We identified 61 children admitted with pandemic H1N1 influenza. We excluded 3 because the onset of symptoms occurred late in their admission. The first child was admitted on May 8, 2009, and the last on July 22, 2009. depicts the epidemic curve for the entire 2008/09 influenza season, including cases of pandemic H1N1 influenza.
Figure 1 Epidemic curve of seasonal influenza A and pandemic H1N1 influenza at a large pediatric hospital in Toronto, Canada. Specimens originated from inpatients, outpatients and patients seen in the emergency department. Pandemic H1N1 polymerase chain reaction (more ...)
A total of 200 children were admitted with seasonal influenza A during the previous 5 influenza seasons. We present aggregated data for these children because there were no significant differences across the seasons in terms of demographic characteristics, risk factors or outcomes.
The children admitted with pandemic H1N1 influenza were significantly older than those admitted with seasonal influenza, with a significantly larger proportion over the age of 5 years ( and ). There were no differences in sex distribution.
Characteristics of 58 children admitted with pandemic H1N1 influenza in 2009 and 200 children admitted with seasonal influenza A during 2004–2009
Age distribution of children admitted to hospital with seasonal influenza A (2004/05 to 2008/09) and pandemic H1N1 influenza (2009).
Clinical features of pandemic H1N1 influenza
Forty-nine of the 58 children with pandemic H1N1 influenza presented with an influenza-like illness (fever and cough with or without additional signs or symptoms). Presenting symptoms in the remaining 9 children were fever and seizures (2), fever and diarrhea (2), fever alone (2 children with immunosuppression); lethargy without fever (1 child with cystic fibrosis); headache without fever (1 child who had received a renal transplant with a ventriculoperitoneal shunt); and fever and transient hematochezia (1). Including this last patient, 21 children (36%) presented with gastrointestinal symptoms consisting of isolated vomiting (7) and vomiting with or without diarrhea (14). Four of these children experienced severe diarrhea; 2 had surgical gastrointestinal stomata, and 1 had presumed toxic shock syndrome.
Influenza-related encephalopathy was suspected in a previously healthy girl less than 5 years old who presented with status epilepticus and altered level of consciousness. Magnetic resonance imaging revealed nonspecific changes in the white matter, and electroencephalography showed focal slowing. Examination of cerebrospinal fluid yielded normal results; results of viral culture and polymerase chain reaction of cerebrospinal fluid were negative. Three other children presented with neurologic symptoms but had probable alternative explanations (see Appendix 1, available at www.cmaj.ca/cgi/content/full/cmaj.091724/DC1
Seventeen children (29%) had radiographic changes compatible with pneumonia. In a child with multiple medical problems and radiographic evidence of pneumonia, blood culture yielded Streptococcus pneumoniae.
Severity of illness and outcomes
The median duration of hospital stay was 4 days (interquartile range 2–7 days) for both the children with pandemic H1N1 influenza and those with seasonal influenza. We found no significant differences between the groups in the need for intensive care or mechanical ventilation (7 [12%] and 19 [10%] respectively, p = 0.57). One child required extracorporeal membrane oxygenation. The trend toward longer duration of intensive care for children with pandemic H1N1 influenza did not reach statistical significance (). Two children with pandemic H1N1 influenza had prolonged stays in the ICU (30 and 61 days), which culminated in hospital stays of 69 and 65 days respectively. No deaths occurred among the children with pandemic H1N1 influenza, as compared with 1 death among those with seasonal influenza.
Underlying medical conditions
Underlying medical conditions known to be risk factors for severe influenza9
were present in 46 (79%) of the children admitted with pandemic H1N1 influenza and 146 (73%) of those admitted with seasonal influenza. Five of the 12 previously healthy children with pandemic H1N1 were less than 2 years old. shows the distribution of selected risk factors for severe influenza. Children with pandemic H1N1 influenza were more likely to have asthma than children with seasonal influenza. Asthma remained a significant independent risk factor after we controlled for age by logistic regression (p
Table 2 Prevalence of underlying risk factors for severe influenza9 among children admitted with pandemic H1N1 influenza in 2009 and those admitted with seasonal influenza A during 2004–2009
Among the children admitted with pandemic H1N1 influenza, the spectrum of asthma severity appeared broad (see Appendix 2, available at www.cmaj.ca/cgi/content/full/cmaj.091724/DC1
) and did not seem to predict the need for intensive care, although numbers were small. Almost half of the children with pandemic H1N1 influenza who were admitted to the ICU had asthma (). Two children with clinical features suggestive of acute respiratory distress syndrome required mechanical ventilation, one of whom required extracorporeal membrane oxygenation. A further 2 were admitted to the ICU for management of their bronchospasm but did not require mechanical ventilation. Details of the 11 children with asthma admitted in previous influenza seasons are presented in Appendix 3 (available at www.cmaj.ca/cgi/content/full/cmaj.091724/DC1
). No differences in clinical characteristics of asthma between the 2 groups of children were apparent, although small numbers precluded statistical analysis.
Data on height and weight were available for 35 of the children with pandemic H1N1 influenza. Two satisfied criteria for obesity,11
of whom 1 child, who also had asthma, required intensive care. Five of the 23 without height data had weights above the 97th percentile. Two of these 5 children required intensive care: 1 child had asthma, and the other had seizures.
Twelve (21%) of the children with pandemic H1N1 influenza received antiviral therapy with oseltamivir. This comprised 8 children admitted to the ICU, 3 who had severe immunosuppression (2 of whom presented within 48 hours after symptom onset) and 1 who had presumed viral pneumonia and severe bronchospasm (with no previous history of asthma); this last patient was transferred to the ICU but was managed at a lower intensity. Three of the 4 children admitted to the ICU who did not receive antiviral therapy had shown marked clinical improvement by the time pandemic H1N1 influenza was confirmed. The fourth child (described in Appendix 1, at www.cmaj.ca/cgi/content/full/cmaj.091724/DC1
) was less than 6 months of age, and influenza was not felt to be a sufficiently severe component of the illness for the benefits of treatment to outweigh the risks. The youngest child to receive oseltamivir in hospital was 2.5 years of age.
All but 2 of the children with pandemic H1N1 influenza received parenteral antibacterial therapy.
The presenting features of pandemic H1N1 influenza in the children in our series are similar to those described recently.6
The majority of the children in the initial series in the United States were between 10 and 18 years old;5
similarly, in a series in Chicago, the attack rate was higher in the group aged 5–14 years than in the group less than 5 years old.10
Data from Mexico on severe respiratory illness (regardless of definitive H1N1 diagnosis) showed a significant increase in the proportion affected among children aged 10–19 years, although not as dramatic as the increase among those aged 25–44 years, and a corresponding decrease in the proportion affected among children less than 5 years old.12
Against this apparent trend to increased age, the early Mexican epidemiologic studies found that children less than 2 years old were most affected, with attack rates falling progressively with increasing age.13
Both early case series of individuals admitted to hospital described children with a mean age more in keeping with our group with seasonal influenza.3,4
The rate of hospital admission was highest among children less than 5 years old in both Chicago10
and New York.14
Detailed breakdown by age of our cohort reveals considerable year-to-year variability in the number of children less than 2 years old, with relatively low numbers in the group with pandemic H1N1 influenza (). Although proportionately similar numbers were noted among children aged 2–5 years, the pattern was significantly different among children more than 5 years old; higher proportions of the children with pandemic H1N1 influenza were distributed in this older category (). Older children may have had some pre-existing or cross-reactive immunity to influenza strains circulating in previous seasons, which did not protect them against pandemic H1N1 influenza.15
However, community epidemiologic data are essential to assist in interpreting the observed difference in the ages of children admitted to hospital.
Our clinical impression of slightly more severe disease among admitted patients with pandemic H1N1 influenza was not borne out by rates or duration of ICU admission, or by length of hospital stay. Our impression remains that there is a small group of children who are more adversely affected by this virus. However, we have insufficient numbers to identify characteristics of this group. Obesity has been reported to be prevalent among patients with severe H1N1 influenza.6,16
In our cohort, all 3 children who were either obese (according to body mass index) or possibly obese (according to weight alone) and required intensive care had a high-risk medical condition. None of the children with pandemic H1N1 influenza in our study died, although 1 child required protracted extracorporeal membrane oxygenation therapy.
The most striking finding in our study was the high prevalence of asthma among children admitted with pandemic H1N1 influenza compared with those admitted in previous influenza seasons. Asthma has been identified as a significant risk factor for pandemic H1N1 influenza requiring hospital admission, present in 21%–30% in the larger samples.10,14
However, there are few published pediatric data, particularly regarding the severity of asthma or the clinical course and outcomes of children with asthma. Comparisons between pandemic H1N1 influenza and seasonal influenza in children with asthma are lacking. Most prior data on seasonal influenza did not present asthma separately from other chronic lung diseases. Asthma or reactive airways disease was listed as part of the underlying condition in only 3 of 36 children who died of pandemic H1N1 influenza; all of these children also had neurologic impairment.7
Our experience suggests that asthma is a more significant risk factor for pandemic H1N1 influenza requiring hospital admission than for seasonal influenza and that children with mild asthma are also at risk. Of note, more than 50% of the children with asthma admitted to our hospital with pandemic H1N1 influenza presented with evidence of pneumonia, with or without bronchospasm.
Bias may have been introduced into our comparison of pandemic H1N1 influenza and seasonal influenza in previous years because of the possible influence of the pandemic publicity on admission criteria. We believe that this is unlikely, however, because a dedicated team of specialists offered emergency staff consistent, round-the-clock consultation on all potential admissions. Even if such a bias were to exist, it would apply across all underlying conditions and would not affect our conclusions regarding risk factors.
We cannot estimate the rate of admission to hospital because of pandemic H1N1 influenza without population-based epidemiologic data. This is an area for imminent future research. Such studies should focus on age and underlying asthma in particular. There are limited data to support the efficacy of influenza vaccination in reducing asthma exacerbations,17
particularly in older children,18
although previous concerns about safety in asthma have been assuaged. Asthma has therefore been an indication for influenza vaccination for several years, but uptake is low.19
The current influenza season offers a good opportunity to improve the evidence base in this population and consequently change practice.
This study is limited by its retrospective design, single-centre origin and lack of community epidemiologic data. Although this series remains the second largest published to date, and the largest from a single centre, the numbers of children admitted were small. This limits our ability to identify additional risk factors in subgroups of children and precludes multivariable analysis other than the exploration of the potential confounding effect of age on asthma as a risk factor. The indicators of influenza severity may have been influenced by factors unrelated to disease severity, such as availability of hospital or ICU beds. Nonetheless, we chose them as outcome measures because they have a major impact on resource planning, and because treatment-independent events, such as death and long-term sequelae from influenza infection, are too infrequent to be used as comparative outcome measures in samples of this size.
In our cohort, pandemic H1N1 influenza did not appear to cause more severe disease than seasonal influenza A. Asthma was a more significant risk factor for severe disease among children with pandemic H1N1 influenza than among those with seasonal influenza. Because the risk of severe disease appears to have no clear relation to the severity of asthma, even children with mild asthma should receive vaccination and be considered for pre-emptive antiviral therapy.