Oakland, Calif. –
The combination vaccine for measles, mumps, rubella and chickenpox (MMRV) is
associated with double the risk of febrile seizures for 1- to 2-year-old
children compared with same-day administration of the separate vaccine for MMR
(measles, mumps, rubella) and the varicella (V) vaccine for chicken pox,
according to a Kaiser Permanente Division of Research study appearing online in
the journal Pediatrics. A febrile seizure is a
brief, fever-related convulsion but it does not lead to epilepsy or seizure
disorders, researchers explained.
Funded by the U.S.
Centers for Disease Control, the study analyzed 459,000 children 12 to 23 months
old from numerous health systems across the United States receiving their first
dose of measles-containing vaccine and found MMRV to be associated with a
two-fold increased risk of fever and febrile seizures 7-10 days after
vaccination compared with same-day
administration of a separate shot for MMR and the varicella (chickenpox)
vaccine. This study found that the risk for a febrile seizure after the first
dose of MMRV vaccine is low, although it is higher than after MMR vaccine and
varicella vaccine administered as separate injections.
The study found no
evidence of an increased febrile seizure risk after any measles vaccine beyond
7-10 days post vaccination.
“Because the risk of
febrile seizure is higher for the quadrivalent (combination) vaccine, providers
recommending MMRV should communicate to parents that it increases the risk of
fever and febrile seizure over that already associated with measles-containing
vaccines,” said the study’s lead investigator Nicola Klein, MD, Ph.D.,
co-director of the Kaiser Permanente Vaccine Study Center. “But concerned
parents should understand that the risk for febrile seizures after any
measles-containing vaccine is low: less than 1 febrile seizure per 1,000
injections.”
The CDC recently
recommended that either vaccine may be used for first dose for 1-2 year olds,
however families without a strong preference for MMRV should receive separate
MMR +V vaccines, Klein said. The CDC reiterates that providers who consider
using MMRV should discuss with families and caregivers the risk and benefits.
“While this study and
the resulting CDC recommendations are very important and ones our pediatricians
will follow, it is also important to emphasize that it is more common for a
child to have a febrile seizure caused by a simple cold than by an
immunization. And though febrile seizures are a very scary event for a family,
they are not dangerous and do not lead to later epilepsy or seizure disorders,”
said Randy Bergen, MD, a Kaiser Permanente pediatrician and infectious disease specialist
at Kaiser Permanente-Walnut Creek.
Kaiser Permanente
researchers used its electronic health records and Vaccine Safety Datalink data
from 2000 to 2008 to assess seizures and fever visits among children aged 12-23
months following MMRV and separate MMR +V. They compared seizure risk following
MMRV to MMR +V using regression analyses and by incorporating chart-reviewed
febrile seizure cases.
The Vaccine Safety
Datalink project is a collaborative effort between CDC's Immunization Safety
Office and eight managed care organizations: Kaiser Permanente Northern
California, Kaiser Permanente Southern California, Kaiser Permanente Colorado,
Kaiser Permanente Northwest, Health Partners, Group Health Cooperative,
Marshfield Clinic and Harvard Pilgrim Health Care. The VSD project was
established in 1990 to monitor immunization safety and address the gaps in
scientific knowledge about rare and serious events following immunization. The
VSD shares electronic health records from the organizations’ health systems.
MMRV was licensed
by the FDA in 2005. MMRV was
subsequently recommended by the Advisory Committee on Immunization Practices
(ACIP) in 2006. Although prelicensure studies of MMRV among 1-2 year olds noted
higher rates of fever and measles-like rash one to two weeks post vaccination
when compared with separate MMR + V, it was unknown at the time of MMRV’s
licensure whether a higher rate of fevers was similarly associated with
increased risk of febrile seizures.
In February 2008, Kaiser Permanente researchers alerted the ACIP to preliminary
evidence of an increased risk of febrile seizures following MMRV. This study
represents additional data on twice as many vaccines.
“The Vaccine Safety
Datalink, which we used to conduct this study, is a premiere example of how
different managed care organizations can leverage their electronic medical
records to improve vaccine safety and monitoring,” Klein said.
This
is the latest in a series of Kaiser Permanente studies undertaken to better
understand the protective effects and risks of vaccines. Recent published
studies found children of parents who refuse vaccines are nine times more
likely to get chickenpox and 23 times more likely to get whooping cough
compared to fully immunized children. A study published last year found that
herpes zoster, also known as shingles, is very rare among children who have
been vaccinated against chicken pox. A recent study in the Journal
of the American Medical Association found that the pneumococcal
vaccination is not associated with a reduced risk of heart attacks or strokes
in middle-aged men.
Additional
authors on this paper include:
Bruce Fireman, MS, from the Kaiser Permanete Division of Research;
Katherine Yih, MPH, PhD, from Harvard Pilgrim HealthCare Institute and Harvard
Medical School, Boston, MA; Edwin Lewis, MPH, from the Kaiser Permanente
Vaccine Study Center; Martin Kulldorff, PhD, from Harvard Pilgrim Healthcare
Institute; Paula Ray, MPH, from the Kaiser Permanente Vaccine Study Center; Roger
Baxter, MD, from the Kaiser
Permanente Vaccine Study Center; Simon Hambridge, MD, PhD, from Kaiser
Permanente, Denver, Co; James Nordin, MD, MPA, from Health Partners Research
Foundation, Minneapolis, MN; Allison Naleway, PhD, Kaiser Permanente, Portland,
OR; Edward A. Belongia, MD, from Marshfield Clinic Research Foundation; Tracy
Lieu, MD, MPH, from Harvard Pilgrim Health Care Institute; James Baggs, PhD,
from the Immunization Safety Office, CDC; Eric Weintraub, MPH, from the Vaccine
Safety Datalink. Funding for the study was provided by the Vaccine Safety
Datalink contract with America’s Health Insurance Plans, funded by the Centers
for Disease Control and Prevention.
