, Besecker B, Macre JE, Leikauf GD. Zinc deficiency increases organ damage and mortality in a murine model of polymicrobial sepsis. Crit Care Med. 2009;37:1380– 88. 61
Cvijanovich N, Lin R, Allen GL, et al. Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 2007;30:146–55. 62
HR. Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model Pediatr of sepsis. Crit Care
Med. Sazawal S, Black RE, Ramsan M, et al. Effect of zinc supplementation on mortality in children aged 1–48 months: A community-based randomized 2007;369:927–34. trial.
Lancet. Javadi P, Buchman TG, Stromberg PE, Husain KD, Dunne WM, Woolsey CA, Turnbull IR, et al. High-dose exogenous iron following cecal ligation and puncture increases mortality rate in mice and is associated with an increase in gut epithelial and splenic apoptosis. Crit Care Med. 2004;32:1178– 85. 65
preventing, diagnosing, and treating neonatal sepsis. PLoS Med. 2010;7:e1000213. 66
shock--the potential of gene arrays. Crit Care. 2012;16:204. 67
absorption. J Nutr. 2000;130:1378–83.
Schlesinger L, Arevalo M, Arredondo S, Lonnerdal B, Stekel A. Zinc supplementation impairs monocyte function. Acta Paediatr. 1993;82:734–38. 69
Diaz M, Lonnerdal B, Stekel A. Effect of a zinc- fortified formula on immunocompetence and growth of malnourished infants. Am J Clin Nutr. 1992;56:491–98.
Bao S, Liu M, Lee B, Besecker B, Lai JP, Guttridge DC, et al. Zinc modulates the innate immune response in vivo to polymicrobial sepsis through regulation of NF-κB . Am J Physiol Lung Cell Mol Physiol. 2010;298:744–54.