1978;61;720 Pediatrics

Karin B. Nelson and Jonas H. Ellenberg

Prognosis in Children With Febrile Seizures

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720 PEDIATRICS Vol. 61 No. 5 May 1978
Prognosis in Children With Febrile Seizures
Karin B. Nelson, M.D., and Jonas H. Ellenberg, Ph.D.
From the Developmental Neurology Branch and Office ofBiometry and Epidemiology. National Instituts of
Neumlogical and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, M aryland
ABSTRACT. Febrile seizures occurred in 3.5% of white and
4.2% of black children who were followed up in a large
prospectively defined cohort. The frequency of adverse
outcomes was examined in this population and risk factors
were identified. Among 1,706 children with febrile seizures,
no deaths or persistent motor deficits occurred as sequelae of
seizures. Todds paresis occurred in 0.4% . Risk factors
identified for epilepsy after. febrile seizures were family
history of afebrile seizures, preexisting neurological abnor-
mality, and complicated initial seizure. Of the 60% of
children with febrile seizures who had none of these factors,
1% developed epilepsy by age 7 years. A single risk factor
was present in 34% , of whom 2% developed epilepsy. Of the
6% with two or more of these factors, 10% developed
epilepsy.
After an initial brief febrile seizure, 1.4% experienced a
subsequent attack which lasted 30 minutes or longer; none of
these children had an afebrile seizure by the age of 7
years.
Febnle seizures were associated with an increased risk of
intellectual deficit only among children with preexisting
neurological or developmental abnormality, and in those
who developed subsequent afebrile seizures. A third of the
children with febrile seizures had a recurrence, and 9% had
three or more recurrences. The major predictor of recur-
rence was early age at onset. Pediatrics 61:720-727, 1978,
febrile seizures, heiniplegia, epilepsy, minor motor seizures,
mental retardation.
Febrile seizures are a common clinical prob-
lem, yet there is no consensus as to whether, or in
what circumstances, vigorous efforts to treat
febrile seizures are justifiable.5 One factor
underlying the diversity of opinion on optimal
therapy is uncertainty concerning the magnitude
of risks facing children with febrile seizures.
Available studies provide no quantitative esti-
mates of the risks for some outcomes, and widely
divergent estimates for others. Previous reports
have often concerned hospitalized children or
those referred to specialty clinics, or have
involved retrospective ascertainment of febrile
seizures in patients who have sought medical
attention for other serious problems; none of
these provides a satisfactory basis for the estima-
tion of risk in the general population of children
with febrile seizures. Some studies have included
children with intrinsically brain-damaging ill-
nesses such as meningitis, and others have
included children who had afebrile seizures
before ever having a seizure with fever. Few
investigations have had a defined base population
which could provide the denominator data
required for estimations of risk.
The study reported here examined the frequen-
cy of unfavorable sequelae of febrile seizures in a
large prospectively established population which
was not selected for medical care sought for
seizures or their complications. Earlier reports
from this population have examined the frequen-
cy of epilepsy6 and of deficits in intelligence and
early academic performance7 in children who
have experienced febrile seizures. The present
study concerns the risk of death, persisting motor
disability, Todds paresis, and recurrences of
febrile seizures, including the frequency of
complicated febnle seizures following an initial
uncomplicated attack. Additional data on risk
factors for epilepsy and for mental retardation
after febrile seizures are also presented.
METHODS
Approximately 54,000 pregnant women partic-
ipating in the National Institute of Neurological
and Communicative Disorders and Stroke Collab-
orative Perinatal Project (NCPP) between 1959
Received January 13; accepted for publication February 15,
1978.
ADDRESS FOR REPRINTS: (K.B.N.) 7550 W isconsin
Avenue, Room 8C04, Bethesda, M D 20014.
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ARTICLES 721
and 1966 recei ved prenatal care and were del i v-
ered of thei r babi es at one of 12 cooperati ng
urban teachi ng hospi tal s. The sampl i ng f rame and
general methodol ogy f or thi s study have been
descri bed el sewhere.8
M edi cal hi stori es whi ch i ncl uded questi ons
about the occurrence of sei zures were recorded
when study chi l dren were aged 4, 8, 12, 18, and
24 months, and annual l y thereaf ter to the age of 7
years. Records f rom the physi ci an or medi cal
f aci l i ty were revi ewed f or each medi cal l y
attended sei zure reported.
