Original ArticleFebrile Seizure Risk after Vaccination in Children One to Five Months of Age
Introduction
Febrile seizure is the most common type of seizure in childhood, occurring in up to 5% of children.1 Febrile seizure can occur during infections with a variety of pathogens.2, 3 Febrile seizure has also been associated with certain types of vaccines. The timing of fever and febrile seizure after vaccination depends on whether the vaccine contains a live-attenuated virus, which requires several days to replicate before inducing a febrile response, or contains inactivated components, which may elicit a febrile response within the first 24 hours. The febrile seizure risk with current US live and inactivated vaccines has been studied in children ages six through 23 months, but not in younger children.4, 5 The US Advisory Committee on Immunization Practices (ACIP) recommends that all children less than six months old receive six vaccines to prevent eight infectious diseases.6 There are five inactivated vaccines including hepatitis B (HepB) with doses recommended at birth and at one to two months of age, and diphtheria-tetanus-acellular pertussis (DTaP), Haemophilus influenzae type b (Hib), pneumococcal conjugate (PCV), and inactivated poliovirus (IPV) vaccines with doses recommended at two and four months of age. A live-attenuated rotavirus (RV) vaccine is also recommended at two and four months of age.
The febrile seizure literature reflects a lack of consensus about whether febrile seizure should be diagnosed in children less than six months of age. There are three frequently cited febrile seizure definitions that list different minimum ages. A National Institutes of Health consensus statement published in 1980 described febrile seizure as usually occurring between ages 3 months and 5 years.7 In 1993, the International League Against Epilepsy defined febrile seizure as occurring in childhood after age one month.8 In 2008, the American Academy of Pediatrics published a simple febrile seizure clinical practice guideline that defined febrile seizure as occurring in children between ages six and 60 months.9 That document did not state the rationale for setting the lower age limit at six months, but a separate systematic review stated that, in practice, the lower age limit is generally considered to be six months because of the concern about serious infections such as meningitis presenting with seizure and fever possibly being mistaken for febrile seizure in children under six months.10
Our objective was to estimate the febrile seizure risk during the time from vaccination through the following day associated with US vaccines administered to children aged one through five months.
Section snippets
Materials and Methods
The Vaccine Safety Datalink (VSD) is a collaboration between the Centers for Disease Control and Prevention and several integrated health care organizations (sites) in the United States that perform vaccine safety research and surveillance.11 Nine sites contributed data to the present study. The VSD population includes over eight million members annually and has been shown to be representative of the general US population in terms of demographic and socioeconomic variations.12
We identified
Results
Our study population had 585,342 vaccination visits. Following these, 72 patients had an ED or an inpatient visit associated with a convulsion ICD-9 code (30 during the risk interval and 42 during the control interval). Medical records were available for 65 of these patients (Fig). There were 31 patients with probable seizures, including 11 seizures without fever, 15 febrile seizures, and five seizures with fever other than febrile seizure. Among the seizures with fever other than febrile
Discussion
Seizures with fever that met the definition of probable febrile seizure occurred after vaccination in children aged three to five months (and possible febrile seizures also occurred in children ages one to two months). The majority of these seizures were labeled as febrile seizure in routine clinical practice, even after the publication of a US clinical practice guideline that stated the lower age limit for febrile seizure to be six months.9 The relative risk of febrile seizure occurring on the
References (26)
- et al.
Role of viral infections in the etiology of febrile seizures
Pediatr Neurol
(2006) - et al.
The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety
Vaccine
(2014) - et al.
Demographic characteristics of members of the Vaccine Safety Datalink (VSD): a comparison with the United States population
Vaccine
(2015) - et al.
A new method for active surveillance of adverse events from diphtheria/tetanus/pertussis and measles/mumps/rubella vaccines
Lancet
(1995) - et al.
Post-licensure comparison of the safety profile of diphtheria/tetanus/whole cell pertussis/haemophilus influenza type b vaccine and a 5-in-1 diphtheria/tetanus/acellular pertussis/haemophilus influenza type b/polio vaccine in the United Kingdom
Vaccine
(2010) - et al.
Predictive value of seizure ICD-9 codes for vaccine safety research
Vaccine
(2009) - et al.
Generalized convulsive seizure as an adverse event following immunization: case definition and guidelines for data collection, analysis, and presentation
Vaccine
(2004) - et al.
Febrile seizures
BMJ
(2015) - et al.
Relationship between five common viruses and febrile seizure in children
Arch Dis Child
(2007) - et al.
Febrile seizure risk after vaccination in children 6 to 23 months
Pediatrics
(2016)
Measles-mumps-rubella-varicella combination vaccine and the risk of febrile seizures
Pediatrics
Centers for Disease Control and Prevention
Febrile seizures: long-term management of children with fever-associated seizures
Pediatrics
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2021, Journal of Allergy and Clinical Immunology: In PracticeCitation Excerpt :Because all vaccines can cause fever in young children, they are all associated with a small risk of febrile seizures. The incidence of febrile seizures would be 1 per 1250 to 2500 doses after the first dose of measles-containing vaccines.111 MMRV is associated with a higher risk of febrile seizures than MMR and varicella vaccines given separately the same visit and caregivers can be offered either option.
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Funding source: This study was funded by the Centers for Disease Control and Prevention. No external funding was obtained for this study.
Financial disclosure: Dr. Klein reports receiving research support from GlaxoSmithKline, MedImmune, Merck & Co., Pfizer, Protein Science, and Sanofi-Pasteur for unrelated studies. Dr. Naleway reports receiving research funding from MedImmune, Merck & Co., and Pfizer for unrelated studies. The remaining authors have no financial relationships to disclose.
Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention.