Randomized, Double-blind, Placebo-controlled Clinical Trial of the Efficacy of Treatment with Zinc or Vitamin A in Infants and Young Children with Severe Acute Lower Respiratory Infection

Background: Acute lower respiratory infection (ALRI) is a leading cause of childhood death. Zinc supplementation prevents ALRI. Vitamin A supplementation reduces childhood mortality, but its benefit concerning ALRI-specific mortality is unproven.

Objective: The objective was to evaluate the effect of zinc and vitamin A on the clinical recovery of children with severe ALRI.

Design: In a controlled trial with a factorial design, 153 children aged 2-24 mo who were hospitalized with severe ALRI were randomly assigned to receive 10 mg zinc as acetate (twice daily for 5 d) plus vitamin A placebo, 10 000 micro g retinol equivalents vitamin A (twice daily for 4 d) plus zinc placebo, zinc plus vitamin A, or zinc and vitamin A placebos. The main outcome variable was the time for resolution of very ill status; other outcomes were resolution of fever, tachypnea, and feeding difficulty.

Results: Recovery rates from very ill status and from fever in zinc-treated boys were 2.6 times (P = 0.004) and 3 times (P = 0.003) those in non-zinc-treated children; feeding difficulty and tachypnea were not significantly different between groups after an adjusted analysis. Recovery rates were not significantly different between groups on the basis of vitamin A treatment. At discharge, serum zinc was 6.06 micro mol/L higher (P = 0.001) in the zinc-treated children, and serum retinol was 0.387 micro mol/L higher (P = 0.001) in the vitamin A-treated children.

Conclusion: Zinc treatment significantly reduces duration of fever and very ill status in boys, but not in girls, with severe ALRI. Vitamin A treatment of children with severe ALRI had no significant beneficial effect.