The protocol of the NCPP al so speci f i ed a
regul ar schedul e of standardi zed exami nati ons f or
al l parti ci pati ng chi l dren. Neurol ogi cal and
devel opmental status pri or to any sei zure was
eval uated usi ng a pedi atri c exami nati on at 4
months of age, an overal l i mpressi on f ol l owi ng
the admi ni strati on of the Bayl ey Scal es of M ental
and M otor Devel opment at 8 months, and a
pedi atri c and neurol ogi cal exami nati on per-
f ormed at 1 year of age. A gl obal rati ng of
neurol ogi cal l y or devel opmental l y suspect or
abnormal on any of these tests perf ormed bef ore
the f i rst sei zure l ed to the cl assi f i cati on of that
chi l d as other than normal .
At the ti me of her regi strati on i nto the NCPP,
each pregnant woman was asked whether she, the
f ather of the baby, or any pri or l i vebom chi l d had
ever experi enced sei zures, convul si ons, or epi l ep-
sy. A detai l ed descri pti on, i ncl udi ng presence of
f ever, sei zure number, and age at onset, was
sol i ci ted i n the event of a posi ti ve repl y.
The measure of i ntel l i gence was the f ul l -scal e
I Q, W echsl er I ntel l i gence Scal es f or Chi l dren, at
7 years of age.
The NCPP protocol di d not requi re reporti ng
of treatment. Onl y 13% of chi l dren i n thi s seri es
are known to have recei ved conti nuous anti con-
vul sant therapy f or one month or more. No bl ood
drug l evel determi nati ons were perf ormed i n thi s
study, and prophyl acti c therapy undertaken
wi thout such moni tori ng of compl i ance i s appar-
entl y i nef f ecti ve.9 For these reasons, treatment
was not consi dered as a f actor i n these anal yses.
The i mportance of f actors potenti al l y predi c-
ti ve of morbi di ty was exami ned f or each f actor
separatel y and i n addi ti on i n a mul ti vari ate
f ormat usi ng f orward stepwi se regressi on. Si nce
most predi ctor and outcome vari abl es were
di chotomous (ei ther present or absent), the
assumpti on of normal cy necessary f or the appl i ca-
ti on of standard di stri buti on theory resul ts was
not tenabl e. Theref ore, t val ues were consi dered
as onl y rough gui des to si gni f i cance.1#{ 176} A f ter sel ec-
ti on of the i mportant predi ctors by means of the
l i near regressi on model , esti mati on of morbi di ty
was accompl i shed usi ng a mul ti pl e l ogi sti c
model . The W al ker-Duncan method of i terati ve
maxi mum l i kei thood was used to esti mate the
parameters of the mul ti pl e l ogi sti c model .12
Def i ni ti ons
A chi l d was consi dered to have had a f ebri l e
sei zure i f the f i rst sei zure he ever experi enced was
accompani ed by f ever, occurred between the ages
of 1 month and 7 years, and was not symptomati c
of recogni zed acute neurol ogi cal i l l ness. Chi l dren
wi th i l l nesses such as meni ngi ti s, l ead encepha-
l opathy, marked systemi c dehydrati on, and
sei zures af ter i mmuni zati on procedures were
excl uded; approxi matel y 11% of chi l dren wi th
sei zures and f ever were excl uded on the basi s of
thi s cri teri on.
Compl ex f ebri l e sei zures were those wi th
one or more of the f ol l owi ng characteri sti cs: more
than 15 mi nutes durati on, more than one sei zure
in 24 hours, or f ocal f eatures.
A chi l d wi th recurrent af ebnl e sei zures bef ore
48 months but none af ter 48 months of age, or
si ngl e (i ncl udi ng cl ustered wi thi n a si x-week
peri od) asymptomati c af ebri l e sei zures, whether
recent or remote, was cl assi f i ed as havi ng af eb-
ri l e sei zures. The term epi l epsy was reserved
f or chi l dren who had recurrent asymptomati c
af ebri l e sei zures of whi ch at l east one occurred
af ter the age of 48 months.
M i nor motor sei zures was a cl i ni cal cl assi f i -
cati on i ndi cati ng toni c, hemi toni c, myocl oni c, or
aki neti c sei zures. The term atypi cal absence
i ndi cated attacks of i nterrupti on or al terati on of
consci ousness, accompani ed by autonomi c di stur-
bances or promi nent automati sms or changes of
af f ect, i n chi l dren who di d not have mi nor motor
sei zures. EEC cri teri a were not empl oyed
because EEGs were not routi nel y avai l abl e, but
no chi l d i n thi s group who had an EEC demon-
strated a 3/sec spi ke-wave traci ng.
