Febrile seizures after 2009 influenza A (H1N1) vaccination and infection: a nationwide registry-based study

Background During the 2009 influenza A (H1N1) pandemic, a monovalent pandemic strain vaccine containing the oil-in-water adjuvant AS03 (Pandemrix®) was offered to the Norwegian population. The coverage among children reached 54 %. Our aim was to estimate the risk of febrile seizure in children after exposure to pandemic influenza vaccination or infection. Methods The study population comprised 226,889 children born 2006–2009 resident in Norway per October 1st, 2009. Febrile seizure episodes were defined by emergency hospital admissions / emergency outpatient hospital care with International Classification of Diseases, Version 10, codes R56.0 or R56.8. The self-controlled case series method was applied to estimate incidence rate ratios (IRRs) in pre-defined risk periods compared to the background period. The total observation window was ± 180 days from exposure day. Among 113,068 vaccinated children, 656 (0.6 %) had at least one febrile seizure episode. Results The IRR of febrile seizures 1–3 days after vaccination was 2.00 (95 % confidence interval [CI]: 1.15–3.51). In the period 4–7 days after vaccination, no increased risk was observed. Among the 8172 children diagnosed with pandemic influenza, 84 (1.0 %) had at least one febrile seizure episode. The IRR of febrile seizures on the same day as a diagnosis of influenza was 116.70 (95 % CI: 62.81–216.90). In the period 1–3 days after a diagnosis of influenza, a tenfold increased risk was observed (IRR 10.12, 95 % CI: 3.82 – 26.82). Conclusions In this large population-based study with precise timing of exposures and outcomes, we found a twofold increased risk of febrile seizures 1–3 days after pandemic influenza vaccination. However, we found that pandemic influenza infection was associated with a much stronger increase in risk of febrile seizures.