Nelson, 1978

1978;61;720PediatricsKarin B. Nelson and Jonas H. Ellenberg

Prognosis in Children With Febrile Seizures

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720 PEDIATRICS Vol. 61 No. 5 May 1978


Karin B. Nelson, M.D., and Jonas H. Ellenberg, Ph.D.

From the Developmental Neurology Branch and Office ofBiometry and Epidemiology. National Instituts ofNeumlogical and Communicative Disorders and Stroke, National Institutes of Health, Bethesda, Maryland

ABSTRACT. Febrile seizures occurred in 3.5% of white and4.2% of black children who were followed up in a largeprospectively defined cohort. The frequency of adverseoutcomes was examined in this population and risk factorswere identified. Among 1,706 children with febrile seizures,no deaths or persistent motor deficits occurred as sequelae ofseizures. Todds paresis occurred in 0.4%. Risk factorsidentified for epilepsy after. febrile seizures were familyhistory of afebrile seizures, preexisting neurological abnor-mality, and complicated initial seizure. Of the 60% ofchildren with febrile seizures who had none of these factors,1% developed epilepsy by age 7 years. A single risk factorwas present in 34%, of whom 2% developed epilepsy. Of the6% with two or more of these factors, 10% developedepilepsy.

After an initial brief febrile seizure, 1.4% experienced asubsequent attack which lasted 30 minutes or longer; none ofthese children had an afebrile seizure by the age of 7years.

Febnle seizures were associated with an increased risk ofintellectual deficit only among children with preexistingneurological or developmental abnormality, and in thosewho developed subsequent afebrile seizures. A third of thechildren with febrile seizures had a recurrence, and 9% hadthree 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 inwhat circumstances, vigorous efforts to treatfebrile seizures are justifiable.5 One factorunderlying the diversity of opinion on optimaltherapy is uncertainty concerning the magnitudeof risks facing children with febrile seizures.Available studies provide no quantitative esti-mates of the risks for some outcomes, and widelydivergent estimates for others. Previous reportshave often concerned hospitalized children orthose referred to specialty clinics, or haveinvolved retrospective ascertainment of febrile

seizures in patients who have sought medicalattention for other serious problems; none ofthese provides a satisfactory basis for the estima-tion of risk in the general population of childrenwith febrile seizures. Some studies have includedchildren with intrinsically brain-damaging ill-nesses such as meningitis, and others haveincluded children who had afebrile seizuresbefore ever having a seizure with fever. Fewinvestigations have had a defined base populationwhich could provide the denominator datarequired for estimations of risk.

The study reported here examined the frequen-cy of unfavorable sequelae of febrile seizures in alarge prospectively established population whichwas not selected for medical care sought forseizures or their complications. Earlier reportsfrom this population have examined the frequen-cy of epilepsy6 and of deficits in intelligence andearly academic performance7 in children whohave experienced febrile seizures. The presentstudy concerns the risk of death, persisting motordisability, Todds paresis, and recurrences offebrile seizures, including the frequency ofcomplicated febnle seizures following an initialuncomplicated attack. Additional data on riskfactors for epilepsy and for mental retardationafter febrile seizures are also presented.

METHODS

Approximately 54,000 pregnant women partic-ipating in the National Institute of Neurologicaland 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 WisconsinAvenue, Room 8C04, Bethesda, MD 20014.

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ARTICLES 721

and 1966 received prenatal care and were deliv-ered of their babies at one of 12 cooperatingurban teaching hospitals. The sampling frame andgeneral methodology for this study have beendescribed elsewhere.8

Medical histories which included questionsabout the occurrence of seizures were recordedwhen study children were aged 4, 8, 12, 18, and24 months, and annually thereafter to the age of 7years. Records from the physician or medicalfacility were reviewed for each medicallyattended seizure reported.

The protocol of the NCPP also specified aregular schedule of standardized examinations forall participating children. Neurological anddevelopmental status prior to any seizure wasevaluated using a pediatric examination at 4months of age, an overall impression followingthe administration of the Bayley Scales of Mentaland Motor Development at 8 months, and apediatric and neurological examination per-formed at 1 year of age. A global rating ofneurologically or developmentally suspect orabnormal on any of these tests performed beforethe first seizure led to the classification of thatchild as other than normal.

At the time of her registration into the NCPP,each pregnant woman was asked whether she, thefather of the baby, or any prior livebom child hadever experienced seizures, convulsions, or epilep-sy. A detailed description, including presence offever, seizure number, and age at onset, wassolicited in the event of a positive reply.

The measure of intelligence was the full-scaleIQ, Wechsler Intelligence Scales for Children, at7 years of age.

The NCPP protocol did not require reportingof treatment. Only 13% of children in this seriesare known to have received continuous anticon-vulsant therapy for one month or more. No blooddrug level determinations were performed in thisstudy, and prophylactic therapy undertakenwithout such monitoring of compliance is appar-ently ineffective.9 For these reasons, treatmentwas not considered as a factor in these analyses.

The importance of factors potentially predic-tive of morbidity was examined for each factorseparately and in addition in a multivariateformat using forward stepwise regression. Sincemost predictor and outcome variables weredichotomous (either present or absent), theassumption of normalcy necessary for the applica-tion of standard distribution theory results wasnot tenable. Therefore, t values were consideredas only rough guides to significance.1#{176} After selec-tion of the important predictors by means of the

linear regression model, estimation of morbiditywas accomplished using a multiple logisticmodel. The Walker-Duncan method of iterativemaximum likeithood was used to estimate theparameters of the multiple logistic model.12

Definitions

A child was considered to have had a febrileseizure if the first seizure he ever experienced wasaccompanied by fever, occurred between the agesof 1 month and 7 years, and was not symptomaticof recognized acute neurological illness. Childrenwith illnesses such as meningitis, lead encepha-lopathy, marked systemic dehydration, andseizures after immunization procedures wereexcluded; approximately 11% of children withseizures and fever were excluded on the basis ofthis criterion.

Complex febrile seizures were those withone or more of the following characteristics: morethan 15 minutes duration, more than one seizurein 24 hours, or focal features.

A child with recurrent afebnle seizures before48 months but none after 48 months of age, orsingle (including clustered within a six-weekperiod) asymptomatic afebrile seizures, whetherrecent or remote, was classified as having afeb-rile seizures. The term epilepsy was reservedfor children who had recurrent asymptomaticafebrile seizures of which at least one occurredafter the age of 48 months.

Minor motor seizures was a clinical classifi-cation indicating tonic, hemitonic, myoclonic, orakinetic seizures. The term atypical absenceindicated attacks of interruption or alteration ofconsciousness, accompanied by autonomic distur-bances or prominent automatisms or changes ofaffect, in children who did not have minor motorseizures. EEC criteria were not employedbecause EEGs were not routinely available, butno child in this group who had an EEC demon-strated a 3/sec spike-wave tracing.

RESULTS

There were 1,821 children who met the statedcriteria for febrile seizures. Of these, 1,706 or 94%were followed up to the age of 7 years and formthe sample for this study. There were 732 whitechildren, 883 black children, and 91 children ofother ethnic backgrounds, mainly Puerto Rican.The prevalence of febrile convulsions at 7 years inthe NCPP was 34.8/1,000 for white children and42.4/1,000 for black children (X2i = 13.7,P < .001). More boys had febrile seizures thangirls (36.6 vs. 32.8/1,000 for whites and 46.4 vs.38.5/1,000 for blacks), but the difference between


70

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50

40

30

H

20-

10

N-1263 N125

722 PROGNOSIS OF FEBRILE SEIZURES

I 1AFEBRLE EPilEPSY

N- 39179

FAMILY HISTORYNIPP CHU.DRENWffH FEBRILESEIZURES

FIG. 1. Frequency of epilepsy and afebrile seizures accordingto family seizure history. Far-left column indicates frequencyof these outcomes among children of NCPP who had no

antecedent febrile seizures.

sexes within race was significant only amongblack children (X2i 7.0, P < .009).

The average age at onset of febrile seizures was23.3 months for 760 girls and 23.2 months for 933boys (age at onset was unknown for 13 children).Of the 77% of children for whom the illnessaccompanying the first febnle seizure was docu-mented, 38% had upper respiratory tract infec-lions or pharyngitis, 23% had otitis media, 15%had pneumonia, 7% had acute gastroenteritis, 5%had roseola infantum, 1.4% had the flu, and12% had other ailments.

Death

No deaths occurred in temporal relationshipwith asymptomatic febrile seizures. There weretwo deaths in children who had had febrileseizures earlier. Both of these children werequadriplegic and severely retarded before anyseizure, and both died of pneumonia, 4 and 30months, respectively, after their last febrileseizures.

Motor Deficits

In no instance did persisting hemiplegia oranother motor deficit develop during or immedi-ately after an asymptomatic febrile seizure. Acuteinfantile hemiplegia presenting with fever andseizure was found only among children withseizures symptomatic of recognizable specific

illness (usually infectious) of the CNS; childrenwith such symptomatic seizures were excluded bydefinition from this cohort. In only one case ofacute infantile hemiplegia was the classificationsymptomatic considered equivocal. This was achild in whom pneumococcal bacteremia wasdocumented during the acute illness associatedwith the fever and seizure, followed by hemipar-esis. Because of the possibility of metastaticinfectious foci in the CNS, this child was classifiedas having a symptomatic seizure with fever. If thischild were included, the frequency of hemiparesisafter febrile seizures would be 1/1,707, or0.06%.

Todds paresis, defined as postictal weaknesslasting a week or less, was observed in seven cases,or 0.4% of children with febrile seizures. Toddsparesis was associated with the first seizure of thechilds life in four cases and with the secondseizure in three cases. Four children with Toddsparesis were considered neurologically normal onexamination before the first febrile seizure, andthree were suspect. One child subsequently devel-o_ an afebrile focal seizure disorder affectingthe side which had been weak postictally.

Epilepsy and Afebrile SeizuresSuspect or abnormal neurological and develop-

mental status of the child before any seizure andcomplex features of the first febrile seizure werefound in a previous study from the NCPP to beimportant predictors of subsequent epilepsy.6 Inthe present investigation, a history of seizureswithout fever in a parent or prior-born sibling,ascertained prenatally, was also found to be asignificant predictor. Such a history was presentin 5.6% of children with febrile seizures, and wasassociated with a threefold increase in the rate oflater epilepsy, as compared with those with nofamily history of seizures (52 vs. 16/1,000;X2i = 4.6, P :L .032, Fig. 1). There was a similarincrease of risk for any afebrile seizure (25 to 73/1,000, X2i 6.0, P : .014).

A family history of febrile seizures only wasidentified in 7.3%. There was no increase in thefrequency of subsequent epilepsy in the presenceof a family history of febrile seizures only whencompared with a negative family seizure history(16 vs. 16/1,000), and a moderate but not statisti-cally significant increase for subsequent afebrileseizures (25 vs. 40/ 1,000). The comparison ofchildren with a family history of febrile convul-sions only with those with a family history ofafebrile seizures also did not produce a statisti-cally significant difference in risk, although theobserved increases were large for both the


ARTICLES 723

TABLE I

ESTIMATES OF RISK OF Epi.spsy

RiskGroup

% ofFebrileCohort

FamilyHLStOry#{176}

PriorStatust

FirstSeizureTyp4

No. Risk (%)

Epilepsy Afebrile Seizures

Obsewed Estimated Obsewed Estimated

No febrileseizures

, 39,179 0.5 0.9

1 60 - - - 971 0.9 0.8 1.9 1.62 34 -

-

+

+

-

-

-

+

-

264 222 542

56 J

2.3 2.7 1.4 2.0 2.1 2.53.6 J 3.0 J

2.3 3.3 3.2 . 3.0 4.1 3.85.4 J 5.3 J

3 6 -+

+

+

+

+

-

+

+

-

+

+

6122

947

4

9.8 6.69.1 9.2

? 9.6 7.814.3 7.2

0.0 J 20.3

13.1 8.213.6 10.3

12.8 9.614.3 12.6

0.0 23.0

0_ indicates absence of history of afebrile seizures in parent or sibling; + indicates presence.

t- indicates normal neurological status before any seizure; + indicates abnormal or suspect.:1:- indicates first seizure type pure; + indicates first seizure type complex.Not included are 99 children of unknown family history, unknown prior status, or unknown first seizure type.

outcomes of afebrile seizures (40 vs. 73/1,000) andepilepsy (16 vs. 52/1,000).

