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Original Investigation |

Effect of Age on the Risk of Fever and Seizures Following Immunization With Measles-Containing Vaccines in Children

Ali Rowhani-Rahbar, MD, MPH, PhD1; Bruce Fireman, MA1; Edwin Lewis, MPH1; James Nordin, MD, MPH2; Allison Naleway, PhD3; Steven J. Jacobsen, MD, PhD4; Lisa A. Jackson, MD, MPH5; Alison Tse, ScD6; Edward A. Belongia, MD7; Simon J. Hambidge, MD, PhD8; Eric Weintraub, MPH9; Roger Baxter, MD1; Nicola P. Klein, MD, PhD1
[+] Author Affiliations
1Kaiser Permanente Vaccine Study Center, Oakland, California
2HealthPartners Institute for Education and Research, Minneapolis, Minnesota
3Kaiser Permanente Center for Health Research, Portland, Oregon
4Kaiser Permanente Department of Research and Evaluation, Pasadena, California
5Group Health Research Institute, Seattle, Washington
6Department of Population Medicine, Harvard Pilgrim Health Care Institute, Boston, Massachusetts
7Marshfield Clinic Research Foundation, Marshfield, Wisconsin
8Kaiser Permanente Institute for Health Research, Denver, Colorado
9Immunization Safety Office, Centers for Disease Control and Prevention, Atlanta, Georgia
JAMA Pediatr. 2013;167(12):1111-1117. doi:10.1001/jamapediatrics.2013.2745.
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Importance  The first dose of live attenuated measles-containing vaccines is associated with an increased risk of febrile seizures 7 to 10 days following immunization among 12- to 23-month-old children. The combination measles, mumps, rubella, and varicella vaccine is associated with a 2-fold increased risk of febrile seizures 7 to 10 days following immunization compared with the separately administered measles, mumps, and rubella and varicella vaccines. It is unknown whether the magnitude of these increased risks depends on age at immunization.

Objective  To examine the potential modifying effect of age on the risk of fever and seizures following immunization with measles-containing vaccines.

Design, Setting, and Participants  Retrospective cohort study at 8 Vaccine Safety Datalink sites of a total of 840 348 children 12 to 23 months of age who had received a measles-containing vaccine from 2001 through 2011.

Exposures  Any measles-containing vaccines and measles-containing vaccines by type.

Main Outcomes and Measures  Fever and seizure events occurring during a 42-day postimmunization observation period.

Results  In the analysis of any measles-containing vaccines, the increased risk of seizures during the 7- to 10-day risk interval, using the remainder of the observation period as the control interval, was significantly greater among older children (relative risk, 6.5; 95% CI, 5.3-8.1; attributable risk, 9.5 excess cases per 10 000 doses; 95% CI, 7.6-11.5) than among younger children (relative risk, 3.4; 95% CI, 3.0-3.9; attributable risk = 4.0 excess cases per 10 000 doses; 95% CI, 3.4-4.6). The relative risk of postimmunization fever was significantly greater among older children than among younger children; however, its attributable risk was not. In the analysis of vaccine type, measles, mumps, rubella, and varicella vaccine was associated with a 1.4-fold increase in the risk of fever and 2-fold increase in the risk of seizures compared with measles, mumps, and rubella vaccine administered with or without varicella vaccine in both younger and older children.

Conclusions and Relevance  Measles-containing vaccines are associated with a lower increased risk of seizures when administered at 12 to 15 months of age. Findings of this study that focused on safety outcomes highlight the importance of timely immunization of children with the first dose of measles-containing vaccines.

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Figure 1.
Incidence Rate (per 1000 Person-years) of Fever (A) and Seizures (B) by Age During the Risk Interval (Days 7-10) and Control Interval (Days 0-6 and 11-42) Following Immunization With a Measles-Containing Vaccine
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Figure 2.
Incidence Rate (per 1000 Person-years) of Fever (A) and Seizures (B) by Age and Vaccine Type (Measles, Mumps, Rubella, and Varicella [MMRV] or Measles, Mumps, and Rubella Vaccine Administered With or Without Varicella Vaccine [MMR±V]) 7 to 10 Days Following Immunization
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