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Paediatrica Indonesiana

November 

VOLUME 50

NUMBER 6

Original Article

Correlation between serum zinc level


and simple febrile seizure in children
Lusiana Margaretha, Nurhayati Masloman

Abstract
Background 6LPSOH IHEULOH VHL]XUH LV WKH PRVW FRPPRQ IRUP
RI VHL]XUH ZKLFK RFFXUV GXULQJ FKLOGKRRG SHULRG =LQF RQH RI
PLFURHOHPHQWVLQKXPDQERG\KDVDQLPSRUWDQWUROHLQFHQWUDO
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.
.DQGRX+RVSLWDO7LQJNDW,,,7HOLQJ+RVSLWDODQG3DQFDUDQ.DVLK
+RVSLWDO0DQDGRRQ$SULOWK-XQHWK
Results'LDJQRVLVIRUIHEULOHZLWKRXWVHL]XUHSDWLHQWVZHUHZLWK
DFXWH UHVSLUDWRU\ WUDFW LQIHFWLRQ $5,   GHQJXH KHPRUUKDJLF
IHYHU '+) DFXWHGLDUUKHDZLWKRXWGHK\GUDWLRQDQG$5,
ZLWK'+)ZKLOHVLPSOHIHEULOHVHL]XUHZHUH$5,ILYHDFXWH
diarrhea without dehydration and one ARI with DHF. There
ZHUH QR VLJQLILFDQW GLIIHUHQFHV RI DJH JHQGHU DQG QXWULWLRQDO
VWDWXVLQWZRJURXSV)DPLO\KLVWRU\RIIHEULOHVHL]XUHIHEULOHSHULRG
and body temperature in two groups were significantly different.
Mean serum zinc level in simple febrile seizure and febrile without
VHL]XUH ZHUH  PROO DQG  PROO UHVSHFWLYHO\ 0HDQ
serum zinc level in simple febrile seizure children with seizure
SHULRG  PLQXWHV  PLQXWHV DQG  PLQXWHV ZHUH
 6' PROO 6' PROODQG 6' 
PROOUHVSHFWLYHO\
Conclusions There is correlation between serum zinc level and
VLPSOH IHEULOH VHL]XUH 7KH OHVVHU VHUXP ]LQF OHYHO WKH ORQJHU
duration of seizure occurs in simple febrile seizure. [Paediatr
Indones. 2010;50:326-30].
Keywords: febrile, seizure, zinc

eizure is a paroxysmal motor activity which


last for several moments and originated from
abnormal electrical generation inside the
brain. Febrile seizure is the most common
form of seizures among all childrens neurological
problems; commonly affect children under 5 years of
age.7KHLQFLGHQFHRIIHEULOHFRQYXOVLRQLVRI
all children.7KHSHDNRQVHWLVDJHWRPRQWKV
ZKHUHLQPRVWFDVHIHEULOHVHL]XUHPRVWRIWHQRFFXUV
DWWKHDJHRIPRQWKVWR\HDUV%R\VKDYHDKLJKHU
incidence than girls.46LPSOHIHEULOHVHL]XUHLWVHOILVD
form of seizures that often occurs during childhood.
6LPSOHIHEULOHVHL]XUHKDVDJRRGSURJQRVLVEXWWKH
simple febrile seizure is a sign of an acute infection
occurs in the child's body. =LQF ZKLFK LV WKH
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.
=LQFZKLFKLVRQHRIPLFURHOHPHQWVLQKXPDQERG\KDV
an important role in central nervous system formation.
Defeciency in zinc activates receptor N-methyl-DDVSDUWDWHZKLFKFDXVHVDIHEULOHVHL]XUH This leads

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Reprint request to /XVLDQD 0DUJDUHWKD 0' 'HSDUWPHQW RI &KLOG
+HDOWK0HGLFDO6FKRRO6DP5DWXODQJL8QLYHUVLW\3URI5'.DQGRX
*HQHUDO+RVSLWDO-O5D\D7DQDZDQJNR0DQDGR,QGRQHVLD7HO
)D[(PDLO lu514n4@yahoo.com

