Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: A meta‐analysis of randomized, double‐blind and placebo‐controlled trials

Wang, Linlin; Song, Yuanlin

doi:10.1111/crj.12646

Cited by 55 publications

(45 citation statements)

References 20 publications

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“…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.…”

Section: Discussioncontrasting

confidence: 77%

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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

Brown

Kukka²,

Mårtensson³

2020

bmjpo

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BackgroundDespite advances in vaccination and case management, pneumonia remains the single largest contributor to early child mortality worldwide. Zinc has immune-enhancing properties, but its role in adjunctive treatment of pneumonia in low-income and middle-income countries (LMICs) is controversial and research still active.MethodsSystematic review and meta-analysis of randomised controlled trials of zinc and placebo in pneumonia in children aged 2 to 60 months in LMICs. Databases included MEDLINE, the Cochrane Library, EMBASE, LILACS, SciELO, the WHO portal, Scopus, Google Scholar and ClinicalTrials.gov. Inclusion criteria included accepted signs of pneumonia and clear measure of outcome. Risk of bias was independently assessed by two authors. ORs with 95% CI were used for calculating the pooled estimate of dichotomous outcomes including treatment failure and mortality. Time to recovery was expressed as HRs. Sensitivity analyses considering risk of bias and subgroup analyses for pneumonia severity were performed.ResultsWe identified 11 trials published between 2004 and 2019 fulfilling the a priori defined criteria, 7 from South Asia and 3 from Africa and 1 from South America. Proportional treatment failure was comparable in both zinc and placebo groups when analysed for all patients (OR 0.95 (95% CI 0.80 to 1.14)) and only for those with severe pneumonia (OR 0.93 (95% CI 0.75 to 1.14)). No difference was seen in mortality between zinc and placebo groups (OR 0.64 (95% CI 0.31 to 1.31)). Time to recovery from severe pneumonia did not differ between the treatment and control groups for patients with severe pneumonia (HR 1.01 (95% CI 0.89 to 1.14)). Removal of four studies with high risk of bias made no difference to the conclusions.ConclusionThere is no evidence that adjunctive zinc treatment improves recovery from pneumonia in children in LMICs.Trial registration numberCRD42019141602.

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Section: Discussioncontrasting

confidence: 77%

“…28 30 31 33-36 We identified two additional large RCTs with a total number of 1151 children 31 38 published since the search for the last metaanalysis was undertaken in October 2015. 23 We found no evidence of effect on any outcome parameter. Our findings are largely concordant with previous meta-analyses.…”

Section: Discussioncontrasting

confidence: 51%

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

Brown

Kukka²,

Mårtensson³

2020

bmjpo

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“…Among children aged over 6 months, one MA showed an 18% reduction in all-cause mortality in those over 12 months ( Brown et al, 2009 ), but two other MAs demonstrated no effect on mortality (GRADE –High and Very Low) ( Lazzerini & Wanzira, 2016 ; Mayo-Wilson et al, 2014 ). Furthermore, three MAs demonstrated a reduction in incidence and duration of all-cause diarrhoea (GRADE –Moderate) ( Lazzerini & Wanzira, 2016 ; Brown et al., 2009 ; Mayo-Wilson et al., 2014 ), and one MA identified a significant reduction in mortality when used as an adjunct to treatment for severe pneumonia ( Wang & Song, 2017 ). A further four MAs noted improved, albeit across different anthropometric indices, with zinc supplementation ( Brown et al., 2009 ; Ramakrishnan, Nguyen & Martorell, 2008 ; Imdad et al., 2011 ; Liu et al., 2018 ), with more marked improvements when supplemented after two years of age ( Liu et al, 2018 ).…”

Section: Resultsmentioning

confidence: 99%

Antimicrobial and micronutrient interventions for the management of infants under 6 months of age identified with severe malnutrition: a literature review

Campion-Smith

Kerac

McGrath³

et al. 2020

PeerJ

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Background Infants under 6 months (U6M) contribute a significant proportion of the burden and mortality of severe malnutrition globally. Evidence of underlying aetiology in this population is sparse, but it is known that the group includes ex-preterm and low birthweight (LBW) infants. They represent a unique population given their dependence on breastmilk or a safe, secure alternative. Nutrition agencies and health providers struggle to make programming decisions on which interventions should be provided to this group based upon the 2013 WHO Guidelines for the ‘Management of Severe Acute Malnutrition in Infants and Young Children’ since there are no published interventional trial data focussed on this population. Interim guidance for this group might be informed by evidence of safety and efficacy in adjacent population groups. Methodology A narrative literature review was performed of systematic reviews, meta-analyses and randomised controlled trials of antimicrobial and micronutrient interventions (antibiotics, deworming, vitamin A, vitamin D, iron, zinc, folic acid and oral rehydration solution (ORS) for malnutrition) across the population groups of low birthweight/preterm infants, infants under 6 months, infants and children over 6 months with acute malnutrition or through supplementation to breastfeeding mothers. Outcomes of interest were safety and efficacy, in terms of mortality and morbidity. Results Ninety-four articles were identified for inclusion within this review. None of these studied interventions exclusively in severely malnourished infants U6M. 64% reported on the safety of studied interventions. Significant heterogeneity was identified in definitions of study populations, interventions provided, and outcomes studied. The evidence for efficacy and safety across population groups is reviewed and presented for the interventions listed. Conclusions The direct evidence base for medical interventions for severely malnourished infants U6M is sparse. Our review identifies a specific need for accurate micronutrient profiling and interventional studies of micronutrients and oral fluid management of diarrhoea amongst infants U6M meeting anthropometric criteria for severe malnutrition. Indirect evidence presented in this review may help shape interim policy and programming decisions as well as the future research agenda for the management of infants U6M identified as malnourished.

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“…In evaluating the role of zinc in severe pneumonia, the most recent systematic review (SR) was used 4. While this included fewer studies than previous reviews,5 it used only the most methodologically rigorous studies with a lack of heterogeneity that allowed for data synthesis and increased statistical power.…”

Section: Commentarymentioning

confidence: 99%

Should zinc be used as an adjunct therapy in severe pneumonia in Western Europe?

Mclean

2019

Arch Dis Child

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Efficacy of zinc given as an adjunct to the treatment of severe pneumonia: A meta‐analysis of randomized, double‐blind and placebo‐controlled trials

Abstract: Background: Pneumonia is a major cause of morbidity and mortality of children. Zinc is known to play a central role in the immune system. The deficiency of zinc increased susceptibility to infectious diseases.

Cited by 55 publications

References 20 publications

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

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

Antimicrobial and micronutrient interventions for the management of infants under 6 months of age identified with severe malnutrition: a literature review

Should zinc be used as an adjunct therapy in severe pneumonia in Western Europe?

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