Cited by 170Epilepsy research and treatmentPharmacovigilance and Adverse Drug ReactionsVirology and Viral Diseases

The DOI matches its Crossref record; 26 of the 26 references it cites were found in a registry or an index.

MMR Vaccination and Febrile Seizures: Evaluation of Susceptible Subgroups and Long-term Prognosis

Vestergaard, Mogens, Hviid, Anders, Madsen, Kreesten Meldgaard, Wohlfahrt, Jan, Thorsen, Poul, Schendel, Diana, Melbye, Mads, Olsen, Jørn·2004·JAMA

DOI 10.1001/jama.292.3.351

Open this paper in CoChat — free account

Abstract

CONTEXT: The rate of febrile seizures increases following measles, mumps, and rubella (MMR) vaccination but it is unknown whether the rate varies according to personal or family history of seizures, perinatal factors, or socioeconomic status. Furthermore, little is known about the long-term outcome of febrile seizures following vaccination. OBJECTIVES: To estimate incidence rate ratios (RRs) and risk differences of febrile seizures following MMR vaccination within subgroups of children and to evaluate the clinical outcome of febrile seizures following vaccination. DESIGN, SETTING, AND PARTICIPANTS: A population-based cohort study of all children born in Denmark between January 1, 1991, and December 31, 1998, who were alive at 3 months; 537,171 children were followed up until December 31, 1999, by using data from the Danish Civil Registration System and 4 other national registries. MAIN OUTCOME MEASURES: Incidence of first febrile seizure, recurrent febrile seizures, and subsequent epilepsy. RESULTS: A total of 439,251 children (82%) received MMR vaccination and 17,986 children developed febrile seizures at least once; 973 of these febrile seizures occurred within 2 weeks of MMR vaccination. The RR of febrile seizures increased during the 2 weeks following MMR vaccination (2.75; 95% confidence interval [CI], 2.55-2.97), and thereafter was close to the observed RR for nonvaccinated children. The RR did not vary significantly in the subgroups of children that had been defined by their family history of seizures, perinatal factors, or socioeconomic status. At 15 to 17 months, the risk difference of febrile seizures within 2 weeks following MMR vaccination was 1.56 per 1000 children overall (95% CI, 1.44-1.68), 3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a history of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55) for children with a personal history of febrile seizures. Children with febrile seizures following MMR vaccinations had a slightly increased rate of recurrent febrile seizures (RR, 1.19; 95% CI, 1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI, 0.33-1.50) compared with children who were nonvaccinated at the time of their first febrile seizure. CONCLUSIONS: MMR vaccination was associated with a transient increased rate of febrile seizures but the risk difference was small even in high-risk children. The long-term rate of epilepsy was not increased in children who had febrile seizures following vaccination compared with children who had febrile seizures of a different etiology.

Integrity signals

Registry

Crossref · 10.1001/jama.292.3.351

Cites

26 of 26 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Categorical Data Analysis
Hapeman, D. E., & Agresti, A. (1991) · Technometrics · doi:10.1080/00401706.1991.10484817 · Cited by 9,407
Modeling and variable selection in epidemiologic analysis
Greenland, S. (1989) · American Journal of Public Health · doi:10.2105/ajph.79.3.340 · Cited by 2,208
The Danish National Hospital Register. A valuable source of data for modern health sciences.
Andersen, T. F., Madsen, M., Jørgensen, J. O. L., Mellemkjoer, L., & Olsen, J. H. (1999) · PubMed · Cited by 2,026
- Statistical Models for Epidemiology
Broemeling, L. D. (2013) · Chapman & Hall/CRC eBooks · doi:10.1201/b15382-9 · Cited by 1,346
Manual of the International Statistical Classification of Diseases, Injuries, and Causes of Death.
Schneider, B. A. (1953) · The Quarterly Review of Biology · doi:10.1086/399926 · Cited by 1,000
The Danish Medical Birth Registry.
Lb, K., & Olsen, J. (1998) · PubMed · Cited by 803
A population-based study of measles, mumps, and rubella vaccination and autism.
Madsen, K. M., Hviid, A., Vestergaard, M., Schendel, D., Wohlfahrt, J., Thorsen, P., Olsen, J., & Melbye, M. (2002) · New England Journal of Medicine · doi:10.1056/nejmoa021134 · Cited by 710
Predictors of Epilepsy in Children Who Have Experienced Febrile Seizures
Nelson, K. B., & Ellenberg, J. H. (1976) · New England Journal of Medicine · doi:10.1056/nejm197611042951901 · Cited by 674
Factors Prognostic of Unprovoked Seizures after Febrile Convulsions
Annegers, J. F., Hauser, W. A., Shirts, S. B., & Kurland, L. T. (1987) · New England Journal of Medicine · doi:10.1056/nejm198702263160901 · Cited by 631
Measles, Mumps, and Rubella--Vaccine Use and Strategies for Elimination of Measles, Rubella, and Congenital Rubella Syndrome and Control of Mumps: Recommendations of the Advisory Committee on Immunization Practices (ACIP)
Watson, J., Hadler, S. C., Dykewicz, C. A., Reef, S. E., & Phillips, L. (1998) · PsycEXTRA Dataset · doi:10.1037/e547712006-001 · Cited by 584