RESULTS
There were 1,821 chi l dren who met the stated
cri teri a f or f ebri l e sei zures. Of these, 1,706 or 94%
were f ol l owed up to the age of 7 years and f orm
the sampl e f or thi s study. There were 732 whi te
chi l dren, 883 bl ack chi l dren, and 91 chi l dren of
other ethni c backgrounds, mai nl y Puerto Ri can.
The preval ence of f ebri l e convul si ons at 7 years i n
the NCPP was 34.8/1,000 f or whi te chi l dren and
42.4/1,000 f or bl ack chi l dren (X2i = 13.7,
P < .001). M ore boys had f ebri l e sei zures than
gi rl s (36.6 vs. 32.8/1,000 f or whi tes and 46.4 vs.
38.5/1,000 f or bl acks), but the di f f erence between
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70
60
5 0
4 0
30
H
2 0 -
10
N-1263 N1 2 5
722 PROGNOSIS OF FEBRILE SEIZURES
I 1 AF EBRLE
EPilEPSY
N- 3 9 1 7 9
FAMILY HISTORY
NI PP CHU.DRENW ffH FEBRILESEIZURES
FI G. 1. Fr equency of epilepsy and afebr ile seizur es accor ding
to f am ily seiz ure history . Far-lef t colum n indicates f requency
of these outcom es am ong children of N CPP w ho had no
antecedent f ebrile seiz ures.
sex es w ithin race w as signif icant only am ong
black children (X 2i 7.0, P < .009).
T he av erage age at onset of f ebrile seiz ures w as
23.3 m onths f or 760 girls and 23.2 m onths f or 933
boy s (age at onset w as unk now n f or 13 children).
Of the 77% of children f or w hom the illness
accom pany ing the f irst f ebnle seiz ure w as docu-
m ented, 38% had upper respiratory tract inf ec-
lions or phary ngitis, 23% had otitis m edia, 15%
had pneum onia, 7% had acute gastroenteritis, 5%
had roseola inf antum , 1.4% had the f lu, and
12% had other ailm ents.
Death
N o deaths occurred in tem poral relationship
w ith asy m ptom atic f ebrile seiz ures. T here w ere
tw o deaths in children w ho had had f ebrile
seiz ures earlier. B oth of these children w ere
quadriplegic and sev erely retarded bef ore any
seiz ure, and both died of pneum onia, 4 and 30
m onths, respectiv ely , af ter their last f ebrile
seiz ures.
Motor Def icits
In no instance did persisting hem iplegia or
another m otor def icit dev elop during or im m edi-
ately af ter an asy m ptom atic f ebrile seiz ure. A cute
inf antile hem iplegia presenting w ith f ev er and
seiz ure w as f ound only am ong children w ith
seiz ures sy m ptom atic of recogniz able specif ic
illness (usually inf ectious) of the CN S ; children
w ith such sy m ptom atic seiz ures w ere ex cluded by
def inition f rom this cohort. In only one case of
acute inf antile hem iplegia w as the classif ication
sy m ptom atic considered equiv ocal. T his w as a
child in w hom pneum ococcal bacterem ia w as
docum ented during the acute illness associated
w ith the f ev er and seiz ure, f ollow ed by hem ipar-
esis. B ecause of the possibility of m etastatic
inf ectious f oci in the CN S , this child w as classif ied
as hav ing a sy m ptom atic seiz ure w ith f ev er. If this
child w ere included, the f requency of hem iparesis
af ter f ebrile seiz ures w ould be 1/1,707, or
0.06% .
T odds paresis, def ined as postictal w eak ness
lasting a w eek or less, w as observ ed in sev en cases,
or 0.4% of children w ith f ebrile seiz ures. T odds
paresis w as associated w ith the f irst seiz ure of the
childs lif e in f our cases and w ith the second
seiz ure in three cases. Four children w ith T odds
paresis w ere considered neurologically norm al on
ex am ination bef ore the f irst f ebrile seiz ure, and
three w ere suspect. One child subsequently dev el-
o_ an af ebrile f ocal seiz ure disorder af f ecting
the side w hich had been w eak postictally .
Epilepsy and Afebrile Seizures
S uspect or abnorm al neurological and dev elop-
m ental status of the child bef ore any seiz ure and
com plex f eatures of the f irst f ebrile seiz ure w ere
f ound in a prev ious study f rom the N CPP to be
im portant predictors of subsequent epilepsy .6 In
the present inv estigation, a history of seiz ures
w ithout f ev er in a parent or prior-born sibling,
ascertained prenatally , w as also f ound to be a
signif icant predictor. S uch a history w as present
in 5.6% of children w ith f ebrile seiz ures, and w as
associated w ith a threef old increase in the rate of
later epilepsy , as com pared w ith those w ith no
f am ily history of seiz ures (52 v s. 16/1,000;
X 2i = 4.6, P :L .032, Fig. 1). T here w as a sim ilar
increase of risk f or any af ebrile seiz ure (25 to 73/
1,000, X2 i 6.0, P : .014).
