Paediatrica Indonesiana

VOLUME 52 March NUMBER 2

Original Article

Correlation between brain injury biomarkers and

Glasgow coma scale in pediatric sepsis
Nahari Arifin, Irawan Mangunatmadja, Antonius Pudjiadi, Sudung O. Pardede

S
Abstract
Background 6HSVLVLQFKLOGUHQZLWKRUZLWKRXWPXOWLSOHRUJDQ
IDLOXUH FDXVHV LQFUHDVHG VXVFHSWLELOLW\ WR EUDLQ LQMXU\ GXH WR
V\VWHPLF LQVXOWV %UDLQ LQMXU\ LQ VHSVLV LV GLIILFXOW WR UHFRJQL]H
HSVLVLVDPDMRUKHDOWKSUREOHPFDXVLQJKLJK
PRUWDOLW\UDWHVLQLQIDQWVDQGFKLOGUHQ6HYHUH
VHSVLVDQGVHSWLFVKRFNDUHFRQGLWLRQVZLWK
PXOWLRUJDQ IDLOXUH NQRZQ WR EH D OHDGLQJ
FOLQLFDOO\1HXURQVSHFLILFHQRODVH16(DQG6%KDYHEHHQ
H[WHQVLYHO\VWXGLHGLQEUDLQLQMXULHVDQGDSSHDUWREHSURPLVLQJ
DOWHUQDWLYHELRPDUNHUV
Objectives 7RGHWHUPLQHLIWKHUHLVDFRUUHODWLRQEHWZHHQWKH
FDXVH RI PRUWDOLW\ LQ SHGLDWULF VHSVLV 3UHYDOHQFH
GDWDYDU\DPRQJFRXQWULHV,QDQHSLGHPLRORJLF
VWXG\LQWKH8QLWHG6WDWHVUHSRUWHGWKHSUHYDOHQFHRI
*ODVJRZFRPDVFDOH*&6DQG16(DVZHOODV6%OHYHOVLQ
FKLOGUHQZLWKVHSVLV
Methods :HSHUIRUPHGDQDQDO\WLFDOVWXG\RQVHSWLFFKLOGUHQ
DJHG!\HDUV*&6VFRUHVZHUHDVVHVVHGRQWKHILUVWDQGWKLUG
GD\VRIDGPLVVLRQ%ORRGVSHFLPHQVWRWHVWIRU16(DQG6%
ZHUHGUDZQRQWKHILUVWGD\RIDGPLVVLRQDQGVWRUHGDW&IRU
IXUWKHUDQDO\VLVDWWKHHQGRIWKHVWXG\
VHYHUHVHSVLVWREHSHUSHRSOH The highest
SUHYDOHQFHZDVLQWKHQHRQDWHDQGLQIDQWDJHJURXS
ZKLOHVWHHSGHFOLQHVLQSUHYDOHQFHZHUHREVHUYHGLQ
WKH\HDUDJHJURXS
0XOWLSOHRUJDQIDLOXUHPD\LQYROYHDQ\RUJDQ
GXULQJVHSVLV5$OWKRXJKWKHFHQWUDOQHUYRXVV\VWHP
Results2XWRISDWLHQWVPHWWKHLQFOXVLRQFULWHULD3RVW
DQDO\VLV RQH VXEMHFW ZLWK 16( DERYH WKH PD[LPXP OHYHO ZDV
H[FOXGHG1HJDWLYHFRUUHODWLRQVZHUHIRXQGEHWZHHQ*&6VFRUH
DQG16(DVZHOODVEHWZHHQ*&6DQG6%OHYHOV$QDO\VLV
UHYHDOHGDVLJQLILFDQW52&IRU16(EXWQRWIRU6%16(
FRQFHQWUDWLRQRIJ/ZDVWKHFXWRIISRLQWIRU*&6VFRUHV
EHORZ
Conclusions 7KHUH ZHUH QHJDWLYH FRUUHODWLRQV EHWZHHQ *&6
DQG16(OHYHOVDVZHOODVEHWZHHQ*&6DQG6%OHYHOV7KH
SUHGLFWLYHYDOXHRI16(OHYHOZDVDFXWRIISRLQWRIJ/IRU
*&6VFRUHVEHORZ[Paediatr Indones. 2012;52:111-17]
Keywords: pediatric sepsis, brain injury biomarkers,
neuron specific enolase, protein S-100B, Glasgow
coma scale
&16 KDV VHOHFWLYH SURWHFWLYH EDUULHUV LW LV DOVR
YXOQHUDEOHWRV\VWHPLFLQVXOWGXULQJVHSVLV+RZHYHU
WKH PHFKDQLVPV DUH QRW IXOO\ XQGHUVWRRG 6HSWLF
HQFHSKDORSDWK\ DFFRXQWV IRU PRVW PDQLIHVWDWLRQV
RI&16LQYROYHPHQWZLWKDSUHYDOHQFHRI
,Q FRQWUDVW WR DGXOWV KHPRG\QDPLF LQVWDELOLW\ LV
FRPPRQLQSHGLDWULFVHSVLVDQGPD\GHYHORSLQWRD
K\SR[LFLVFKHPLFLQMXU\LQWKH&16
&OLQLFDOPDQLIHVWDWLRQVRI&16QHXURQDOLQMXU\
LQ VHSWLF FKLOGUHQ DUH FKDOOHQJLQJ DQG GLIILFXOW WR
)URPWKH'HSDUWPHQWRI&KLOG+HDOWK8QLYHUVLW\RI,QGRQHVLD0HGLFDO
6FKRRO&LSWR0DQJXQNXVXPR+RVSLWDO-DNDUWD,QGRQHVLD
Reprint requests to: 1DKDUL $ULILQ 'HSDUWPHQW RI &KLOG +HDOWK
8QLYHUVLW\RI,QGRQHVLD0HGLFDO6FKRRO&LSWR0DQJXQNXVXPR+RVSLWDO
-O 'LSRQHJRUR  -DNDUWD 7HO  (PDLO hari2705@
gmail.com
Paediatr Indones, Vol. 52, No. 2, March 2012 111
 Nahari Arifin et al: &RUUHODWLRQEHWZHHQEUDLQLQMXU\ELRPDUNHUVDQG*ODVJRZ&RPD6FDOHLQSHGLDWULFVHSVLV

