Pediatric Drugs

, Volume 5, Issue 11, pp 717–722 | Cite as

Placing the Risk of Seizures with Pediatric Vaccines in a Clinical Context

  • Robert L. Davis
  • William Barlow
Current Opinion


In this review we discuss the relationship between commonly administered childhood vaccines such as diphtheria-tetanus-whole cell pertussis (DTP) and measles-mumps-rubella (MMR), and the risk of nonfebrile and febrile seizure. We summarize data from the Vaccine Safety Datalink Study and other studies that suggest that DTP and MMR vaccine are associated with a transiently increased risk of febrile seizures, and cause between 5–9 and 25–34 additional extra febrile seizures per 100 000 immunized children, respectively. DTP and MMR do not appear to increase the risk of nonfebrile seizures.

We discuss some methodologic challenges in studies of vaccines and seizures. Because there is no adequate comparison group that would allow for the study of seizures long after vaccination, studies of seizures are limited to acute events shortly following vaccination. Additionally, while seizures following vaccination are worrisome to parents and physicians alike, observational studies of the neurodevelopmental outcomes of these children are particularly problematic. We discuss how such studies are confounded by the natural history of predisposition to febrile seizures and by the increased diagnostic scrutiny that children with febrile seizures might undergo. Nevertheless, current data suggest that children with febrile seizures do not experience long-term negative effects.

Finally, we discuss the creation of new clinics designed specifically to assist physicians in managing the vaccination of children with a personal or family history of seizures. Data from these clinics suggest that vaccination is safe for children with a personal or family history of seizures, but statistical power has been limited. We conclude by discussing the introduction of new vaccines, and note that, even with widespread use, it will take many years before we can be knowledgeable about the risk of rare events with these newly licensed products.


Pertussis Febrile Seizure Pertussis Vaccine Thiomersal Afebrile Seizure 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



There were no sources of funding used in the preparation of this manuscript, and the authors have no conflicts of interest to report that are directly relevant to the contents of this manuscript.