A f am ily history of f ebrile seiz ures only w as
identif ied in 7.3% . T here w as no increase in the
f requency of subsequent epilepsy in the presence
of a f am ily history of f ebrile seiz ures only w hen
com pared w ith a negativ e f am ily seiz ure history
(16 v s. 16/1,000), and a m oderate but not statisti-
cally signif icant increase f or subsequent af ebrile
seiz ures (2 5 v s. 40/ 1,000). T he com parison of
children w ith a f am ily history of f ebrile conv ul-
sions only w ith those w ith a f am ily history of
af ebrile seiz ures also did not produce a statisti-
cally signif icant dif f erence in risk , although the
observ ed increases w ere large f or both the
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ARTICLES 723
TA BL E I
ESTI M A TES O F R I SK O F Ep i .spsy
Risk
Group
% of
Febrile
Cohort
Family
HLStOry#{176}
Prior
Statust
F irst
Seizure
Typ4
N o. R isk (% )

Epilepsy Afebrile Seizures
Obsewed Estimated Obsewed Estimated
No f ebri l e
sei zures
, 39,179 0.5 0.9
1 60 - - - 971 0.9 0.8 1.9 1.6
2 34 -
-
+
+
-
-
-
+
-
264
222 542
56 J
2.3 2.7
1.4 2.0 2.1 2.5
3.6 J 3.0 J
2.3 3.3
3.2 . 3.0 4.1 3.8
5.4 J 5.3 J
3 6 -
+
+
+
+
+
-
+
+
-
+
+
61
22
94
7
4
9.8 6.6
9.1 9.2
? 9.6 7.8
14.3 7.2
0.0 J 20.3
13.1 8.2
13.6 10.3
12.8 9.6
14.3 12.6
0.0 23.0
0_ i ndi cates absence of hi story of af ebri l e sei zures in p a r en t or sib lin g; + in d ica t es p r esen ce.
t- i ndi cates normal neurol ogi cal status bef ore any sei zure; + i ndi cates abnormal or suspect.
:1:- i ndi cates f i rst sei zure type pure; + in d ica t es fir st seizu r e type compl ex.
Not i ncl uded are 99 chi l dren of unknown f ami l y hi story, unknown pri or status, or unknown f i rst sei zure type.
outcomes of af ebri l e sei zures (40 vs. 73/1,000) and
epi l epsy (16 vs. 52/1,000).
The combi ned predi cti ve abi l i ty of these and
other f actors was assessed, usi ng mul ti vari ate
f orward stepwi se regressi on. A ge at onset, race,
sex, f ami l y hi story of f ebri l e sei zures, and number
of f ebri l e sei zures di d not contri bute si gni f i cant
addi ti onal predi cti ve power to the f actors of
f ami l y hi story of af ebri l e sei zures, pri or neurol og-
i cal status, and f i rst sei zure type.
Once ri sk f actors were i denti f i ed by means of
mul ti vari ate regressi on, the mul ti pl e l ogi sti c
model was used to predi ct the ri sk of epi l epsy and
af ebri l e sei zures. The esti mates of ri sk f or each
conf i gurati on of the ri sk f actors are gi ven i n Tabl e
I . A l ow-ri sk group (ri sk group 1) was def i ned to
i ncl ude chi l dren who were normal bef ore any
sei zure, who had an uncompl i cated i ni ti al f ebri l e
sei zure, and who had no f ami l y hi story of af ebri l e
sei zures. Thi s l ow-ri sk group consti tuted 60% of
chi l dren wi th f ebnl e sei zures, and of them, 9.3/
1,000 or 0.9% devel oped epi l epsy, a rate not
stati sti cal l y si gnf f i cantl y hi gher than that of chi l -
dren who had no f ebri l e sei zures (9.3 vs. 5.1/
1,000). Ni neteen per thousand of thi s l ow-ri sk
group, or 1.9%, had any af ebri l e sei zure, whi ch
does di f f er si gni f i cantl y f rom the rate i n chi l dren
wi th no f ebri l e sei zures (18.5 vs. 9.1/1,000;
X 2i = 8.2, P : .004).
Chi l dren i n whom one ri sk f actor was present
were 34% of those wi th f ebri l e sei zures (ri sk group
2, Tabl e I ). Of thi s group, 20.3/1,000 or 2.0%
devel oped epi l epsy and 29.5/1,000 or 3.0% devel -
oped af ebri l e sei zures. For nei ther epi l epsy nor
any af ebri l e sei zures were the rates stati sti cal l y
si gni f i cantl y hi gher than i n the l ow-ri sk group,
but f or both these outcomes group 2 chi l dren
were at hi gher ri sk than chi l dren who had no
f ebri l e sei zures (P < .01). The absol ute magni -
hi de of the ri sk remai ned smal l . I n group 1 pl us
group 2, whi ch i ncl uded 94% of chi l dren wi th
f ebri l e sei zures, the ri sk of epi l epsy was 1.3% and
the ri sk of af ebnl e sei zures was 2.2%.
Chi l dren wi th two or more ri sk f actors (ri sk
group 3) were at a si gni f i cantl y i ncreased ri sk of
both epi l epsy and af ebri l e sei zures as compared
wi th those i n whom onl y a si ngl e ri sk f actor was
present. Ri sk group 3 consti tuted approxi matel y
6% of chi l dren wi th f ebri l e sei zures. Of thi s group,
96/1,000 or 10% (vs. 20.3/1,000 i n group 2;
X 2i = 12.6, P < .001) devel oped epi l epsy and
128/1,000 or 13% devel oped an af ebri l e sei zure
l ater (vs. 29.5/1,000 i n group 2; X 2i = 16.1,
P< .001).
Previ ous reports have suggested an i mportant
prognosti c rol e f or l engthy i ni ti al f ebri l e
sei zures. 3 6 I n thi s popul ati on, the 74 chi l dren
whose f i rst f ebri l e sei zure l asted 30 mi nutes or
more consti tuted 4.3% of pati ents wi th f ebri l e
sei zures. Of these chi l dren, three or 4.1% became
epi l epti c and 5.4% had an af ebri l e sei zure by the
age of 7 years. The i ncrease i n ri sk of subsequent
epi l epsy associ ated wi th f i rst f ebri l e sei zures
l asti ng hal f an hour or more di d not reach
stati sti cal si gni f i cance (40.5 vs. 15.1/1,000 f or
chi l dren wi th uncompl i cated i ni ti al sei zure).
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TABLE I I
724 P R O G NO S IS O F F E BR ILE S E IZUR E S
M ENTAL RETARDATiON I N CHI LDREN W I T H AFEBRI L E SEI Z URES CL ASSI FI ED BY PRI OR
NEUROL OGI CAL ST AT US AND SUBSEQUENT AFEBRI L E SEI Z URES
Prior Total Subsequent A febrile S eizures
\7ei rological
, . - A
Status
No.
No
No. (Rate)
W ith M ental
Retardation
Yes
No. No. (Rate)
W it/i M ental
Retardation
Normal 1,266 1,237 39 (31.5) 29 4 (137.9)
Other than normal 355 338 39 (115.4) 17 9 (529.4)
Totalt 1,706 1,654 81 (49.0) 52 14 (269.2)
No.! 1,000.
tincludes 85 cases with unknown prior status.
Ninety-one percent of children who developed
epilepsy following febrile seizures (31 of 34 chil-
dren) had never had a febrile seizure which lasted
30 minutes or more.
Children with febrile seizures developed atypi-
cal absence attacks more frequently than did
children who had no febrile seizures (5.9 vs. 1.5/
1,000; X2i 15.9, P < .001), but this increase was
not greater than the increase in risk of epilepsy of
all types after febrile seizures.
M ental Retardation and Learning Disorder
The effect of febrile seizures on the whole
range of tested intelligence was examined in a
previous study of this population. I n 431 sibling
pairs, there was no deficit in I Q at 7 years in
children with only febrile seizures, as compared
with their siblings who were seizure-free.7 The
subgroup of children who were not neurologically
or developmentally normal before any seizure
did, however, score below their normal siblings.
I n this study, early learning disorder occurred
with the same frequency in children who had
experienced febrile seizure as in control
siblings.
The development of afebnle seizures after
febrile seizures was associated with a fivefold
increase in frequency of mental retardation (I Q
less than 70) at 7 years (269 vs. 49.0/1,000;
x2 42.4, P < .001, Table I I ). The same rela-
tionship was observed both among children
considered normal before any seizure (P < .01)
and in those thought to be previously suspect or
abnormal (P < .001). There were 14 children in
whom mental impairment coexisted with afebrile
seizures. I ntellectual impairment was particularly
frequent in children who developed minor motor
epilepsy following febrile seizures; seven of the
eight children with minor motor seizures were
mentally retarded at 7 years. (M ental retardation
was also very common in children with minor
motor seizures who had never had a febrile
seizure.) Five of the six of these children with
mental retardation whose prior status was known
were abnormal before any seizure.
