The NEW ENGLAND JOURNAL of MEDICINE

FEBRILE seizures are the most common type of seizure and occur in 2 to 4 percent of all
children.1 2 3 4 Approximately one third of children who have a febrile seizure have a
recurrence.2 , 4 5 6 Only the age at the time of the first febrile seizure is a consistent
predictor of the risk of recurrent febrile seizures,5 although recent studies have found an
increase in risk associated with a family history of febrile seizures.7 8 9 A family history
of epilepsy, a complex febrile seizure as the first seizure, and neurodevelopmental
abnormalities have been identified as indications for anticonvulsant prophylaxis to
prevent recurrence of febrile seizures,6 but these factors are not consistently associated
with a higher risk of recurrence.5 Few other predictors of recurrence have been identified.
We conducted this study to identify predictors of recurrent febrile seizures. In addition to
reexamining factors that have been studied in previous reports, this study was specifically
designed to examine the episode of illness during which the initial febrile seizure
occurred in order to identify other predictors of recurrent febrile seizures.

Methods
Children with first febrile seizures were enrolled in an ongoing prospective cohort study
from June 1989 through February 1991 and were followed to determine whether febrile
seizures recurred. The children were identified through the pediatric emergency
departments of Bronx Municipal Hospital Center, North Central Bronx Hospital, and
Montefiore Medical Center in Bronx, New York, and YaleNew Haven Hospital in New
Haven, Connecticut. The logs for all visits to the four emergency departments were
reviewed twice each week to identify potentially eligible patients. Nine children seen
after a first febrile seizure in the private practice of one of the authors were also included
and are grouped with the patients at Montefiore Medical Center.

Eligibility
A febrile seizure was defined as a seizure that occurred while the child had a rectal
temperature of at least 101F (38.3C) or an axillary temperature of at least 100F
(37.8C) documented either in the emergency department or in the history. Children with
previous febrile or unprovoked seizures were excluded, as were children with intracranial
infections. Some definitions of febrile seizures have lower and upper age limits (for
example, three months to five years6). Such limits reflect conventions but are not
founded on an etiologic basis and are not universally accepted.7 In this study, children
between the ages of 1 month and 10 years were considered eligible. For a child to be
included, his or her parents or guardian had to have a telephone and had to speak either
English or Spanish.

Interview with Parents

The parents of children who were identified in the emergency department logs as having
had first febrile seizures received a letter that explained the study and invited them to

participate. A research assistant trained in interviewing techniques by the investigators

then called and obtained their informed consent. The parents were interviewed with use
of a standardized questionnaire in either English or Spanish. The interviewer first asked a
brief series of screening questions to verify that the child had never previously had a
febrile or unprovoked seizure; children with such a history were excluded. A history of
neonatal seizures was not grounds for exclusion,10 but such a history was reported only
once. The records of all interviews were reviewed for errors, and the responses were
coded on an ongoing basis by the principal investigator.
The interviewer elicited a complete description of the seizure from the parent or, if the
parent did not witness the seizure, from someone who did. Descriptions of seizures were
compiled from the medical records and the interview, and each seizure was classified on
the basis of this information by an expert in epileptology and pediatric neurology. If
necessary, the parent or other witness was called back for clarification. As in previous
studies,2 , 7 seizures were considered complex if they were focal in onset, if they were
prolonged, or if there was more than one seizure during the course of the illness. Any
seizure with secondary generalization was classified as a focal-onset seizure.11 Todd's
paresis was taken as evidence of a focal seizure. A seizure was classified as prolonged if
it lasted more than 10 minutes.7 If a child had more than one seizure without fully
regaining consciousness between seizures, the seizures were counted as one continuous
seizure.11 A febrile seizure could have more than one complex feature.
Information was also obtained about the illness during which the seizure occurred,
including the duration of fever before the seizure (<1 hour, 1 to 24 hours, or >24 hours),
the highest body temperature that was recorded before or just after the seizure, and other
symptoms of illness. Parents were asked whether there was a family history of febrile and
unprovoked seizures and whether the child had any preexisting neurodevelopmental
problems.
Information about the seizure, the symptoms of the illness, the diagnosis, the child's
temperature (both as reported by the parents and on arrival at the hospital), and the results
of laboratory tests was obtained from the medical records. Temperatures measured at the
hospital were considered the most reliable because they were measured and recorded by
medically trained personnel. With few exceptions, temperatures were recorded in degrees
Fahrenheit. There was a predominance of temperatures recorded in whole degrees,
suggesting a preference on the part of care givers for rounded measurements and hence
error in the recording of temperatures. Because this error is linked to the Fahrenheit scale,
temperatures were not converted and analyzed in degrees Celsius. Celsius equivalents are
provided in parentheses. Occasionally, the temperature was not recorded or was less than
101F despite a diagnosis of febrile seizure. When it was available, the temperature
measured at home and recorded in the chart while the child was in the hospital was
considered an adequate substitute. There were some children (n = 14) who were included
in the cohort on the basis of the parents' report of a temperature of at least 101F and a
diagnosis of febrile seizure in the medical record but for whom no temperature was
recorded in the chart. These 14 children were, however, excluded from the analysis of

temperature and risk of recurrence. Children were ineligible for the study if the sole
documentation of fever was a report based on tactile assessment.

Follow-up
After the initial interview, the patents were called every three months to determine
whether the child had had any further seizures. Whenever possible, documentation of the
recurrence was obtained from the medical record. The follow-up period for this report
extended from study entry through March 1992.

Statistical Analysis
We used statistical methods that take into account the variable length of follow-up.12 13
14 15 The product-limit method was used to calculate the risk of recurrence at various
times after the first seizure.12 Standard errors and 95 percent confidence intervals were
calculated with an approximate Greenwood formula.14 The results are displayed by
means of KaplanMeier curves. Univariate and multivariate analyses were performed
for both continuous and discrete variables with the Cox proportional-hazards model.12 13
14 The rate ratio was used as a measure of the magnitude of the association between a
variable and the risk of recurrence. For the purposes of this report, data were censored
(treated as though follow-up had terminated) when a child had an unprovoked seizure.

Results
There were 356 children who met all the entry criteria and whose parents were
interviewed. One parent declined further participation in the study. Eight children were
excluded because no follow-up information could be obtained after the initial interview.
This report is therefore based on the 347 children for whom at least one follow-up call
was made: 119 (34 percent) from YaleNew Haven Hospital, 154 (44 percent) from
Bronx Municipal Hospital Center, 48 (14 percent) from North Central Bronx Hospital,
and 26 (7 percent) from Montefiore Medical Center. The median length of follow-up was
20 months (range, 2 to 31). Of these 347 children, 335 (97 percent) were followed for 6
months or more, 283 (82 percent) for 12 months or more, and 203 (59 percent) for 18
months or more. Seven children were treated continuously with phenobarbital, and
phenobarbital was prescribed for three children to be administered only during a febrile
illness, despite the acknowledged ineffectiveness of this kind of therapy.6 , 16 So far, 32
children (9 percent) have been lost to follow-up after less than one year.

Overall Risk of Recurrence

Ninety-four children (27 percent)
had recurrent febrile seizures. The
risk of recurrence was 14 percent
(95 percent confidence interval, 10
to 18 percent) at 6 months, 25 percent (95 percent confidence interval, 20 to 30 percent)
at 12 months, 27 percent (95 percent confidence interval, 22 to 32 percent) at 18 months,

and 30 percent (95 percent confidence interval, 24 to 35 percent) at 24 months (Fig.

1Figure 1KaplanMeier Curve for the Risk of a Recurrence after a First Febrile
Seizure.). These results are comparable to those of most other studies.5 There were no
appreciable differences in the risk of recurrence among the four hospitals.

Predictors of Recurrence
Table 1Table 1Univariate Association
between Each Variable and the Risk of
Recurrence.* lists the risk factors that
were examined, the number of
children with each risk factor, the
number and percentage who had
recurrences, and the univariate rate
ratio (with 95 percent confidence intervals) from the proportional-hazards model.

Duration of the Recognized Fever

One year after the initial febrile
seizure, the risk of recurrence was
44 percent (95 percent confidence
interval, 32 to 55 percent) for
children whose parents had been
aware of the fever for less than 1 hour before the seizure occurred, 23 percent (95 percent
confidence interval, 17 to 29 percent) for those with fever lasting 1 to 24 hours, and 13
percent (95 percent confidence interval, 5 to 20 percent) for those with fever lasting more
than 24 hours (Fig. 2Figure 2KaplanMeier Curves for the Risk of a Recurrence after a
First Febrile Seizure as a Function of the Duration of Recognized Fever before the First
Febrile Seizure.). The unadjusted rate ratio for the duration of fever before the seizure (<1
hour, 1 to 24 hours, or >24 hours) was 0.48, indicating an approximate halving of the
recurrence rate with each reduction from one category to the next shorter one.

Temperature
A rectal temperature of at least 101F (38.3C) was recorded at the hospital for 312 (90
percent) of the children. Twenty-one children (6 percent) had temperatures below 101F
when measured in the emergency department; however, the temperature according to the
history as recorded in their medical records was 101F or more. For 14 children,
information about the temperature was missing or it was below 101F. In the interview,
the parents of these children reported measuring a temperature of 101F or more, and the
diagnosis in the medical record was febrile seizure. These 14 children were included in
the cohort but were excluded from the analyses of temperature.
The risk of recurrence decreased
with increasing temperature (Fig.
3Figure 3KaplanMeier Curves

for the Risk of a Recurrence after a First Febrile Seizure as a Function of the Child's
Temperature When Evaluated for the First Febrile Seizure.). The risk of recurrence one
year after the initial febrile seizure was 35 percent (95 percent confidence interval, 17 to
56 percent) for children whose temperature was recorded as 101F (38.3C), 30 percent
(95 percent confidence interval, 18 to 41 percent) for those with temperatures of 102F
(38.9C), 26 percent (95 percent confidence interval, 17 to 36 percent) for those with
temperatures of 103F (39.4C), 20 percent (95 percent confidence interval, 12 to 29
percent) for temperatures of 104F (40.0C), and 13 percent (95 percent confidence
interval, 2 to 23 percent) for temperatures of 105F (40.6C) or higher (P for trend =
0.024). The unadjusted rate ratio was 0.82 for every increase of 1 degree Fahrenheit
above 101F, indicating an average 18 percent decrease in the recurrence of febrile
seizures for each additional 1 degree Fahrenheit.
The association between temperature and the risk of recurrence persisted after
stratification according to the duration of recognized fever, especially among children
whose seizures occurred less than one hour after the recognition of fever. Among these
children the risk of recurrence at 12 months according to temperature was 71 percent for
children with temperatures of 101F, 48 percent for 102F, 44 percent for 103F, 26
percent for 104F, and 0 percent for 105F or more.

Age at First Febrile Seizure

The median age at the time of the first febrile seizure was 18 months (range, 1 month to
9.5 years). Eleven children (3 percent) were more than five years of age when the first
febrile seizure occurred. The risk of recurrence one year after the first febrile seizure in
children less than 18 months old was 30 percent (95 percent confidence interval, 23 to 37
percent), and that in children 18 months old or older was 18 percent (95 percent
confidence interval, 12 to 24 percent).

Family History
Among the 340 children for whom information on family history was available, 81 (24
percent) each had a first-degree relative (parent or full sibling) who had had febrile
seizures. At one year, the risk of recurrence was 36 percent (95 percent confidence
interval, 25 to 46 percent) for those with a family history of febrile seizures and 20
percent (95 percent confidence interval, 15 to 26 percent) for those without such a family
history.
Fifteen children (4 percent) each had a first-degree relative with a single unprovoked
seizure or epilepsy. At one year the risk of recurrence was 36 percent (95 percent
confidence interval, 11 to 61 percent) for those with a family history of unprovoked
seizures or epilepsy and 24 percent (95 percent confidence interval, 19 to 28 percent) for
those without such a family history.

Complex Febrile Seizures

There was no evidence of an increased risk of recurrence among children whose initial
febrile seizure was complex. Furthermore, no single complex feature (including status
epilepticus) or combination of complex features was associated with a substantial
increase in the risk of recurrence.

Neurodevelopmental Abnormalities
There was no evidence of an increased risk of recurrent febrile seizures among the 21
children (6 percent) with neurodevelopmental abnormalities. Seven (33 percent) of these
children had unprovoked seizures, at which point data on them were censored from
further analysis of recurrent febrile seizures. Five of these seven began therapy with
anticonvulsant medications.

Sex and Race or Ethnic Group

The risk of recurrence was not significantly higher among boys than among girls. The
racial and ethnic distribution of the children in this study reflects the fact that the
populations from which the patients were drawn were largely black and Hispanic. There
was no indication that the risk of recurrence was greater in any of the three ethnic or
racial groups studied (blacks, whites, and Hispanics).

Multivariable Analysis
To control for individual effects of
related variables, the Cox
proportional-hazards model was
used for multivariable analyses.
Children for whom data were
missing on one or more variables (n
= 22) were excluded from this
analysis. All the variables described above were tested simultaneously in the model. Only
the variables with a statistically significant association with recurrence were retained.
These were temperature, duration of fever before the seizure, age at onset, and family
history of febrile seizures (Table 2Table 2Multivariable Cox Proportional-Hazards Model
of Predictors of Recurrent Febrile Seizures.*). The nonsignificant risk factors were
entered into the final model one at a time to generate an estimate of the rate ratio after
adjustment for the significant risk factors (Table 2).

Discussion
Febrile seizures were once considered a form of epilepsy.17 18 19 Largely as a result of
two epidemiologic studies,2 , 10 febrile seizures are now recognized as a benign
syndrome distinct from, although associated with, epilepsy.20 In the wake of an era in
which continuous phenobarbital prophylaxis was routinely used even for a single simple
febrile seizure21 , 22 and in the light of the growing evidence of the adverse side effects
of phenobarbital,23 24 25 the 1980 Consensus Development Panel devised guidelines for

decreasing the use of drug prophylaxis and identified limited circumstances in which it
might still be appropriate to consider prophylactic treatment.6 Of the factors that were
identified by the panel, only a young age at onset has been consistently associated with an
increased risk of recurrence.5 The other factors a family history of epilepsy, complex
features, and neurodevelopmental abnormalities are predictors of later epilepsy in
children who have febrile seizures.2 , 10 , 26 , 27 Current data indicate that anticonvulsant
prophylaxis against febrile seizures does not alter the risk of unprovoked seizures.6 , 26 ,
27 Hence, although the guidelines were meant to limit the use of anticonvulsant agents to
the children most likely to benefit from therapy, for the most part they did not identify
those at highest risk for recurrent febrile seizures.
In addition to the factors identified in the consensus-development conference, we
examined the circumstances in which the first febrile seizure occurred, specifically the
duration of recognized fever before the seizure and the temperature. Temperature has
been correlated with the risk of recurrence in two smaller studies.9 , 28 In a much larger
sample, we found a trend toward decreasing risk with increasing temperature. This
finding is consistent with a threshold model of febrile seizures and suggests that different
children have different temperature thresholds above which they may have a seizure.
Temperatures measured at the hospital after the seizure are only approximations of the
children's temperatures at the time of the seizures. Furthermore, there was evidence
suggesting inaccuracies in the recording of temperature. In general, such errors attenuate
the association between temperature and the risk of recurrence.29 Thus, it is likely that
the association is even stronger than we have described. Of course, it is also unlikely that
the height of the fever is the sole factor triggering a febrile seizure.
The duration of recognized fever before the seizure was another strong predictor of
recurrence. The biologic mechanisms underlying this association are not yet clear. Longer
follow-up may help clarify whether this pattern is consistent over the course of several
recurrences and may determine how this information can best be used in planning and
evaluating strategies for prevention.
Most previous studies of febrile seizures have reported an association between young age
at onset and an increased risk of recurrence.5 , 9 This relation appears to be due to the
longer period during which a younger child is at risk, rather than a greater tendency to
have seizures.9 , 30
All studies that have focused on a history of febrile seizures in a first-degree relative,
including this one, have found such a history to be associated with an increase in the risk
of recurrence.7 8 9 The results of studies that examined the effect of a family history of
epilepsy are conflicting. A large study in Rochester, Minnesota, found virtually no
difference in the risk of recurrence among children with a family history of epilepsy (25
percent) and those without such a history (23 percent).7 Our study results tend to agree
with those of the Rochester study, although ours are less conclusive.
The literature on the relation between complex febrile seizures and the risk of recurrence
is also inconsistent. The findings of our study are similar to those of the National

