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Vaccine. 2020 Feb 24;38(9):2166-2171. doi: 10.1016/j.vaccine.2020.01.046. Epub 2020 Feb 1.

The risk of febrile seizures following influenza and 13-valent pneumococcal conjugate vaccines.

Author information

Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA; Division of Infectious Diseases, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA. Electronic address:
FDA Center for Biologics Evaluation and Research, Silver Spring, MD, USA.
Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
OptumInsight Life Sciences, Boston, MA, USA.
Aetna, Blue Bell, PA, USA.
Humana Healthcare Research (HHR), USA(7).
HealthCore, Inc., Alexandria, VA, USA.



Evidence on the risk of febrile seizures after inactivated influenza vaccine (IIV) and 13-valent pneumococcal conjugate vaccine (PCV13) is mixed. In the FDA-sponsored Sentinel Initiative, we examined risk of febrile seizures after IIV and PCV13 in children 6-23 months of age during the 2013-14 and 2014-15 influenza seasons.


Using claims data and a self-controlled risk interval design, we compared the febrile seizure rate in a risk interval (0-1 days) versus control interval (14-20 days). In exploratory analyses, we assessed whether the effect of IIV was modified by concomitant PCV13 administration.


Adjusted for age, calendar time and concomitant administration of the other vaccine, the incidence rate ratio (IRR) for risk of febrile seizures following IIV was 1.12 (95% CI 0.80, 1.56) and following PCV13 was 1.80 (95% CI 1.29, 2.52). The attributable risk for febrile seizures following PCV13 ranged from 0.33 to 5.16 per 100,000 doses by week of age. The age and calendar-time adjusted IRR comparing exposed to unexposed time was numerically larger for concomitant IIV and PCV13 (IRR 2.80, 95% CI 1.63, 4.83), as compared to PCV13 without concomitant IIV (IRR 1.54, 95% CI 1.04, 2.28), and the IRR for IIV without concomitant PCV13 suggested no independent effects of IIV (IRR 0.94, 95% CI 0.63, 1.42). Taken together, this suggests a possible interaction between IIV and PCV13, though our study was not sufficiently powered to provide a precise estimate of the interaction.


We found an elevated risk of febrile seizures after PCV13 vaccine but not after IIV. The risk of febrile seizures after PCV13 is low compared to the overall risk in this population of children, and the risk should be interpreted in the context of the importance of preventing pneumococcal infections.


13-valent pneumococcal conjugate vaccine; Febrile seizure; Influenza vaccine; PCV13

Conflict of interest statement

Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [CJ and DM are employed by the Food and Drug Administration and participated in the design and conduct of the study, interpretation of the data, review and approval of the manuscript, and decision to submit the manuscript for publication. WKY receives research support from GlaxoSmithKline. ATK is currently an employee of RTI Health Solutions, a business unit of Research Triangle Institute, which conducts work for government, public and private organizations, including pharmaceutical companies. The work described in this manuscript was completed while AK was an employee of the Harvard Pilgrim Health Care Institute before she became an employee of RTI Health Solutions. LZ and RCT are currently employees of RTI International, and LL is currently and employee of Karyopharm Therapeutics Inc. All other authors have no potential conflicts of interest.].

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