Effect of Age on the Risk of Fever and Seizures Following Immunization With Measles-Containing Vaccines in Children | Infectious Diseases | JAMA Pediatrics | JAMA Network
[Skip to Navigation]
Access to paid content on this site is currently suspended due to excessive activity being detected from your IP address 18.204.227.34. Please contact the publisher to request reinstatement.

Author Ali Rowhani-Rahbar, MD, discusses Effect of Age on the Risk of Fever and Seizures Following Immunization With Measles-Containing Vaccines in Children.

1.
Atkinson W, Wolfe C, Hamborsky J, eds. Epidemiology and Prevention of Vaccine-Preventable Diseases. 12th ed. Washington, DC: The Public Health Foundation; 2012.
2.
Marin  M, Broder  KR, Temte  JL, Snider  DE, Seward  JF; Centers for Disease Control and Prevention (CDC).  Use of combination measles, mumps, rubella, and varicella vaccine: recommendations of the Advisory Committee on Immunization Practices (ACIP).  MMWR Recomm Rep. 2010;59(RR-3):1-12.PubMedGoogle Scholar
3.
US vaccination coverage reported via NIS. Centers for Disease Control and Prevention website. http://www.cdc.gov/vaccines/stats-surv/nis/default.htm#nis. Accessed September 20, 2013.
4.
Klein  NP, Fireman  B, Yih  WK,  et al; Vaccine Safety Datalink.  Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures.  Pediatrics. 2010;126(1):e1-e8.PubMedGoogle ScholarCrossref
5.
Barlow  WE, Davis  RL, Glasser  JW,  et al; Centers for Disease Control and Prevention Vaccine Safety Datalink Working Group.  The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine.  N Engl J Med. 2001;345(9):656-661.PubMedGoogle ScholarCrossref
6.
Griffin  MR, Ray  WA, Mortimer  EA, Fenichel  GM, Schaffner  W.  Risk of seizures after measles-mumps-rubella immunization.  Pediatrics. 1991;88(5):881-885.PubMedGoogle Scholar
7.
Jacobsen  SJ, Ackerson  BK, Sy  LS,  et al.  Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting.  Vaccine. 2009;27(34):4656-4661.PubMedGoogle ScholarCrossref
8.
Vestergaard  M, Hviid  A, Madsen  KM,  et al.  MMR vaccination and febrile seizures: evaluation of susceptible subgroups and long-term prognosis.  JAMA. 2004;292(3):351-357.PubMedGoogle ScholarCrossref
9.
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(8949):567-569.PubMedGoogle ScholarCrossref
10.
Strebel PM, Papania MJ, Dayan GH, Halsey NA. Measles vaccine. In: Plotkin SA, Orenstein WA, Offit PA, eds. Vaccines. 5th ed. Philadelphia, PA: Saunders Elsevier; 2008.
11.
Verburgh  ME, Bruijnzeels  MA, van der Wouden  JC,  et al.  Incidence of febrile seizures in the Netherlands.  Neuroepidemiology. 1992;11(4-6):169-172.PubMedGoogle ScholarCrossref
12.
Vestergaard  M, Christensen  J.  Register-based studies on febrile seizures in Denmark.  Brain Dev. 2009;31(5):372-377.PubMedGoogle ScholarCrossref
13.
Van der Berg  BJ, Yerushalmy  J.  Studies on convulsive disorders in young children, I: incidence of febrile and nonfebrile convulsions by age and other factors.  Pediatr Res. 1969;3(4):298-304.PubMedGoogle ScholarCrossref
14.
Huang  WT, Gargiullo  PM, Broder  KR,  et al; Vaccine Safety Datalink Team.  Lack of association between acellular pertussis vaccine and seizures in early childhood.  Pediatrics. 2010;126(2):263-269.PubMedGoogle ScholarCrossref
15.
Tse  A, Tseng  HF, Greene  SK, Vellozzi  C, Lee  GM; VSD Rapid Cycle Analysis Influenza Working Group.  Signal identification and evaluation for risk of febrile seizures in children following trivalent inactivated influenza vaccine in the Vaccine Safety Datalink Project, 2010-2011.  Vaccine. 2012;30(11):2024-2031.PubMedGoogle ScholarCrossref
16.
Chen  RT, DeStefano  F, Davis  RL,  et al.  The Vaccine Safety Datalink: immunization research in health maintenance organizations in the USA.  Bull World Health Organ. 2000;78(2):186-194.PubMedGoogle Scholar
17.
DeStefano  F; Vaccine Safety Datalink Research Group.  The Vaccine Safety Datalink project.  Pharmacoepidemiol Drug Saf. 2001;10(5):403-406.PubMedGoogle ScholarCrossref
18.
Baggs  J, Gee  J, Lewis  E,  et al.  The Vaccine Safety Datalink: a model for monitoring immunization safety.  Pediatrics. 2011;127(suppl 1):S45-S53.PubMedGoogle ScholarCrossref
19.
Yih  WK, Kulldorff  M, Fireman  BH,  et al.  Active surveillance for adverse events: the experience of the Vaccine Safety Datalink project.  Pediatrics. 2011;127(suppl 1):S54-S64.PubMedGoogle ScholarCrossref
20.
Lieu  TA, Kulldorff  M, Davis  RL,  et al; Vaccine Safety Datalink Rapid Cycle Analysis Team.  Real-time vaccine safety surveillance for the early detection of adverse events.  Med Care. 2007;45(10)(suppl 2):S89-S95.PubMedGoogle ScholarCrossref
21.
Klein  NP, Lewis  E, Baxter  R,  et al.  Measles-containing vaccines and febrile seizures in children age 4 to 6 years.  Pediatrics. 2012;129(5):809-814.PubMedGoogle ScholarCrossref
22.
Gillet  Y, Steri  GC, Behre  U,  et al.  Immunogenicity and safety of measles-mumps-rubella-varicella (MMRV) vaccine followed by one dose of varicella vaccine in children aged 15 months-2 years or 2-6 years primed with measles-mumps-rubella (MMR) vaccine.  Vaccine. 2009;27(3):446-453.PubMedGoogle ScholarCrossref
23.
Blatter  MM, Klein  NP, Shepard  JS,  et al.  Immunogenicity and safety of two tetravalent (measles, mumps, rubella, varicella) vaccines coadministered with hepatitis a and pneumococcal conjugate vaccines to children twelve to fourteen months of age.  Pediatr Infect Dis J. 2012;31(8):e133-e140.PubMedGoogle ScholarCrossref
24.
Peltola  H, Heinonen  OP.  Frequency of true adverse reactions to measles-mumps-rubella vaccine: a double-blind placebo-controlled trial in twins.  Lancet. 1986;1(8487):939-942.PubMedGoogle ScholarCrossref
25.
Glanz  JM, McClure  DL, Xu  S,  et al.  Four different study designs to evaluate vaccine safety were equally validated with contrasting limitations.  J Clin Epidemiol. 2006;59(8):808-818.PubMedGoogle ScholarCrossref
26.
Rowhani-Rahbar  A, Klein  NP, Dekker  CL,  et al; Risk Interval Working Group of the Clinical Immunization Safety Assessment Network.  Biologically plausible and evidence-based risk intervals in immunization safety research.  Vaccine. 2012;31(1):271-277.PubMedGoogle ScholarCrossref
27.
Orenstein  WA, Markowitz  L, Preblud  SR, Hinman  AR, Tomasi  A, Bart  KJ.  Appropriate age for measles vaccination in the United States.  Dev Biol Stand. 1986;65:13-21.PubMedGoogle Scholar
28.
Kuter  BJ, Brown  ML, Hartzel  J,  et al; Study Group for ProQuad.  Safety and immunogenicity of a combination measles, mumps, rubella and varicella vaccine (ProQuad).  Hum Vaccin. 2006;2(5):205-214.PubMedGoogle ScholarCrossref
Original Investigation
December 2013

