Best Evidence Topics
  • Send this BET as an Email
  • Make a Comment on this BET

What clinical features impact morbidity and mortality in children with influenza?

Three Part Question

In [children with influenza A (H1N1) infection who present to the emergency department], what [clinical features] accurately [predict morbidity and mortality]?

Clinical Scenario

A 2 year old child with history of prematurity with NICU stay presents with cough, runny nose and fever. She has not had an influenza vaccination this year. Parents have been using antipyretics without resolution of symptoms. The child has chest x-ray and laboratory studies performed. A nasal swab is positive for influenza A. The family is concerned about her prognosis given the past medical history.

Search Strategy

Medline 1966-05/15 using OVID interface, Cochrane Library (2015), and Embase

[(Exp influenza A) AND (exp mortality)]. Limit to all children (0-18 years), prospective, and English language.

Search Outcome

75 papers were identified, including two large-scale prospective clinical trials and one recent meta-analysis

Relevant Paper(s)

Author, date and country Patient group Study type (level of evidence) Outcomes Key results Study Weaknesses
Al Subaie SS, Al Saadi MA
May 2011
Saudi Arabia
1103 children with influenza like illnessProspective cohort studyChildren with underlying disease had more complications, respiratory or GI 70% had underlying medical condition,94% had fever,all case treated with oseltamivirSingle center study, lack of community data, only a few admitted children
Gill PJ, Ashdown HF, Wang K, Heneghan C, Roberts NW, Harnden A, Mallett S.
Feb 2015
28 articles that reported data from 27 studies (14 086 children)Meta-analysisThe primary outcome was admission to hospital as a proxy for complications of influenza or influenza-like illness.Strong risk factors for hospital admission were neurological disorders (OR 4.6), prematurity (OR 4.3), sickle cell disease (OR 3.5), immunosuppression (2.4), diabetes (OR 2.3), and age younger than 2 years (OR 2.5)Many studies were done in hospital ambulatory care or emergency department settings,details of risk factor classifications were also often incomplete
Randolph AG, Vaughn F, Sullivan R, Rubinson L, Thompson BT, Yoon G, Smoot E, Rice TW, Loftis LL, Hel
838 PICU patientsretrospective and prospective observational cohort studyThe associations of mortality with patient-related factors (demographics, underlying health conditions, bacterial coinfections) and influenza-related clinical syndromesPreexisting neurologic conditions or immunosuppression, encephalitis (1.7% of cases), myocarditis (1.4% of cases), early presumed MRSA lung coinfection, and female gender were mortality risk factors. Among previously healthy children, only early presumed MRSA coinfection of the lung (relative risk: 8) remained a mortality risk factorPICU patients, missing data elements, 1 year study


The H1N1 virus continues to circulate worldwide and is associated with significant morbidity and mortality. It is important to recognize the prognostic risk factors to direct patient care and treatment.

Clinical Bottom Line

Independent risk factors for influenza-related complications in children include prematurity, chronic neurological disorders, sickle cell disease, immunosuppression, diabetes,female gender,and age younger than 2 years. Efforts need to be focused on immunizing children to avoid severe disease and minimize complications.


  1. Al Subaie SS, Al Saadi MA Features associated with severe disease in hospitalized children with 2009 influenza A (H1N1) infection at a university hospital in Riyadh, Saudi Arabia. Annals of Saudi Medicine 2012;32(1):53-58
  2. Gill PJ, Ashdown HF, Wang K, Heneghan C, Roberts NW, Harnden A, Mallett S Identification of children at risk of influenza-related complications in primary and ambulatory care: a systematic review and meta-analysis. Lancet Respir Med. 2015;3(2):139-49
  3. Randolph AG, Vaughn F, Sullivan R, Rubinson L, Thompson BT, Yoon G, Smoot E, Rice TW, Loftis LL, Helfaer M, Doctor A, Paden M, Flori H, Babbitt C, Graciano AL, Gedeit R, Sanders RC, Giuliano JS, Zimme Critically ill children during the 2009-2010 influenza pandemic in the United States Pediatrics 2011 128(6):e1450-e1458.