Delaying Childhood Vaccines Ups Postvaccine Seizure Risk

Larry Hand

May 19, 2014

Delaying the first measles-mumps-rubella vaccine (MMR) or the first measles-mumps-rubella-varicella vaccine (MMRV) beyond the age of 15 months may more than double a 2-year-old's risk for postvaccination seizures, researchers report in an article published online May 19 in Pediatrics.

In practice, however, the rate of increase may only mean that instead of 3 to 4 of 10,000 children possibly having seizures, the higher risk might increase incidence to 7 to 9 of 10,000 children.

Susan J. Hambridge, MD, PhD, from the Institute for Health Research, Kaiser Permanente Colorado, Denver, and colleagues conducted an analysis of a cohort of 323,247 US children born from 2004 to 2008 with data in the Vaccine Safety Datalink database. They analyzed both first doses of individual vaccines given during the first 2 years of life and first occurrences of seizures.

They found no association between timing of infant vaccination and postvaccination seizures for 1-year-olds. However, the incident rate ratio for seizures within 7 to 10 days after first MMR doses given at 12 to 15 months of age came to 2.65 (95% confidence interval [CI], 1.99 - 3.55) compared with 6.53 (95% CI, 3.15 - 13.53) for seizures after first MMR doses given between 16 and 23 months. For the MMRV vaccine, the incident rate ratio for seizures after a first doses at 12 to 15 months came to 4.95 (95% CI, 3.68 - 6.66) compared with 9.80 (95% CI, 4.35 - 22.06) for first doses given at 16 to 23 months.

The increased risk, researchers write, "is likely due to a complex interplay between the immunogenicity of the vaccines, the genetic and physiologic susceptibility of the child, and the age-based maturation of the child's immune system; as the immune system matures in the second year of life it also becomes capable of greater febrile response to immune stimulants, such as vaccines."

The authors conclude, "It is known that the risk of seizure peaks at 16 to 18 months of life regardless of vaccination status; therefore delaying MMR or MMRV vaccine until this age may result in more febrile seizures."

Other Research

"MMR and MMRV are actually known to cause a low level of febrile seizures, so this is a complicated statistical study," Geoffrey A. Weinberg, MD, from the Department of Pediatrics at the University of Rochester School of Medicine and Dentistry in New York, told Medscape Medical News. "The finding of seizures after these vaccines is not new. The new thing is that administering them at the recommended 12 to 15 months is better in terms of less seizures than it is to delay them after 15 months."

MMR vs MMRV

Why MMRV would carry a higher risk than MMR is unclear, and Dr. Weinberg said he is comfortable working with either MMR plus a separate varicella vaccine or MMRV.

In combining MMR and varicella into MMRV, manufacturers had to increase the dosage of varicella compared with the regular single vaccine, he said. "It also turns out that you get a little bit better measles protective antibodies when you use the combined product rather than separate product, so that raises the confounder that maybe it's that the measles are somehow adjuvanted and you're having more measles effect."

Whether a child gets MMR plus varicella or MMRV can depend on several factors, including a particular practice's schedule for all vaccines for all children and a child's resistance to multiple shots.

Although the overall results of the new study point to double the risk for delaying the vaccines, in everyday practice, Dr. Weinberg notes, this is still a low risk. "Twice the risk is twice a very low number," he said. "In every 10,000 kids, you might get 4 extra seizures."

Another important factor is that the risk only applies to the first dose, not later doses, he said.

This research was supported by the Vaccine Safety Surveillance and Assessment Projects with America's Health Insurance Plans, funded by the Centers for Disease Control and Prevention. The authors and Dr. Weinberg have disclosed no relevant financial relationships.

Pediatrics. Published online May 19, 2014.

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