DQDO\]H *&6 LV DQ REMHFWLYH H[DPLQDWLRQ WR DVVHVV 0RGLILHG SHGLDWULF *&6 VFRUHV DQG QHXURORJLF
WKH GHJUHH RI &16 LQMXU\ DOWKRXJK LW LV QRW YHU\ H[DPLQDWLRQV ZHUH REWDLQHG RQ WKH ILUVW GD\ RI
VHQVLWLYH (OHFWURHQFHSKDORJUDSK\ ((* SURYLGHV DGPLVVLRQ
WKH PRVW VHQVLWLYH GLDJQRVWLF ZRUNXS DQG PD\ EH
XVHGIRUDVVHVVLQJQHXURQDOGDPDJHDVZHOODVKDYLQJ
SURJQRVWLFYDOXHLQVHSWLFFKLOGUHQ+RZHYHUWKH Table 1. 5WDLGEVUEJCTCEVGTKUVKEU
QHHG IRU VRSKLVWLFDWHG LQIUDVWUXFWXUH DQG H[SHUWLVH %JCTCEVGTKUVKEU 6QVCN
P
LVFXPEHUVRPHDQGOLPLWVWKHXVHRI((*LQFOLQLFDO
Median age, years (range) 

VHWWLQJV,PDJLQJWHFKQLTXHV05,DQG&7DUHDOVR Sex, n
VHQVLWLYHIRUH[WHQVLYHVWUXFWXUDOGDPDJHEXWWKH\DUH  /CNG 11
QRWXVHIXOIRUGHWHFWLQJPLQRUDEQRUPDOLWLHV  (GOCNG 19
Age group, n
$VDQDOWHUQDWLYHELRPDUNHUVVXFKDV16(DQG  6QFFNGT
[GCTU 17
6%DUHSURPLVLQJDVREMHFWLYHDQGSUDFWLFDOFOLQLFDO  5EJQQNCIGF
[GCTU 12
WRROVIRUGHWHFWLQJHDUO\&16LQVXOW%RWKELRPDUNHUV  #FQNGUEGPV
[GCTU 1
Nutritional status, n
KDYHEHHQH[WHQVLYHO\VWXGLHGLQSHGLDWULFQHRQDWDO  /CNPQWTKUJGF 1
SRSXODWLRQV ZLWK K\SR[LFLVFKHPLF HQFHSKDORSDWK\  7PFGTPQWTKUJGF 
+,( KHDG LQMXULHV SRVWFDUGLDF DUUHVW DQG VHSWLF  0QTOCN 12
 1XGTYGKIJV 
VKRFN 7KH SURJQRVWLF YDOXH RI WKHVH ELRPDUNHUV  1DGUG 1
IRU QHXURORJLF GHWHULRUDWLRQ DQG GHDWK KDV EHHQ Septic severity, n
HVWDEOLVKHGLQVHYHUDOVWXGLHV  5GRUKUYKVJQWVQTICPF[UHWPEVKQP 19
 5GXGTGUGRUKU 5
5HFHQWVWXGLHVRI&16ELRPDUNHUVLQSHGLDWULF  5GRVKEUJQEM 
VHSVLVKDYHEHHQOLPLWHGVRZHDLPHGWRILQGSUDFWLFDO Diagnosis, n
DQG DFDGHPLFDOO\ IHDVLEOH WRROV IRU DVVHVVLQJ EUDLQ  2PGWOQPKCRNGWTCNGHHWUKQP 
 &GPIWGJGOQTTJCIKEHGXGT 5
LQMXU\$VLQVRPHSUHYLRXVVWXGLHVZHDVVHVVHG&16  7TKPCT[VTCEVKPHGEVKQP 
ELRPDUNHUVSURJQRVWLFYDOXHVIRUERWKQHXURORJLFDQG  #DFQOKPCNKPHGEVKQP 5
FOLQLFDORXWFRPHV  #DFQOKPCNRQUVQRGTCVKXG 1
Underlying disease, n
 6WOQTOCNKIPCPE[ 5
 2QUVQRGTCVKXG 2
Methods  )WKNNCKP$CTTGU[PFTQOG 1
 6JCNCUUGOKC 1
 %GTGDTCNRCNU[ 1
7KHVWXG\ZDVFDUULHGRXWLQWKHLQWHQVLYHFDUHXQLWV HIV 1
DQGSHGLDWULFZDUGVRIWKUHHVWDWHRZQHGKRVSLWDOV  6WDGTEWNQUKU 1
 9KVJQWVWPFGTN[KPIFKUGCUG 18
LQ &HQWUDO DQG :HVW -DNDUWD DQG ZDV DSSURYHG
Anemia ( Hb < 12 g/dL ), n
E\ WKH 0HGLFDO (WKLFV &RPPLWWHH 8QLYHUVLW\ RI  0QCPGOKC 9
,QGRQHVLD7KHGXUDWLRQRIWKHVWXG\ZDVPRQWKV  #PGOKC 21
EHWZHHQ -XO\  DQG 0DUFK  6XEMHFWV Leukocyte count, n
 0QTOCN 4
ZHUHREWDLQHGE\FRQVHFXWLYHVDPSOLQJDQGWKHLU  .GWMQE[VQUKU 21
SDUHQWVFDUHJLYHUVFRQVHQWHGWRWKHLUSDUWLFLSDWLRQ  .GWMQRGPKC 5
LQWKLVVWXG\,QFOXVLRQFULWHULDZHUHSDWLHQWVZLWK Platelet count, n
 0QTOCN 9
VHSVLV&OLQLFDODQGODERUDWRU\GDWDZHUHUHFRUGHG  6JTQODQE[VQRGPKC 
RQWKHILUVWGD\RIDGPLVVLRQ:HH[FOXGHGSDWLHQWV  6JTQODQE[VQUKU 8
ZLWKNQRZQRUVXVSHFWHGPHQLQJLWLVHQFHSKDOLWLV NSE, n
 0QTOCN 18
EUDLQDEVFHVVLQIOLFWHGRUQRQLQIOLFWHGWUDXPDWLF  #DPQTOCN 11
EUDLQLQMXU\SDUR[\VPDODQGEUDLQGLVRUGHUVPLOGWR S-100B, n
VHYHUHWUDXPDSULPDU\RUVHFRQGDU\PDOLJQDQF\DV  0QTOCN 25
 #DPQTOCN 5
ZHOODVKHPRGLDO\VHGSDWLHQWVGXHWRLWVLQIOXHQFH Outcome, n
RQ 6% FOHDUDQFH $OO VXEMHFWV ZHUH UHFHLYHG  5WTXKXGF 25
SURSHU PDQDJHPHQW IRU WKHLU VHSWLF FRQGLWLRQ  &KGF 5

