MMRV and Seizures

Source: Klein NP, Lewis E, Baxter R, et al. Measles-containing vaccines and febrile seizures in children aged 4 to 6 years. Pediatrics. 2012;129(5):809-814; doi:10.1542/peds.2011-3198.  See AAP Grand Rounds commentary by Dr. Robert Tolan, Jr (subscription required).

PICO
Question: Among US children aged 4 to 6 years, do measles-containing vaccines lead to an increased risk of febrile seizures?
Question type: Intervention
Study design: Retrospective cohort

This CDC-based study provided some reassuring news regarding combined measles-mumps-rubella-varicella (MMRV) vaccine administered to 4 to 6 year-old children.  Prior studies had found a slight increased risk associated with MMRV, compared to separate MMR and V (MMR + V) vaccines for the first dose at 1 year of age with an excess risk of 1 additional seizure per 2300 doses of MMRV.  In this new study, no significant difference was noted in febrile seizures among children in this older population receiving MMRV (1 per 86,750 vaccine doses) versus MMR + V (0 per 67,438 doses).  Good news allowing us to be reassuring about the combined vaccine in 4 - 6 year olds.

When one observes only 1 event in the two groups comprising over 150,000 vaccine doses, standard statistical methodology could be misleading.  Just because no events were observed of course doesn't imply the risk is actually zero.  A few years ago, Michael Aldous penned a nice commentary on "zero numerators" in AAP Grand Rounds.  It is particularly helpful to pay attention to confidence intervals in this situation, also a topic examined in a prior AAP Grand Rounds.  Confidence intervals provide a look at worst-case scenarios in statistical analysis; if the worst-case number still looks pretty good, that's very reasssuring.  In the current article, the authors did just that, and the results show that, at worst, MMRV vaccine likely has a risk of febrile seizure no greater than 1 in 15,500 doses, while MMR + V was no greater than 1 in 18,000. 

These vaccine studies were carried out using data from the Vaccine Safety Datalink Project of the CDC, which monitors adverse vaccine events in 10 managed care organizations.