326Paediatr Indones, Vol. 50, No. 6, November 2010

Lusiana Margaretha et al: Correlation between serum zinc level and simple febrile seizure

to estimates that these neurotransmitter systems are


also modulated by zinc.
5HFHQWO\VWXGLHVUHYHDOWKDWORZVHUXP]LQFOHYHO
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
VHL]XUHLVVWLOOYHU\OLPLWHGVRWKHDXWKRUVZDQWHGWR
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
IHEULOHVHL]XUHLQFKLOGUHQ,WZDVKHOGDW5'.DQGRX
+RVSLWDO7LQJNDW,,,7HOLQJ+RVSLWDODQG3DQFDUDQ
.DVLK +RVSLWDO 0DQDGR IURP $SULO WK  XQWLO
-XQHWK
We included children of aged 6 month to less
than 5 years with simple febrile seizure with no
GHFUHDVHRIFRQVFLRXVQHVVDIWHUVHL]XUHQRUHFXUUHQW
VHL]XUHV ZLWKLQ  KRXUV DQG SDUHQWV RU JXDUGLDQV
VLJQHGWKHLQIRUPHGFRQVHQW:HH[FOXGHGVXEMHFWV
ZKR H[SHULHQFHG DFXWH GLDUUKHD ZLWK GHK\GUDWLRQ
FKURQLFGLDUUKHDPDOQXWULWLRQHOHFWURO\WHLPEDODQFH
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.
'DWDFROOHFWHGLQFOXGHDQDPQHVLVIRUPRIWKHQDPH
JHQGHUDJHGXUDWLRQRIIHYHUGXUDWLRQRIVHL]XUHIDPLO\
history of simple febrile seizure and history of present
LOOQHVV 3K\VLFDO H[DPLQDWLRQ RI ERG\ ZHLJKW ERG\
KHLJKWSK\VLRORJLFDOUHIOH[HVSDWKRORJLFDOUHIOH[HVDQG
meningeal signs were generally checked and recorded.
Laboratory examination of blood samples were taken
by an experienced officer. Venous blood was taken
IRU URXWLQH EORRG WHVW PDODULD VOLGH KHPRJORELQ
KHPDWRFULW ZKLWH EORRG FHOOV DQG SODWHOHWV  VHUXP
zinc in all patients and serum electrolytes (serum
VRGLXPSRWDVVLXPDQGFDOFLXP RQO\RQVLPSOHIHEULOH
seizure group patients. Blood samples was taken as

PDQ\ DV  PO  PO RI EORRG ZDV LQVHUWHG LQ WKH
Ethylene Diamine Tetra Acetate (EDTA) tube for
URXWLQHEORRGWHVWPOLQDPOGLVSRVDEOHV\ULQJH
IRUVHUXPHOHFWURO\WHWHVWDQGWKHUHPDLQLQJPORI
blood in the other disposable tube without EDTA for
the examination of serum zinc levels.
Fever was defined as axillary body temperature
JUHDWHUWKDQRUHTXDOWRGHJUHHV&HOVLXVZKLFKLV
measured using a digital thermometer with a precision
GHJUHHV&HOVLXVIRUPLQXWH'XUDWLRQRIIHYHUZDV
estimated in hours based on parents report. Duration
RIVHL]XUHZDVPHDVXUHGLQPLQXWHVEDVHGRQSDUHQWV
RU JXDUGLDQV REVHUYDWLRQV 6LPSOH IHEULOH VHL]XUH ZDV
IHEULOHVHL]XUHZKLFKODVWHGEULHIOHVVWKDQPLQXWHV
JHQHUDO WRQLF DQGRU FORQLF JHQHUDOO\ VWRSSHG LWVHOI
QRQHXURORJLFDODEQRUPDOLWLHVSRVWLFWDOZLWKRXWIRFDO
PRYHPHQWDQGGRHVQRWUHFXUUHQWZLWKLQKRXUV
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
DGQH[DWROXQJSDUHQFK\PDOZKLFKODVWHGOHVVWKDQ
GD\VPDUNHGE\IHYHUVRUHWKURDWG\VSQHDFRXJKUXQQ\
QRVHURXJKEUHDWKLQJVRXQG Dengue hemorrhagic
fever was diagnosed based on WHO criteria.Acute
GLDUUKHDLVZDWHU\GHIHFDWLRQPRUHWKDQWKUHHWLPHVDGD\
ZLWKRUZLWKRXWEORRGDQGRUPXFXVLQWKHIHFHVODVWHG
QRPRUHWKDQZHHNElectrolyte disturbances was
GLVWXUEDQFHVLQWKHOHYHOVRIVHUXPVRGLXPSRWDVVLXPDQG
FDOFLXPHLWKHULQFUHDVHRUGHFUHDVHOHYHOV Nutritional
status was determined based body weight compared to
body height patients plotted on the CDC curve according
to their age and sex.
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YHUVLRQ  'HVFULSWLYH DQDO\VLV ZDV XVHG IRU
FKLOGUHQ FKDUDFWHULVWLFV ORJLVWLF UHJUHVVLRQ DQDO\VLV
DQGFRUUHODWLRQFRHIILFLHQW6SHDUPDQUKRWRILQGRXW
the correlation between serum zinc level and simple
febrile seizure in children. To find out the correlation
EHWZHHQ VHUXP ]LQF OHYHO DQG GXUDWLRQ RI VHL]XUH
simple regression analysis was performed. P values of
<0.05 were considered significant.

