DOI: 10.1542/peds.2008-0939
2008;121;1281-1286 Pediatrics
Febrile Seizures
Steering Committee on Quality Improvement and Management, Subcommittee on
the Child With Simple Febrile Seizures
Febrile Seizures: Clinical Practice Guideline for the Long-term Management of
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CLINICAL PRACTICE GUIDELINE
Febrile Seizures: Clinical Practice Guideline for the
Long-term Management of the Child With Simple
Febrile Seizures
Steering Committee on Quality Improvement andManagement, Subcommittee on Febrile Seizures
ABSTRACT
Febrile seizures are the most common seizure disorder in childhood, affecting 2%
to 5% of children between the ages of 6 and 60 months. Simple febrile seizures are
defined as brief (�15-minute) generalized seizures that occur once during a
24-hour period in a febrile child who does not have an intracranial infection,
metabolic disturbance, or history of afebrile seizures. This guideline (a revision of
the 1999 American Academy of Pediatrics practice parameter [now termed clinical
practice guideline] “The Long-term Treatment of the Child With Simple Febrile
Seizures”) addresses the risks and benefits of both continuous and intermittent
anticonvulsant therapy as well as the use of antipyretics in children with simple
febrile seizures. It is designed to assist pediatricians by providing an analytic
framework for decisions regarding possible therapeutic interventions in this pa-
tient population. It is not intended to replace clinical judgment or to establish a
protocol for all patients with this disorder. Rarely will these guidelines be the only
approach to this problem. Pediatrics 2008;121:1281–1286
The expected outcomes of this practice guideline include:
1. optimizing practitioner understanding of the scientific basis for using or avoid-
ing various proposed treatments for children with simple febrile seizures;
2. improving the health of children with simple febrile seizures by avoiding
therapies with high potential for adverse effects and no demonstrated ability to
improve children’s long-term outcomes;
3. reducing costs by avoiding therapies that will not demonstrably improve children’s long-term outcomes; and
4. helping the practitioner educate caregivers about the low risks associated with simple febrile seizures.
The committee determined that with the exception of a high rate of recurrence, no long-term effects of simple
febrile seizures have been identified. The risk of developing epilepsy in these patients is extremely low, although
slightly higher than that in the general population. No data, however, suggest that prophylactic treatment of children
with simple febrile seizures would reduce the risk, because epilepsy likely is the result of genetic predisposition rather
than structural damage to the brain caused by recurrent simple febrile seizures. Although antipyretics have been
shown to be ineffective in preventing recurrent febrile seizures, there is evidence that continuous anticonvulsant
therapy with phenobarbital, primidone, or valproic acid and intermittent therapy with diazepam are effective in
reducing febrile-seizure recurrence. The potential toxicities associated with these agents, however, outweigh the
relatively minor risks associated with simple febrile seizures. As such, the committee concluded that, on the basis of
the risks and benefits of the effective therapies, neither continuous nor intermittent anticonvulsant therapy is
recommended for children with 1 or more simple febrile seizures.
INTRODUCTION
Febrile seizures are seizures that occur in febrile children between the ages of 6 and 60 months who do not have an
intracranial infection, metabolic disturbance, or history of afebrile seizures. Febrile seizures are subdivided into 2
categories: simple and complex. Simple febrile seizures last for less than 15 minutes, are generalized (without a focal
component), and occur once in a 24-hour period, whereas complex febrile seizures are prolonged (�15 minutes), are
focal, or occur more than once in 24 hours.1 Despite the frequency of febrile seizures (2%–5%), there is no unanimity
of opinion about management options. This clinical practice guideline addresses potential therapeutic interventions
in neurologically normal children with simple febrile seizures. It is not intended for patients with complex febrile
seizures and does not pertain to children with previous neurologic insults, known central nervous system abnor-
www.pediatrics.org/cgi/doi/10.1542/
peds.2008-0939
doi:10.1542/peds.2008-0939
All clinical reports from the American
Academy of Pediatrics automatically expire
5 years after publication unless reaffirmed,
revised, or retired at or before that time.
The guidance in this report does not
indicate an exclusive course of treatment
or serve as a standard of medical care.
