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Abstract & Commentary
Source: Barlow WE, et al. N Engl J Med. 2001;345:656-661.
Most children in the world are exposed to pertussis vaccine and measles, mumps, and rubella vaccine during the first 2 years of life, as a part of a routine immunization schedule. No other exposure to a biological agent is as widespread. Therefore, special attention must be paid to whether immunization is a significant cause for seizure cases, even if the risk is small.
Current vaccine consists of diptheria, tetanus, and pertussis as an acellular combined vaccine at 2, 4, 6, and 18 months of age. Measles, mumps, and rubella (MMR) vaccines are typically coadminstered at 12 months of age. Early studies suggested an elevated risk of seizures and encephalopathy with the DTP vaccine, but more recent analyses suggest that the risk extends only to febrile seizures, and lasts for a few days after the administration of vaccine. MMR vaccine administration has also been linked to an increased risk of febrile seizures, with the increased risk typically peaking at 7-14 days after administration of vaccine, coinciding with post-vaccination fever.
The outcome of children who develop febrile seizures following these vaccinations are unknown. Barlow et al are one of the first groups to address these issues.
Barlow and colleagues examined the medical records of 679,942 children from the western United States who received health care through the Kaiser-Permanente system. The relative risk of febrile seizures following administration of DTP and MMR vaccines was calculated and determined to be approximately 6-fold for DTP, with the risk significant only on the day of vaccination. The additional risk of febrile seizures was approximately 3-fold higher during the 8th-14th day following vaccination. Barlow et al could attribute only 6-9 febrile seizure events/100,000 vaccinated to DTP vaccination and 25-34 febrile seizure events/100,000 vaccinated to MMR vaccination. No increased risk of afebrile seizures could be attributed to either vaccination.
Follow-up identified 41 children as having febrile seizures temporarily correlated to vaccination; 521 children had febrile seizures not temporarily correlated to vaccination. No significant difference separated vaccine- and nonvaccine-associated seizures with respect to risk of future epilepsy or developmental delay.
This paper highlights that both the DTP and MMR vaccines are associated with a transient increased risk of febrile seizures for 1 and 8-14 days following vaccination. No evidence shows that the long-term significance of these seizures differs no more than standard febrile seizures. The number of febrile seizures attributable to vaccine must be interpreted in light of the overall risk of childhood febrile seizures at ± 5%. Among 100,000 children, about 5000 would be vulnerable to febrile seizure. No parents could plausibly attribute this seizure to either the DTP or MMR vaccines. Considering the well-established health benefits of these vaccines, the tiny increase in febrile seizures seems a risk well taken. —Rosario Trifiletti
Trifiletti, MD, PhD, Assistant Professor, Neurology and Pediatrics, New York Presbyterian Hospital-Cornell Campus, is Assistant Editor of Neurology Alert.