Results
7KHUHZHUHFKLOGUHQZLWKIHEULOHZLWKRXWVHL]XUHDQG
FKLOGUHQZLWKVLPSOHIHEULOHVHL]XUH7KHFDXVHRI

Paediatr Indones, Vol. 50, No. 6, November 2010327

Lusiana Margaretha et al: Correlation between serum zinc level and simple febrile seizure

fever was described in Table 16XEMHFWVFKDUDFWHULVWLFV


were shown in Table 2 6LPSOH UHJUHVVLRQ DQDO\VLV
shows there was a significant correlation between

VHUXP]LQFOHYHODQGGXUDWLRQRIVHL]XUH 3 
and there was also a strong correlation between those
variables (Figure 1 and Table 3).

Table 1. Patient diagnosis


Diagnosis
ARI
DHF
Acute diarrhea without dehydration
ARI + DHF
Jumlah

Simple febrile seizure


(n=25)
19
0
5
1
25

Febrile without seizure


(n=25)
12
6
6
1
25

ARI = acute respiratory tract infection; DHF = dengue hemorrhagic fever

Table 2. Characteristics of patients in both groups


Simple febrile seizure
(n=25)

Febrile without seizure


(n=25)

16
9

16
9

1.98 (1.00)

2.27 (1.27)

11
11
2
1

12
11
2
0

7
1
1
3
13

3
0
1
0
21

P = 0.004

16
9

6
19

P = 0.013

39.01 (0.56)
38.78 to 39.24

38.64 (0.45)
38.46 to 38.83

8.83 (1.23)
8.33 to 9.34

13.72 (0.45)
12.84 to 14.59

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

P = 0.006

P < 0.001
rs = 0.867

3
18
4

Tabel 3. Serum zinc level in simple febrile seizure patients based on duration of seizure occured
Duration of seizure
<5 minutes
5-<10 minutes
10-15 minutes
Total

n
3
18
4
25

Mean
10,27
9,02
6,90
8,83

SD
0,25
0,81
0,98
1,22

328Paediatr Indones, Vol. 50, No. 6, November 2010

CI 95%
9,64 to 10,89
8,62 to 9,43
5,34 to 8.46
8,33 to 9.34

Minimal
10,00
7,20
5,60
5,60

Maximal
10,50
10,10
7,80
10,50

F
16,785

P
<0,001

Lusiana Margaretha et al: Correlation between serum zinc level and simple febrile seizure

Figure 1. Serum zinc level based on duration of seizure occured in simple febrile seizure group

Discussion
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respiratory tract infection (ARI). Tomoum et al
stated that infection was caused mostly by viral
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and non specific infection. Gender distribution in both
JURXS ZHUH QRW VLJQLILFDQWO\ GLIIHUHQW VLPLODU ZLWK
Ganesh et al7 study. While Lestari found that simple
febrile seizure mostly occurred in boy (:  
6LPSOHIHEULOHVHL]XUHDUHPRVWO\RIRFFXUDWDJHG
PRQWK while some studies stated that it was
RFFXUUHGDWDJHGPRQWKVWR\HDUV Based on
WKLVZHLQFOXGHGRQO\FKLOGUHQXQGHUILYH\HDUROG
It is believed that simple febrile seizure is
occurred as a combination between genetic and
HQYLURQPHQWIDFWRUV6LPLODUZLWK/HVWDUL we found
that family history of febrile seizure and duration of
fever associated with simple febrile seizure condition.
,QWKHRWKHUVWXG\FKLOGUHQKDVIDPLO\KLVWRU\RI
VLPSOHIHEULOHVHL]XUHDQGKDVDKLVWRU\RIHSLOHSV\
in their family. Livingston had said that seizure must
RFFXU LQ ILUVW  KRXUV DIWHU RQVHW RI IHYHU Body
temperature also play a role in simple febrile seizure
event. Nelson and Hirzt said that body temperature
RIC or more was a risk factor.
We found negative correlation between serum
]LQFOHYHODQGVLPSOHIHEULOHVHL]XUHHYHQW U 
3 6RPHVWXGLHVDOVRVWDWHGWKDWVHUXP]LQF