Show all 26 references

Sorted by citations

Immunisation against infectious disease
SALISBURY, D. M., Ramsay, M. E., & Noakes, K. (2006) · Stationery Office eBooks · Cited by 636
Vaccines for measles, mumps and rubella in children
Demicheli, V., Rivetti, A., Debalini, M. G., & Di Pietrantonj, C. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004407.pub3 · Cited by 372
Adverse Effects of Vaccines: Evidence and Causality
Stratton, K. R., Ford, A. Q., Rusch, E., & Clayton, E. W. (2013) · Cited by 346
Measles-Mumps-Rubella-Varicella Combination Vaccine and the Risk of Febrile Seizures
Klein, N. P., FIREMAN, B. H., Yih, W. K., Lewis, E. M., Kulldorff, M., Ray, P., Baxter, R. P., Hambidge, S. J., Nordin, J. D., Naleway, A. L., et al. (2010) · PEDIATRICS · doi:10.1542/peds.2010-0665 · Cited by 316
Adverse reactions to vaccines practice parameter 2012 update
Kelso, J. M., Greenhawt, M., Li, J. T., Nicklas, R. A., Bernstein, D. I., Blessing-Moore, J., Cox, L., Khan, D. A., Lang, D. M., Oppenheimer, J. J., et al. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.04.003 · Cited by 293
“As with any fever in young children, this increases the risk of febrile seizures; however, such seizures do not have any sort of long-term sequelae.(92,93) For reasons that are not clear, when the MMR is given in a combination vaccine with varicella (ie, measles, mumps, rubella, and varicella vaccine), there is a 2-fo…”
Background
Safety of Vaccines Used for Routine Immunization of US Children: A Systematic Review
Maglione, M., Das, L., Raaen, L. B., Smith, A. C., Chari, R., Newberry, S. J., Shanman, R., Perry, T., Goetz, M. B., & Gidengil, C. A. (2014) · PEDIATRICS · doi:10.1542/peds.2014-1079 · Cited by 244
Role of Brain Inflammation in Epileptogenesis
Choi, J., & Koh, S. (2008) · Yonsei Medical Journal · doi:10.3349/ymj.2008.49.1.1 · Cited by 215
“Vaccines Vaccines, including measles-mumps-rubella (MMR) and diphtheria-tetanus-pertussis (DTP), are associated with an increased risk of febrile seizures in the first three years of life.(47) MMRassociated seizures often occur at 7 to 14 days after vaccination, while DTP-associated seizures typically occur on the day…”
Background
Vaccines for measles, mumps, rubella, and varicella in children
Pietrantonj, C. D., Rivetti, A., Marchione, P., Debalini, M. G., & Demicheli, V. (2020) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004407.pub4 · Cited by 202
Role of Viral Infections in the Etiology of Febrile Seizures
Millichap, J. G., & Millichap, J. G. (2006) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2006.06.004 · Cited by 180
The Danish vaccination register
Krause, T. G., Jakobsen, S., Haarh, M., & Mølbak, K. (2012) · Eurosurveillance · doi:10.2807/ese.17.17.20155-en · Cited by 169
Personalized vaccines: the emerging field of vaccinomics
Poland, G. A., Ovsyannikova, I. G., & Jacobson, R. M. (2008) · Expert Opinion on Biological Therapy · doi:10.1517/14712598.8.11.1659 · Cited by 164
“55) for children with a personal history of febrile seizures [62] .”
Background
Common variants associated with general and MMR vaccine–related febrile seizures
Feenstra, B., Pasternak, B., Geller, F., Carstensen, L., Wang, T., Huang, F., Eitson, J. L., Hollegaard, M. V., Svanström, H., Vestergaard, M., et al. (2014) · Nature Genetics · doi:10.1038/ng.3129 · Cited by 152
“In the discovery stage, we conducted four genome-wide association scans: (1) MMR-related febrile seizures versus controls (2) MMR-related febrile seizures versus MMR-unrelated febrile seizures; (3) MMR-unrelated febrile seizures versus controls; and (4) febrile seizures overall versus controls.”
Method
The Long-Term Risk of Epilepsy after Febrile Seizures in Susceptible Subgroups
Vestergaard, M., Pedersen, C. B., Sidenius, P., Olsen, J., & Christensen, J. (2007) · American Journal of Epidemiology · doi:10.1093/aje/kwk086 · Cited by 143
“We have shown previously that febrile seizures provoked by vaccination against measles, mumps, and rubella were associated with a similar rate ratio of epilepsy compared with febrile seizures provoked by fever of a different etiology ( 27 ).”
Longitudinal cohort studies of the prognosis of epilepsy: contribution of the National General Practice Study of Epilepsy and other studies
Shorvon, S. D., & Goodridge, D. M. (2013) · Brain · doi:10.1093/brain/awt223 · Cited by 134
“…2002; Piperidou et al, 2002; Borusiak and Herbold, 2003; Tarkka et al., 2003; Lee and Ong, 2004; Metsäranta et al., 2004; Okumara et al., 2004; Vestergaard et al., 2004, 2007; Yücel et al., 2004; Birca et al., 2005; Yu et al., 2007; Hussain et al., 2008), both community and hospital-based,…”
Background
Febrile seizures: risks, evaluation, and prognosis.
Graves, R., Oehler, K., & Tingle, L. (2012) · PubMed · Cited by 131
Application Of Pharmacogenomics To Vaccines
Poland, G. A., Ovsyannikova, I. G., & Jacobson, R. M. (2009) · Pharmacogenomics · doi:10.2217/pgs.09.25 · Cited by 127
A Review of Febrile Seizures: Recent Advances in Understanding of Febrile Seizure Pathophysiology and Commonly Implicated Viral Triggers
Sawires, R., Buttery, J. P., & Fahey, M. C. (2022) · Frontiers in Pediatrics · doi:10.3389/fped.2021.801321 · Cited by 127
