Paediatrica Indonesiana

VOLUME 50 NUMBER 6 November 2O1O

Original Article
326 Paediatr Indones, Vol. 50, No. 6, November 2010
Correlation between serum zinc level
and simple febrile seizure in children
Lusiana Margaretha, Nurhayati Masloman
Abstract
Background Simple febrile seizure is the most common form
of seizure which occurs durin, childhood period. zinc, one of
microelements in human bodv, has an important role in central
nervous system formation.
Objectives To find out serum zinc level in simple febrile seizure
patients and the correlation between serum zinc level and simple
febrile seizure.
Methods This cros-sectional study was conducted at R. D.
Kandou Hospital, 1in,kat lll 1elin, Hospital and Pancaran Kasih
Hospital, Manado on April 5th - June 15th, 2OO9.
Results Dia,nosis for febrile without seizure patients were 12 with
acute respiratorv tract infection (ARl), 6 den,ue hemorrha,ic
fever (DHl), 6 acute diarrhea without dehvdration and 1 ARl
with DHl, while simple febrile seizure were 19 ARl, five acute
diarrhea without dehydration and one ARI with DHF. There
were no si,nificant differences of a,e, ,ender and nutritional
status in two ,roups. lamilv historv of febrile seizure, febrile period
and body temperature in two groups were significantly different.
Mean serum zinc level in simple febrile seizure and febrile without
seizure were o.o3 umol/l and 13.72 umol/l, respectivelv. Mean
serum zinc level in simple febrile seizure children with seizure
period <5 minutes, 5-<1O minutes and 1O-15 minutes were
1O.27 ( SD O.25) umol/l, 9.O2 (SD O.o1) umol/l and 6.9O (SD)
O.9o umol/l, respectivelv.
Conclusions There is correlation between serum zinc level and
simple febrile seizure. 1he lesser serum zinc level, the lon,er
duration of seizure occurs in simple febrile seizure. [Paediatr
Indones. 2010;50:326-30].
Keywords: febrile, seizure, zinc
lrom the Department of Child Health, Medical School, Sam Ratulan,i
Universitv, Prof. dr. RD Kandou Oeneral Hospital, Manado, lndonesia.
Reprint request to: lusiana Mar,aretha, MD, Department of Child
Health, Medical School, Sam Ratulan,i Universitv, Prof. R.D. Kandou
Oeneral Hospital, Jl. Rava 1anawan,ko, Manado 95263. lndonesia. 1el.
62-131-o21652.lax. 62-131-o59O91. l-mail: lu514n4@yahoo.com
S
eizure is a paroxysmal motor activity which
last for several moments and originated from
abnormal electrical generation inside the
brain.
1
Febrile seizure is the most common
form of seizures among all childrens neurological
problems; commonly affect children under 5 years of
age.
2,3
1he incidence of febrile convulsion is 2-5' of
all children.
3
1he peak onset is a,e 1o to 22 months,
where in most case, febrile seizure most often occurs
at the a,e of 6 months to 3 vears. Bovs have a hi,her
incidence than girls.
4
Simple febrile seizure itself is a
form of seizures that often occurs during childhood.
Simple febrile seizure has a ,ood pro,nosis, but the
simple febrile seizure is a sign of an acute infection
occurs in the child's body.
1,3
zinc, which is the
largest component of metalloenzyme is an essential
micronutrient that can be found in almost every
cell.
5
Decline serum zinc level in simple febrile seizure
patients is suggested secondary due to other causes.
zinc which is one of microelements in human bodv has
an important role in central nervous system formation.
Defeciency in zinc activates receptor N-methyl-D-
aspartate, which causes a febrile seizure.
6,7
This leads
Lusiana Margaretha et al: Correlation between serum zinc level and simple febrile seizure
Paediatr Indones, Vol. 50, No. 6, November 2010 327
to estimates that these neurotransmitter systems are
also modulated by zinc.
o
Recentlv, studies reveal that low serum zinc level
has contribution in the occurrence of simple febrile
seizure. Of all these results show that zinc plays a role
in the occurrence of febrile seizure. Research on the
decline serum zinc level in children with simple febrile
seizure is still verv limited, so the authors wanted to
determine the correlation between serum zinc level
and simple febrile seizure in children. The aim of this
study was to find out serum zinc level in simple febrile
seizure and the correlation between serum zinc level
and simple febrile seizure in children.
