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June 28, 2010 -- The risk of fever-related seizures in infants nearly doubles with the four-in-one measles-mumps-rubella-chickenpox vaccine (MMRV) compared to when the measles-mumps-rubella (MMR) vaccine and chickenpox vaccine are given separately, according to a new study.
Even so, the risk of febrile seizures -- convulsions brought on by fever -- is low with either approach, says researcher Nicola P. Klein, MD, PhD, a research scientist at the Kaiser Permanente Northern California Division of Research and co-director of the Kaiser Permanente Vaccine Study Center, Oakland.
"Overall, the risk for febrile seizures from all measles-containing vaccines is low, less than 1 febrile seizure per 1,000 doses," Klein says. "However, MMRV is associated with a doubling of the risk of febrile seizures among 1-2-year-olds when compared with children who received separate, same-day administration of MMR and V."
Put another way: "For a 1- to 2-year-old child who receives MMRV instead of MMR plus V, there will be one additional seizure for every 2,300 doses," Klein says.
4-in-1 Vaccine: Back Story
The four-in-one vaccine, called ProQuad, was licensed by the FDA in 2005 and later recommended by the CDC's Advisory Committee on Immunization Practices (ACIP) as a way to cut down on the number of shots children needed. The ACIP originally said the four-in-one was preferred over the separate MMR and chickenpox shots.
But Klein and others involved in the CDC-sponsored vaccine safety surveillance known as the Vaccine Safety Datalink reported to the CDC in 2008 that the seizure rate among infants given the four-in-one was about twofold higher than those given the vaccines in two injections.
After that report, the recommendation changed, Klein says, from a preference for the four-in-one to no preference. Currently, the ACIP advises health care providers to discuss the benefits and risks of the four-in-one and to use the MMR and chickenpox vaccines separately for the first dose unless the parent or caregiver expresses a preference for the four-in-one.
Much of the time, the question was a moot point, Klein says, as manufacturing issues (not related to safety, according to the CDC) limited supplies of the four-in-one vaccine.
But ProQuad has recently become available again, says Pamela Eisele, a spokeswoman for Merck, which makes the vaccine.
Vaccines and Seizures Data
In the newly published report, Klein and her team looked at reports of seizures and fevers among more than 376,000 infants given the vaccines in two injections and more than 83,000 given the four-in-one.
"There is a doubling of risk with MMRV, but it's [still] slight," she tells WebMD. "There is a low risk overall."
About Febrile Seizures
About one in 25 infants has one or more febrile seizures, defined as convulsions brought on by high fever, says Randy Bergen, MD, a pediatric infectious disease specialist at Kaiser Permanente in Walnut Creek, Calif.
"They are very scary to observe," he says. Most last only 30 seconds to 2 minutes or so, he says. The child may stiffen and roll his eyes. "From a medical point of view, febrile seizures are not in any way considered dangerous," Bergen says. Children who have the seizures don't have a greater chance of getting epilepsy or brain damage.
Comparing Vaccines: Second Opinion
"This is a confirmatory study, this is not new information," says John Bradley, MD, a member of the American Academy of Pediatrics' Committee on Infectious Diseases and director of the Division of Infectious Diseases, Rady Children's Hospital of San Diego, who reviewed the study for WebMD.
"For probably two years we have been aware that if you give MMRV you get a higher fever and more febrile seizures than if you give them separately," he says.
Still, the information is important for parents to know, he says, even though the increased risk with the 4-in-1 is slight compared to giving MMR and varicella separately.
Bradley says the information only applies to the first dose of vaccine, not the second, given around kindergarten age. "This phenomenon of febrile seizures only occurs in the infants," he says, because of brain immaturity. Peak age is 14 to 18 months, according to the CDC, and that overlaps with when the first doses of measles and chickenpox vaccines are recommended.
The stance of the AAP committee, Bradley says, is that both vaccines are acceptable but that parents need the information about seizure risks to make an informed decision, weighing the lower seizure risk with the need for another injection for the first dose. (The combination is generally preferred for the second dose, according to the ACIP guidelines.)
4-in1 Vaccine: Manufacturer's Input
Merck resumed shipments of ProQuad in May, Eisele says. "The number of doses that will be available is approximately 1.4 million."
She adds in a statement: "Febrile seizures are known to occur after many illnesses and do occur, although rarely, after vaccinations."
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John Bradley, MD, member, American Academy of Pediatrics Committee on Infectious Diseases; director, Division of Infectious Diseases, Rady Children's Hospital of San Diego.
Pediatrics, published online June 28, 2010.
Randy Bergen, MD, pediatric infectious disease specialist, Kaiser Permanente, Walnut Creek, Calif.
Pamela Eisele, spokeswoman, Merck.
CDC: "Questions and Answers about MMRV Vaccine Safety."
Morbidity and Mortality Weekly Report, May 7, 2010.
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