112Paediatr Indones, Vol. 52, No. 2, March 2012

 Nahari Arifin et al: &RUUHODWLRQEHWZHHQEUDLQLQMXU\ELRPDUNHUVDQG*ODVJRZ&RPD6FDOHLQSHGLDWULFVHSVLV

6LQJOH VSHFLPHQV RI 16( DQG 6% ZHUH Results

FROOHFWHG IURP HOLJLEOH VXEMHFWV RQ WKH ILUVW GD\ RI
DGPLVVLRQ $OO VSHFLPHQV ZHUH FHQWULIXJHG IUR]HQ 7KLUW\ILYHSDWLHQWVPHWWKHLQFOXVLRQFULWHULDEXW
o& DQG DQDO\]HG E\ WKH HQG RI VWXG\ 16( WKUHH VXEMHFWV SDUHQWV GLG QRW FRQVHQW DQG WZR
PHDVXUHPHQWZDVSHUIRUPHGXVLQJ1H[XV'[ NSE VXEMHFWVKDGVSHFLPHQVZLWKJURVVYLVLEOHKHPRO\VLV
1DQRJHQ,QF6DQ'LHJR&$6SHFLPHQVZLWKJURVV 7KXV GDWD ZHUH REWDLQHG IURP  FRQVHFXWLYH
RUYLVLEOHKHPRO\VLVZHUHGLVFDUGHG16(FRQFHQWUDWLRQ VXEMHFWV 6HUXP VSHFLPHQ DQDO\VLV E\ WKH HQG RI
J/ZDVFRQVLGHUHGQRQIDWDO6%DQDO\VLV VWXG\UHYHDOHGRQHVSHFLPHQZLWKRXWKHPRO\VLVKDG
ZDVSHUIRUPHGXVLQJ1H[XV'[61DQRJHQ,QF DQ16(OHYHODERYHWKHPD[LPXP!PJ/
6DQ'LHJR&$6%FRQFHQWUDWLRQJ/ZDV
FRQVLGHUHGWREHQRQIDWDO
&RQWLQXRXVGDWDDUHUHSUHVHQWHGDVPHGLDQDQG
UDQJH ZKLOH FDWHJRULFDO GDWD DUH VKRZQ DV FRXQWV
7KHFOLQLFDOPDWHULDOZDVGLFKRWRPLVHGXVLQJFOLQLFDO
HQGSRLQWVRIJRRGYHUVXVEDGRXWFRPHV&KLVTXDUH
DQG )LVKHUV H[DFW WHVW ZHUH XVHG WR DQDO\]H GDWD
6SHFLILFLW\DQGVHQVLWLYLW\RI16(DQG6%ZHUH
FDOFXODWHG&RUUHODWLRQRI16(DQG6%WR*&6
PHDVXUHPHQW FDSDELOLW\ RI WKH (OLVD .LW VR WKDW
VXEMHFW ZDV H[FOXGHG 7KHUHIRUH WKH UHPDLQLQJ
GDWD IRU VXEVHTXHQW FRUUHODWLRQ DQDO\VLV RI 16(
ZDV IURP  VXEMHFWV )RU 6% QR VXEMHFWV
ZHUHH[FOXGHGIRUDWRWDORIVXEMHFWVDYDLODEOH
IRU 6% DQDO\VLV  3DWLHQW FKDUDFWHULVWLFV DUH
VXPPDUL]HGLQTable 1
7KH*&6LVFDWHJRUL]HGLQWROHYHOVRIEUDLQ
LQMXU\GHFUHDVHG FRQVFLRXVQHVV PLOG WR QRUPDO
ZHUHFDOFXODWHGXVLQJ6SHDUPDQVFRHIILFLHQWDQDO\VLV  PRGHUDWH  DQG VHYHUH  2I
5HFHLYHURSHUDWLQJ FKDUDFWHULFWLF 52& DQDO\VLV WKH  VXEMHFWV  VXEMHFWV ZHUH LQ WKH PLOG WR
ZDV DOVR SHUIRUPHG $OO VWDWLVWLFDO DQDO\VHV ZHUH QRUPDO FDWHJRU\  ZHUH PRGHUDWH DQG  ZHUH
SHUIRUPHG XVLQJ6366VRIWZDUHYHUVLRQ6366 VHYHUH6L[VXEMHFWVLQWKHVHYHUHFDWHJRU\KDGIDWDO
,QF,/86$ RXWFRPHV

