Influenza-Associated Neurologic Complications in Hospitalized Children

Abstract

Objectives: To define the incidence and characteristics of influenza-associated neurologic complications in a cohort of children hospitalized at a tertiary care pediatric hospital with laboratory-confirmed influenza and to identify associated clinical, epidemiologic, and virologic factors.

Study design: This was an historical cohort study of children aged 0.5-18.0 years old hospitalized between 2010 and 2017 with laboratory-confirmed influenza. Children with immune compromise or a positive test due to recent receipt of live virus vaccine or recently resolved illness were excluded. Influenza-associated neurologic complications were defined as new-onset neurologic signs/symptoms during acute influenza illness without another clear etiology.

Results: At least 1 influenza-associated neurologic complication was identified in 10.8% (95% CI 9.1-12.6%, n = 131 of 1217) of hospitalizations with laboratory-confirmed influenza. Seizures (n = 97) and encephalopathy (n = 44) were the most commonly identified influenza-associated neurologic complications, although an additional 20 hospitalizations had other influenza-associated neurologic complications. Hospitalizations with influenza-associated neurologic complications were similar in age and influenza type (A/B) to those without. Children with a pre-existing neurologic diagnosis (n = 326) had a greater proportion of influenza-associated neurologic complications compared with those without (22.7% vs 6.4%, P < .001). Presence of a pre-existing neurologic diagnosis (aOR 4.6, P < .001), lack of seasonal influenza vaccination (aOR 1.6, P = .020), and age ≤5 years (aOR 1.6, P = .017) were independently associated with influenza-associated neurologic complications.

Conclusions: Influenza-associated neurologic complications are common in children hospitalized with influenza, particularly those with pre-existing neurologic diagnoses. A better understanding of the epidemiology and factors associated with influenza-associated neurologic complications will direct future investigation into potential neuropathologic mechanisms and mitigating strategies. Vaccination is recommended and may help prevent influenza-associated neurologic complications in children.

Keywords: encephalopathy; epidemiology; influenza; pediatric; seizure.

Figure 1 online:

Flow diagram of study population.

Figure 2 online:

Proportion (y-axis) and number (*) of hospitalizations with an influenza-associated neurologic complication by season. ⁺p-value represents difference in proportion by year.

Figure 3:

Frequency of neurologic complications. A. Among the overall cohort (n=1,217); B. Among those with a pre-existing neurologic diagnosis (n=326); C. Among those without a pre-existing neurologic diagnosis (n=876). Of the seizures (n=39) in panel C, 29 were febrile seizures.

Figure 4 online:

Proportion (y-axis) and number (*) of hospitalizations with an influenza-associated neurologic complication by pre-existing neurologic disorder. PND (pre-existing neurological diagnosis), NG (neurogenetic), metab (metabolic), DD (developmental delay), ID (intellectual disability).