Except where neurological or developmental
abnormality predated any seizure, or there were
subsequent afebnle seizures, febrile seizures were
not associated with an increase in risk of intellec-
tual impairment.
Co m p l ex Feb r i l e Sei zu r es A f t er the
I nitial Attack
Three quarters of complex seizures occurred as
the first seizure of the child s life. After an initial
uncomplicated febrile seizure, a subsequent
complex attack occurred in 8.0%. Among children
whose first seizure lasted 15 minutes or less, a
subsequent seizure of 30 minutes or longer
occurred in 1.4% and a subsequent seizure of an
hour or longer occurred in 0.7%; none of these
children experienced an afebrile seizure by age 7
years.
Twelve children experienced a febrile seizure
which lasted an hour or more and was focal. I n 11
of the 12, such an attack was the first seizure of
the child s life.
The risk of a complex seizure was approxi-
mately the same for the first as for each subse-
quent febnle seizure; therefore, the overall risk of
a complex seizure by the age of 7 years was
increased in children who experienced multiple
seizures.
R e c u rre n c e s of Febrile Seizures
The most frequent sequela of an initial febrile
seizure was the recurrence of febrile seizures. A
third of children who experienced a febrile
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70
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0 1 2 1 * 2 4 3 9 3 9 4 2 4 0
N 1IS 340 391 100 140 7 4
TA BL E I I I
ARTICLES 725
39
1WOI I Sf l
FIG. 2. Frequency of recurrence (sol i d curve) and mul ti pl e
recurrences (broken curve) of f ebnl e sei zures accordi ng to
age at onset. Points plotted at midpoints of age groupings 2
to 6 months, 7 to 12 months, 13 to 18 months, etc.
sei zure had at l east one recurrence, and hal f of
those who had one recurrence had a f urther
attack. Ni ne percent of the 1,706 chI l dren of thi s
study had three or more recurrences. M al es and
f emal es and whi tes and bl acks di d not di f f er
si gni f i cantl y i n thei r vul nerabi l i ty to recur-
rences.
The l i kel i hood of recurrence was rel ated to age
at onset of f ebri l e sei zures (Fi g. 2). Hal f of the
chi l dren wi th onset i n the f i rst year and 28% wi th
onset af ter the f i rst year had at l east one recur-
rence (x2 = 73.3, P < .001). M ul ti pl e recur-
rences were al so rel ated to earl y onset: of chi l dren
whose f ebri l e sei zures began bef ore the f i rst
bi rthday, 30% l ater experi enced more than one
recurrence, whi l e of those whose onset was af ter
the f i rst bi rthday, 11% had more than a si ngl e
recurrence (x2 82.3, P < .001). The ef f ect of
age at onset on ri sk of recurrence was not
appreci abl y di f f erent i n boys and gi rl s duri ng the
f i rst 48 months of l i f e, the peri od f or whi ch
suf f i ci ent data were avai l abl e f or compari son.
The i nterval between f i rst and second sei zure
vari ed l i ttl e wi th the age at whi ch the i ni ti al
sei zure took pl ace. Of known recurrences, al most
hal f of second attacks took pl ace wi thi n si x
months of the f i rst and 73% i n the year f ol l owi ng
the i ni ti al sei zure (Tabl e I I I ).
Chi l dren whose f i rst f ebri l e sei zure accompa-
ni ed roseol a i nf antum had recurrences wi th the
same f requency as those whose f i rst sei zure
occurred wi th other i l l nesses.
Characteri sti cs of the f i rst f ebnl e sei zure were
not usef ul i n the predi cti on of recurrence; uncom-
pl i cated i ni ti al f ebri l e sei zures were as of ten
f ol l owed by recurrence as were f i rst f ebri l e
I NTERvA L TO RECURRENCE OF FEBRILE SEIZURES
Time (ma)
Fromlstto
2nd Seizure
No. Cumulative
%
0 - 2 114 22
3 - 6 136 47
7-12 135 73
13-24 79 88
25-48 54 98
49-84 10 100
Total 528
sei zures whi ch had compl ex f eatures. Chi l dren
who were not normal bef ore the f i rst f ebri l e
sei zure more of ten had one recurrence (x2 = 4.4,
P : .036), but not mul ti pl e recurrences.
M ul ti vari ate regressi on anal ysi s demonstrated
that the two f actors most rel ated to i ncreased ri sk
of recurrence were earl y age at onset and hi story
of af ebri l e sei zures i n the i mmedi ate f ami l y, and
of these two, age at onset was much more potent
as a predi ctor.
DIS C US S IO N
Thi s study has exami ned a spectrum of adverse
outcomes f ol l owi ng f ebri l e sei zures, and has
f ound those other than recurrences to be i nf re-
quent. Nei ther death nor persi sti ng hemi pl egi a
occurred as sequel ae of f ebnl e sei zures i n the
1,706 chi l dren of thi s sampl e. Death has been
i nf requent i n other recent studi es, except where
preexi sti ng abnormal i ti es of the chi l d, or the
nature of the provoki ng i l l ness, were rel ated. 7 18
W i th regard to subsequent epi l epsy, f ami l y
hi story of af ebnl e sei zures was f ound to add
i ndependent i nf ormati on as a predi ctor to the ri sk
f actors previ ousl y i denti f i ed.6 I n 60% of chi l dren
wi th f ebri l e sei zures, none of these ri sk f actors
(p nor abnormal i ty, compl ex f i rst sei zure type,
and f ami l y sei zure hi story) was present, and the
ri sk of epi l epsy and af ebri l e sei zures by 7 years i n
thi s group was l i ttl e greater than among chi l dren
who had never had a f ebri l e sei zure. I n the smal l
subgroup of chi l dren wi th f ebri l e sei zures who
had two or more of the chi ef ri sk f actors, there
was a sharp i ncrease i n ri sk of epi l epsy and of
af ebri l e sei zures.
Several workers have stressed the rel ati onshi p
of prol onged f ebri l e sei zures to the devel opment
of subsequent epi l epsy. 3 6 I n the seri es reported
here, prol onged durati on of f ebri l e sei zures was
not a maj or determi nant of subsequent epi l epsy.
M ore than 90% of chi l dren who devel oped
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726 PROGNOSIS OF FEBRILE SEIZURES
epilepsy after febrile seizures had never had a
febrile seizure which lasted as long as 30 minutes.
Those children who did have a prolonged febrile
seizure most often experienced it as the first
seizure of their lives,6 before there was an oppor-
tunity to consider them as potential candidates
for treatment. In no case in this series did a child
who had an initial brief febrile seizure and a later
prolonged febrile seizure become epileptic.
Experience in the NCPP, as elsewhere,141921
fails to confirm Livingstons report that children
whose first febnle seizure was prolonged or focal,
or who had a family history of afebrile seizures
(his epilepsy triggered by fever), almost always
become epileptic and almost always by the age of
5 years.3 Similar risk factors have been found by
other investigators to be relevant, but the
frequency and the predictive potency of these
factors have been far less than reported by
Livingston.
Children with febrile seizures did not develop
atypical absence attacks (a seizure type that we
think approximates temporal lobe epilepsy)
proportionately more often than other forms of
epilepsy.
Febnle seizures were associated with an
increased risk of intellectual deficit only among
children with a preexisting neurological or devel-
opment abnormality and in those who developed
subsequent afebrile seizures. Early academic
performance was not affected by febrile
7
A third of children with febrile seizures had a
recurrence, and 9% had three or more such
episodes. As in previous studies, age at onset was
the chief predictor recognized,42223 with onset in
the first year followed by recurrence in half of the
cases. Number of seizures experienced did not
influence later intelligence.7 Once the major
predictors of epilepsy after febrile seizures were
considered, recurrences of febrile seizures were
not found to add significantly to the risk of either
epilepsy or any afebrile seizure.
IMPLICATIONS
I n our opinion, death and hemiparesis are too
infrequent following febrile seizures to provide a
justification for chronic prophylaxis; the harm
resulting from occasional accidental overdosage,
as occurred in two of the 27 effectively treated
children in the Danish series,24 would probably
outweigh the (unproven) benefit of treatment,
with such very uncommon outcomes as target.
Reduction of recurrences and prevention of
afebrile seizures are the major plausible goals for
chronic treatment of febrile seizures. Regular
administration of phenobarbital can decrease the
frequency of recurrence of febrile seizures, and
may decrease the chance that a subsequent febrile
seizure, if it occurs, will be prolonged or focal.2425
Prescribed as prophylaxis for recurrences, treat-
ment might reasonably be given to children
whose first seizure occurred before 1 year of age,
because such children are at relatively high risk of
recurrence, and especially of multiple recur-
rences. However, regular administration of anti-
convulsant medication is difficult to maintain,2526
and treatment with phenobarbital is often
accompanied by behavior disorders.27 Further-
more, no empiric evidence known to us estab-
lishes that the reduction of recurrences of febrile
seizures prevents long-term sequelae.
