Journal of Pediatric Neurology 6 (2008) 129–132 129

IOS Press

Original Article

Role of laboratory diagnostic tests in first

febrile seizure

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Razieh Fallah∗ and Motahhareh Golestan
Department of Pediatrics, Shaheed Sadoughi University of Medical Sciences, Shaheed Sadoughi Hospital, Yazd,
Iran

Received 17 September 2007

Revised 21 December 2007
Accepted 9 January 2008

Abstract. Febrile seizures are the most common form of convulsions, occurring in 2–5% of children. In the approach to a
convulsing febrile patient, discovering the cause of fever and excluding central nervous system infection, serious electrolyte
imbalances and other acute neurologic illnesses are essential. History and physical examination may be helpful. The purpose
of this study was to evaluate significance of laboratory diagnostic tests other than cerebrospinal fluid examination in first febrile
seizures of children. In a descriptive study, medical records of 139 children with first febrile seizure, admitted between March
2004 and August 2005 to Yazd Shaheed Sadoughi Hospital, were evaluated on all laboratory diagnostic done tests (other than
cerebrospinal fluid examination), classification of laboratory tests results (normal, outside of normal range, or significantly
abnormal), number of significant abnormal tests not predicted by history and physical examination, change in management plan
based on biochemical abnormalities and type of febrile seizure. Febrile seizure type was complex in one-third of patients. The
number of laboratory tests performed was 9.24 ± 2.4 (range one to 16). Significantly abnormal test results were seen in 12% of
patients. Patients less than one year old and those with complex febrile seizures had the greatest number of significantly abnormal
test results. Significantly abnormal tests results not predicted by history and physical examination were seen in three cases (one
with asymptomatic hypocalcemia and two with urinary tract infection), all of whom were less than 1 year old. Routine blood
chemistry analysis is not necessary in children with febrile seizures and only should be ordered based on the patient’s condition
or medical history.

Keywords: Seizure, febrile seizure, laboratory evaluation

1. Introduction such as meningitis or encephalitis is essential in febrile

Seizures are the most common problem in pediatric
neurology, occurring in 10% of children [1]. The initial
steps in the evaluation of a convulsing child depend on
the patient’s clinical status on first presentation to the
physician. Urgent evaluation of infectious etiologies
∗ Correspondence: Razieh Fallah, MD, Shaheed Sadoughi Hos-
pital, Ave sina St, Shahid Ghandi Blvd, Yazd, Iran. Tel.: +98
351 7258188; Fax: +98 351 8224100; E-mail: kavosh252006@
yahoo.com.
convulsions. The role of laboratory diagnostic tests
is controversial in evaluating the etiology of seizures
and some texts recommend routine evaluation of blood
levels for calcium, glucose, sodium, magnesium and
urea in all convulsing patients [2].
Febrile seizures (FS) are the most common form of
childhood seizures [3]. Population studies in Western
Europe and the USA report a cumulative incidence of
two to 5%. This varies elsewhere in the world between
five to 10% (India), 9% (Japan), and 14% (Guam) [3,
4]. A FS is defined by the International League Against