Methods
This is a cross sectional study to find out the
association between serum zinc level and simple
febrile seizure in children. lt was held at R. D. Kandou
Hospital, 1in,kat lll 1elin, Hospital, and Pancaran
Kasih Hospital Manado from April 5th 2OO9 until
June 15th 2OO9.
We included children of aged 6 month to less
than 5 years with simple febrile seizure with no
decrease of consciousness after seizure, no recurrent
seizures within 21 hours and parents or ,uardians
si,ned the informed consent. We excluded subjects
who experienced acute diarrhea with dehvdration,
chronic diarrhea, malnutrition, electrolvte imbalance,
sepsis. Children aged of 6 months to less than 5
years with fever but without seizure and without
malnutrition served as controls.
Patients were taken randomly. History taking
and physical examination were held by the authors.
Data collected include anamnesis form of the name,
,ender, a,e, duration of fever, duration of seizure, familv
history of simple febrile seizure and history of present
illness. Phvsical examination of bodv wei,ht, bodv
hei,ht, phvsiolo,ical reflexes, patholo,ical reflexes, and
meningeal signs were generally checked and recorded.
Laboratory examination of blood samples were taken
by an experienced officer. Venous blood was taken
for routine blood test (malaria slide, hemo,lobin,
hematocrit, white blood cells and platelets), serum
zinc in all patients and serum electrolytes (serum
sodium, potassium and calcium) onlv on simple febrile
seizure group patients. Blood samples was taken as
manv as 1 ml, O.5 ml of blood was inserted in the
Ethylene Diamine Tetra Acetate (EDTA) tube for
routine blood test, 1.5 ml in a 3 ml disposable svrin,e
for serum electrolvte test and the remainin, 2 ml of
blood in the other disposable tube without EDTA for
the examination of serum zinc levels.
Fever was defined as axillary body temperature
,reater than or equal to 37.5 de,rees Celsius, which is
measured using a digital thermometer with a precision
O.1 de,rees Celsius for 1 minute. Duration of fever was
estimated in hours based on parents report. Duration
of seizure was measured in minutes, based on parents
or ,uardians observations. Simple febrile seizure was
febrile seizure which lasted brief, less than 15 minutes,
,eneral tonic and/or clonic, ,enerallv stopped itself,
no neurolo,ical abnormalities post ictal, without focal
movement and does not recurrent within 21 hours.
12,13
Familiy history of simple febrile seizure was history of
parents or siblings who have experienced simple febrile
seizure. Acute respiratory infections were respiratory
tract infections from upper respiratory tract and its
adnexa to lun, parenchvmal, which lasted less than 11
davs, marked bv fever, sore throat, dvspnea, cou,h, runnv
nose, rou,h breathin, sound.
11-16
Dengue hemorrhagic
fever was diagnosed based on WHO criteria.
17,1o
Acute
diarrhea is waterv defecation more than three times a dav,
with or without blood and/or mucus in the feces, lasted
no more than 1 week.
19,2O
Electrolyte disturbances was
disturbances in the levels of serum sodium, potassium and
calcium, either increase or decrease levels.
21
Nutritional
status was determined based body weight compared to
body height patients plotted on the CDC curve according
to their age and sex.
22
Data analvses were performed bv usin, SPSS
version 15.O. Descriptive analvsis was used for
children characteristics, lo,istic re,ression analvsis
and correlation coefficient Spearman rho to find out
the correlation between serum zinc level and simple
febrile seizure in children. To find out the correlation
between serum zinc level and duration of seizure,
simple regression analysis was performed. P values of
<0.05 were considered significant.
Results
1here were 25 children with febrile without seizure and
25 children with simple febrile seizure. 1he cause of
Lusiana Margaretha et al: Correlation between serum zinc level and simple febrile seizure
328 Paediatr Indones, Vol. 50, No. 6, November 2010
fever was described in Table 1. Subjects characteristics
were shown in Table 2. Simple re,ression analvsis
shows there was a significant correlation between
serum zinc level and duration of seizure (P<O.OO1)
and there was also a strong correlation between those
variables (Figure 1 and Table 3).
