Febrile Seizure Risk after Vaccination in Children One to Five Months of Age

doi:10.1016/j.pediatrneurol.2017.08.005

Pediatric Neurology

Volume 76, November 2017, Pages 72-78

https://doi.org/10.1016/j.pediatrneurol.2017.08.005 Get rights and content

Abstract

Background

The risk of febrile seizure is temporarily increased for a few days after the administration of certain vaccines in children aged six to 23 months. Our objective was to determine the febrile seizure risk following vaccination in children aged one to five months, when six different vaccines are typically administered.

Methods

We identified emergency department visits and inpatient admissions with International Classification of Diseases, Ninth Revision, febrile seizure codes among children enrolled in nine Vaccine Safety Datalink participating health care organizations from 2006 through 2011. Febrile seizures were confirmed by medical record abstraction. We used the self-controlled risk-interval method to compare the incidence of febrile seizure during postvaccination days 0 to 1 (risk interval) versus days 14 to 20 (control interval).

Results

We identified 15 febrile seizure cases that occurred after 585,342 vaccination visits. The case patients were aged three to five months. The patients had received a median of four (range two to six) vaccines simultaneously. The incidence rate ratio of febrile seizure after vaccination was 23 (95% confidence interval 5.13 to 100.8), and the attributable risk was 3.92 (95% confidence interval 1.68 to 6.17) febrile seizure cases per 100,000 persons vaccinated.

Conclusions

Vaccination in children aged three to five months was associated with a large relative risk of febrile seizure on the day of and the day after vaccination, but the risk was small in absolute terms. Postvaccination febrile seizure should not be a concern for the vast majority of children receiving vaccines, but clinicians might take this risk into consideration when evaluating and treating children susceptible to seizures precipitated by fever.

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

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Febrile seizures: long-term management of children with fever-associated seizures

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Cited by (13)

Evaluation of Adverse Reactions to Vaccines
2021, Journal of Allergy and Clinical Immunology: In Practice
Citation 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.
The development and widespread use of vaccination over the past centuries has been the single most impactful intervention in public health, by effectively preventing morbidity and mortality from infectious diseases. Vaccination is generally well tolerated in the vast majority of the population, and the benefits of vaccination largely outweigh the risk of severe adverse events in the majority of patients. Vaccine hesitancy can be a significant concern and lead to infectious disease outbreaks. All health care providers play an important role in maintaining public confidence in vaccines because their attitude and knowledge is often critical in facilitating acceptance of a vaccine. The purpose of this review is to first, provide an understanding of the basic concepts that are relevant to vaccine pharmacovigilance, and secondly, to provide an overview and discuss management of both immune and nonimmune adverse events after vaccination.
Child Neglect by Any Other Name
2020, Pediatric Neurology
The state of vaccine safety science: systematic reviews of the evidence
2020, The Lancet Infectious Diseases
Citation Excerpt :
Other than mild acute and transient arthralgia or arthritis, which is very common in adult women after rubella vaccine, all these adverse reactions are rare (approximately 0·01–0·1%) or very rare (<0·01%). The attributable risk of anaphylaxis after most commonly administered vaccinations is estimated to be 1 in 100 000–1 000 000;54 the attributable risk of febrile seizures after vaccination in children aged 3–5 months is estimated to be 3·92 in 100 000;55 the attributable risk of Guillain-Barré syndrome after influenza vaccination in adults is estimated to be 1–3 in 1 000 000;56–58 and the attributable risk of immune thrombocytopenic purpura after the measles, mumps, and rubella (MMR) vaccination is estimated to be 1–3 in 100 000.59–61 Estimations of risk can also vary depending on the specific vaccine and population in question.
This Review updates the scientific evidence assessing possible causal associations of adverse events following immunisation (AEFI) compiled in the 2012 report from the Institute of Medicine and the 2014 report from the Agency for Healthcare Research and Quality. For 12 of 46 AEFI examined, a causal relationship has been established with at least one vaccine currently routinely recommended to the general USA population: anaphylaxis, arthralgia or arthritis (mild, acute, and transient, not chronic), deltoid bursitis (when vaccine is administered improperly), disseminated varicella infection (in immune deficient individuals for whom the varicella vaccine is contraindicated), encephalitis, febrile seizures, Guillain-Barré syndrome, hepatitis (in immune deficient individuals for whom the varicella vaccine is contraindicated), herpes zoster, immune thrombocytopenic purpura, meningitis, and syncope. Other than mild acute and transient arthralgia or arthritis, which is very common in adult women after rubella vaccine, these adverse reactions are rare or very rare. Vaccines have an excellent safety profile overall and provide protection against infectious diseases to individuals and the general population.
Reactive Seizures After Vaccination in a Thoroughbred Broodmare
2019, Journal of Equine Veterinary Science
Citation Excerpt :
Similar mechanisms may exist involving immunogens from the suspected R. equi or S. equi equi culprits. Epilepsy has been reported in children after influenza vaccination [23,24]; however, this is mostly associated with fever [25]. Similar associations have been investigated for measles–mumps–rubella vaccines in children aged 2 years and younger [26].
A 550 kg Thoroughbred broodmare born in 2007 was evaluated repeatedly over five breeding seasons because of episodic seizures, which occurred only after vaccination. The mare had no health problems other than repetitive reactive, focal seizures that occurred over a 5-year period, in each case after vaccination with inactivated Rhodococcus equi, influenza or equine herpesvirus type 1 or 4 commercial vaccines. Each seizure episode occurred between 24 and 72 hours after vaccination and lasted no longer than 72 hours. No seizure activity was observed at any other time except after vaccination. During each reactive seizure, the mare was treated empirically with diazepam, dexamethasone, and flunixin meglumine. Altrenogest was administered to supplement placental production of progesterone until parturition, and butylscopolamine was administered to decrease suspected uterine contractions during seizure episodes. Each year after the seizure episodes, the mare gave birth prematurely to viable foals. In subsequent seasons, the mare was not vaccinated, resulting in no further seizure episodes. This is the first report of seizure-like activity after vaccination in a horse and suggests that vaccine components may trigger seizures in otherwise healthy animals. Because seizures recurred after each subsequent yearly vaccination and ceased when vaccinations were not administered, cessation of vaccination should be considered for horses thus affected.
Comparing reactogenicity of COVID-19 vaccine boosters: a systematic review and meta-analysis
2024, Expert Review of Vaccines
Combined measles-mumps-rubella-varicella vaccine and febrile convulsions: the risk considered in the broad context
2023, Expert Review of Vaccines

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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.

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Original ArticleFebrile Seizure Risk after Vaccination in Children One to Five Months of Age

Abstract

Background

Methods

Results

Conclusions

Introduction

Section snippets

Materials and Methods

Results

Discussion

Pediatr Neurol

Vaccine

Vaccine

Lancet

Vaccine

Vaccine

Vaccine

Febrile seizures

BMJ

Relationship between five common viruses and febrile seizure in children

Arch Dis Child

Febrile seizure risk after vaccination in children 6 to 23 months

Pediatrics

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

Original Article
Febrile Seizure Risk after Vaccination in Children One to Five Months of Age