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.
The study, published online in the journal Pediatrics, confirms what experts tracking the vaccines have been reporting and adds to preliminary findings by the same group of researchers.
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.