Review
The global burden of paediatric and neonatal sepsis: a systematic review

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Summary

The incidence of sepsis is highest in neonates and children, yet the global burden of sepsis in these age groups has not been assessed. We reviewed available evidence from observational epidemiological studies to estimate the global burden and mortality of sepsis in neonates and children. We did a systematic review and meta-analysis of studies reporting population-based sepsis incidence in neonates and children, published between 1979 and 2016. Our search yielded 1270 studies, 23 of which met the inclusion criteria; 16 were from high-income countries and seven from middle-income countries. 15 studies from 12 countries reported complete data and were included in the meta-analysis. We found an aggregate estimate of 48 (95% CI 27–86) sepsis cases and 22 (14–33) severe sepsis cases in children per 100 000 person-years. Mortality ranged from 1% to 5% for sepsis and 9% to 20% for severe sepsis. The population-level estimate for neonatal sepsis was 2202 (95% CI 1099–4360) per 100 000 livebirths, with mortality between 11% and 19%. Extrapolating these figures on a global scale, we estimate an incidence of 3·0 million cases of sepsis in neonates and 1·2 million cases in children. Although these results confirm that sepsis is a common and frequently fatal condition affecting neonates and children globally, few population-based data are available from low-income settings and the lack of standardisation of diagnostic criteria and definition of sepsis in the reviewed studies are obstacles to the accurate estimation of global burden. Robust epidemiological monitoring to define global sepsis incidence and mortality in children is urgently needed.

Introduction

A recent resolution by WHO listed sepsis as a key health-care priority for the coming decade,1 recognising that sepsis—defined as life-threatening infection due to a dysregulated host response to infection2—is a major contributor to global morbidity and mortality.3, 4 Peak sepsis incidence and mortality occur in the extreme age groups, with newborn babies, young children, and elderly people at highest risk.5, 6, 7 Despite improvements in care, neonatal and paediatric mortality due to severe sepsis is around 11% in high-income countries.8

Global burden of disease studies have extensively characterised the burden of severe infections on childhood mortality in low-income countries.9 In 2013, 2·3 million children under the age of 5 years died from infectious diseases such as lower respiratory infection (708 600 deaths), diarrhoea (474 900 deaths), and malaria (570 000 deaths). These reports commonly classify the cause of death by type of infection, rather than by presence of sepsis, which is the common final pathophysiological pathway to organ dysfunction and death from most infectious diseases.10 Although single studies have reported the incidence of population-level sepsis in high-income countries, data on global incidence of paediatric sepsis are absent.

The WHO resolution1 urges member states to measure the prevalence of sepsis, and to develop and implement monitoring and evaluation tools for sepsis. The resolution also requests that the Director-General of WHO publish a report on sepsis and its global consequences by the end of 2018. Comprehensive knowledge of the global burden of sepsis is crucial to justify, design, and monitor initiatives on prevention, diagnosis, and treatment of this time-critical and often preventable disease.

Our primary aim was to systematically review the available evidence on population-based sepsis incidence across paediatric age groups. Our secondary aim was to do a meta-analysis of population-based paediatric sepsis data to estimate the global number of sepsis cases in children and neonates.

Section snippets

Search strategy and selection criteria

We did a systematic literature search and review according to a predesigned protocol (see appendix). Data collection was based on three strategies: a search for published or unpublished (grey) literature in international databases; a manual search of reference lists of articles identified as a result of the database search, and other relevant articles identified by the authors; and, queries to national experts in selected regions where reliable data were unavailable. 13 international and

Results

Our search yielded 1270 results, of which 214 studies were eligible for full-text screening (figure 1). 17 records were excluded due to missing full texts and of the remaining 197 studies, 174 were excluded after full-text review. 23 studies from 16 countries met the inclusion criteria. Interrater agreement (κ) was 0·591 (moderate agreement). 16 studies were from high-income countries, and seven from middle-income countries. No study from low-income countries was included. Three studies were

Discussion

To our knowledge, we provide the largest meta-analysis of population-based neonatal and paediatric sepsis epidemiology, including data from 12 middle-income and high-income countries on four continents in 15 studies reporting complete data. Heterogeneity of data was considerable, and the inclusion criteria used in the studies might have led to considerable bias. Because of insufficient data from all low-income and most middle-income countries, our estimates of global burden for neonatal and

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