A longitudinal cohort study of childhood MMR vaccination and seizure disorder among American children

Background: Measles (rubeola) is a highly contagious infectious disease with significant morbidity/mortality. Measles-Mumps-Rubella (MMR) is a live-attenuated vaccine used in the United States (US) to prevent measles. This retrospective longitudinal cohort study evaluated childhood MMR vaccination and the risk of a seizure episode and seizure disorder.

Methods: The Independent Healthcare Research Database (IHRD) composed of records prospectively generated from Florida Medicaid was analyzed using SAS to identify persons continuously enrolled from birth for 120 months. Two cohorts were examined: 23,486 persons received at least one dose of MMR vaccine between 12 and 17 months (vaccinated) and 41,725 persons not receiving a measles-containing vaccine (unvaccinated). The daily incidence rate of an initial seizure episode (ICD-9 code: 780.3x) and seizure disorder (ICD-9 code: 345.xx) following an initial seizure episode diagnoses were examined using Cox proportional hazards ratio (HR) and time-trend models post-MMR vaccination compared to unvaccinated persons and in a self-controlled case-series (SCCS).

Results: The daily incidence rate of an initial seizure episode diagnosed from 6 to 11 days post-MMR vaccination in comparison to 12 to17 months among unvaccinated persons was significantly increased (unadjusted HR = 5.73, p < 0.0001 and adjusted HR = 5.94, p < 0.0001) in HR models. The daily incidence rate of an eventual seizure disorder diagnosis among those diagnosed with an initial seizure episode from 6 to 11 days post-MMR vaccination was significantly increased (unadjusted HR = 17.7, p < 0.01 and adjusted HR = 17.4, p < 0.01) in comparison to the daily incidence rate of an eventual seizure disorder diagnosis among those diagnosed with an initial seizure episode from 12 to 17 months among unvaccinated persons. Time-trend analyses revealed a significantly increased rate ratio (RR) for an initial seizure episode (RR = 4.64, p < 0.0001) and seizure disorder (RR = 5.51, p < 0.0001) diagnoses. Time-trend SCCS analyses revealed a significantly increased daily incidence rate of an initial seizure episode (RR = 3.80, p < 0.0001) when comparing periods from 6 to 11 days post-MMR vaccination to 49-60 days post-MMR vaccination. The incidence rate of an eventual seizure disorder diagnosis among those with an initial seizure episode diagnosis from 6 to 11 days post-MMR vaccination compared to 49-60 days post-MMR vaccination was significantly increased (RR = 4.15, p < 0.01).

Conclusion: Seizure episode and seizure disorder are rare consequences of routine childhood MMR vaccination.