level in children with simple febrile seizure was lower


than those without.=LQFFDQPRGXODWHJOXWDPLF
GHFDUER[\ODVHDFLGDFWLYLW\DQHQ]\PHZKLFKKDVDQ
LPSRUWDQWUROHLQ*$%$V\QWKHVLV=LQFDOVRKDVUROH
in neurotransmitter like glutamic and their receptor.
=LQF DOVR IDFLOLWDWHV LQKLELWLRQ HIIHFW RI FDOFLXP
on N-methyl-D-aspartate receptor which inhibits
QHXURQDO H[FLWDWLRQ DFWLYLW\ 'XULQJ K\SR]LQFHPLD
N-methyl-D-aspartate receptor is activated and
febrile seizure occurs.7KHVHFRQGLWLRQVMXVWLI\WKDW
QHXURWUDQVPLWWHUV\VWHPLVPRGXODWHGE\]LQF=LQFZDV
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which can produce piridoxal from piridoxal phosphate.
After that piridoxal can modulate glutamic acid
decarboxylase activity and GABA synthesis.
,Q RXU VWXG\ DOO VXEMHFWV KDG KDYH VHL]XUH
GXUDWLRQ OHVV WKDQ  PLQXWHV :H IRXQG WKDW WKH
ORZHU RI VHUXP ]LQF OHYHO WKH ORQJHU GXUDWLRQ RI
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simple febrile seizure event and its duration.

References
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.OLHJPDQ 50 -HQVRQ +% HGLWRUV 1HOVRQ WH[WERRN RI
SHGLDWULFVth(G3KLODGHOSKLD:%6DXQGHUV&R
S
 $PHULFDQ $FDGHP\ RI 3HGLDWULF )HEULOH VHL]XUHV FOLQLFDO
practice guideline for the long-term management of the child
ZLWKVLPSOHIHEULOHVHL]XUHV3HGLDWULFV
 $PHULFDQ $FDGHP\ RI 3HGLDWULF 3UDFWLFH SDUDPHWHU WKH
neurodiagnostic evaluation of the child with a first a simple
IHEULOHVHL]XUH3HGLDWULFV
 :ROI 3 6KLQQDU 6 )HEULOH VHL]XUHV ,Q 0DULD %/ HGLWRU
&XUUHQW PDQDJHPHQW LQ FKLOG QHXURORJ\ rd Ed. London:
%&'HFNHU,QFS.
 &RXVLQV5-=LQF,Q=LHJOHU(()LOHU/--UHGLWRUV3UHVHQW
knowledge in nutrition. 7th(G:DVKLQJWRQ'&,/6,3UHVV
S
 *X\WRQ$&+DOO-(7H[WERRNRIPHGLFDOSK\VLRORJ\th Ed.
3KLODGHOSKLD:%6DXQGHUVS
 *DQHVK5-DQDNLUDPDQ/6HUXP]LQFOHYHOVLQFKLOGUHQZLWK
VLPSOHIHEULOHVHL]XUH&OLQ3HGLDWU.

Paediatr Indones, Vol. 50, No. 6, November 2010329

Lusiana Margaretha et al: Correlation between serum zinc level and simple febrile seizure
 6PDUW7*+RVLH$00LOOHU36=QLRQV0RGXODWRUVRI
excitatory and inhibitory synaptic activity. Neuroscientist.

 -HOLWD6&KDLUDQL/'DUZLQ6'HZL5=LQFGHILFLHQF\DV
a risk factor of febrile seizure. Presented onth Indonesian
&RQJUHVV2I3HGLDWULFV6XUDED\D-XO\thth .
 %XUKDQRJOX 0 7XWXQFXRJOXV 6 &RNHU & 7HNJXO +
Ozgur. Hypozincaemia in febrile convulsion. Eur J Pediatr.
.
 6WUDQG7$&KDQG\R5.%DKO5(IIHFWLYHQHVVDQGHIILFDF\
of zinc for the treatment of acute diarrhea in young children.
3HGLDWULFV.
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,VPDHO6HGLWRUV%XNX$MDU1HXURORJL$QDN-DNDUWD%3
,'$,S.
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 )LVFKHU&+DUYH\3Low risk of adverse effects from zinc
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SURJUDPF>FLWHG-XQH@$YDLODEOHIURPKWWS
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in prevention of childhood diarrhea and respiratory illnesses:
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++DGLQHJRUR656HGLWRUV%XNXDMDULOPXNHVHKDWDQDQDN
-DNDUWD%DJLDQ,OPX.HVHKDWDQ$QDN).8,S
.
 :LGDJGRBlood zinc levels and clinical severity of dengue
hemorrhagic fever in children. 6RXWKHDVW$VLDQ-7URS0HG
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330Paediatr Indones, Vol. 50, No. 6, November 2010





















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