MMR Vaccination and Febrile Seizures: Evaluation of Susceptible Subgroups and Long-term Prognosis. Vestergaard M, Hviid A, Madsen KM, Wohlfahrt J, Thorsen P, Schendel D, Melbye M, and Olsen J. JAMA 2004;292:351-357.
Explanatory note: “Febrile seizures” are common among children and they generally have an uneventful outcome. These seizures can occur (and re-occur) between 9 months and 5 years of age when children develop fever. They rarely develop into epilepsy. There is a strong tendency within a family to develop febrile seizures.
Measles-mumps-rubella (MMR) vaccine is well tolerated and is rarely associated with severe adverse events. However, about 10% of children who receive MMR vaccine for the first time will develop a fever between 5 and 12 days later. A small proportion of these children may develop a febrile seizure.
How common are febrile seizures after MMR vaccination? Are there subgroups of children at higher risk for febrile seizure after receiving MMR? What is the long term outcome for children who had a febrile seizure after MMR vaccination?
This study included all children born in Denmark between January 1, 1991, and December 31, 1998, who were alive at 3 months of age—a total of 537,171 children followed until December 31, 1999.
Using data from the Danish Civil Registration System and 4 other Danish national registries, researchers compared demographic data with MMR vaccination status and reports of febrile seizures and epilepsy.
The investigators analyzed whether febrile seizures were more or less common after MMR vaccination and whether febrile seizures after vaccination were associated with long-term effects, such as epilepsy. They also considered the findings in terms of a personal or family history of seizures, whether there were perinatal risk factors, and socioeconomic status.
A total of 439,251 of the children (82%) received MMR vaccination. Febrile seizures occurred in 17,986 children; 973 (5%) of these febrile seizures occurred within 2 weeks of MMR vaccination.
Children were more than 2.5 times as likely to have a febrile seizure during the 2 weeks following MMR vaccination than at other times. However, the overall increase was small: for each 1,000 children vaccinated, one or two children more than usual had a febrile seizure.
Children who had previously had a febrile seizure were at increased risk for having a febrile seizure within two weeks of receiving MMR vaccination. Children who had a febrile seizure after MMR vaccination also had an increased risk of seizures with other illnesses when they had fever.
Having a febrile seizure following MMR vaccination was not more likely if there was a family member with a history of febrile seizures. However, the rate of febrile seizure was higher for children who had a sibling with epilepsy. Having a febrile seizure after MMR vaccination did not increase the risk of epilepsy.
The risk for febrile seizure did not differ among subgroups of children that had been defined by their family history of seizures, perinatal factors, or socioeconomic status.
Children may experience a small increase in the rate of febrile seizures during the 2 weeks after MMR vaccination. However, these children had the same likelihood of developing epilepsy as children who had febrile seizures for other reasons.
MMR vaccination has protected millions of children from these devastating diseases. This very large study showed that receiving MMR vaccine is followed by a brief period of increased risk of febrile seizure, most likely due to the fever caused by the vaccination. This increased risk was small even in those at greatest risk of febrile seizures.