Childhood Febrile Seizures: Overview and Implications
Jones, T., & Jacobsen, S. J. (2007) · International Journal of Medical Sciences · doi:10.7150/ijms.4.110 · Cited by 117
“With regard to MMR vaccination, the risk of febrile seizures increases by 1.5 and 3.0 fold, with the peak occurring 1-2 weeks after vaccination [30;32]; an additional 25-34 febrile seizures have been Int.”
BackgroundInfluential
Vaccines for measles, mumps and rubella in children
Demicheli, V., Jefferson, T., Rivetti, A., & Price, D. (2005) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004407.pub2 · Cited by 106
Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b
Sun, Y., Christensen, J., Hviid, A. P., Li, J., Vedsted, P., Olsen, J., & Vestergaard, M. (2012) · JAMA · doi:10.1001/jama.2012.165 · Cited by 95
“Unlike our previous studies, we had access to data on the day of vaccination instead of only the week of vaccination.(18,19)”
MethodResult
Vaccines for measles, mumps, rubella, and varicella in children
Pietrantonj, C. D., Rivetti, A., Marchione, P., Debalini, M. G., & Demicheli, V. (2021) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd004407.pub5 · Cited by 114
Measles, mumps, and rubella virus vaccine (M–M–R™II): A review of 32 years of clinical and postmarketing experience
Lievano, F. A., Galea, S. A., Thornton, M., Wiedmann, R. T., Manoff, S. B., Tran, T. N., Amin, M. A., Seminack, M. M., Vagie, K. A., Dana, A., et al. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.08.057 · Cited by 88
The mortality and morbidity of febrile seizures
Chungath, M., & Shorvon, S. D. (2008) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0922 · Cited by 83
Effect of Age on the Risk of Fever and Seizures Following Immunization With Measles-Containing Vaccines in Children
Rowhani‐Rahbar, A., FIREMAN, B. H., Lewis, E. M., Nordin, J. D., Naleway, A. L., Jacobsen, S. J., Jackson, L. A., Kawai, A. T., Belongia, E. A., Hambidge, S. J., et al. (2013) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2013.2745 · Cited by 79
Register-based studies on febrile seizures in Denmark
Vestergaard, M., & Christensen, J. (2009) · Brain and Development · doi:10.1016/j.braindev.2008.11.012 · Cited by 71
“The long-term risk of epilepsy was not increased in children who had febrile seizures following vaccination compared with those who had febrile seizures of a different aetiology [9].”
Influential
Risk of febrile seizures after first dose of measles–mumps–rubella–varicella vaccine: a population-based cohort study
MacDonald, S. E., Dover, D. C., Simmonds, K., & Svenson, L. W. (2014) · Canadian Medical Association Journal · doi:10.1503/cmaj.140078 · Cited by 68
Genome-wide association study of febrile seizures implicates fever response and neuronal excitability genes
Skotte, L., Fadista, J., Bybjerg‐Grauholm, J., Appadurai, V., Hildebrand, M. S., Hansen, T. F., Banasik, K., Grove, J., Albiñana, C., Geller, F., et al. (2021) · Brain · doi:10.1093/brain/awab260 · Cited by 67
Risk of Febrile Seizures and Epilepsy after Vaccination with Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type B
Johnson, A. (2012) · Journal of Emergency Medicine · doi:10.1016/j.jemermed.2012.05.027 · Cited by 63
The Safety and Immunogenicity of a Quadrivalent Measles, Mumps, Rubella and Varicella Vaccine in Healthy Children
Lieberman, J. M., Williams, W. R., Miller, J. M., BLACK, S. B., Shinefield, H. R., Henderson, F. W., Marchant, C. D., Werzberger, A., Halperin, S. A., Hartzel, J. S., et al. (2006) · The Pediatric Infectious Disease Journal · doi:10.1097/01.inf.0000220209.35074.0b · Cited by 59
“The fevers were generally brief and occurred between 5 and 12 days postvaccination, the same time period during which fevers after vaccination with MMR or monovalent measles vaccine occur.(24,25) Given the enhanced antibody titers against measles virus observed in recipients of MMRV and the timing of the fevers, we sp…”
Background
Adverse reactions to vaccines
Kelso, J. M., Li, J. T., Nicklas, R. A., Blessing-Moore, J., Cox, L., Lang, D. M., Oppenheimer, J., Portnoy, J. M., Randolph, C., Schuller, D. E., et al. (2009) · Annals of Allergy Asthma & Immunology · doi:10.1016/s1081-1206(10)60350-x · Cited by 59
Adverse Events Following Measles, Mumps, and Rubella Vaccine in Adults Reported to the Vaccine Adverse Event Reporting System (VAERS), 2003–2013
Sukumaran, L., McNeil, M. M., Moro, P. L., Lewis, P. W., Winiecki, S. K., & Shimabukuro, T. T. (2015) · Clinical Infectious Diseases · doi:10.1093/cid/civ061 · Cited by 59
The Immunogenetics of Smallpox Vaccination
Stanley, S. L., Frey, S. E., Taillon‐Miller, P., Guo, J., Miller, R. D., Koboldt, D. C., Elashoff, M. R., Christensen, R. G., Saccone, N. L., & Belshe, R. B. (2007) · The Journal of Infectious Diseases · doi:10.1086/518794 · Cited by 58
“tibility to this condition [50].”
Febrile Seizures
Leung, A. K. C., & Robson, W. L. M. (2007) · Journal of Pediatric Health Care · doi:10.1016/j.pedhc.2006.10.006 · Cited by 57
Evaluation and treatment of the child with febrile seizure.
Millar, J. (2006) · PubMed · Cited by 56
Measles Vaccines
Strebel, P. M., Papania, M. J., Gastañaduy, P. A., & Goodson, J. L. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-35761-6.00037-7 · Cited by 55
Etiologies for Seizures Around the Time of Vaccination
Verbeek, N. E., Jansen, F. E., Bondt, P. E. V.-D., de Kovel, C. G. F., van Kempen, M. J. A., Lindhout, D., Knoers, N. V. A. M., van der Maas, N., & Brilstra, E. H. (2014) · PEDIATRICS · doi:10.1542/peds.2014-0690 · Cited by 54
Safety of Measles-Containing Vaccines in 1-Year-Old Children
Klein, N. P., Lewis, E. M., FIREMAN, B. H., Hambidge, S. J., Naleway, A. L., Nelson, J. C., Belongia, E. A., Yih, W. K., Nordin, J. D., Hechter, R. C., et al. (2015) · PEDIATRICS · doi:10.1542/peds.2014-1822 · Cited by 50
Vaccines for measles, mumps and rubella in children
Demicheli, V., Rivetti, A., Debalini, M. G., & Pietrantonj, C. D. (2013) · Evidence-Based Child Health A Cochrane Review Journal · doi:10.1002/ebch.1948 · Cited by 52
Evaluation of Potentially Common Adverse Events Associated With the First and Second Doses of Measles-Mumps-Rubella Vaccine
LeBaron, C. W., Bi, D., Sullivan, B. J., Beck, C., & Gargiullo, P. M. (2006) · PEDIATRICS · doi:10.1542/peds.2006-0678 · Cited by 49
Vaccination, seizures and ‘vaccine damage’
Brown, N. J., Berkovic, S. F., & Scheffer, I. E. (2007) · Current Opinion in Neurology · doi:10.1097/wco.0b013e3280555160 · Cited by 50
A collaborative approach to investigating the risk of thrombocytopenic purpura after measles–mumps–rubella vaccination in England and Denmark
Andrews, N. J., Stowe, J., Miller, E., Svanström, H., Johansen, K., Bonhoeffer, J., & Hviid, A. P. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.06.009 · Cited by 47
Risk of serious neurologic disease after immunization of young children in Britain and Ireland
Ward, K. N., Bryant, N. J., Andrews, N. J., Bowley, J. S., Ohrling, A., Verity, C. M., Ross, E. M., & Miller, E. (2007) · PEDIATRICS · doi:10.1542/peds.2006-3743 · Cited by 46
Epilepsy and vaccinations: Italian guidelines
Pruna, D., Balestri, P., Zamponi, N., Grosso, S., Gobbi, G., Romeo, A., Franzonı, E., Osti, M., Capovilla, G., Longhi, R. C., et al. (2013) · Epilepsia · doi:10.1111/epi.12306 · Cited by 46
“In Vestergaard et al., 2004 published a large retrospective cohort study; the study cohort consisted of children born in Denmark between 1991 and 1998 (data were collected from Danish Civil Registration System and from other four national registries).”
Method
Postlicensure epidemiology of childhood vaccination: the Danish experience
Hviid, A. P. (2006) · Expert Review of Vaccines · doi:10.1586/14760584.5.5.641 · Cited by 45
Comparison of epidemiologic methods for active surveillance of vaccine safety
McClure, D. L., Glanz, J. M., Xu, S., Hambidge, S. J., Mullooly, J. P., & Baggs, J. M. (2008) · Vaccine · doi:10.1016/j.vaccine.2008.03.074 · Cited by 44
Prospective case control study of iron deficiency and the risk of febrile seizures in children in South Korea
Jang, H. N., Yoon, H. S., & Lee, E. H. (2019) · BMC Pediatrics · doi:10.1186/s12887-019-1675-4 · Cited by 43
Efficacy of varicella (VZV) vaccination: an update for the clinician
Wang, L., Zhu, L., & Zhu, H. (2016) · Therapeutic Advances in Vaccines · doi:10.1177/2051013616655980 · Cited by 42
“This risk period has been defined variably in clinical and epidemiologic studies as 8–14 days, 7–12 days, or 5–12 days [Barlow et al. 2001; Jacobsen et al. 2009; Vestergaard et al. 2004].”
Causality assessment of adverse events following immunization: the problem of multifactorial pathology
Bellavite, P. (2020) · F1000Research · doi:10.12688/f1000research.22600.2 · Cited by 42
Effect of vaccinations on seizure risk and disease course in Dravet syndrome
Verbeek, N. E., van der Maas, N., Sonsma, A. C. M., Ippel, E. F., Bondt, P. E. V.-D., Hagebeuk, E. E. O., Jansen, F. E., Geesink, H. H., Braun, K. P. J., de Louw, A. J. A., et al. (2015) · Neurology · doi:10.1212/wnl.0000000000001855 · Cited by 39
“Our estimated seizure IRR following MMR vaccines in DS does not differ from the relative seizure risk in the general pediatric population.(1,18,19,28,29) These findings suggest that although absolute seizure risks after various vaccinations are substantial in DS, vaccine-specific relative seizure risks for the general…”
Background
Risk factors of recurrence of febrile seizures in children in a tertiary care hospital in Kanpur: A one year follow up study
Midha, T., Kumar, N., & Rao, Y. K. (2018) · Annals of Indian Academy of Neurology · doi:10.4103/aian.aian_472_17 · Cited by 38
Validation of the French national health insurance information system as a tool in vaccine safety assessment: Application to febrile convulsions after pediatric measles/mumps/rubella immunization
Hanf, M., Quantin, C., Farrington, P., Benzenine, É., Hocine, M. N., Velten, M., Tubert‐Bitter, P., & Escolano, S. (2013) · Vaccine · doi:10.1016/j.vaccine.2013.09.052 · Cited by 38
MMR and MMRV vaccines
Kowalzik, F., Faber, J., & Knuf, M. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.07.051 · Cited by 37
Overview of the Clinical Consult Case Review of adverse events following immunization: Clinical Immunization Safety Assessment (CISA) network 2004–2009