Variations, taking into account individual
circumstances, may be appropriate.
KeyWord
fever
Abbreviation
AAP—American Academy of Pediatrics
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American Academy of Pediatrics
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malities, or a history of afebrile seizures. This clinical
practice guideline is a revision of a 1999 American Acad-
emy of Pediatrics (AAP) clinical practice parameter, “The
Long-term Treatment of the Child With Simple Febrile
Seizures.”2
For a child who has experienced a simple febrile
seizure, there are potentially 4 adverse outcomes that
theoretically may be altered by an effective therapeutic
agent: (1) decline in IQ; (2) increased risk of epilepsy; (3)
risk of recurrent febrile seizures; and (4) death. Neither
a decline in IQ, academic performance or neurocognitive
inattention nor behavioral abnormalities have been
shown to be a consequence of recurrent simple febrile
seizures.3 Ellenberg and Nelson4 studied 431 children
who experienced febrile seizures and observed no sig-
nificant difference in their learning compared with sib-
ling controls. In a similar study by Verity et al,5 303
children with febrile seizures were compared with con-
trol children. No difference in learning was identified,
except in those children who had neurologic abnormal-
ities before their first seizure.
The second concern, increased risk of epilepsy, is
more complex. Children with simple febrile seizures
have approximately the same risk of developing epilepsy
by the age of 7 years as does the general population (ie,
1%).6 However, children who have had multiple simple
febrile seizures, are younger than 12 months at the time
of their first febrile seizure, and have a family history of
epilepsy are at higher risk, with generalized afebrile sei-
zures developing by 25 years of age in 2.4%.7 Despite
this fact, no study has demonstrated that successful
treatment of simple febrile seizures can prevent this later
development of epilepsy, and there currently is no evi-
dence that simple febrile seizures cause structural dam-
age to the brain. Indeed, it is most likely that the in-
creased risk of epilepsy in this population is the result of
genetic predisposition.
In contrast to the slightly increased risk of developing
epilepsy, children with simple febrile seizures have a
high rate of recurrence. The risk varies with age. Chil-
dren younger than 12 months at the time of their first
simple febrile seizure have an approximately 50% prob-
ability of having recurrent febrile seizures. Children
older than 12 months at the time of their first event have
an approximately 30% probability of a second febrile
seizure; of those who do have a second febrile seizure,
50% have a chance of having at least 1 additional recur-
rence.8
Finally, there is a theoretical risk of a child dying
during a simple febrile seizure as a result of documented
injury, aspiration, or cardiac arrhythmia, but to the com-
mittee’s knowledge, it has never been reported.
In summary, with the exception of a high rate of
recurrence, no long-term adverse effects of simple febrile
seizures have been identified. Because the risks associ-
ated with simple febrile seizures, other than recurrence,
are so low and because the number of children who
have febrile seizures in the first few years of life is so
high, to be commensurate, a proposed therapy would
need to be exceedingly low in risks and adverse effects,
inexpensive, and highly effective.
METHODS
To update the clinical practice guideline on the treat-
ment of children with simple febrile seizures, the AAP
reconvened the Subcommittee on Febrile Seizures. The
committee was chaired by a child neurologist and con-
sisted of a neuroepidemiologist, 2 additional child neu-
rologists, and a practicing pediatrician. All panel mem-
bers reviewed and signed the AAP voluntary disclosure
and conflict-of-interest form. The guideline was re-
viewed by members of the AAP Steering Committee on
Quality Improvement andManagement; members of the
AAP Sections on Neurology, Pediatric Emergency Med-
icine, Developmental and Behavioral Pediatrics, and
Epidemiology; members of the AAP Committees on Pe-
diatric Emergency Medicine and Medical Liability and
Risk Management; members of the AAP Councils on
Children With Disabilities and Community Pediatrics;
and members of outside organizations including the
Child Neurology Society and the American Academy of
Neurology.
A comprehensive review of the evidence-based liter-
ature published since 1998 was conducted with the aim
of addressing possible therapeutic interventions in the
management of children with simple febrile seizures.
The review focused on both the efficacy and potential
adverse effects of the proposed treatments. Decisions
were made on the basis of a systematic grading of the
quality of evidence and strength of recommendations.
The AAP established a partnership with the Univer-
sity of Kentucky (Lexington, KY) to develop an evidence
report, which served as a major source of information for
these practice-guideline recommendations. The specific
issues addressed were (1) effectiveness of continuous
anticonvulsant therapy in preventing recurrent febrile
seizures, (2) effectiveness of intermittent anticonvulsant
therapy in preventing recurrent febrile seizures, (3) ef-
fectiveness of antipyretics in preventing recurrent febrile
seizures, and (4) adverse effects of either continuous or
intermittent anticonvulsant therapy.
In the original practice parameter, more than 300
medical journal articles reporting studies of the natural
history of simple febrile seizures or the therapy of these
seizures were reviewed and abstracted.2 An additional
65 articles were reviewed and abstracted for the update.
Emphasis was placed on articles that differentiated sim-
ple febrile seizures from other types of seizures, that
carefully matched treatment and control groups, and
that described adherence to the drug regimen. Tables
were constructed from the 65 articles that best fit these
criteria. A more comprehensive review of the literature
on which this report is based can be found in a forth-
coming technical report (the initial technical report can
be accessed at http://aappolicy.aappublications.org/cgi/
content/full/pediatrics;103/6/e86). The technical report
also will contain dosing information.
The evidence-based approach to guideline development
requires that the evidence in support of a recommendation
be identified, appraised, and summarized and that an ex-
plicit link between evidence and recommendations be de-
fined. Evidence-based recommendations reflect the quality
of evidence and the balance of benefit and harm that is
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anticipated when the recommendation is followed. The
AAP policy statement “Classifying Recommendations for
Clinical Practice Guidelines”9 was followed in designating
levels of recommendations (see Fig 1 and Table 1).
RECOMMENDATION
On the basis of the risks and benefits of the effective
therapies, neither continuous nor intermittent anticon-
vulsant therapy is recommended for children with 1 or
more simple febrile seizures.
● Aggregate evidence quality: B (randomized, controlled
trials and diagnostic studies with minor limitations).
● Benefit: prevention of recurrent febrile seizures,
which are not harmful and do not significantly in-
crease the risk for development of future epilepsy.
● Harm: adverse effects including rare fatal hepatotox-
icity (especially in children younger than 2 years who
are also at greatest risk of febrile seizures), thrombo-
cytopenia, weight loss and gain, gastrointestinal dis-
turbances, and pancreatitis with valproic acid and hy-
peractivity, irritability, lethargy, sleep disturbances,
and hypersensitivity reactions with phenobarbital;
lethargy, drowsiness, and ataxia for intermittent diaz-
epam as well as the risk of masking an evolving central
nervous system infection.
● Benefits/harms assessment: preponderance of harm
over benefit.
● Policy level: recommendation.
BENEFITS AND RISKS OF CONTINUOUS ANTICONVULSANT
THERAPY
Phenobarbital
Phenobarbital is effective in preventing the recurrence of
simple febrile seizures.10 In a controlled double-blind
study, daily therapy with phenobarbital reduced the rate
of subsequent febrile seizures from 25 per 100 subjects
per year to 5 per 100 subjects per year.11 For the agent to
be effective, however, it must be given daily and main-
tained in the therapeutic range. In a study by Farwell et
al,12 for example, children whose phenobarbital levels
were in the therapeutic range had a reduction in recur-
rent seizures, but because noncompliance was so high,
an overall benefit with phenobarbital therapy was not
identified.
The adverse effects of phenobarbital include hyperac-
tivity, irritability, lethargy, sleep disturbances, and hy-
persensitivity reactions. The behavioral adverse effects
FIGURE 1
Integrating evidence-quality appraisal with an assessment of the anticipated balance
between benefits and harms if a policy is conducted leads to designation of a policy as a
strong recommendation, recommendation, option, or no recommendation. RCT indi-
cates randomized, controlled trial.