1304-2580/08/$17.00  2008 – IOS Press and the authors. All rights reserved
130 R. Fallah and M. Golestan / Laboratory tests in febrile seizures
Epilepsy as a seizure occurring in association with a
febrile illness in the absence of a central nervous sys-
tem (CNS) infection or acute electrolyte imbalance
in children older than 1 month without prior afebrile
seizures [5]. According to Berg, FS are defined as oc-
curring between 6 months and 6 years of age [6]. They
are further classified as simple and complex. A FS
is complex if it is focal or focal findings are present
during the postictal period, prolonged (lasting more
than 10–15 minutes) or occurrence of more than one
seizure during the febrile illness [1,7]. In approaching
a convulsing febrile patient, discovering the cause of
fever and excluding CNS infection, serious electrolyte
imbalance and other acute neurological illnesses are
essential. A detailed history, physical and neurologi-
cal examinations are also helpful in this regard. The
purpose of this study was to evaluate the significance
of laboratory diagnostic tests other than cerebrospinal
fluid (CSF) examination in the first FS.
2. Materials and methods
In a descriptive study, medical records of all chil-
dren with the final diagnosis of first FS, admitted be-
tween March 2004 and August 2005 to Yazd Shaheed
Sadoughi Hospital, were reviewed. Variables such as
age, sex, number of all laboratory diagnostic tests (oth-
er than CSF examination) including sodium, potassi-
um, glucose, calcium, urea, magnesium, creatinine,
alanine aminotransferase, aspartate aminotransferase,
complete blood count, C-reactive protein (CRP), ery-
throcyte sedimentation rate, blood culture, urine anal-
ysis, urine culture, stool examination and stool culture,
class of laboratory test results (normal, outside of nor-
mal range, significantly abnormal), number of patients
in whom significantly abnormal tests not determined
by history and physical examination, change in man-
agement plan based on biochemical abnormalities and
type of FS, were carefully recorded. Each of following
findings was considered significantly abnormal: blood
glucose <50 mg/dL, serum calcium <7 mg/dL, serum
sodium <120 and > 160 mmol/L, blood potassium lev-
els <3.5 and >5.5 mmol/L, hemoglobin level <9 g/dL,
total leukocyte count > 20,000, CRP = +3 to +4, pos-
itive cultures, elevated liver enzymes > 2 times of nor-
mal limit and abnormal renal function (serum creati-
nine > 1.5 mg/dL or blood urea nitrogen >18 mg/dL).
If, based on history and physical examination, a sig-
nificant laboratory abnormality was not expected, yet a
significantly abnormal laboratory test result was found,
it was considered to be a significantly abnormal test not
predicted by history and physical examination.
Children with a history of afebrile seizures, evidence
of central nervous infection and underlying neurolog-
ical disorders were excluded. The data were analyzed
using SPSS 13 statistical software. Chi-square analy-
sis was used for data analysis of qualitative variables.
Differences were considered significant at P values <
0.05.
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3. Results
One hundred and thirty nine patients with the final
diagnosis of first FS were selected in this study. Medi-
cal records of 63 girls (45%) and 76 boys (55%) within
the age range of 6 months – 6 years (mean 2.03 ± 1.21
years) were reviewed. Type of FS was simple in 93
(67%) and complex in 46 cases (33%). The mean num-
ber of laboratory diagnostic tests performed was 9.24
(± 2.4) (range one to 16). Results of laboratory tests
were normal in 91 (66%), out of normal range in 31
(22%) and significantly abnormal in 17 (12%) cases.
As shown in Table 1, patients aged less than 1 year
(P = 0.001) and complex FS cases (P = 0.0001) had
a greater number of abnormal test results. Nearly 13%
of girls and 12% of boys had significantly abnormal
laboratory test results which meant that sex had no ef-
fects on frequency of abnormality (P = 0.05). Hypo-
glycemia (blood glucose level < 50 mg/dL), seizure-
induced hypocalcemia (calcium < 7 mg/dL), signifi-
cant hypo- or hypernatremia, hypo- or hyperkalemia,
abnormal liver function tests, kidney dysfunction and
positive blood and abnormal stool cultures were not
seen. Urinary tract infection (UTI) was detected in
four patients and sodium <130 mmol/L was seen in six
cases. Significantly, abnormal tests were not predict-
ed by history and physical examination in three cas-
es: one had asymptomatic hypocalcemia (calcium =
7.5 mg/dL) and two had UTI. All were aged less than 1
year. CRP was negative in 57%, +1 in 18%, +2 in 16%,
+3 in 8% and not done in 1%. Leukopenia (leukocyte
count < 5000/mm 3) and leukocytosis (leukocyte count
>15,000 mm 3 ) were seen in nearly 7% and 28% of
the patients, respectively. Leukopenia was mild and
transient, in the range of total leukocyte count of 4400–
4800/mm 3 and due to viral infection. Definite leukope-
nia (leukocyte count < 4000/mm 3) was not seen in any
patients. Anemia (hemoglobin level < 10.5 g/dL) and
microcytic red blood cells (mean corpuscular volume
< 70 fL) were found in 15.8% and 15% of patients,
 R. Fallah and M. Golestan / Laboratory tests in febrile seizures 131

Table 1
Results of laboratory tests in two age groups and types of febrile seizure
Parameters Normal Outside normal Significantly Total P
range abnormal
<1 year 14 10 5 29 0.001
>1 year 77 21 12 110
Simple febrile seizure 61 23 9 93 0.0001
Complex febrile seizure 30 8 8 46

Table 2
Comparison of laboratory data results in both types of febrile seizure

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Parameters Range Normal Simple febrile Complex P
range seizure febrile seizure
(mean ± SD) (mean ± SD)
Age of patients (years) 0.5–6 − 2.1 ± 1.2 1.8 ± 1.1 0.291
Blood glucose (mg/dL) 54–190 60–100 107.01 ± 27.8 115.46 ± 27.6 0.09
Blood calcium (mg/dL) 7.5–11 8.8–10.8 9 ± 0.7 9.191 ± 0.6 0.25
Leukocyte count (/mm3 ) 3,400–31,500 6,000–15,000 12,380 ± 6,000 12,440 ± 5,900 0.95
Hemoglobin level (g/dL) 3.9–15.3 10.5–14 11.8 ± 1 11.3 ± 1.7 0.01
Mean corpuscular volume (fL) 54.7–90 70–86 75.4 ± 5 75 ± 7.8 0.74
Serum sodium level (mmol/L) 124–147 138–145 137.3 ± 4 136.9 ± 4.2 0.57
Number of laboratory examination 1–16 − 9 ± 2.4 9.7 ± 2.3 0.08

respectively. Nearly 10% of patients had a change in
management plan based on biochemical abnormalities.
Specifically, UTI was treated based on positive urine
culture, microcytic anemia evaluated and treated for
iron deficiency, asymptomatic hypocalcemia was cor-
rected, fluid therapy was changed based on serum sodi-
um level, and antibiotic therapy was given based on
CRP = +3 to +4.
When comparing mean age, hemoglobin, sodium,
glucose and calcium blood level, mean corpuscular vol-
ume, total leukocyte count and number of laboratory
tests in both types of FS, statistically significant differ-
ences were seen only in hemoglobin, where the level
was lower in complex FS (P = 0.019), as in Table 2.
Mean serum sodium in children with more than one
FS in 24 hours (136.55 ± 4.01 mmol/L) did not differ
from those febrile children whose seizures did not recur
within that period (137.34 ± 4.17 mmol/L) (P = 0.44).
4. Discussion
Seizures are common in children and 5% of all med-
ical attendances to the accident and emergency depart-
ment are attributable to seizures [8]. Depending on the
hospital attended and the clinician seen, about 70% of
these children are admitted and undergo varying de-
grees of investigation [9]. The aim of this study was to
assess the role of laboratory diagnostic tests other than
CSF examination in the first FS. This study showed
that FS is more frequent in boys, consistent with prior
work [10]. In this study, one-third of FS were complex,
in agreement with Berg and Simar’s results [11].
UTI was detected in 3% of our patients, but in one
retrospective study, the percentage was 1% (12) and
in another one, it was 6% [13]. Two of our UTI pa-
tients were younger than 1-year-old and asymptomat-
ic. Therefore, the recommendation from another study
stating, “a child who has had a simple FS and no source
of infection in whom has been found clinically, should
have a urine sample (clean catch, suprapubic aspira-
tion or catheter specimen) taken for microscopy and
culture” [14], must be considered.
Significantly, abnormal laboratory tests were seen in
12% of our patients. These results are similar to Dun-
lop et al. [15]. No significant abnormalities were found
in serum sodium, glucose and blood urea nitrogen, cal-
cium, and magnesium in this study, in agreement with
others that recommend routine blood cell counts and
determination of serum electrolyte, glucose, calcium,
urea and magnesium, are of limited value in the evalu-
ation of a child older than 6 months with a FS [16–25].
The mean serum sodium in children with more than one
FS in 24 hours did not differ from those whose seizures
did not recur within the period, which supports another
study [26].
Complex febrile convulsions increase the risk of fur-
ther FS, epilepsy and CNS infection. Children with
complex FS, those less than 18 months, those who had
antibiotics and in whom no focus for infection was
found should be admitted [14]. In this study, age less
than 1 year and complex FS patients showed more sig-
132 R. Fallah and M. Golestan / Laboratory tests in febrile seizures
nificantly abnormal results. Therefore, FS must be
considered more seriously in such patients. More at-
tention is needed in taking their history and physical
examination and further studies must be done in this
field.
Other studies indicated that anemia and iron deficien-
cy were more prevalent in FS patients [27,28]. In this
study, mean hemoglobin level was lower in complex
FS. Anemia decreases brain blood and oxygen supply
and fever can also intensify negative effects of anemia
on the brain and may cause seizures; as complex FS are
more complicated, the effect of the anemia might be
more notable and further studies are needed to research
this effect.
Although many children who present to the hospi-
tal with febrile convulsions are managed appropriately,
a large number are over-investigated and over-treated,
based on the clinical experience of the treating doc-
tor. Considering significantly abnormal tests not pre-
dicted by history and physical examination were seen
in just a few patients, routine blood chemistry anal-
ysis (complete blood count, serum level of glucose,
calcium, sodium, potassium, urea and magnesium) is
not necessary in children with FS and should only be
ordered based on individual clinical circumstances in-
cluding historical or clinical findings such as vomit-
ing, diarrhea, dehydration and failure to return to base-
line alertness. We conclude that diagnostic procedures
should be performed only based on patients’ condition
or medical history.
References
[1] M.V. Johnston, Seizures in childhood, in: Nelson Textbook of
Pediatrics, (17th ed.), R.E. Behrman, R.M. Kliegman and H.B.
Jenson, eds, Philadelphia: Saunders, 2004, pp. 1993–2009.
[2] S. Duman ans S.H. Ginsburg, Neurologic problems, epilepsy
(seizures), in: Problem – Oriented Medical Diagnosis, (6th
ed.), H. Friedman, ed., New York: Little, Brown & Co., 1996,
p. 409.
[3] S. Shinnar, Febrile seizures, in: Pediatric Neurology: Princi-
ples & Practice, (4th ed.), K.F. Swaiman, S. Ashwal and D.M.
Ferriero, eds, Philadelphia: Mosby, 2006, pp. 1078–1086.
[4] Guidelines for epidemiologic studies on epilepsy. Commission
on Epidemiology and Prognosis, International League Against
Epilepsy, Epilepsia 34 (1993), 592–596.
[5] C. Waruiru and R. Appleton, Febrile seizures: an update, Arch
Dis Child 89 (2004), 751–756.
[6] A.T. Berg, Are febrile seizures provoked by a rapid rise in
temperature? Am J Dis Child 147 (1993), 1101–1103.
[7] R.E. Behrman and R.M. Kliegman, Paroxysmal disorders.
Nelson Essentials of Pediatrics, (5th ed.), Philadelphia: WB
Saunders, 2006.
[8] K. Armon, T. Stephenson, V. Gabriel et al., Determining
the common medical presenting problems to an accident and
emergency department, Arch Dis Child 84 (2001), 390–392.
[9] A. Sweeney, J. Gibbs, F. Monteil, R. Appleton and I. Choonara,
The management of febrile seizures in the Mersey Region,
Dev Med Child Neurol 38 (1996), 578–584.
[10] D.K. Pal, S.L. Kugler, D.E. Mandelbaum and M. Durner,
Phenotypic features of familial febrile seizures: case-control
study, Neurology 60 (2003), 410–414.
[11] A.T. Berg and S. Shinnar, Complex febrile seizures, Epilepsia
37 (1996), 126–133.
[12] S.J. Teach and P.A. Geil, Incidence of bacteremia, urinary tract
This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited.
infections, and unsuspected bacterial meningitis in children
with febrile seizures, Pediatr Emerg Care 15 (1999), 9–12.
[13] J.L. Trainor, L.C. Hampers, S.E. Krug and R. Listernick, Chil-
dren with first-time simple febrile seizures are at low risk of
serious bacterial illness, Acad Emerg Med 8 (2001), 781–787.
[14] K. Armon, T. Stephenson, R. MacFaul, P. Hemingway, U.
Werneke and S. Smith, An evidence and consensus based
guideline for the management of a child after a seizure, Emerg
Med J 20 (2003), 13–20.
[15] S. Dunlop and J. Taitz, Retrospective review of the manage-
ment of simple febrile convulsions at a tertiary paediatric in-
stitution, J Paediatr Child Health 41 (2005), 647–651.
[16] L.G. Sadleir and I.E. Scheffer, Febrile seizures, BMJ 334
(2007), 307–311.
[17] N. Rutter and O.R. Smales, Role of routine investigations in
children presenting with their first febrile convulsion, Arch Dis
Child 52 (1977), 188–191.
[18] N.P. Rosman, Evaluation of the child who convulses with
fever, Paediatr Drugs 5 (2003), 457–461.
[19] N. Uemura, A. Okumura, T. Negoro and K. Watanabe, Clinical
features of benign convulsions with mild gastroenteritis, Brain
Dev 24 (2002), 745–749.
[20] J. Heijbel, S. Blom and P.G. Bergfors, Simple febrile con-
vulsions. A prospective incidence study and an evaluation of
investigations initially needed, Neuropadiatrie 11 (1980), 45–
56.
[21] M.A. Gerber and B.C. Berliner, The child with a ’simple’
febrile seizure. Appropriate diagnostic evaluation, Am J Dis
Child 135 (1981), 431–433.
[22] D. Teng, P. Dayan, S. Tyler et al., Risk of intracranial patho-
logic conditions requiring emergency intervention after first
complex febrile seizure episode among children, Pediatrics
117 (2006), 304–308.
[23] R.D. Kenney and J.A. Taylor, Absence of serum chemistry
abnormalities in pediatric patients presenting with seizures,
Pediatr Emerg Care 8 (1992), 65–66.
[24] M.M. Nypaver, S.L. Reynolds, R.R. Tanz and A.T. Davis,
Emergency department laboratory evaluation of children with
seizures: dogma or dilemma? Pediatr Emerg Care 8 (1992),
13–16.
[25] N. Landfish, M. Gieron-Korthals, R.E. Weibley and V. Pan-
zarino, New onset childhood seizures. Emergency department
experience, J Fla Med Assoc 79 (1992), 697–700.
[26] J.E. Thoman, P.K. Duffner and J.L. Shucard, Do serum sodi-
um levels predict febrile seizure recurrence within 24 hours?
Pediatr Neurol 31 (2004), 342–344.
[27] A.S. Daoud, A. Batieha, F. Abu-Ekteish, N. Gharaibeh, S.
Ajlouni and S. Hijazi, Iron status: a possible risk factor for
the first febrile seizure, Epilepsia 43 (2002), 740–743.
[28] Naveed-ur-Rehman and A.G. Billoo, Association between
iron deficiency anemia and febrile seizures, J Coll Physicians
Surg Pak 15 (2005), 338–340.