 T


NSE (microgram/L)









      

GCS
Figure 1%QTTGNCVKQPDGVYGGP)%5CPF05'

Paediatr Indones, Vol. 52, No. 2, March 2012 113

 Nahari Arifin et al: &RUUHODWLRQEHWZHHQEUDLQLQMXU\ELRPDUNHUVDQG*ODVJRZ&RPD6FDOHLQSHGLDWULFVHSVLV

$EQRUPDO 16( OHYHOV ZHUH IRXQG LQ  RI 

ROC Curve of NSE
VXEMHFWV RQ WKH ILUVW GD\ RI DGPLVVLRQ 7HQ VXEMHFWV
ZHUH LQ WKH PRGHUDWHVHYHUH EUDLQ LQMXU\ FDWHJRU\
 ZKLOH WZR VXEMHFWV ZHUH LQ WKH QRUPDO FDWHJRU\
value at 8.1 Pg/L &KLVTXDUH WHVW VKRZHG D VLJQLILFDQW UHODWLRQVKLS
EHWZHHQOHYHORIFRQVFLRXVQHVVDQG16(OHYHO55
 DQG&,WR&RUUHODWLRQDQDO\VLV
XVLQJ 6SHDUPDQ 5KR FRHIILFLHQWVKRZHG D QHJDWLYH
Sensitivity

FRUUHODWLRQU DQG3 DVGHSLFWHG

 in Figure 15HFHLYHURSHUDWRUFKDUDFWHULVWLFVEDVHG
RQGLFKRWRPLVHGGDWDZHUHLGHQWLILHG$VSUHVHQWHG
in Figure 2DQ16(OHYHORIJ/ZDVWKHFXWRII

SRLQWIRU*&6VFRUHVRIZLWKVHQVLWLYLW\
DQGVSHFLILFLW\7KHDUHDXQGHUFXUYH$8&

ZDV&,WR
%DVHG RQ PHGLDQ OHYHO  RI  VXEMHFWV KDG
DEQRUPDO 6% OHYHOV )LYH RI WKHVH VXEMHFWV KDG
 PRGHUDWHO\VHYHUHO\ GHFUHDVHG FRQVFLRXVQHVV RQH
      VXEMHFWKDGQRUPDOFRQVFLRXVQHVV2QGD\WKUHHQR
5RGEKEKV[ LPSURYHPHQW ZDV REVHUYHG LQ HLWKHU RI  VXEMHFWV
ZLWKPRGHUDWHO\VHYHUHO\GHFUHDVHGFRQVFLRXVQHVVRU
Figure 24GEGKXGTQRGTCVQTEJCTCEVGTKUVKEHQT)%5
PLOGO\ GHFUHDVHG FRQVFLRXVQHVV %LYDULDWH DQDO\VLV
UEQTGDGNQY05'XCNWGRNQVVGFCVWI.YKVJ
UGPUKVKXKV[CPFURGEKEKV[
%+
XVLQJ GLFKRWRPLVHG FOLQLFDO GDWD RI VHYHULW\ DQG
VQ PRUWDOLW\UHYHDOHGDVLJQLILFDQWUHODWLRQVKLSRI6%


T


S100b (microgram/L)









      

