Articles
Identification of children at risk of influenza-related complications in primary and ambulatory care: a systematic review and meta-analysis

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Summary

Background

Interventions to prevent influenza-related complications are recommended for individuals at the greatest risk of serious clinical deterioration. However, guidelines are based on consensus opinion rather than evidence, and do not specify risk factors in children. We aimed to provide an evidence-based definition of children who are most at risk of such complications.

Methods

In this systematic review, we searched the Medline and Medline In Process, Embase, Science Citation Index, and CINAHL databases for studies published between inception and April 3, 2013. We included studies that reported data for underlying disorders and complications in children presenting in primary or ambulatory care with influenza or influenza-like illness. We requested unpublished data from investigators of studies that had obtained, but not published, relevant data. We analysed data with univariable meta-analysis and individual patient data multivariable meta-analysis methods. The primary outcome was admission to hospital as a proxy for complications of influenza or influenza-like illness.

Findings

We included 28 articles that reported data from 27 studies (14 086 children). Strong risk factors for hospital admission were neurological disorders (univariable odds ratio [OR] 4· 62, 95% CI 2·82–7·55), prematurity (4·33, 2·47–7·58), sickle cell disease (3·46, 1·63–7·37), immunosuppression (2·39, 1·24–4·61), diabetes (2·34, 1·20–4·58), and age younger than 2 years (2·51, 1·71–3·69). However, reactive airways disease including asthma (1·36, 0·82–2·26) and obesity (0·99, 0·61–1·62) were not found to be risk factors. On the basis of individual patient data multivariable analysis (1612 children, four studies), the risk of hospital admission was higher in children with more than one risk factor than in children with just one risk factor, when age younger than 2 years was included as a risk factor (92 [74%] of 124 vs 428 [52%] of 817; difference 22%, 95% CI 13–30%, p<0·0001).

Interpretation

We identified prematurity as a new strong risk factor for influenza-related complications in children. Our findings also support the inclusion of neurological disorders, sickle cell disease, immunosuppression, diabetes, and age younger than 2 years as risk factors in existing guidelines. Interventions to prevent influenza-related complications should be prioritised in these groups, but should also be considered for other children, especially those with more than one risk factor or severe underlying comorbidities.

Funding

UK National Institute for Health Research.

Introduction

Influenza in children is a major burden on health-care resources, especially during epidemics and pandemics.1, 2 Around a quarter of otherwise healthy children who develop influenza or influenza-like illness have further complications3 including pneumonia, otitis media, neurological complications, and death.1

At-risk children (ie, children with underlying medical disorders) are at increased risk of influenza-related complications.4 Around 20% of children who present with influenza or influenza-like illness have at least one medical disorder,5 and the presence of comorbidities increases the rates of influenza-related hospital admissions almost six times in children aged 5 to 14 years (from 0·1 per 1000 children to 0·56 per 1000).6 After being admitted to hospital, such at-risk patients are also at higher risk of further complications.7

The UK Department of Health8 and the WHO Strategic Advisory Group of Experts on Immunization9 recommend influenza vaccination in specific groups who are considered to be at high risk of serious complications. The US Advisory Committee on Immunization Practices recommends that all individuals aged 6 months and older should receive annual influenza vaccinations,10 but still recommends that antiviral medications should be targeted at specific high-risk groups.11 However, these definitions of high-risk groups have several limitations: the level of detail used to define risk groups is inconsistent, the quality of evidence cited is variable, and risk factors are not specifically defined for children. Previous studies aiming to identify risk factors for influenza-related complications have also not defined these risks specifically in children.12, 13

An understanding of risk factors in children is important, in view of the different comorbidity profiles encountered in paediatric versus adult populations and the high burden of disease associated with influenza in children.9 Additionally, early intervention to prevent complications is important, because 35% of influenza-related deaths in children occur before their admission to hospital, according to data from the USA.14 We aimed to provide an evidence-based definition of which children presenting with influenza or influenza-like illness in primary or ambulatory care are at increased risk of developing influenza-related complications through a systematic review of published and unpublished data.

Section snippets

Search strategy and selection criteria

We systematically searched Medline and Medline In Process (OvidSP)[1946–], Embase(OvidSP) [1974–], Science Citation Index (Web of Science, Thomson Reuters)[1945–], and CINAHL(EbscoHOST)[1980–] from inception to April 3, 2013. Our search strategy (appendix), combined subject headings with free text search terms encompassing both established risk categories defined by the UK Department of Health,8 the US Advisory Committee on Immunization Practices (ACIP),11 and WHO,9 and more recently identified

Results

We identified 10 360 records, from which 148 full-text articles were assessed (figure 1). Of these, we included 28 articles, which reported data from 27 studies (table 1). The review included 14 086 children, of whom 3086 (22%) had an underlying disorder (ie, comorbidity not including age younger than 2 years). Rates of hospital admission varied tenfold between studies (6–65%) and the prevalence of comorbidities ranged from 3% to 82%. Most studies included patients with pandemic influenza (20

Discussion

Prematurity, neurological disorders, sickle cell disease, immunosuppression, diabetes, and age younger than 2 years were all risk factors for hospital admission in children who presented with influenza or influenza-like illness in primary or ambulatory care. Unlike the other factors identified in this systematic review, prematurity is not defined as an at-risk disorder in any existing guidelines. The presence of more than one coexisting condition significantly increases the risk of hospital

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