Meta‐analysis of randomized controlled trials of zinc supplementation for the prevention of acute lower respiratory tract infection (ALRI) in children aged 1 to 59 months: the importance of ALRI case definition

Abstract

Daily/weekly oral zinc supplementation has been shown to significantly reduce the risk of ALRI/pneumonia in young children. However, a recent meta‐analysis only included trials from South Asia, and did not consider the effect of variations in case definition. We performed an updated and expanded meta‐analysis to estimate the effect of zinc on the incidence of ALRI or pneumonia in children below 5 years of age, accounting for case definitions. Trials were included if treatment allocation was random, concealed and duration was >3 months. Studies were grouped by method of ALRI diagnosis: 1) ‘WHO criteria’ (i.e., tachypnea); 2) ‘Clinical’ diagnosis of severe ALRI/pneumonia; 3) ‘Maternal report’. Pooled incidence rate ratios (IRRs) and 95% confidence intervals (CI) were estimated by fixed‐effects models using inverse variance weighting. Pooled IRRs: WHO criteria (3 trials) – 0.99 (95% CI, 0.89 – 1.09); Clinical (3 trials) – 0.78 (95% CI, 0.68 – 0.91); Maternal report (6 trials) – 1.02 (95% CI, 0.97 – 1.09). Therefore, in young children, zinc supplementation significantly reduced the incidence of ALRI defined by criteria that were relatively specific for severe ALRI/pneumonia, but not ALRI defined by WHO criteria or maternal report. We conclude that, 1) zinc supplementation reduces the risk of severe ALRI and pneumonia; 2) ALRI case definition substantially impacts on inferences related to the efficacy of preventive interventions.