MALMO, SWEDEN – Giving a combined MMR vaccine and a varicella vaccine separately on the same day in children with personal or family history of febrile convulsions while utilizing the more convenient MMRV vaccine in those without such a history showed promise as a means of reducing the overall risk of febrile convulsions attributable to vaccination, Corinne Willame said at the annual meeting of the European Society for Paediatric Infectious Diseases.
She presented a post hoc analysis of an enormous, German observational study that demonstrated an increased risk of hospitalization for febrile convulsions 5-12 days after receiving the first dose of the Priorix-Tetra MMRV vaccine, with no alternative plausible cause of the convulsions ().
The original study was conducted in more than 180,000 children under the age of 5 years, 90% of whom were 11- 23 months. The increased risk associated with MMRV, compared with MMR alone or MMR plus V separately on the same day, was similar in magnitude to what had previously been reported for the ProQuad MMRV vaccine, suggesting a class effect for the quadrivalent vaccines.
Because genetic predisposition is known to be associated with increased risk of febrile convulsions, Ms. Willame of GlaxoSmithKline in Wavre, Belgium, and her coinvestigators conducted an exploratory analysis investigating whether the presence of a personal or first-degree family history of febrile convulsions impacted the risk of developing febrile convulsions following a first dose of MMRV, compared with MMR alone or MMR and V administered separately on the same day. They found that indeed it did, according to Ms. Willame.
They analyzed the data in multiple ways. The first scenario compared the risk of febrile convulsions in 74,631 children 5-12 days after receiving the MMRV vaccine with a roughly equal number of children who received the MMR vaccine. Study subjects were matched for age, sex, month of vaccination, and insurance provider. The febrile convulsion incidence rate was 6.03 cases per 10,000 children in MMRV recipients and 2.55 per 10,000 in those who got MMR. Then they reanalyzed the data after subtracting all children with a baseline personal history of febrile convulsions from the pool of MMRV recipients: The febrile convulsion rate in the MMRV group dropped to 5.27 cases per 10,000.
Next, they did the same analysis in more than 64,000 matched children who got either MMRV or MMR plus V separately. For the whole cohort of MMRV recipients, the febrile convulsion rate was 6.53 cases per 10,000 vaccine recipients, dropping to 5.95 per 10,000 if children with a personal history of febrile convulsions were removed. The relative risk of febrile convulsions was 150% greater in the overall MMRV group than with MMR plus V, but only 58% greater when the children with a personal history of febrile seizures were excluded from the MMRV population.
Unfortunately, the parent study didn’t record whether a history of febrile convulsions was present in first-degree family members. The investigators therefore turned to the published literature on the subject and constructed conditional probability analyses based upon a 20%-40% likelihood of a positive family history in children with a personal history, and a 5% likelihood in those children without such a history. In this scenario, when children with a personal or hypothetical family history of febrile convulsions were subtracted from the MMRV group, the result was a febrile convulsion incidence rate of 3.27-4.41 cases per 10,000 MMRV recipients in the comparison with MMR and 3.63-4.95 per 10,000 in the comparison with MMR plus V.
Ms. Willame emphasized that her analysis must be considered hypothesis generating because it’s post hoc and relies upon published estimates of the prevalence of a positive family history of febrile convulsions. The febrile convulsion risk differences she found with the different vaccination strategies should be confirmed in studies that collect family history data of febrile seizures at an individual level.
Her study was funded by her employer, GlaxoSmithKline.