Collaborative Perinatal Project.2 Others, however, have reported that either specific
complex features9 or complex features in certain subgroups of patients7 were associated
with an increased risk of recurrence.
A large proportion of seizures in our study were complex. It is possible that the procedure
for recruiting patients through emergency departments led us to identify children with
more severe seizures and caused the underrepresentation of children with simple seizures
who were treated in a pediatrician's office and sent home. Although this may have
happened to a small degree, it is uncommon for a child with a first febrile seizure not to
be referred to an emergency department for a full sepsis workup, including a lumbar
puncture. The high proportion of complex seizures was due largely to our methods of
obtaining the descriptions of seizures.31 Information from parents about features of
complex seizures was frequently missing from medical records; such records have
generally been the primary source of information about seizures in other studies,7
although some investigators have not specified how this information was collected.9 , 32
Furthermore, the degree of agreement among three independent pediatric neurologists in
classifying each seizure as complex or simple was good to excellent.33 Thus, it is
unlikely that the high proportion of complex seizures was due to the selection of the
patients or to idiosyncrasies in our classification criteria.
Finally, children with neurodevelopmental abnormalities were not at increased risk for
recurrent febrile seizures, although several had unprovoked seizures. Other studies have
already demonstrated that this is a group at high risk for epilepsy.2 , 10 There is, however,
no evidence that treating the first febrile seizure reduces that risk.26 , 27 Moreover,
treatment is associated with a high incidence of cognitive and behavioral side effects.23
24 25 Thus, there does not appear to be any justification for treating a child after a single
febrile seizure, even if neurodevelopmental problems are present.
Some pediatric neurologists argue strongly against long-term therapy, even for complex
or recurrent febrile seizures.34 , 35 A recently proposed alternative is intermittent
treatment with agents such as benzodiazepines or the use of antipyretics only when fever
is present.36 , 37 The risks and benefits of these approaches have yet to be fully explored.
Because of the tendency in the past to consider febrile seizures a form of epilepsy, most
studies of recurrent febrile seizures have focused on predictors of epilepsy. With the
exception of age, these studies, as a group, have not identified consistent, strong
predictors of recurrence. We focused on factors related to the occurrence of the initial
febrile seizure, not just those related to the later development of epilepsy. The duration of
recognized fever and the temperature appear to provide useful information about which
children are at very high risk and which at very low risk for recurrence.
Supported by a FIRST award (1R29 NS27728) to Dr. Berg and a grant (1R01 NS26151)
to Dr. Shinnar from the National Institute of Neurological Disorders and Stroke.
Presented in part at the American Epilepsy Society Meeting, Philadelphia, December 8
11, 1991.

We are indebted to the interviewers, Nancy Bassett and Toby Gillman, for their dedicated
work on this project and to all the parents of the children who participated in this study;
to Drs. Mervyn Susser and Zena Stein, who supported this project in its earliest phases; to
Dr. Theodore Holford, who kindly provided consultation throughout the study; and to the
New York City Health and Hospitals Corporation, Bronx Municipal Hospital Center,
North Central Bronx Hospital, Montefiore Medical Center, and YaleNew Haven
Hospital for their cooperation.

Source Information
From the Department of Pediatrics, Yale School of Medicine, New Haven, Conn. (A.T.B.,
E. D.S.); the Departments of Neurology (S.S., M.A.) and Pediatrics (S.S., M.E.S., E.F.C.)
and the MontefioreEinstein Epilepsy Management Center (S.S., M.A.), Montefiore
Medical Center, Albert Einstein College of Medicine, Bronx, N.Y.; and the Gertrude
Sergievsky Center, Columbia University College of Physicians and Surgeons, New York
(S.S., W.A.H.). Address reprint requests to Dr. Berg at the Department of Pediatrics, Yale
University School of Medicine, 333 Cedar St., New Haven, CT 06510