The combined predictive ability of these andother factors was assessed, using multivariateforward stepwise regression. Age at onset, race,sex, family history of febrile seizures, and numberof febrile seizures did not contribute significantadditional predictive power to the factors offamily history of afebrile seizures, prior neurolog-ical status, and first seizure type.

Once risk factors were identified by means ofmultivariate regression, the multiple logisticmodel was used to predict the risk of epilepsy andafebrile seizures. The estimates of risk for eachconfiguration of the risk factors are given in TableI. A low-risk group (risk group 1) was defined toinclude children who were normal before anyseizure, who had an uncomplicated initial febrileseizure, and who had no family history of afebrileseizures. This low-risk group constituted 60% ofchildren with febnle seizures, and of them, 9.3/1,000 or 0.9% developed epilepsy, a rate notstatistically signfficantly higher than that of chil-dren who had no febrile seizures (9.3 vs. 5.1/1,000). Nineteen per thousand of this low-riskgroup, or 1.9%, had any afebrile seizure, whichdoes differ significantly from the rate in childrenwith no febrile seizures (18.5 vs. 9.1/1,000;X2i = 8.2, P : .004).

Children in whom one risk factor was presentwere 34% of those with febrile seizures (risk group2, Table I). Of this group, 20.3/1,000 or 2.0%developed epilepsy and 29.5/1,000 or 3.0% devel-

oped afebrile seizures. For neither epilepsy norany afebrile seizures were the rates statisticallysignificantly higher than in the low-risk group,but for both these outcomes group 2 childrenwere at higher risk than children who had nofebrile seizures (P < .01). The absolute magni-hide of the risk remained small. In group 1 plusgroup 2, which included 94% of children withfebrile seizures, the risk of epilepsy was 1.3% andthe risk of afebnle seizures was 2.2%.

Children with two or more risk factors (riskgroup 3) were at a significantly increased risk ofboth epilepsy and afebrile seizures as comparedwith those in whom only a single risk factor waspresent. Risk group 3 constituted approximately6% of children with febrile seizures. Of this group,96/1,000 or 10% (vs. 20.3/1,000 in group 2;X2i = 12.6, P < .001) developed epilepsy and128/1,000 or 13% developed an afebrile seizurelater (vs. 29.5/1,000 in group 2; X2i = 16.1,P< .001).

Previous reports have suggested an importantprognostic role for lengthy initial febrileseizures.36 In this population, the 74 childrenwhose first febrile seizure lasted 30 minutes ormore constituted 4.3% of patients with febrileseizures. Of these children, three or 4.1% becameepileptic and 5.4% had an afebrile seizure by theage of 7 years. The increase in risk of subsequentepilepsy associated with first febrile seizureslasting half an hour or more did not reachstatistical significance (40.5 vs. 15.1/1,000 forchildren with uncomplicated initial seizure).


TABLE II


MENTAL RETARDATiON IN CHILDREN WITH AFEBRILE SEIZURES CLASSIFIED BY PRIORNEUROLOGICAL STATUS AND SUBSEQUENT AFEBRILE SEIZURES

Prior Total Subsequent A febrile S eizures\7eirological ,.- AStatus

No.

No

No. (Rate)With MentalRetardation

Yes

No. No. (Rate)Wit/i MentalRetardation

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 developedepilepsy following febrile seizures (31 of 34 chil-dren) had never had a febrile seizure which lasted30 minutes or more.

Children with febrile seizures developed atypi-cal absence attacks more frequently than didchildren who had no febrile seizures (5.9 vs. 1.5/1,000; X2i 15.9, P < .001), but this increase wasnot greater than the increase in risk of epilepsy ofall types after febrile seizures.

Mental Retardation and Learning Disorder

The effect of febrile seizures on the wholerange of tested intelligence was examined in aprevious study of this population. In 431 siblingpairs, there was no deficit in IQ at 7 years inchildren with only febrile seizures, as comparedwith their siblings who were seizure-free.7 Thesubgroup of children who were not neurologicallyor developmentally normal before any seizuredid, however, score below their normal siblings.In this study, early learning disorder occurredwith the same frequency in children who hadexperienced febrile seizure as in controlsiblings.