Williams, S. E., Klein, N. P., Halsey, N. A., Dekker, C. L., Baxter, R. P., Marchant, C. D., LaRussa, P. S., Sparks, R. C., Tokars, J. I., Pahud, B. A., et al. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.07.044 · Cited by 37
“involving seizures, cerebral edema, and hepatic abnormalities after MMR and hepatitis BHib combination vaccine was judged to be probably related to a prolonged febrile seizure [36].”
Background
Glia-neuronal interactions in ictogenesis and epileptogenesis: role of inflammatory mediators
Vezzani, A., Auvin, S., Ravizza, T., & Aronica, E. (2012) · Europe PMC (PubMed Central) · Cited by 34
The "urban myth" of the association between neurological disorders and vaccinations
Gasparini, R., Panatto, D., Lai, P. L., & Amicizia, D. (2015) · Journal of preventive medicine and hygiene · doi:10.15167/2421-4248/jpmh2015.56.1.467 · Cited by 34
“[66], who considered a sample of 439,251 Danish children.”
Background
Use of the Australian Childhood Immunisation Register for vaccine safety data linkage
Gold, M., Dugdale, S., Woodman, R. J., & McCaul, K. A. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.04.021 · Cited by 33
Adverse Events following 12 and 18 Month Vaccinations: a Population-Based, Self-Controlled Case Series Analysis
Wilson, K. R., Hawken, S., Kwong, J. C., Deeks, S. L., Crowcroft, N. S., van Walraven, C., Potter, B. K., Chakraborty, P. K., Keelan, J. E., Pluscauskas, M., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027897 · Cited by 32
“Additional reassurance can be derived from previous studies that identified no long-term consequences related to vaccine associated febrile seizures [5,6].”
BackgroundResultInfluential
Febrile seizures after 2009 influenza A (H1N1) vaccination and infection: a nationwide registry-based study
Bakken, I. J., Aaberg, K. M., Ghaderi, S., Gunnes, N., Trogstad, L., Magnus, P. M., & Håberg, S. E. (2015) · BMC Infectious Diseases · doi:10.1186/s12879-015-1263-7 · Cited by 30
“org/publicdomain/ze [7–12].”
Vaccinations and febrile seizures
Cendes, F., & Sankar, R. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03032.x · Cited by 30
“At least three large epidemiologic studies have found that measles, mumps, and rubella (MMR) vaccine increases the risk of seizures in general or FS specifically (Farrington et al., 1995; Barlow et al., 2001; Vestergaard et al., 2004).”
Background
Glia–Neuron Interactions in Ictogenesis and Epileptogenesis
Vezzani, A., Auvin, S., Ravizza, T., & Aronica, E. (2012) · Oxford University Press eBooks · doi:10.1093/med/9780199746545.003.0048 · Cited by 30
Febrile seizures following measles and varicella vaccines in young children in Australia
Macartney, K. K., Gidding, H. F., Trinh, L. T. T., Wang, H., McRae, J. E., Crawford, N. W., Gold, M., Kynaston, A., Blyth, C. C., Zurynski, Y. A., et al. (2014) · Vaccine · doi:10.1016/j.vaccine.2014.10.071 · Cited by 29
Temporal Data Mining for Adverse Events Following Immunization in Nationwide Danish Healthcare Databases
Svanström, H., Callréus, T., & Hviid, A. P. (2010) · Drug Safety · doi:10.2165/11537630-000000000-00000 · Cited by 28
Immunogenicity and Safety of Measles-Mumps-Rubella, Varicella and Haemophilus influenzae Type b Vaccines Administered Concurrently With a Fourth Dose of Heptavalent Pneumococcal Conjugate Vaccine Compared With the Vaccines Administered Without Heptavalent Pneumococcal Conjugate Vaccine
BLACK, S. B., Cimino, C. O., Hansen, J. R., Lewis, E. M., Ray, P., Corsaro, B. G., Graepel, J., & Laufer, D. S. (2006) · The Pediatric Infectious Disease Journal · doi:10.1097/01.inf.0000207409.92198.6f · Cited by 27
The Influence of Vaccine on Febrile Seizure
Li, X., Lin, Y., Yao, G., & Wang, Y. (2017) · Current Neuropharmacology · doi:10.2174/1570159x15666170726115639 · Cited by 26
“In previous large epidemiologic studies, MMR vaccine increases the risk of FS, particularly, in two weeks following MMR vaccination [27, 28].”
Result
Safety and Immunogenicity of M-M-RII (Combination Measles–Mumps–Rubella Vaccine) in Clinical Trials of Healthy Children Conducted Between 1988 and 2009
Kuter, B. J., Brown, M. L. H., Wiedmann, R. T., Hartzel, J. S., & Musey, L. K. (2016) · The Pediatric Infectious Disease Journal · doi:10.1097/inf.0000000000001241 · Cited by 24
“Fever may cause seizure in some children.(24) Febrile seizures usually occur among children 6–59 months of age with a peak age at 14–18 months.”
Background
Chiropractic Antivaccination Arguments
Busse, J. W., Morgan, L., & Campbell, J. B. (2005) · Journal of Manipulative and Physiological Therapeutics · doi:10.1016/j.jmpt.2005.04.011 · Cited by 23
Vaccine and Immunization Surveillance in Ontario (VISION) – Using linked health administrative databases to monitor vaccine safety
Wilson, K. R., Hawken, S., Kwong, J. C., Deeks, S. L., Crowcroft, N. S., & Manuel, D. G. (2012) · Vaccine · doi:10.1016/j.vaccine.2012.06.004 · Cited by 23
Pharmacovigilance des vaccins
Autret‐Leca, E., Grimaldi‐Bensouda, L., Jonville‐Béra, A. ‐., & Beau-Salinas, F. (2005) · Archives de Pédiatrie · doi:10.1016/j.arcped.2005.10.020 · Cited by 23
Pharmacovigilance in children: detecting adverse drug reactions in routine electronic healthcare records. A systematic review
Black, C., Tagiyeva, N., Helms, P. J. B., & Moir, D. (2015) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12645 · Cited by 22
