Elsevier

Vaccine

Volume 27, Issue 34, 23 July 2009, Pages 4656-4661
Vaccine

Observational safety study of febrile convulsion following first dose MMRV vaccination in a managed care setting

https://doi.org/10.1016/j.vaccine.2009.05.056Get rights and content

Abstract

Background

A combined measles, mumps, rubella, varicella live vaccine (MMRV, Merck and Co., Inc., US) was recently licensed in the US. Pre-licensure clinical trial data showed a significant increase in fever in days 5–12 following MMRV vaccination as compared to the vaccines given separately (MMR + V). This post-licensure retrospective cohort study was undertaken to assess the incidence of febrile convulsion following MMRV.

Methods

Children ages 12–60 months who received a first dose of MMRV in February 2006–June 2007 in a managed care organization were included in the study. Subjects were optimally matched on age, sex, and calendar date of vaccination to children who received MMR + V concomitantly in November 2003–January 2006, before MMRV licensure. Potential cases of febrile convulsion were identified through administrative data and adjudicated by expert panel, according to pre-specified criteria.

Results

During the 30 days post-vaccination, there were 128 and 94 potential convulsion cases among the 31,298 children in the MMRV and MMR + V cohorts, respectively. After review of available medical charts and adjudication, there were 84 cases of confirmed febrile convulsion, 44 (1.41/1000) and 40 (1.28/1000) in the MMRV and MMR + V cohorts, respectively (RR = 1.10, 95% CI = 0.72, 1.69). In days 5–12 following vaccination, a pre-specified period of interest, the respective numbers were 22 (0.70/1000) and 10 (0.32/1000) (RR = 2.20, 95% CI = 1.04, 4.65).

Conclusion

These data suggest that the risk of febrile convulsion is increased in days 5–12 following vaccination with MMRV as compared to MMR + V given separately during the same visit, when post-vaccination fever and rash are also increased in clinical trials. While there was no evidence of an increase in the overall month following vaccination, the elevated risk during this time period should be communicated and needs to be balanced with the potential benefit of a combined vaccine.

Section snippets

Background

ProQuad™, a combined formulation of measles, mumps, rubella, and varicella (MMRV) vaccine that contains components of two Merck vaccines, MMR-II™(MMR) and VARIVAX™ (V), was approved in the United States (US) in September 2005. Before MMRV was available, MMR and V were usually given concomitantly as two separate injections [1]. The new combined vaccine offers several advantages [2]. For parents and providers, the administration of a single vaccine, compared to two, can reduce the time, effort

Study setting

Kaiser Permanente Southern California (KPSC) is a large managed care organization that geographically spans from Bakersfield in the Southern San Joaquin Valley to San Diego, at the Mexican border. In 2006, KPSC had a membership of over 3.2 million, with a racial/ethnic composition similar to that seen in the source population. The majority of healthcare for members is delivered in one of 12 medical centers or their affiliated outpatient facilities. A fraction of emergent and specialty care is

Cohort characteristics

Of the 31,298 children in the index cohort, 31,043 (99%) were between the ages of 12 and 23 months and 255 were ages 24–60 months (Table 1). There were 15,337 (49%) girls and approximately 7000 children (22%) were non-Hispanic Whites. Nearly a third of vaccines were administered from February through April and less than 20% from November through January.

Results of adjudication of potential convulsion events

Of the 370 potential convulsion events, 138 cases had a claims record or visit outside the KPSC system, while 232 cases were seen within the

Discussion

In this report, we observed a modestly increased incidence of febrile convulsion in children receiving MMRV as compared to an historical comparison group that received MMR + V. This increase was concentrated in days 5–12 following vaccination as expected from the increased incidence of fever during that period in clinical trials [3], [4], [5], [6], [7]. This increased risk was attenuated by the end of 1 month of follow-up, with little overall difference in risk. For days 5–12 following

Acknowledgements

The authors thank the members of the Safety Review Committee (Drs. Allen Hauser (chair, Columbia University), Neal Halsey (Johns Hopkins University) and Samy Suissa (McGill University) for their critical and thoughtful comments and members of the adjudication panel (Drs. S. Michael Marcy (chief), Robert (Bo) Riewerts and Suresh Gurbani, Kaiser Permanente Southern California) for their diligent review of potential cases of febrile convulsion. Ms. Bianca Cheung (Kaiser Permanente Southern

References (17)

  • M.B. Koslap-Petraco et al.

    Societal impact of combination vaccines: experiences of physicians, nurses, and parents

    J Pediatr Health Care

    (2008)
  • J. Bonhoeffer et al.

    Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation

    Vaccine

    (2004)
  • E.T. Luman et al.

    Uptake of varicella vaccination among young children in the United States: a success story in eliminating racial and ethnic disparities

    Pediatrics

    (2006)
  • H. Shinefield et al.

    Evaluation of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children

    Pediatr Infect Dis J.

    (2005)
  • H. Shinefield et al.

    Dose-response study of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children

    Pediatr Infect Dis J

    (2005)
  • B.J. Kuter et al.

    Safety and immunogenicity of a combination measles, mumps, rubella and varicella vaccine (ProQuad)

    Hum Vaccine

    (2006)
  • J.M. Lieberman et al.

    The safety and immunogenicity of a quadrivalent measles, mumps, rubella and varicella vaccine in healthy children: a study of manufacturing consistency and persistence of antibody

    Pediatr Infect Dis J

    (2006)
  • K.S. Reisinger et al.

    A combination measles, mumps, rubella, and varicella vaccine (ProQuad) given to 4- to 6-year-old healthy children vaccinated previously with M-M-RII and Varivax

    Pediatrics

    (2006)
There are more references available in the full text version of this article.

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