The development of afebnle seizures afterfebrile seizures was associated with a fivefoldincrease in frequency of mental retardation (IQless than 70) at 7 years (269 vs. 49.0/1,000;x2 42.4, P < .001, Table II). The same rela-tionship was observed both among childrenconsidered normal before any seizure (P < .01)and in those thought to be previously suspect orabnormal (P < .001). There were 14 children inwhom mental impairment coexisted with afebrileseizures. Intellectual impairment was particularlyfrequent in children who developed minor motorepilepsy following febrile seizures; seven of theeight children with minor motor seizures were

mentally retarded at 7 years. (Mental retardationwas also very common in children with minormotor seizures who had never had a febrileseizure.) Five of the six of these children withmental retardation whose prior status was knownwere abnormal before any seizure.

Except where neurological or developmentalabnormality predated any seizure, or there weresubsequent afebnle seizures, febrile seizures werenot associated with an increase in risk of intellec-tual impairment.

Complex Febrile Seizures After theInitial Attack

Three quarters of complex seizures occurred asthe first seizure of the childs life. After an initialuncomplicated febrile seizure, a subsequentcomplex attack occurred in 8.0%. Among childrenwhose first seizure lasted 15 minutes or less, asubsequent seizure of 30 minutes or longeroccurred in 1.4% and a subsequent seizure of anhour or longer occurred in 0.7%; none of thesechildren experienced an afebrile seizure by age 7years.

Twelve children experienced a febrile seizurewhich lasted an hour or more and was focal. In 11of the 12, such an attack was the first seizure ofthe childs 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 ofa complex seizure by the age of 7 years wasincreased in children who experienced multipleseizures.

Recurrences of Febrile Seizures

The most frequent sequela of an initial febrileseizure was the recurrence of febrile seizures. Athird of children who experienced a febrile


70

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43

32

-

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391-. \15 14 13

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I I , I I , I I .10 12 1* 24 39 39 42 40

N 1IS 340 391 100 140 74

TABLE III

ARTICLES 725

39

1WOIISfl

FIG. 2. Frequency of recurrence (solid curve) and multiplerecurrences (broken curve) of febnle seizures according toage at onset. Points plotted at midpoints of age groupings 2

to 6 months, 7 to 12 months, 13 to 18 months, etc.

seizure had at least one recurrence, and half ofthose who had one recurrence had a furtherattack. Nine percent of the 1,706 chIldren of thisstudy had three or more recurrences. Males andfemales and whites and blacks did not differsignificantly in their vulnerability to recur-rences.

The likelihood of recurrence was related to ageat onset of febrile seizures (Fig. 2). Half of thechildren with onset in the first year and 28% withonset after the first year had at least one recur-rence (x2 = 73.3, P < .001). Multiple recur-rences were also related to early onset: of childrenwhose febrile seizures began before the firstbirthday, 30% later experienced more than onerecurrence, while of those whose onset was afterthe first birthday, 11% had more than a singlerecurrence (x2 82.3, P < .001). The effect ofage at onset on risk of recurrence was notappreciably different in boys and girls during thefirst 48 months of life, the period for whichsufficient data were available for comparison.

The interval between first and second seizurevaried little with the age at which the initialseizure took place. Of known recurrences, almosthalf of second attacks took place within sixmonths of the first and 73% in the year followingthe initial seizure (Table III).

Children whose first febrile seizure accompa-nied roseola infantum had recurrences with thesame frequency as those whose first seizureoccurred with other illnesses.

Characteristics of the first febnle seizure werenot useful in the prediction of recurrence; uncom-plicated initial febrile seizures were as oftenfollowed by recurrence as were first febrile

INTERvAL TO RECURRENCE OF FEBRILE SEIZURES

Time (ma)Fromlstto2nd Seizure

No. Cumulative%

0-2 114 223-6 136 477-12 135 73

13-24 79 8825-48 54 9849-84 10 100Total 528

seizures which had complex features. Childrenwho were not normal before the first febrileseizure more often had one recurrence (x2 = 4.4,P : .036), but not multiple recurrences.

Multivariate regression analysis demonstratedthat the two factors most related to increased riskof recurrence were early age at onset and historyof afebrile seizures in the immediate family, andof these two, age at onset was much more potentas a predictor.