Fever following immunization
Tapiainen, T., & Heininger, U. (2005) · Expert Review of Vaccines · doi:10.1586/14760584.4.3.419 · Cited by 22
Risk of convulsions in children after monovalent H1N1 (2009) and trivalent influenza vaccines: A database study
Stowe, J., Andrews, N. J., Bryan, P. T., Seabroke, S., & Miller, E. (2011) · Vaccine · doi:10.1016/j.vaccine.2011.10.029 · Cited by 21
Vaccine Safety
Destefano, F. R., Offit, P. A., & Fisher, A. K. (2017) · Elsevier eBooks · doi:10.1016/b978-0-323-35761-6.00082-1 · Cited by 22
ORIGINAL ARTICLE: Vaccination of children – a systematic review
Örtqvist, A. K., Blennow, M., Carlsson, R. M., La, H., Lindberg, A., LINDQVIST, L., Magnusson, M., Nilsson, L. J., Norlund, A., Nyrén, O., et al. (2010) · Acta Paediatrica · doi:10.1111/j.1651-2227.2010.01823.x · Cited by 22
A retrospective population‐based study on seizures related to childhood vaccination
von Spiczak, S., Helbig, I., Drechsel‐Bäuerle, U., Muhle, H., van Baalen, A., van Kempen, M. J. A., Lindhout, D., Scheffer, I. E., Berkovic, S. F., Stephani, U., et al. (2011) · Epilepsia · doi:10.1111/j.1528-1167.2011.03134.x · Cited by 20
A systematic review on the application of pharmacoepidemiology in assessing prescription drug-related adverse events in pediatrics
Luo, X., Cappelleri, J. C., & Frush, K. S. (2007) · Current Medical Research and Opinion · doi:10.1185/030079907x182211 · Cited by 19
Combined measles-mumps-rubella-varicella vaccine and febrile convulsions: the risk considered in the broad context
Casabona, G., Berton, O., Singh, T., Knuf, M., & Bonanni, P. (2023) · Expert Review of Vaccines · doi:10.1080/14760584.2023.2252065 · Cited by 18
“The occurrence of FC has also been shown to be higher in children who received the MMR vaccine than in unvaccinated individuals [77–79].”
BackgroundResult
Exploring the risk factors for vaccine-associated and non-vaccine associated febrile seizures in a large pediatric cohort
Tartof, S. Y., Tseng, H. F., Liu, A. L., Qian, L., Sy, L. S., Hechter, R. C., Marcy, S. M., & Jacobsen, S. J. (2014) · Vaccine · doi:10.1016/j.vaccine.2014.03.044 · Cited by 17
Vaccine-Associated Neurological Adverse Events: A Case Report and Literature Review
Tian, M., Yang, J. Y., Li, L., Li, J., Lei, W., & Shu, X. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666191119095132 · Cited by 17
Post-Licensure Safety of the Meningococcal Group C Conjugate Vaccine
Andrews, N. J., Stowe, J., Miller, E., & Taylor, B. (2007) · Human Vaccines · doi:10.4161/hv.3.2.3878 · Cited by 16
“Infants Meningococcal �7 to �1 0��39 (0��19�0��81) [12] Group C 0 to 3 0��60 (0��27�1��31) [11] 4 to 7 0��65 (0��34�1��24) [13] 8 to 14 0��52 (0��30�0��91) [20] 0 to 14 0��57 (0��36� 0��86) [44] ��P (dose 3) �7 to �1 1��46 (0��51�4��24) [5] 0 to 3 1��04 (0��28�3��91) [3] �oddlers Meningococcal �7 to �1 0��86 (0��32�2�…”
Science for vaccine policy: Independent review of the September 2025 ACIP processes, deliberations and votes
Asturias, E. J., Chen, L. H., Shaw, A. C., Moser, C. A., Maldonado, Y., Zucker, J. R., Chu, H. Y., Talbot, H. K., Cineas, S., Lyons, K., et al. (2025) · Vaccine · doi:10.1016/j.vaccine.2025.127876 · Cited by 15
“No long-term safety concerns have been identified [35].”
Immunogenicity and reactogenicity following MMR vaccination in 5–7-month-old infants: a double-blind placebo-controlled randomized clinical trial in 6540 Danish infants
Vittrup, D. M., Jensen, A., Sørensen, J. K., Zimakoff, A. C., Malon, M., Charabi, S., Johansen, M., Simões, E. A. F., Kirkby, N. S., Buus, S., et al. (2024) · EClinicalMedicine · doi:10.1016/j.eclinm.2023.102421 · Cited by 15
“31 MMR has been widely used for decades without observing negative long-term effects, 31 however evaluation of rare long-term events must await pragmatic population-based observational studies.”
Background
Sicherheit von Impfstoffen
Weißer, K., Barth, I., & Keller‐Stanislawski, B. (2009) · Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz · doi:10.1007/s00103-009-0961-y · Cited by 15
A postmarket safety comparison of 2 vaccination strategies for measles, mumps, rubella and varicella in Italy
Cocchio, S., Zanoni, G., Opri, R., Russo, F., Baldo, V., & Collaborative group (2015) · Human Vaccines & Immunotherapeutics · doi:10.1080/21645515.2015.1101198 · Cited by 14
“Attenuated viral vaccines against measles, mumps, rubella and varicella have been associated with several adverse events, including fever and febrile seizures.(1-5) After the combined vaccine was licensed, the Advisory Committee on Immunization Practices stated that the administration of separate measles, mumps, rubel…”
Background
Risk factors and familial clustering for fever 7–10 days after the first dose of measles vaccines
Klein, N. P., Lewis, E. M., McDonald, J. C., FIREMAN, B. H., Naleway, A. L., Glanz, J. M., Jackson, L. A., Donahue, J. G., Jacobsen, S. J., Weintraub, E., et al. (2017) · Vaccine · doi:10.1016/j.vaccine.2017.02.013 · Cited by 14
Safety after BBIBP-CorV (Sinopharm) COVID-19 Vaccine in Adolescents Aged 10–17 Years in Thailand
