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November 3, 2004

MMR Vaccination and Febrile Seizures

JAMA. 2004;292(17):2083-2084. doi:10.1001/jama.292.17.2083-a

To the Editor: The study by Dr Vestergaard and colleagues1 showed that measles, mumps, and rubella (MMR) vaccination was associated with only a small transient increased risk of febrile seizures and no risk of epilepsy. We believe a more extensive discussion of the potential for confounding by contraindication in the authors’ nonrandomized design would have made their findings more convincing. In a cohort study, if the prescribing physician or parent is aware of febrile seizures and epilepsy as possible adverse vaccine effects, and information on the child’s prognosis is available to the physician, bias by contraindication may lead to an underestimate of true adverse effects because patients at highest risk for the adverse event will be preferentially unvaccinated.2,3 Long before the study began in 1991 there had been several reports of a possible link between febrile seizures, epilepsy, and measles vaccination,4 which could have led to this confounding bias, especially since only a minority of children (18%) did not receive the vaccine. A decreasing time trend in relative risk of febrile seizures from 1.0 in week 6 to 0.75 in weeks 157-260 after vaccination, and a relative risk for epilepsy of 0.7 (an estimate lower than 1.0) further support this contention.