DISCUSSION

This study has examined a spectrum of adverseoutcomes following febrile seizures, and hasfound those other than recurrences to be infre-quent. Neither death nor persisting hemiplegiaoccurred as sequelae of febnle seizures in the1,706 children of this sample. Death has beeninfrequent in other recent studies, except wherepreexisting abnormalities of the child, or thenature of the provoking illness, were related.718

With regard to subsequent epilepsy, familyhistory of afebnle seizures was found to addindependent information as a predictor to the riskfactors previously identified.6 In 60% of childrenwith febrile seizures, none of these risk factors(p nor abnormality, complex first seizure type,and family seizure history) was present, and therisk of epilepsy and afebrile seizures by 7 years inthis group was little greater than among childrenwho had never had a febrile seizure. In the smallsubgroup of children with febrile seizures whohad two or more of the chief risk factors, therewas a sharp increase in risk of epilepsy and ofafebrile seizures.

Several workers have stressed the relationshipof prolonged febrile seizures to the developmentof subsequent epilepsy.36 In the series reportedhere, prolonged duration of febrile seizures wasnot a major determinant of subsequent epilepsy.More than 90% of children who developed



epilepsy after febrile seizures had never had afebrile seizure which lasted as long as 30 minutes.Those children who did have a prolonged febrileseizure most often experienced it as the firstseizure of their lives,6 before there was an oppor-tunity to consider them as potential candidatesfor treatment. In no case in this series did a childwho had an initial brief febrile seizure and a laterprolonged febrile seizure become epileptic.

Experience in the NCPP, as elsewhere,141921fails to confirm Livingstons report that childrenwhose first febnle seizure was prolonged or focal,or who had a family history of afebrile seizures(his epilepsy triggered by fever), almost alwaysbecome epileptic and almost always by the age of5 years.3 Similar risk factors have been found byother investigators to be relevant, but thefrequency and the predictive potency of thesefactors have been far less than reported byLivingston.

Children with febrile seizures did not developatypical absence attacks (a seizure type that wethink approximates temporal lobe epilepsy)proportionately more often than other forms ofepilepsy.

Febnle seizures were associated with anincreased risk of intellectual deficit only amongchildren with a preexisting neurological or devel-opment abnormality and in those who developedsubsequent afebrile seizures. Early academicperformance was not affected by febrile

7

A third of children with febrile seizures had arecurrence, and 9% had three or more suchepisodes. As in previous studies, age at onset wasthe chief predictor recognized,42223 with onset inthe first year followed by recurrence in half of thecases. Number of seizures experienced did notinfluence later intelligence.7 Once the majorpredictors of epilepsy after febrile seizures wereconsidered, recurrences of febrile seizures werenot found to add significantly to the risk of eitherepilepsy or any afebrile seizure.

IMPLICATIONS

In our opinion, death and hemiparesis are tooinfrequent following febrile seizures to provide ajustification for chronic prophylaxis; the harmresulting from occasional accidental overdosage,as occurred in two of the 27 effectively treatedchildren in the Danish series,24 would probablyoutweigh the (unproven) benefit of treatment,with such very uncommon outcomes as target.

Reduction of recurrences and prevention ofafebrile seizures are the major plausible goals forchronic treatment of febrile seizures. Regular

administration of phenobarbital can decrease thefrequency of recurrence of febrile seizures, andmay decrease the chance that a subsequent febrileseizure, if it occurs, will be prolonged or focal.2425Prescribed as prophylaxis for recurrences, treat-ment might reasonably be given to childrenwhose first seizure occurred before 1 year of age,because such children are at relatively high risk ofrecurrence, and especially of multiple recur-rences. However, regular administration of anti-convulsant medication is difficult to maintain,2526and treatment with phenobarbital is oftenaccompanied by behavior disorders.27 Further-more, no empiric evidence known to us estab-lishes that the reduction of recurrences of febrileseizures prevents long-term sequelae.

Sixty percent of children with febrile seizuresdid not have the risk factors associated withsubsequent epilepsy. This low-risk group wouldnot seem an appropriate target population forchronic treatment aimed at the prevention ofafebrile seizures. The 34% of children with febrileseizures in whom a single risk factor was presentwere at increased, but not at high, risk.