GCS

Figure 3%QTTGNCVKQPDGVYGGP)%5CPF5$

114Paediatr Indones, Vol. 52, No. 2, March 2012

 Nahari Arifin et al: &RUUHODWLRQEHWZHHQEUDLQLQMXU\ELRPDUNHUVDQG*ODVJRZ&RPD6FDOHLQSHGLDWULFVHSVLV

DEQRUPDOLW\ZLWKERWKVHSWLFVHYHULW\55  LQDOOVHSWLFVXEMHFWVFRPSDUHGWRQRUPDOFKLOGUHQ

&,  WR  DQG PRUWDOLW\ 55    &, DV FRQWUROV %HVLGHV WKH GLIIHUHQFH LQ VXEMHFWV
 WR  &RUUHODWLRQ DQDO\VLV XVLQJ 6SHDUPDQ FKDUDFWHULVWLFVIURPWKH+VXet alVWXG\WKHLQFUHDVH
5KR FRHIILFLHQW VKRZHG D QHJDWLYH FRUUHODWLRQ U  RI16(FRQFHQWUDWLRQLQVRPHVXEMHFWVPD\EHGXHWR
3 DVGHSLFWHGLQFigure 35HFHLYHU
RSHUDWRU FKDUDFWHULVWLFV EDVHG RQ GLFKRWRPLVHG GDWD
VKRZHG 6% OHYHO RI  J/ WR EH WKH FXWRII
SRLQWIRUD*&6VFRUHZLWKVHQVLWLYLW\DQG
VSHFLILFLW\7KH$8&ZDVZLWK&,
WR+RZHYHUVLQFHWKH3YDOXHZDVJUHDWHU
WKDQWKH52&FXUYHSURGXFHGZDVVWDWLVWLFDOO\
LQVLJQLILFDQW
Discussion
7KLV VWXG\ DLPHG WR GHWHUPLQH LI WKHUH ZHUH
FRUUHODWLRQVEHWZHHQ*&6DVDFOLQLFDOSDUDPHWHU
DQG 16( DQG 6% DV EUDLQ LQMXU\ PDUNHUV LQ
HDUO\KHPRG\QDPLFLQVWDELOLW\6XEVHTXHQWO\WKHVH
VXEMHFWVPD\KDYHGHYHORSHGK\SR[LFLVFKHPLFEUDLQ
LQMXU\ EHIRUH DQ\ FOLQLFDO VLJQV VXFK DV GHFUHDVHG
*&6 VFRUH +RZHYHU HU\WKURF\WHV DQG SODWHOHWV
DUHDOVRDQDEXQGDQWVRXUFHRIGHIHFWLYH16(GXH
WR KHPRO\VLV RU LPPXQRORJLF PHFKDQLVPV GXULQJ
VHSVLV7KXVLQFUHDVHG16(FRQFHQWUDWLRQLQVHUXP
LV QRW VROHO\ IURP QHXURQ RU DWURJOLDO VRXUFHV
&RUUHODWLRQDQDO\VLVXVLQJ6SHDUPDQ5KRFRHIILFLHQW
UHYHDOHGDFRUUHODWLRQRIEHWZHHQ*&6VFRUH
DQG 16( FRQFHQWUDWLRQ 6LPLODU UHVXOWV ZHUH
UHSRUWHG E\ *XDQ et al LQ FKLOGUHQ ZLWK WUDXPDWLF
EUDLQ LQMXU\ 7KH\ IRXQG D FRUUHODWLRQ RI 
EHWZHHQ*&6DQGVHUXP16( Ross et alQRWHGD
VLPLODUFRUUHODWLRQFRHIILFLHQWRIEHWZHHQ*&6
SHGLDWULF VHSVLV 7R GDWH OLPLWHG GDWD LV DYDLODEOH
UHJDUGLQJWKHSURSHUWLHVRIWKHVHWZRELRPDUNHUVLQ
SHGLDWULFVHSVLV
1HXURORJLF PDQLIHVWDWLRQ LQ VHSVLV UHODWHG WR
HQFHSKDORSDWK\LVJHQHUDOO\VHHQDVGHFUHDVHGOHYHO
RIFRQVFLRXVQHVVRUGHFUHDVHG*&6VFRUHV(LGHOPDQ
et alGHVFULEHGWKDWLIVFRUHVRIGHFUHDVHGWROHVV
WKDQPRUWDOLW\LVLQFUHDVHGIURPWR,Q
DJUHHPHQWZLWKWKHVHILQGLQJVRIRXUVXEMHFWVZLWK
VHYHUHO\GHFUHDVHGFRQVFLRXVQHVVKDGIDWDORXWFRPHV
LQRXUWULDO'LFKRWRPRXVDQDO\VLVSHUIRUPHGZLWK&KL
VTXDUHWHVWUHYHDOHGDVLJQLILFDQWUHODWLRQVKLSEHWZHHQ
DQG 16( LQ FHUHEURVSLQDO IOXLG &6)22 )XUWKHU
VWXG\ WR FRPSDUH &6) DQG VHUXP 16( WR *&6 LV
QHHGHGWRGHWHUPLQHWKHXVHIXOQHVVRI&6)16(DV
DELRPDUNHURIEUDLQLQMXU\LQFKLOGUHQZLWKVHSVLV
5HFHLYHURSHUDWRUFKDUDFWHULVWLFFXUYHZDVPDGHWR
DQDO\]HWKHUHODWLRQVKLSRIVHUXP16(FRQFHQWUDWLRQ
WR*&6VFRUHDWWKHWLPHRIDGPLVVLRQ7KHSUHGLFWHG
FXWRIIYDOXHZDVJ/IRU*&6VFRUHEHORZ
)HZ VWXGLHV KDYH LQYHVWLJDWHG WKH UHODWLRQVKLS RI
*&6 VFRUH DV D FOLQLFDO RXWFRPH WR D VLQJOH 16(
PHDVXUHPHQWIRUSUHGLFWLYHYDOXHV
6%SURWHLQLVDFDOFLXPELQGLQJHQ]\PHIRXQG
*&6 DQG GHDWK 55   &,  WR 
2WKHU QHXURORJLFDO ILQGLQJV LQ VHSVLV DUH VHL]XUHV
SDUDO\VLV DQG OHVV FRPPRQO\ DVWHUL[LV WUHPRUV
FUDQLDOQHUYHSDUDO\VLVDQGQXFKDOULJLGLW\6HL]XUHV
DQGD[RQDOW\SHORZHUPRWRUQHXURQSDUDO\VLVZHUH
REVHUYHGLQVHSWLFVXEMHFWV7KLVILQGLQJPD\EHUHODWHG
WRVHSVLVDVRQHIRUPRIVHSWLFHQFHSKDORSDWK\RUPD\
EHUHODWHGWRWKHXQGHUO\LQJGLVRUGHU,WLVNQRZQWKDW
XQGHUO\LQJGLVHDVHVPD\FRQWULEXWHWRWKHVHYHULW\RI
VHSVLVDQGGLIIHUHQWFOLQLFDOPDQLIHVWDWLRQV
16( FRQFHQWUDWLRQV ZHUH LQFUHDVHG LQ DOO
VHYHUHVHSVLVDQGVHSWLFVXEMHFWVZLWKPXOWLSOHRUJDQ
G\VIXQFWLRQ6RPHVXEMHFWVZLWKQRHYLGHQFHRIRUJDQ
G\VIXQFWLRQDOVRKDGLQFUHDVHG16(FRQFHQWUDWLRQ
