Influenza Vaccine Effectiveness Against Pediatric Death in the United States: 2016–2025
Influenza vaccination was strongly associated with lower risk of flu-related death in children.
*Case-cohort observational study; Level 3 (OCEBM).
Citation
Leonard JS, Reinhart K, Lu P-J, et al. Influenza Vaccine Effectiveness Against Pediatric Death in the United States: 2016–2025. Pediatrics. 2026;158(2):e2026076453.
Background
Seasonal flu can rarely cause death in children, including those without chronic illness. Pediatric flu deaths have increased in recent seasons while childhood flu vaccination coverage has declined.
Patients
Reported United States flu-associated deaths in children aged 6 months to 17 years from 2016–2025, excluding the very low-flu 2020–2021 season. Children younger than 6 months and deaths without vaccination status were excluded from main vaccine effectiveness analyses.
Intervention
Full current-season influenza vaccination at least 14 days before illness onset.
Control
Unvaccinated children, compared using state, age, season, and month-specific vaccination coverage from national surveys.
Outcome
Laboratory-confirmed flu-associated pediatric death.
Follow-up Period
Eight influenza seasons, 2016–2017 through 2024–2025, excluding 2020–2021.
Results
| Group | Deaths analyzed | Fully vaccinated among deaths | Estimated reduction in death risk |
|---|---|---|---|
| All children | 1086 | 194 of 1086 | 80% (95% confidence interval 75 to 84) |
| With underlying medical conditions | 530 | 124 of 530 | 77% (95% confidence interval 71 to 82) |
| Without known conditions | 556 | 70 of 556 | 87% (95% confidence interval 84 to 89) |
The control reflected available background vaccination coverage, not an assigned treatment. Number needed to vaccinate could not be calculated because population death risks were not provided.
Limitations
Observational design cannot prove causation. Some flu deaths may have been missed if testing was not done. Vaccination status and medical conditions may have been misclassified. National survey vaccination coverage may overestimate true coverage, though sensitivity analyses still showed protection.
Funding
No relevant funding disclosed; CDC surveillance study.
Clinical Application
Strongly reinforce annual flu vaccination for all eligible children, including healthy children and those with chronic conditions.
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