The small, relatively high-risk group defined bypossession of two or more risk factors showed a20-fold increase in the risk of epilepsy, anddeserves consideration for chronic treatment.However, it is not known whether treatment afterthe onset of febrile seizures can prevent theeventual development of afebrile seizures. Chin-ical trials may be warranted to investigatewhether medical intervention, especially if aimedat the high-risk group, is efficacious in the preven-lion of subsequent epilepsy, and safe enough to bejustifiable for use in children of whom asubstantial majority would not become epilepticeven if untreated.

At present, there is no empiric evidence thatchronic treatment with anticonvulsant medica-lion influences, positively or negatively, the long-term prognosis of children with febrile seizures.

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febrile seizure: A study of current pediatric prac-lice. I Pedkztr 87:485, 1975.

2. Bray PF: Neurology in Pediatrics. Chicago, Year BookMedical Publishers, 1969, p 36.

3. Hammill JF, Carter 5: Febrile convulsions. N Engll Med274:563, 1966.

4. More about febrile convulsions, editorial. Br Med I1:591, 1975.

5. Prichard JS: Convulsive disorders in children, somenotes on the diagnosis and treatment. Pediatr ClinNorth Am 21:981, 1974.

6. Nelson KB, Ellenberg JH: Predictors of epilepsy inchildren who have experienced febrile seizures. N


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Engi I Med 295: 1029, 1976.7. Ellenberg JH, Nelson KB: Febrile seizures and later

intellectual performance. Arch Neurol 35:17,1978.

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12. Halperin M, Blackwelder WC, Verter JI: Estimation ofthe multivariate logistic risk function: A compar-ison of the discnminant function and maximumlikelihood approaches. I Chronic Dis 24:125, 1971.

13. Livingston S: comprehensive Management of Epilepsyin infancy, Childhood and Adolescence. Spring-field, Ill, Charles C Thomas Publisher, 1972, p 26.

14. Lennox-Buchthal M: Febrile convulsions, a reappraisal.Electroencephalogr Clin Neuraphysiol 32(suppl):1973.

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16. Aicardi J, Chevrie J-J: Febrile convulsions: Neurologicalsequelae and mental retardation, in Brazier MAB,Coceani F (eds): Brain Dysfunction in InfantileFebrile Convulsions. New York, Raven Press, 1976,pp 247-257.

17. Frantzen E, Lennox-Buchthal M, Nygaard A: Longitu-dinal EEG and clinical study of children withfebrile convulsions. Electroencephalogr Clin Neuro-physiol 24:197, 1968.

18. Tibbles JAR, Brown BStJ: Acute hemiplegia of child-hood. Can Med Assoc I 113:309, 1975.

19. van den Berg BJ, Yerushalmy J: Studies on convulsivedisorders in young children: I. Incidence of febrileand nonfebrile convulsions by age and other factors.

Pediatr Res 3:298, 1969.20. Hauser WA, Kurland LT: The epidemiology of epilepsy

in Rochester, Minnesota, 1935 through 1967.EpilepSia 16:1, 1975.

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22. Wallace SJ: Recurrence of febrile convulsions. Arch DisChild 49:763, 1974.

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ACKNOWLEDGMENTWe are grateful for the invaluable assistance of the late

Mrs. Reba Goldman in the course of this study.The Collaborative Study of Cerebral Palsy, Mental Retar-

dation and Other Neurological and Sensory Disorders ofInfancy and Childhood is supported by the National Instituteof Neurological and Communicative Disorders and Stroke.The following institutions participate: Boston Lying-InHospital; Brown University; Charity Hospital, New Orleans;Childrens Hospital of Buffalo; Childrens Hospital of Phil-adelphia; Childrens Medical Center, Boston; ColumbiaUniversity; Johns Hopkins University; Medical College ofVirginia; New York Medical College; Pennsylvania Hospital;University of Minnesota; University of Oregon; University ofTennessee; Office of Biometry and Epidemiology, and theDevelopmental Neurology Branch, NINCDS.

CORRECTION

The article Growth of Children With Downs Syndrome: Birth to Age 3Years, by Cronk (Pediatrics 61:564, April 1978), was supported in part byMaternal and Child Health Study Project 928 and bygrant HD 5341-03 fromthe National Institute of Child Health and Human Development.


1978;61;720PediatricsKarin B. Nelson and Jonas H. Ellenberg


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