Thonginnetra, S., Tawinprai, K., Niemsorn, K., Promsena, P., Tandhansakul, M., Kasemlawan, N., Ruangkijpaisal, N., Banomyong, N., Phattraprayoon, N., Rangkakulnuwat, P., et al. (2022) · Vaccines · doi:10.3390/vaccines10101765 · Cited by 13
Elevated Inflammatory Mediators in Adults with Oculorespiratory Syndrome following Influenza Immunization: a Public Health Agency of Canada/Canadian Institutes of Health Research Influenza Research Network Study
Al-Dabbagh, M. A., Lapphra, K., Scheifele, D. W., Halperin, S. A., Langley, J. M., Cho, P., Kollmann, T. R., Li, Y., Serres, G. D., Fortuno, E. S., et al. (2013) · Clinical and Vaccine Immunology · doi:10.1128/cvi.00659-12 · Cited by 13
“(15) found that at 15 to 17 months of age, the risk difference of febrile seizures within 2 weeks following measles, mumps, and rubella (MMR) vaccination was 3.”
Background
The weight of MMRV-related febrile convulsions among other clinical factors contributing to febrile convulsions in children
Gavrielov‐Yusim, N., Hoshen, M. B., Singer, S. R., Neumann, L., & Balicer, R. D. (2014) · Vaccine · doi:10.1016/j.vaccine.2014.07.024 · Cited by 13
Methodology for computing the burden of disease of adverse events following immunization
McDonald, S., Nijsten, D., Bollaerts, K., Bauwens, J., Praet, N., van der Sande, M. A. B., Bauchau, V., Smedt, T. D., Sturkenboom, M., & Hahné, S. J. M. (2018) · Pharmacoepidemiology and Drug Safety · doi:10.1002/pds.4419 · Cited by 12
“For instance, for febrile convulsions, we excluded the risk of suffering recurrent seizures (small increased rate of recurrence; estimated at 19% 16 ).”
Background
Modelling Hospitalisation Ratios for Febrile Convulsions and Severe Varicella Under Combined Measles, Mumps, Rubella, and Varicella (MMRV—Priorix-Tetra™) Compared to Separate MMR + V Vaccination
Bauchau, V., Holle, L. V., & Cohen, C. (2015) · Drug Safety · doi:10.1007/s40264-015-0326-4 · Cited by 12
“• There were no health consequences later in life from hospitalisation for FC or varicella [24, 25].”
Background
Neurologic Safety Monitoring of COVID-19 Vaccines
Thakur, K. T., Epstein, S., Bilski, A. E., Balbi, A. M., Boehme, A. K., Brannagan, T. H., Wesley, S. F., & Riley, C. (2021) · Neurology · doi:10.1212/wnl.0000000000012703 · Cited by 11
“Notably, there is no association between the MMR vaccine and the development of epilepsy.(47)”
Background
Seasonal Variation and Risk of Febrile Seizures: A Danish Nationwide Cohort Study
Christensen, K. J., Dreier, J. W., Skotte, L., Feenstra, B., Grove, J., Børglum, A. D., Mitrovič, M., Cotsapas, C. J., & Christensen, J. (2022) · Neuroepidemiology · doi:10.1159/000522065 · Cited by 11
Comprehensive Assessment of Serious Adverse Events Following Immunization by Health Care Providers
Williams, S. E., Edwards, K. M., Baxter, R. P., LaRussa, P. S., Halsey, N. A., Dekker, C. L., Vellozzi, C. J., Marchant, C. D., Donofrio, P. D., Reimschisel, T. E., et al. (2013) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2013.01.028 · Cited by 11
“Examples include extensive limb swelling after diphtheria, tetanus and acellular pertussis vaccine, 32 large local reactions after several vaccines, [33] [34] [35] sterile abscesses after vaccines containing alum, 36 febrile seizures occurring after measlescontaining vaccines, 13, 37 and anaphylaxis or other immediate…”
Knowledge synthesis of benefits and adverse effects of measles vaccination: the Lasbela balance sheet
Ledogar, R. J., Fleming, J. R., & Andersson, N. (2009) · BMC International Health and Human Rights · doi:10.1186/1472-698x-9-s1-s6 · Cited by 11
Measles
Elliman, D. A. C., & Sengupta, N. (2005) · Current Opinion in Infectious Diseases · doi:10.1097/01.qco.0000168383.93647.47 · Cited by 11
Adverse Reactions to Vaccines for Infectious Diseases
Kelso, J. M., & Greenhawt, M. (2014) · Elsevier eBooks · doi:10.1016/b978-0-323-08593-9.00086-3 · Cited by 10
Physicians and Nurses Knowledge, Attitude, and Practices in the Management of Childhood Fever in Hebron Pediatric Clinics
Zubedeh, M. A., Mayaleh, A. A., Qtait, M. T., & sayej, S. O. P. (2016) · Journals & Books Hosting (International Knowledge Sharing Platform) · Cited by 10
Increased emergency room visits or hospital admissions in females after 12-month MMR vaccination, but no difference after vaccinations given at a younger age
Wilson, K. R., Ducharme, R., Ward, B. J., & Hawken, S. (2014) · Vaccine · doi:10.1016/j.vaccine.2014.01.010 · Cited by 10
Is SARS-CoV-2 vaccination safe and effective for elderly individuals with neurodegenerative diseases?
Shi, Y., Guo, M., Yang, W., Liu, S., Zhu, B., Yang, L., Yang, C., & Liu, C. (2021) · Expert Review of Vaccines · doi:10.1080/14760584.2021.1911653 · Cited by 9
“MMR vaccine No significant association between MMR vaccination and MS risk [50] Submit vaccines Hepatitis B vaccine No increased risk of MS [51]”
Background
Effect of inactivated COVID-19 vaccines on seizure frequency in patients with epilepsy: A multicenter, prospective study
Fang, X., Hu, S., Han, T., Yang, T., Hu, J., Song, Y., Li, C., Ma, A., Li, Y., Kong, Q., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.984789 · Cited by 9
Adverse Events Following Immunization- The Known Unknowns and Black Box
Das, M. K. (2023) · The Indian Journal of Pediatrics · doi:10.1007/s12098-023-04555-3 · Cited by 10

Authors: Vestergaard, M., Hviid, A., Madsen, K. M., Wohlfahrt, J., Thorsen, P., Schendel, D., Melbye, M., & Olsen, J.
Affiliations: Aarhus University (DK)
ORCID: Vestergaard, Mogens
Hviid, Anders
Wohlfahrt, Jan
Schendel, Diana
Melbye, Mads
Olsen, Jørn
Venue: JAMA
Publisher: American Medical Association (AMA)
Published: 2004-07-21
Volume: 292
Issue: 3
Pages: 351
ISSN: 0002-9955 (ISSN-L)
0098-7484
DOI: 10.1001/jama.292.3.351
OpenAlex: W2144921754
Cited by: 170
References: 26
Citations by year: 2026: 5 · 2025: 3 · 2024: 5 · 2023: 7 · 2022: 4 · 2021: 11 · 2020: 7 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 9 · 2015: 11 · 2014: 12 · 2013: 13 · 2012: 13
FWCI: 5.43
Type: journal article
Language: en
Open access: closed
Locations: JAMA (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Clinical Neurology › Epilepsy research and treatment
Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Toxicology › Pharmacovigilance and Adverse Drug Reactions
Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
Keywords: MMR vaccination, febrile seizures, MMR vaccine, vaccine adverse events, recurrent febrile seizures, epilepsy, family history of seizures, perinatal factors, socioeconomic status, incidence rate ratio, risk difference, children, Denmark
MeSH terms: Child, Preschool, Seizures, Febrile, Denmark, Humans, Infant, Prognosis, Registries, Risk, Cohort Studies, Measles-Mumps-Rubella Vaccine

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

MMR Vaccination and Febrile Seizures: Evaluation of Susceptible Subgroups and Long-term Prognosis

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks