Objective: To evaluate the efficacy of supplementation with zinc and vitamin A in Indigenous children hospitalised with acute lower respiratory infection (ALRI).
Design: Randomised controlled, 2-by-2 factorial trial of supplementation with zinc and vitamin A.
Setting and participants: 187 Indigenous children aged < 11 years hospitalised with 215 ALRI episodes at Alice Springs Hospital (April 2001 to July 2002).
Interventions: Vitamin A was administered on Days 1 and 5 of admission at a dose of 50 000 IU (infants under 12 months), or 100 000 IU; and zinc sulfate was administered daily for 5 days at a daily dose of 20 mg (infants under 12 months) or 40 mg.
Main outcome measure: Time to clinical recovery from fever and tachypnoea, duration of hospitalisation, and readmission for ALRI within 120 days.
Results: There was no clinical benefit of supplementation with vitamin A, zinc or the two combined, with no significant difference between zinc and no-zinc, vitamin A and no-vitamin A or zinc + vitamin A and placebo groups in time to resolution of fever or tachypnoea, or duration of hospitalisation. Instead, we found increased morbidity; children given zinc had increased risk of readmission for ALRI within 120 days (relative risk, 2.4; 95% CI, 1.003–6.1).
Conclusion: This study does not support the use of vitamin A or zinc supplementation in the management of ALRI requiring hospitalisation in Indigenous children living in remote areas. Even in populations with high rates of ALRI and poor living conditions, vitamin A and zinc therapy may not be useful. The effect of supplementation may depend on the prevalence of deficiency of these micronutrients in the population.
- 1. d’Espaignet ET, Kennedy K, Paterson BA, Measey ML. From infancy to young adulthood: health status in the Northern Territory. Darwin: Territory Health Services, 1998.
- 2. Chang AB, Masel JP, Boyce NC, Torzillo PJ. Respiratory morbidity in central Australian Aboriginal children with alveolar lobar abnormalities. Med J Aust 2003; 178: 490-494. <MJA full text>
- 3. Yamey G. Zinc supplementation prevents diarrhoea and pneumonia. BMJ 1999; 319: 1521-1522.
- 4. Bhutta ZA, Black RE, Brown KH, et al. Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators’ Collaborative Group. J Pediatr 1999; 135: 689-697.
- 5. Villamor E, Mbise R, Spiegelman D, et al. Vitamin A supplements ameliorate the adverse effect of HIV-1, malaria, and diarrheal infections on child growth. Pediatrics 2002; 109: E6.
- 6. Brown N, Roberts C. Vitamin A for acute respiratory infection in developing countries: a meta-analysis. Acta Paediatr 2004; 93: 1437-1442.
- 7. Christian P, West KP. Interactions between zinc and vitamin A: an update. Am J Clin Nutr 1998; 68 (2 Suppl): S435-S441.
- 8. Smith JC, McDaniel EG, Fan FF, Halsted JA. Zinc: a trace element essential in vitamin A metabolism. Science 1973; 181: 954-955.
- 9. Rahman MM, Vermund SH, Wahed MA, et al. Simultaneous zinc and vitamin A supplementation in Bangladeshi children: randomised double blind controlled trial. BMJ 2001; 323: 314-318.
- 10. Porea TJ, Belmont JW, Mahoney DH. Zinc-induced anemia and neutropenia in an adolescent. J Pediatr 2000; 136: 688-690.
- 11. Valery PC, Torzillo PJ, Boyce NC, et al. Zinc and vitamin A supplementation in Australian Indigenous children with acute diarrhoea: a randomised controlled trial. Med J Aust 2005; 182: 530-535. <MJA full text>
- 12. World Health Organization. Cough or difficult breathing. IMCI (Integrated Mangement of Childhood Illness) referral guide: management of the child with a serious infection or severe malnutrition. Geneva: WHO, 2000.
- 13. Stephensen CB, Franchi LM, Hernandez H, et al. Adverse effects of high-dose vitamin A supplements in children hospitalized with pneumonia. Pediatrics 1998; 101: E3.
- 14. Brooks WA, Yunus M, Santosham M, et al. Zinc for severe pneumonia in very young children: double-blind placebo-controlled trial. Lancet 2004; 363: 1683-1688.
- 15. Ruel MT, Rivera JA, Santizo MC, et al. Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children. Pediatrics 1997; 99: 808-813.
- 16. Black RE. Therapeutic and preventive effects of zinc on serious childhood infectious diseases in developing countries. Am J Clin Nutr 1998; 68: S476-S479.
- 17. Bogden JD. Influence of zinc on immunity in the elderly. J Nutr Health Aging 2004; 8: 48-54.
- 18. Sugarman B,Epps LR. Zinc and Chlamydia trachomatis. Proc Soc Exp Biol Med 1985; 179: 382-387.
- 19. Mustafa MG, Cross CE, Munn RJ, Hardie JA. Effects of divalent metal ions on alveolar macrophage membrane adenosine triphosphatase activity. J Lab Clin Med 1971; 77: 563-571.
- 20. Griffiths JK. The vitamin A paradox. J Pediatr 2000; 137: 604-607.
- 21. Si NV, Grytter C, Vy NN, et al. High dose vitamin A supplementation in the course of pneumonia in Vietnamese children. Acta Paediatr 1997; 86: 1052-1055.
- 22. Nacul LC, Kirkwood BR, Arthur P, et al. Randomised, double blind, placebo controlled clinical trial of efficacy of vitamin A treatment in non-measles childhood pneumonia. BMJ 1997; 315: 505-510.
- 23. Srinivas U, Braconier JH, Jeppsson B, et al. Trace element alterations in infectious diseases. Scand J Clin Lab Invest 1988; 48: 495-500.
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