7KLV ILQGLQJ ZDV LQ FRQWUDVW WR D VWXG\ E\ +VX
et al LQ  FKLOGUHQ ZLWK VHYHUH VHSVLV DQG VHSWLF
VKRFN7KH\UHSRUWHGKLJKHU16(FRQFHQWUDWLRQV
PRVWO\ LQ JOLDO FHOOV :H IRXQG 6% SURWHLQ
FRQFHQWUDWLRQVWREHORZHUWKDQWKHH[SHFWHGFXWRII
OHYHO7KLVILQGLQJKLQGHUHGWKHUHDOSLFWXUHRI6%
SURSHUWLHVDVDQHZFXWRIISRLQWRIJ/EDVHG
RQPHGLDQYDOXHZDVXVHG5DZGDWDDQDO\]HGXVLQJ
6SHDUPDQ 5KR FRHIILFLHQW UHYHDOHG D FRUUHODWLRQ RI
$VWXG\E\(OWLQJet alSHUIRUPHGLQFKLOGUHQ
ZLWK WUDXPDWLF EUDLQ LQMXU\ IRXQG D FRUUHODWLRQ RI
*&6VFRUHYHUVXV6%ZLWKDYDOXHRI The
ORZHUFRUUHODWLRQFRHIILFLHQWYDOXHFRPSDUHGWR16(
YDOXHV VXJJHVW WKDW 16( LV D PRUH UHOLDEOH SUHGLFWRU
RI QHXURORJLF RXWFRPHV WKDQ 6% 5XQGJUHQ et
alVWXG\LQJSDWLHQWVDIWHUFDUGLDFDUUHVWUHSRUWHGWKH
VXSHULRULW\RI16(FRPSDUHGWR6%LQSUHGLFWLQJ
QHXURORJLFDO RXWFRPHV ZLWKLQ  WR  KRXUV DIWHU
FDUGLDF DUUHVW 8QOLNH WKDW RI 16( WKH UHVXOWLQJ
6% 52& FXUYH ZDV LQVLJQLILFDQW +RZHYHU
Paediatr Indones, Vol. 52, No. 2, March 2012 115
 Nahari Arifin et al: &RUUHODWLRQEHWZHHQEUDLQLQMXU\ELRPDUNHUVDQG*ODVJRZ&RPD6FDOHLQSHGLDWULFVHSVLV
6%ZDVVLJQLILFDQWO\UHODWHGWRVHSWLFVHYHULW\DQG
GHDWK 6% FRQFHQWUDWLRQV LQ VXEMHFWV ZLWK IDWDO
RXWFRPHVYDULHGIURPWRWLPHVWKHQRUPDOFXWRII
OHYHORIJ/,QFRQWUDVWWR16(6%VHUXP
FRQFHQWUDWLRQLVQRWLQIOXHQFHGE\KHPRO\VLV*OLDO
FHOOGHDWKDQGLQMXU\FRQWULEXWHVWRLWVULVHLQVHUXP
DQG &6) &\WRNLQH DFWLYDWLRQ DQRWKHU PHFKDQLVP
UHODWHGWRWKHLQIODPPDWLRQFDVFDGHLQWXUQGLVUXSWV
WKHEORRGEUDLQEDUULHULQWHJULW\)DWDOLW\KDVEHHQ
DVVRFLDWHG ZLWK KLJK OHYHO RI VHUXP 6% LQ VRPH
VWXGLHV*LYHQWKDW6%LVQRWJOLDOVSHFLILFLW
KDVOHVVRIDUHODWLRQVKLSZLWKVHYHUHFOLQLFDORXWFRPHV
DVFRPSDUHGWR16(+HDUWDQGNLGQH\VDUHWKHPDLQ
RUJDQV SURGXFLQJ VLJQLILFDQW DPRXQWV RI 6% LQ
VHUXP25,QFDVHVRIVHSVLVZLWKPXOWLSOHRUJDQIDLOXUH
YXOQHUDEOHKHPRG\QDPLFGLVWXUEDQFHVHYHQWXDOO\UDLVH
VHUXP 6% FRQFHQWUDWLRQ GXH WR LQMXU\ RI WKHVH
RUJDQV$JHXQGHUO\LQJDQGFRPRUELGGLVHDVHVDQG
FKLOGGHYHORSPHQWDOVWDJHDOVRLQIOXHQFHVHUXP6%
FRQFHQWUDWLRQ
7KH GHVFULSWLYH VWXG\ GHVLJQ LQ WKLV WULDO KDG
VRPHOLPLWDWLRQV:HKDGWKHUHTXLUHGVDPSOHVL]H
IRUSHUIRUPLQJFRUUHODWLRQDQDO\VLVEXWOHVVWKDQWKH
UHTXLUHGVDPSOHVL]HIRUGLFKRWRPRXVDQDO\VLVEHWZHHQ
FOLQLFDOSDUDPHWHUDQGELRPDUNHUVDVLQGLFDWHGE\
WKHZLGHFRQILGHQFHLQWHUYDOV2WKHUOLPLWDWLRQVZHUH
VLQJOHPHDVXUHPHQWVLQVWHDGRIVHULDOPHDVXUHPHQWV
XVHRIRQO\FOLQLFDOSDUDPHWHUVUDWKHUWKDQDOVRXVLQJ
DQG HWKLFDO FOHDUDQFH FDQ EH HDVLHU WR REWDLQ IURP
HQRXJKVXEMHFWV
8QWLOUHFHQWO\WKHXVHRIEUDLQLQMXU\ELRPDUNHUV
LQSHGLDWULFVHSVLVZDVGLVSXWHGDQGRQHVWXG\WHUPHG
16( DQG 6% WR EH VXUURJDWH ELRPDUNHUV 2XU
UHVXOWV VKRZ WKDW 16( DQG 6% DUH SRWHQWLDOO\
XVHIXOELRPDUNHUVIRUXVHLQSHGLDWULFVHSVLVFDVHV
,Q FRQFOXVLRQ FRQVLVWHQW ZLWK SUHYLRXV
VWXGLHV ZH IRXQG D FRUUHODWLRQ EHWZHHQ *&6
VFRUHDQGELRPDUNHUV16(FRQFHQWUDWLRQRIXJ/
IRU D *&6 VFRUH EHORZ  KDG D SUHGLFWLYH YDOXH
6% ZDV DVVRFLDWHG ZLWK WKH FOLQLFDO RXWFRPHV
RIGLVHDVHVHYHULW\DQGGHDWK
References
 &HQWHU IRU 'LVHDVH &RQWURO ,QFUHDVH LQ QDWLRQDO KRVSLWDO
GLVFKDUJHVXUYH\UDWHVIRUVHSWLFHPLD8QLWHG6WDWHV
0RUE0RUWDO:NO\5HS
 $PHULFDQ&ROOHJHRI&KHVW3K\VLFLDQ6RFLHW\RI&ULWLFDO
&DUH0HGLFLQH&RQVHQVXV&RQIHUHQFH'HILQLWLRQVIRUVHSVLV
DQGRUJDQIDLOXUHDQGJXLGHOLQHVIRUWKHXVHRILQQRYDWLYH
WKHUDSLHVLQVHSVLV&ULW&DUH0HG
 %DON 5$ 6HYHUH VHSVLV DQG VHSWLF VKRFN GHILQLWLRQ
HSLGHPLRORJ\ DQG FOLQLFDO PDQLIHVWDWLRQV &ULW &DUH &OLQ