Effect of Age on the Risk of Fever and Seizures Following Immunization With Measles-Containing Vaccines in Children

Author Affiliations
  • 1Kaiser Permanente Vaccine Study Center, Oakland, California
  • 2HealthPartners Institute for Education and Research, Minneapolis, Minnesota
  • 3Kaiser Permanente Center for Health Research, Portland, Oregon
  • 4Kaiser Permanente Department of Research and Evaluation, Pasadena, California
  • 5Group Health Research Institute, Seattle, Washington
  • 6Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts
  • 7Marshfield Clinic Research Foundation, Marshfield, Wisconsin
  • 8Kaiser Permanente Institute for Health Research, Denver, Colorado
  • 9Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia
JAMA Pediatr. 2013;167(12):1111-1117. doi:10.1001/jamapediatrics.2013.2745
Abstract

Importance  The first dose of live attenuated measles-containing vaccines is associated with an increased risk of febrile seizures 7 to 10 days following immunization among 12- to 23-month-old children. The combination measles, mumps, rubella, and varicella vaccine is associated with a 2-fold increased risk of febrile seizures 7 to 10 days following immunization compared with the separately administered measles, mumps, and rubella and varicella vaccines. It is unknown whether the magnitude of these increased risks depends on age at immunization.

Objective  To examine the potential modifying effect of age on the risk of fever and seizures following immunization with measles-containing vaccines.

Design, Setting, and Participants  Retrospective cohort study at 8 Vaccine Safety Datalink sites of a total of 840 348 children 12 to 23 months of age who had received a measles-containing vaccine from 2001 through 2011.

Exposures  Any measles-containing vaccines and measles-containing vaccines by type.

Main Outcomes and Measures  Fever and seizure events occurring during a 42-day postimmunization observation period.

Results  In the analysis of any measles-containing vaccines, the increased risk of seizures during the 7- to 10-day risk interval, using the remainder of the observation period as the control interval, was significantly greater among older children (relative risk, 6.5; 95% CI, 5.3-8.1; attributable risk, 9.5 excess cases per 10 000 doses; 95% CI, 7.6-11.5) than among younger children (relative risk, 3.4; 95% CI, 3.0-3.9; attributable risk = 4.0 excess cases per 10 000 doses; 95% CI, 3.4-4.6). The relative risk of postimmunization fever was significantly greater among older children than among younger children; however, its attributable risk was not. In the analysis of vaccine type, measles, mumps, rubella, and varicella vaccine was associated with a 1.4-fold increase in the risk of fever and 2-fold increase in the risk of seizures compared with measles, mumps, and rubella vaccine administered with or without varicella vaccine in both younger and older children.

Conclusions and Relevance  Measles-containing vaccines are associated with a lower increased risk of seizures when administered at 12 to 15 months of age. Findings of this study that focused on safety outcomes highlight the importance of timely immunization of children with the first dose of measles-containing vaccines.

×