Sixty percent of children with febrile seizures
did not have the risk factors associated with
subsequent epilepsy. This low-risk group would
not seem an appropriate target population for
chronic treatment aimed at the prevention of
afebrile seizures. The 34% of children with febrile
seizures in whom a single risk factor was present
were at increased, but not at high, risk.
The small, relatively high-risk group defined by
possession of two or more risk factors showed a
20-fold increase in the risk of epilepsy, and
deserves consideration for chronic treatment.
However, it is not known whether treatment after
the onset of febrile seizures can prevent the
eventual development of afebrile seizures. Chin-
ical trials may be warranted to investigate
whether medical intervention, especially if aimed
at the high-risk group, is efficacious in the preven-
lion of subsequent epilepsy, and safe enough to be
justifiable for use in children of whom a
substantial majority would not become epileptic
even if untreated.
A t present, there is no empiric evidence that
chronic treatment with anticonvulsant medica-
lion influences, positively or negatively, the long-
term prognosis of children with febrile seizures.
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1. A sn es R S , N ov ick L F, N ealis J, Nguyen M : The first
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2. Bray PF: Neurology in Pediatrics. Chicago, Year Book
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3. Hammill JF, Carter 5: Feb r ile con v u lsion s. N Engll Med
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children who have experienced febrile seizures. N
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13. Livingston S: compr ehensi ve Management of Epi l epsy
i n i nfancy, Chi l dhood and Adol escence. Spr ing-
field, Ill, Charles C T homas Publisher , 1972, p 26.
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ti cs 11:341, 1953.
16. Aicardi J, Chevrie J-J: Febr ile convulsions: Neur ological
sequelae and mental r etar dation, in Br azier M AB,
Coceani F (eds): Br ai n Dysfuncti on i n I nfanti l e
Febr i l e Convul si ons. New York, Raven Press, 1976,
pp 247-257.
17. Frantzen E, Lennox-Buchthal M , Nygaard A: Longitu-
dinal EEG and clinical study of children with
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Pedi atr Res 3:298, 1969.
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in Rochester, M innesota, 1935 thr ough 1967.
Epi l epSi a 16:1, 1975.
2 1 . W allace SJ: Spontaneous fits after convulsions with
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22. W allace SJ: Recur r ence of febr ile convulsions. Ar ch Di s
Chi l d 49:763, 1974.
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24. Faer 0, Kastrup KW , Lykkegaard Nielsen E, et al:
Successful pr ophylaxis of febr ile convulsions with
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25. W olf SM , Car r A, Davis DC, et al: T he value of
phenobarbital in the child who has had a single
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26. Heckmatt JZ , H ouston AB, Clow DJ, et al: Failur e of
phenobarbitone to prevent febrile convulsions. Br
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27. W oLf SM , Forsythe A: Determinants of phenobarbital-
induced hyper activity in childr en with febr ile
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A C K NO W LEDG MENT
W e ar e gr ateful for the invaluable assistance of the late
M r s. Reba Goldman in the cour se of this study.
T he Collabor ative Study of Cer ebr al Palsy, M ental Retar -
dation and Other Neurological and Sensor y Disor der s of
Infancy and Childhood is supported by the National Institute
of Neurological and Communicative Disor der s and Str oke.
T he following institutions participate: Boston L ying-I n
Hospital; Br own Univer sity; Charity Hospital, New Orleans;
Childrens Hospital of Buffalo; Childrens H ospital of Phil-
adelphia; Childrens M edical Center, Boston; Columbia
University; Johns Hopkins University; M edical College of
Virginia; New York M edical College; Pennsylvania Hospital;
University of M innesota; University of Oregon; University of
Tennessee; Office of Biometry and Epidemiology, and the
Developmental Neurology Branch, NINCDS.
C O R R EC TIO N
The article Growth of Children W ith Downs Syndrome: Birth to Age 3
Years, by Cronk (Pedi atr i cs 61:564, April 1978), was supported in part by
M aternal and Child Health Study Project 928 and bygrant H D 5341-03 from
the National Institute of Child Health and Human Development.
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1978;61;720 Pediatrics
Karin B. Nelson and Jonas H. Ellenberg
Prognosis in Children With Febrile Seizures

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