  1. 1.
    Centers for Disease Control and Prevention. National, state and urban area vaccination coverage levels among children aged 19–35 months: United States, 2001. MMWR Morb Mortal Wkly Rep 2002; 51: 664–6Google Scholar
  2. 2.
    Miller DL, Wadsworth J, Ross E. Severe neurological illness: further analyses of the British National Childhood Encephalopathy Study. Tokai J Exp Clin Med 1988; 13 Suppl.: 145–55PubMedGoogle Scholar
  3. 3.
    Howson CP, Howe CJ, Fineberg HV, editors. Adverse effects of pertussis and rubella vaccines: a report of the Committee to Review the Adverse Consequences of Pertussis and Rubella Vaccines. Washington, DC: Institute of Medicine, 1991Google Scholar
  4. 4.
    Walker AM, Jick H, Perea DR, et al. Neurologic events following diphtheria-tetanus-pertussis immunization. Pediatrics 1988; 81: 345–9PubMedGoogle Scholar
  5. 5.
    Griffin MR, Ray WA, Mortimer EA, et al. Risk of seizures after measles-mumps-rubella immunization. Pediatrics 1991; 88: 881–5PubMedGoogle Scholar
  6. 6.
    Barlow W, Davis RL, Glasser J, et al. Seizures following pertussis or measles vaccination: risks and long term outcomes. N Engl J Med 2001; 345: 656–61PubMedCrossRefGoogle Scholar
  7. 7.
    Gale JL, Thapa PB, Wassilak SG, et al. Risk of serious acute neurological illness after immunization with diphtheria-tetanus-pertussis vaccine: a population-based case-control study. JAMA 1994; 271(1): 37–41PubMedCrossRefGoogle Scholar
  8. 8.
    Farrington P, Pugh S, Colville A, et al. A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines. Lancet 1995; 345: 567–9PubMedCrossRefGoogle Scholar
  9. 9.
    Miller E, Ashworth L, Redhead K, et al. Effect of schedule on reactogenicity and antibody persistence of acellular and whole-cell pertussis vaccines: value of laboratory tests as predictors of performance. Vaccine 1997; 15: 51–60PubMedCrossRefGoogle Scholar
  10. 10.
    Ramsay MEB, Rao M, Begg NT. Symptoms after accelerated immunisation. BMJ 1992; 304: 1534–6PubMedCrossRefGoogle Scholar
  11. 11.
    Baraff LJ, Cherry JD, Cody CL, et al. DTP vaccine reactions: effect of prior reactions on rate of subsequent reactions. Dev Biol Stand 1985; 61: 423–8PubMedGoogle Scholar
  12. 12.
    Livengood JR, Mullen JR, White JW, et al. Family history of convulsions and use of pertussis vaccine. J Pediatr 1989 Oct; 115: 527–31PubMedCrossRefGoogle Scholar
  13. 13.
    World Health Organization. Contraindications for vaccines used in EPI. WHO Wkly Epidem Record 1988; 37: 2–4Google Scholar
  14. 14.
    Burgess MA, McIntyre PB, Heath TC. Rethinking contraindications to vaccination. Med J Aust 1998; 168: 476–7PubMedGoogle Scholar
  15. 15.
    Plotkin SA, Mortimer Jr EA, editors. Vaccines. 2nd ed. Philadelphia (PA): WB Saunders, 1994Google Scholar
  16. 16.
    Andrews RM, Kempe AE, Sinn KK, et al. Vaccinating children with a history of serious reactions after vaccination or of egg allergy. Med J Aust 1998; 168: 491–4PubMedGoogle Scholar
  17. 17.
    Gold M, Goodwin H, Botham S, et al. Re-vaccination of 421 children with past history of an adverse vaccine reaction in a special immunization service. Arch Dis Child 2000; 83: 128–31PubMedCrossRefGoogle Scholar
  18. 18.
    Chen RT, Pool V, Takahashi H, et al. Combination vaccines: post-licensure safety evaluation. Clin Infect Dis 2001; 33Suppl. 4: S327–33PubMedCrossRefGoogle Scholar
  19. 19.
    Fine PE, Chen RT. Confounding in studies of adverse reactions to vaccines. Am J Epidemiol 1992; 136: 121–35PubMedGoogle Scholar
  20. 20.
    Feikin DR, Lezotte DC, Hamman RF, et al. Individual and community risks of measles and pertussis associated with personal exemptions to immunization. JAMA 2000; 284: 3145–50PubMedCrossRefGoogle Scholar
  21. 21.
    Vestergaard M, Basso O, Henriksen TB, et al. Risk factors for febrile convulsions. Epidemiology 2002; 13: 282–7PubMedCrossRefGoogle Scholar
  22. 22.
    Verity CM, Greenwood R, Golding J. Long-term intellectual and behavioral outcomes of children with febrile convulsions. N Engl J Med 1998; 338: 1723–8PubMedCrossRefGoogle Scholar
  23. 23.
    Ellenberg JH, Nelson KB. Febrile seizures and later intellectual performance. Arch Neurol 1978; 35: 17–21PubMedCrossRefGoogle Scholar
  24. 24.
    Hirtz DG, Nelson KB, Ellenberg JH. Seizures following childhood immunizations. J Pediatr 1983; 102: 14–8PubMedCrossRefGoogle Scholar
  25. 25.
    Rosenthal S, Chen R, Hadler S. The safety of acellular pertussis vaccine vs whole-cell pertussis vaccine: a postmarketing assessment. Arch Pediatr Adolesc Med 1996; 150(5): 457–60PubMedCrossRefGoogle Scholar
  26. 26.
    Braun MM, Mootrey GT, Salive ME, et al. Infant immunization with acellular pertussis vaccines in the United States: assessment of the first two years’ data from the Vaccine Adverse Event Reporting System (VAERS). Pediatrics 2000; 106(4): E51PubMedCrossRefGoogle Scholar

Copyright information

© Adis Data Information BV 2003

Authors and Affiliations

  1. 1.Departments of Pediatrics and EpidemiologyUniversity of WashingtonSeattleUSA
  2. 2.Center for Health StudiesGroup Health CooperativeSeattleUSA
  3. 3.Department of BiostatisticsUniversity of WashingtonSeattleUSA

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