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MMR and febrile seizures

 

Clinical bottom line

MMR vaccination can produce a fever, and therefore increases the risk of a febrile seizure. The absolute risk is one or two per 1,000 doses of vaccine. Children with a personal history of febrile seizures have a higher risk, of an additional 20 per 1,000 doses of vaccine. There was no association between febrile seizure and later development of epilepsy.


Reference

M Vestergaard et al. MMR vaccination and febrile seizures: evaluation of susceptible subgroups and long-term prognosis. JAMA 2004 292: 351-357.


Background

MMR is generally well tolerated and associated with few adverse effects. It is, however, associated with an increased risk of febrile seizures, probably due to vaccine-induced fever. This study quantifies the short and long term risks.

Study

The study population was all children born in Denmark in the years 1991-1998. As all people born in Denmark have a unique personal identity number, and because this number can be used to link national registries, it makes for the possibility of evaluating rare events in a whole population.

MMR vaccination status was obtained, together with information on febrile seizures or epilepsy on patients discharged from hospital, or seen in outpatients or emergency departments.

Results

The population studied was 540,000 children, with 1.9 million years of follow up. Of these, 440,000 (82%) had MMR vaccination. There were 17,986 children with at least one febrile seizure, of which 973 occurred within two weeks of vaccination.

The rate of first febrile seizure was higher in vaccinated than unvaccinated children, by 10% (relative risk 1.1; 95% CI 1.05 to 1.15). Febrile seizures occurred more frequently in the first and second week after MMR vaccination (relative risk 2.8; 2.6 to 3.0), but not at any time thereafter, up to five years. None of the following factors was associated with higher risk than this: siblings with febrile seizures or epilepsy, sex, birth order, gestational age at birth, birth weight, socioeconomic status or maternal levels of education. Additional risk was in children with a previous history of febrile seizures.

Compared with children who were not vaccinated, the additional risk of febrile seizures within 14 days of MMR vaccination was one or two cases per 1,000 doses of vaccine, so the risk increased from 1 per 1,000 to 2-3 per 1,000. For children with a history of febrile seizures the additional risk was 19 per 1,000 doses, so it increased from 12 to 31 cases per 1,000.

Recurrent seizures

Compared with children who were not vaccinated, recurrent febrile seizures were very slightly increased in children who has one episode of febrile seizure within 14 days of vaccination (relative risk 1.2; 1.01 to 1.4), but no increased risk in those who experienced a seizure after 14 days.

Epilepsy

Compared with children who were not vaccinated, there was no increased risk of epilepsy in children who had a febrile seizure with 14 days of MMR vaccination, or in those who had a febrile seizure after 14 days.

Comment

This is an enormous study from a very important database. MMR vaccination can produce a fever, and therefore increases the risk of a febrile seizure. The absolute risk is one or two per 1,000 doses of vaccine. Children with a personal history of febrile seizures have a higher risk, of an additional 20 per 1,000 doses of vaccine. There was no association between febrile seizure and later development of epilepsy.