Zinc as an adjunct to antibiotics for the treatment of severe pneumonia in children <5 years: a meta-analysis of randomised-controlled trials

Abstract

The effect of Zn, as an adjunct to antibiotics, on the treatment of severe pneumonia in young children is still under debate; therefore, we performed a meta-analysis to evaluate the therapeutic role of Zn for severe pneumonia in children younger than 5 years. PubMed, Cochrane library and Embase databases were systematically searched from inception until October 2015 for randomised-controlled trials (RCT) that assessed the effect of Zn as an adjunct to antibiotics for severe pneumonia. Random-effects model was used for calculating the pooled estimates, and intention-to-treat principle was also applied. Nine RCT involving 2926 children were included. Overall, the pooled results showed that adjunct treatment with Zn failed to reduce the time to recovery from severe pneumonia (hazard ratios (HR) = 1·04; 95 % CI 0·90, 1·19; I 2 = 39 %; P = 0·58), hospital length of stay (HR = 1·04; 95 % CI 0·83, 1·33; I 2 = 57 %; P = 0·74), treatment failure (relative risk (RR) = 0·95; 95 % CI 0·79, 1·14; I 2 = 20 %; P = 0·58) or change of antibiotics (RR = 1·07; 95 % CI 0·79, 1·45; I 2 = 44 %; P = 0·67). In addition, continuous outcomes were consistent while meta-analysed with standard mean difference, and all outcomes remained stable in intention-to-treat analysis. No significant differences were observed in the two groups between death rate, adverse events or recovery times of severe pneumonia indicators. Our results suggested that adjunct treatment with Zn failed to benefit young children in the treatment of severe pneumonia. Considering the clinical heterogeneity, baseline characteristics of children, definition of severe pneumonia and Zn supplement way should be taken into consideration in future research. This study was registered at PRESPERO as CRD42015019798.Key words: Children: Meta-analyses: Severe pneumonia: ZincPneumonia is a leading disease and cause of death in children under 5 years in developing countries (1) . It is reported that 14·9 % of 6·3 million deaths of children <5 years old were caused by pneumonia worldwide (2) . With advances in medicine, economy and society, pneumonia with diarrhoea and measles was responsible for half of the reduction in mortality of children under 5 years from 2000 to 2013 (2) . Although great progress was achieved, only a few countries could reach the goal of Millennium Development Goal 4 to reduce under 5 child mortality by two-thirds between 1990 and 2015, and pneumonia is still the leading cause of child mortality (3) . Therefore, intensive effort should be made in the research of pneumonia.Under-nutrition has been reported to be strongly associated with impaired immune response, (4) and it has been proven to be responsible for greater severity of pneumonia, prolonged course of disease and increased mortality of pneumonia (5) .Zn, as an important micro-element, has an essential role in cellular growth and immune defence, and its deficiency is associated with significant increased susceptibility to various infection pathogens (6)(7)(8) . In a randomised-controlled trial (RCT...

Efficacy of zinc as adjunctive pneumonia treatment in children aged 2 to 60 months in low-income and middle-income countries: a systematic review and meta-analysis

“…Our findings are largely concordant with previous meta-analyses. [20][21][22][23] In difference to Wang and Song, 23 we did not find decreased mortality in the zinc supplementation group. The study by Srinivasan et al 32 with high risk of bias in outcome reporting was driving the results presented by Wang and Song and neither of the two new large studies published since then showed any increased risk of mortality.…”

“…However, the role of adjunctive zinc at presentation in pneumonia is still controversial: meta-analyses published in 2011, 2012 and 2016 [20][21][22] found no effect, while another published in 2018 estimated a significant reduction in mortality (risk ratio 0.43, 95% CI 0.22 to 0.83), but no difference in composite treatment failure rates. 23 The last study was published in 2018 and included studies up to October 2015, 4 years before our search.…”

Zinc as an adjunct therapy in the management of severe pneumonia among Gambian children: randomized controlled trial

“…However, in a stratified analysis, the reduction in mortality was limited to HIV infected children. A recent meta-analysis of nine zinc supplementation trials, as an adjunct treatment of severe pneumonia, did not show any benefit in time to recovery, length of hospital stay, treatment failure or change of antibiotics [ 32 ]. It is also possible that the low specificity of the WHO definition of severe pneumonia may have contributed to the study’s negative result as a lack of specificity in the diagnostic criteria for measuring study outcomes biases the risk/rate ratio towards null values.…”

A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection

“…The duration of the common cold may be reduced in adults and children after administration of zinc >75 mg/day, but not at lower doses; the type of zinc salt used can also have an effect, with greater benefits with zinc acetate compared with other zinc salts (mostly high-quality studies) [219]. However, zinc (10-20 mg/day) had no significant effect on pneumonia in children, failing to reduce the time to recovery from severe pneumonia [220,221], duration of hospital stay [220][221][222], time to clinical recovery [222], or time to recovery from the effects of severe pneumonia including tachypnoea and chest indrawing (all low-to-moderate evidence) [221,222].…”