TY - JOUR
T1 - Zinc supplementation for the prevention of acute lower respiratory infection in children in developing countries
T2 - Meta-analysis and meta-regression of randomized trials
AU - Roth, Daniel E.
AU - Richard, Stephanie A.
AU - Black, Robert E.
N1 - Funding Information:
Training grants from the Canadian Institutes of Health Research and the Alberta Heritage Foundation for Medical Research to D.E.R.
PY - 2010/2/15
Y1 - 2010/2/15
N2 - Background: Routine zinc supplementation is a potential intervention for the prevention of acute lower respiratory infection (ALRI) in developing countries. However, discrepant findings from recent randomized trials remain unexplained. Methods: Randomized trials of zinc supplementation in young children in developing countries were identified by a systematic literature review. Trials included in the meta-analysis met specific criteria, including participants <5 years of age, daily/weekly zinc and control supplementation for greater than 3 months, active household surveillance for respiratory morbidity and use of a case definition that included at least one sign of lower respiratory tract illness. ALRI case definitions were classified on the basis of specificity/severity. Incidence rate ratios (IRRs) were pooled by random-effects models. Meta-regression and sub-group analysis were performed to assess potential sources of between-study heterogeneity. Results: Ten trials were eligible for inclusion (n = 49 450 children randomized). Zinc reduced the incidence of ALRI defined by specific clinical criteria [IRR 0.65, 95% confidence interval (CI) 0.52-0.82], but had no effect on lower-specificity ALRI case definitions based on caregiver report (IRR 1.01, 95% CI 0.91-1.12) or World Health Organization 'non-severe pneumonia' (0.96, 95% CI 0.86-1.08). By meta-regression, the effect of zinc was associated with ALRI case definition, but not with mean baseline age, geographic location, nutritional status or zinc dose. Conclusions: Routine zinc supplementation reduced the incidence of childhood ALRI defined by relatively specific clinical criteria, but the effect was null if lower specificity case definitions were applied. The choice of ALRI case definition may substantially influence inferences from community trials regarding the efficacy of preventive interventions.
AB - Background: Routine zinc supplementation is a potential intervention for the prevention of acute lower respiratory infection (ALRI) in developing countries. However, discrepant findings from recent randomized trials remain unexplained. Methods: Randomized trials of zinc supplementation in young children in developing countries were identified by a systematic literature review. Trials included in the meta-analysis met specific criteria, including participants <5 years of age, daily/weekly zinc and control supplementation for greater than 3 months, active household surveillance for respiratory morbidity and use of a case definition that included at least one sign of lower respiratory tract illness. ALRI case definitions were classified on the basis of specificity/severity. Incidence rate ratios (IRRs) were pooled by random-effects models. Meta-regression and sub-group analysis were performed to assess potential sources of between-study heterogeneity. Results: Ten trials were eligible for inclusion (n = 49 450 children randomized). Zinc reduced the incidence of ALRI defined by specific clinical criteria [IRR 0.65, 95% confidence interval (CI) 0.52-0.82], but had no effect on lower-specificity ALRI case definitions based on caregiver report (IRR 1.01, 95% CI 0.91-1.12) or World Health Organization 'non-severe pneumonia' (0.96, 95% CI 0.86-1.08). By meta-regression, the effect of zinc was associated with ALRI case definition, but not with mean baseline age, geographic location, nutritional status or zinc dose. Conclusions: Routine zinc supplementation reduced the incidence of childhood ALRI defined by relatively specific clinical criteria, but the effect was null if lower specificity case definitions were applied. The choice of ALRI case definition may substantially influence inferences from community trials regarding the efficacy of preventive interventions.
KW - Developing countries
KW - Meta-analysis
KW - Pneumonia
KW - Respiratory tract infections
KW - Systematic review
KW - Zinc
UR - http://www.scopus.com/inward/record.url?scp=77955725737&partnerID=8YFLogxK
U2 - 10.1093/ije/dyp391
DO - 10.1093/ije/dyp391
M3 - Article
C2 - 20156999
AN - SCOPUS:77955725737
SN - 0300-5771
VL - 39
SP - 795
EP - 808
JO - International Journal of Epidemiology
JF - International Journal of Epidemiology
IS - 3
M1 - dyp391
ER -