Table 1. Patient diagnosis
Diagnosis Simple febrile seizure
(n=25)
Febrile without seizure
(n=25)
ARI 19 12
DHF 0 6
Acute diarrhea without dehydration 5 6
ARI + DHF 1 1
Jumlah 25 25
ARI = acute respiratory tract infection; DHF = dengue hemorrhagic fever
Tabel 3. Serum zinc level in simple febrile seizure patients based on duration of seizure occured
Duration of seizure n Mean SD CI 95% Minimal Maximal F P
<5 minutes 3 10,27 0,25 9,64 to 10,89 10,00 10,50 16,785 <0,001
5-<10 minutes 18 9,02 0,81 8,62 to 9,43 7,20 10,10
10-15 minutes 4 6,90 0,98 5,34 to 8.46 5,60 7,80
Total 25 8,83 1,22 8,33 to 9.34 5,60 10,50
Table 2. Characteristics of patients in both groups
Simple febrile seizure
(n=25)
Febrile without seizure
(n=25)
P
Sex
Boys
Girls
Age, yr
Mean (SD)
Nutritional status
Moderate malnutrition
Normal nutrition
Overweight
Obese
Family history
Parents
Siblings
Others relatives
Parents + siblings
None
Duration of fever
<24 hr
JT
Body temperature, C
Mean (SD)
95% CI
Zinc serum level, mol/l
Mean (SD)
95% CI
Duration of seizure, n
<5 minutes
5-<10 minutes
10-15 minutes
16
9
1.98 (1.00)
11
11
2
1
7
1
1
3
13
16
9
39.01 (0.56)
38.78 to 39.24
8.83 (1.23)
8.33 to 9.34
3
18
4
16
9
2.27 (1.27)
12
11
2
0
3
0
1
0
21
6
19
38.64 (0.45)
38.46 to 38.83
13.72 (0.45)
12.84 to 14.59
P = 0.006
P = 0.004
P = 0.013
P < 0.001
r
s
= 0.867
Lusiana Margaretha et al: Correlation between serum zinc level and simple febrile seizure
Paediatr Indones, Vol. 50, No. 6, November 2010 329
Discussion
lrom 5O subjects, mostlv were dia,nosed as acute
respiratory tract infection (ARI). Tomoum et al
23
stated that infection was caused mostly by viral
infection (6O') and manifest in ,astroenteritis, ARl
and non specific infection. Gender distribution in both
,roup were not si,nificantlv different, similar with
Ganesh et al
7
study. While Lestari
21
found that simple
febrile seizure mostly occurred in boy (:~ 1o:13).
Simple febrile seizure are mostlv of occur at a,ed 1o
month,
1,26,29
while some studies stated that it was
occurred at a,ed 12 months to 1 vears.
2O,25
Based on
this, we included onlv children under five vear-old.
It is believed that simple febrile seizure is
occurred as a combination between genetic and
environment factors. Similar with lestari,
21
we found
that family history of febrile seizure and duration of
fever associated with simple febrile seizure condition.
ln the other studv, 21' children has familv historv of
simple febrile seizure and 1' has a historv of epilepsv
in their family.
2o
Livingston had said that seizure must
occur in first 16 hours after onset of fever.
12
Body
temperature also play a role in simple febrile seizure
event. Nelson and Hirzt said that body temperature
of 3o

C or more was a risk factor.

29
We found negative correlation between serum
zinc level and simple febrile seizure event (r~ O.o67,
P< O.OO1). Some studies also stated that serum zinc
Figure 1. Serum zinc level based on duration of sei-
zure occured in simple febrile seizure group
level in children with simple febrile seizure was lower
than those without.
7,9,11
zinc can modulate ,lutamic
decarboxvlase acid activitv, an enzvme which has an
important role in OABA svnthesis. zinc also has role
in neurotransmitter like glutamic and their receptor.
zinc also facilitates inhibition effect of calcium
on N-methyl-D-aspartate receptor which inhibits
neuronal excitation activitv. Durin, hvpozincemia,
N-methyl-D-aspartate receptor is activated and
febrile seizure occurs.
1,6,7
1hese conditions justifv that
neurotransmitter svstem is modulated bv zinc. zinc was
also stimulatin, piridoxal kinase activitv, an enzvme
which can produce piridoxal from piridoxal phosphate.
After that piridoxal can modulate glutamic acid
decarboxylase activity and GABA synthesis.
6,7,3O
ln our studv, all subjects had have seizure
duration less than 15 minutes. We found that the
lower of serum zinc level, the lon,er duration of
seizure occurs (P< O.OO1). Sadleir et al
2o
found that
most children (about o7') had seizure less than 1O
minutes, while 9' had seizure lasted for 15 minutes.
ln conclusion, serum zinc level was associated with
simple febrile seizure event and its duration.
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