and 23 months of age within 42 days of receiving any “measles-containing vaccine” as well as the varicella vaccine (either as a component of the measles vaccine, at the same time as the measles vaccine, or at a different time). The investigators determined that both MMRV and MMR, but not the varicella vaccine alone, are associated with increased outpatient visits for fever and seizures 7 to 10 days after vaccination, with MMRV increasing the risk of fever and seizures twice as much as MMR plus the varicella vaccine. A limitation of this study was that the cases of febrile seizure were determined by the presence of International Classification of Diseases, Ninth Revision, codes for febrile seizure within the medical record. This may have somewhat overestimated the risk of this adverse event.

Another VSD study (Tse et al., 2012) investigated the risk of febrile seizures that followed the receipt of trivalent inactivated influenza vaccine (TIV) which was administered during the 2010-2011 influenza season. The investigators conducted surveillance of adverse events in children between the ages of 6 and 59 months of age who had received a first dose of TIV. Cases of febrile seizures were identified through the analysis of ICD-9 codes and chart review, specifically for patients presenting to emergency departments or those who were hospitalized. In mid-November 2010, a signal was detected that indicated an increased risk of febrile seizures occurring between 0 and 1 days following the first dose of TIV. However, further analysis demonstrated that the risk of febrile seizure was higher after the concomitant administration of both TIV and 13-valent pneumococcal conjugate vaccine (PCV13) compared with the additive risk of febrile seizure after receiving either TIV or PCV13 alone. This risk was highest in children vaccinated at 16 months of age, which is not surprising as studies of the natural history of febrile seizures indicate that the background risk is greatest around this age and progressively falls off in older children. Limitations of this study were that the investigators did not evaluate the possible effects of the concomitant administration of other vaccines (such as DTaP), and due to limited information about attributable causes, the investigators were not able to exclude cases who had intercurrent infections as the cause of the febrile seizure. Importantly, given the results of this study, the vaccine information statement for TIV was updated for the 2011-2012 influenza season to include a statement about the possible increased risk of febrile seizure in young children who concomitantly receive both TIV and PCV13 (CDC, 2012).

A study conducted in The Netherlands (David et al., 2008) evaluated the frequency of adverse events that occurred after infants received pertussis vaccine. In The Netherlands, infants receive this vaccine at 2, 3, 4, and 11 months of age. The study compared the adverse events that occurred after patients received whole-cell pertussis vaccine, acellular pertussis vaccine, or acellular pertussis vaccine along with pneumococcal vaccine. The data were



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