 :DWVRQ 56 &DUFLOOR -$ /LQGH=ZLUEOH :7 &OHUPRQW *
((*DQGLPDJLQJ&705,ILQGLQJV7KHIRUPHU
OLPLWDWLRQZDVGXHWRODFNRISDUHQWDOFRQVHQWZKLOH
WKHODWWHUZDVGXHWRODFNRI((*DYDLODELOLW\LQWKH
,&8VHWWLQJWUDQVSRUWDWLRQGLIILFXOWLHVIRUERWK((*
DQGLPDJLQJSURFHGXUHVDQGXQVWDEOHVXEMHFWFOLQLFDO
FRQGLWLRQV6HULDOPHDVXUHPHQWRIELRPDUNHUVZRXOG
EH LGHDO DV WKH\ FDQ VKRZ PXOWLSOH YDOXHV ZLWKLQ
D FHUWDLQ WLPH IUDPH 5XQGJUHQ et al VWDWHG WKDW
VHULDOELRPDUNHUPHDVXUHPHQWDOVRGHFUHDVHGVRPH
WHFKQLFDOHUURUVLQWKHODERUDWRU\((*DUHVHQVLWLYH
WRROVWRHYDOXDWHEUDLQLQMXU\DQGDUHUHJDUGHGDVWKH
JROGVWDQGDUGSDUWLFXODUO\IRUWKHGHWHFWLRQRIQRW
RQO\HQFHSKDORSDWK\DQGVHYHULW\RIEUDLQGDPDJH
EXW DOVR VXEWOH VHL]XUHV LQ VHGDWHG RU LQWXEDWHG
VXEMHFWV
'HVSLWHWKHOLPLWDWLRQVVRPHDGYDQWDJHVPXVWEH
QRWHG6LQJOHVDPSOHVREWDLQHGIURPDUHJXODUFOLQLFDO
VHWWLQJ PLPLF URXWLQH GDLO\ EHGVLGH SURFHGXUHV ,I
IXWXUH VWXGLHV RI GLIIHUHQW GHVLJQV DUH WR EH FDUULHG
RXWPRUHVXEMHFWVVKRXOGEHUHFUXLWHGVRWKDWOHJDO
116Paediatr Indones, Vol. 52, No. 2, March 2012
/LGLFNHU-$QJXV'&7KHHSLGHPLRORJ\RIVHYHUHVHSVLVLQ
FKLOGUHQLQWKH8QLWHG6WDWHV$P-5HVSLU&ULW&DUH0HG

 *ROGVWHLQ%*LURLU%5DQGROSK$,QWHUQDWLRQDOSHGLDWULF
VHSVLV FRQVHQVXV FRQIHUHQFH GHILQLWLRQV IRU VHSVLV DQG
RUJDQ G\VIXQFWLRQ LQ SHGLDWULFV 3HGLDWU &ULW &DUH 0HG

 6SUXQJ&/3HGX]]L316KDWQH\&+6FKHLQ50:LOVRQ0)
6KHDJUHQ-1HWDO,PSDFWRIHQFHSKDORSDWK\RQPRUWDOLW\
LQ WKH VHSVLV V\QGURPH 7KH 9HWHUDQV $GPLQLVWUDWLRQ
6\VWHPLF6HSVLV&RRSHUDWLYH6WXG\*URXS&ULW&DUH0HG

 +VX $$ )HQWRQ . :HLQVWHLQ 6 &DUSHQWHU - 'DOWRQ +
%HOO0-1HXURORJLFDOLQMXU\PDUNHUVLQFKLOGUHQZLWKVHSWLF
VKRFN3HGLDWU&ULW&DUH0HG
 +HOOVWURP:HVWDV/&RQWLQXRXVHOHFWURHQFHSKDORJUDSK\
PRQLWRULQJ RI WKH SUHWHUP LQIDQW &OLQ 3HULQDWRO 

 0HZDVLQJK /' &KULVWRSKH & )RQWH\QH & 'DFK\
% =LHUHLVHQ ) &KULVWLDHQV ) HW DO 3UHGLFWLYH YDOXH RI
 Nahari Arifin et al: &RUUHODWLRQEHWZHHQEUDLQLQMXU\ELRPDUNHUVDQG*ODVJRZ&RPD6FDOHLQSHGLDWULFVHSVLV
HOHFWURSK\VLRORJ\LQFKLOGUHQZLWKK\SR[LFFRPD3HGLDWU
1HXURO
 6KDUVKDU7&DUOLHU5%HUQDUG)*XLGRX[&%URXODQG-31DUGL
2HWDO%UDLQOHVLRQVLQVHSWLFVKRFNDPDJQHWLFUHVRQDQFH
LPDJLQJVWXG\,QWHQVLYH&DUH0HG
 %HUJHU533LHUFH0&:LVQLHZVNL65$GHOVRQ3'&ODUN
565XSSHO5$HWDO1HXURQVSHFLILFHQRODVHDQG6%
LQFHUHEURVSLQDOIOXLGDIWHUVHYHUHWUDXPDWLFEUDLQLQMXU\LQ
LQIDQWVDQGFKLOGUHQ3HGLDWULFV
 7RSMLDQ$$/LQ50RUULV0&,FKRUG5'URWW+%D\HU
&5HWDO1HXURQVSHFLILFHQRODVHDQG6%DUHDVVRFLDWHG
ZLWKQHXURORJLFRXWFRPHDIWHUSHGLDWULFFDUGLDFDUUHVW3HGLDWU
&ULW&DUH0HG
 1JX\HQ'16SDSHQ+6X)6FKLHWWHFDWWH-6KL/+DFKLPL
,GULVVL6HWDO(OHYDWHGVHUXPOHYHOVRI6EHWDSURWHLQ
DQGQHXURQVSHFLILFHQRODVHDUHDVVRFLDWHGZLWKEUDLQLQMXU\
LQ SDWLHQWV ZLWK VHYHUH VHSVLV DQG VHSWLF VKRFN &ULW &DUH
0HG
 (LGHOPDQ/$3XWWHUPDQ'3XWWHUPDQ&6SUXQJ&/7KH
VSHFWUXPRIVHSWLFHQFHSKDORSDWK\'HILQLWLRQVHWLRORJLHV
DQGPRUWDOLWLHV-$0$
 (EHUVROGW 0 6KDUVKDU 7 $QQDQH ' 6HSVLVDVVRFLDWHG
GHOLULXP,QWHQVLYH&DUH0HG
 <RXQJ *% %ROWRQ &) $UFKLEDOG <0 $XVWLQ 7: :HOOV
*$ 7KH HOHFWURHQFHSKDORJUDP LQ VHSVLVDVVRFLDWHG
HQFHSKDORSDWK\-&OLQ1HXURSK\VLRO
PDUNHURIK\SR[LFEUDLQGDPDJHDQGRXWFRPHDIWHUFDUGLDF
DUUHVWLQKXPDQV&LUFXODWLRQ
 6KDUVKDU7+RSNLQVRQ12UOLNRZVNL2$QQDQH'6FLHQFH
UHYLHZWKHEUDLQLQVHSVLVFXOSULWDQGYLFWLP&ULW&DUH

 7LDLQHQ05RLQH523HWWLOD97DNNXQHQ26HUXPQHXURQ
VSHFLILFHQRODVHDQG6%SURWHLQLQFDUGLDFDUUHVWSDWLHQWV
WUHDWHGZLWKK\SRWKHUPLD6WURNH
 %HUJHU53$GHOVRQ3'5LFKLFKL5.RFKDQHN306HUXP
ELRPDUNHUV DIWHU WUDXPDWLF DQG K\SR[HPLF EUDLQ LQMXULHV
LQVLJKWLQWRWKHELRFKHPLFDOUHVSRQVHRIWKHSHGLDWULFEUDLQ
WRLQIOLFWHGEUDLQLQMXU\'HY1HXURVFL
 *XDQ:<DQJ<O;LD:06LJQLILFDQFHRIVHUXPQHXURQ
VSHFLILFHQRODVHLQSDWLHQWVZLWKDFXWHWUDXPDWLFEUDLQLQMXU\
&KLQ-7UDXPDWRO: 
 5RVV 6$ &XQQLQJKDP 57 -RKQVWRQ &) 1HXURQVSHFLILF
HQRODVHDVDQDLGWRRXWFRPHSUHGLFWLRQLQKHDGLQMXU\%U-
1HXURVXUJ
 (OWLQJ-:'H-DJHU$(7HHONHQ$:&RPSDULVRQRIVHUXP
6 SURWHLQ OHYHOV IROORZLQJ VWURNH DQG WUDXPDWLF EUDLQ
LQMXU\-1HXURO6FL
 5XQGJUHQ 0 7RUEM|UQ . 1LHOVHQF 1 &URQEHUJG 7
-RKQVVRQH3)ULEHUJI+1HXURQVSHFLILFHQRODVHDQG6%
DV SUHGLFWRUV RI RXWFRPH DIWHU FDUGLDF DUUHVW DQG LQGXFHG
K\SRWKHUPLD5HVXVFLWDWLRQ
 5HGO+3HOLQND/%DKUDPL6%ROW]PDQQ/7REHRUQRWWR
 %|WWLJHU%:0|EHV6*OlW]HU5%DXHU+*ULHV$%lUWVFK EHDELRPDUNHURIEUDLQGDPDJHLQVHSVLVUHYLHZ3HGLDWU
3 HW DO $VWURJOLDO SURWHLQ 6 LV DQ HDUO\ DQG VHQVLWLYH &ULW&DUH

Paediatr Indones, Vol. 52, No. 2, March 2012 117