TABLE 1 Guideline Definitions for Evidence-Based Statements
Statement Definition Implication
Strong recommendation A strong recommendation in favor of a particular action is made when
the anticipated benefits of the recommended intervention clearly
exceed the harms (as a strong recommendation against an action is
made when the anticipated harms clearly exceed the benefits) and
the quality of the supporting evidence is excellent. In some clearly
identified circumstances, strong recommendations may be made
when high-quality evidence is impossible to obtain and the
anticipated benefits strongly outweigh the harms.
Clinicians should follow a strong recommendation unless
a clear and compelling rationale for an alternative
approach is present.
Recommendation A recommendation in favor of a particular action is made when the
anticipated benefits exceed the harms but the quality of evidence is
not as strong. Again, in some clearly identified circumstances,
recommendations may be made when high-quality evidence is
impossible to obtain but the anticipated benefits outweigh the
harms.
Clinicians would be prudent to follow a recommendation
but should remain alert to new information and
sensitive to patient preferences.
Option Options define courses that may be taken when either the quality of
evidence is suspect or carefully performed studies have shown little
clear advantage to 1 approach over another.
Clinicians should consider the option in their decision-
making, and patient preference may have a substantial
role.
No recommendation No recommendation indicates that there is a lack of pertinent
published evidence and that the anticipated balance of benefits
and harms is presently unclear.
Clinicians should be alert to new published evidence that
clarifies the balance of benefit versus harm.
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may occur in up to 20% to 40% of patients and may be
severe enough to necessitate discontinuation of the
drug.13–16
Primidone
Primidone, in doses of 15 to 20 mg/kg per day, has also
been shown to reduce the recurrence rate of febrile
seizures.17,18 It is of interest that the derived phenobar-
bital level in a Minigawa and Miura study17 was below
therapeutic (16 �g/mL) in 29 of the 32 children, sug-
gesting that primidone itself may be active in preventing
seizure recurrence. As with phenobarbital, adverse ef-
fects include behavioral disturbances, irritability, and
sleep disturbances.18
Valproic Acid
In randomized, controlled studies, only 4% of children
taking valproic acid, as opposed to 35% of control sub-
jects, had a subsequent febrile seizure. Therefore, val-
proic acid seems to be at least as effective in preventing
recurrent simple febrile seizures as phenobarbital and
significantly more effective than placebo.19–21
Drawbacks to therapy with valproic acid include its
rare association with fatal hepatotoxicity (especially in
children younger than 2 years, who are also at greatest
risk of febrile seizures), thrombocytopenia, weight loss
and gain, gastrointestinal disturbances, and pancreatitis.
In studies in which children received valproic acid to
prevent recurrence of febrile seizures, no cases of fatal
hepatotoxicity were reported.15
Carbamazepine
Carbamazepine has not been shown to be effective in
preventing the recurrence of simple febrile seizures.
Antony and Hawke13 compared children who had been
treated with therapeutic levels of either phenobarbital or
carbamazepine, and 47% of the children in the carbam-
azepine-treated group had recurrent seizures compared
with only 10% of those in the phenobarbital group. In
another study, Camfield et al22 treated children (whose
conditions failed to improve with phenobarbital ther-
apy) with carbamazepine. Despite good compliance, 13
of the 16 children treated with carbamazepine had a
recurrent febrile seizure within 18 months. It is theoret-
ically possible that these excessively high rates of recur-
rences might have been attributable to adverse effects of
carbamazepine.
Phenytoin
Phenytoin has not been shown to be effective in pre-
venting the recurrence of simple febrile seizures, even
when the agent is in the therapeutic range.23,24 Other
anticonvulsants have not been studied for the continu-
ous treatment of simple febrile seizures.
BENEFITS AND RISKS OF INTERMITTENT ANTICONVULSANT
THERAPY
Diazepam
A double-blind controlled study of patients with a his-
tory of febrile seizures demonstrated that administration
of oral diazepam (given at the time of fever) could re-
duce the recurrence of febrile seizures. Children with a
history of febrile seizures were given either oral diaze-
pam (0.33 mg/kg, every 8 hours for 48 hours) or a
placebo at the time of fever. The risk of febrile seizures
per person-year was decreased 44% with diazepam.25 In
a more recent study, children with a history of febrile
seizures were given oral diazepam at the time of fever
and