Paediatrica Indonesiana

VOLUME 51 March ‡ NUMBER 2

Original Article

Randomized controlled trial of erdosteine for acute

cough in children with colds
Yenny, Roni Naning, Amalia Setyati

T
Abstract he common cold is a self-limiting acute,
Background The prevalence of the common cold in children upper respiratory tract infection often with
LVKLJKZLWKRIFDVHVH[KLELWLQJDQDFXWHFRXJKWKHPRVW flu-like symptoms including acute cough,
common complaint by parents. Erdosteine, a recently developed DQG XVXDOO\ FDXVHG E\ YLUXVHV E\
cough medicine, is available for children. Erdosteine has been
UHSRUWHGWRLQFUHDVHPXFRFLOLDU\FOHDUDQFHDFWDVDQDQWLR[LGDQW
rhinovirus).1$FXWHFRXJKLQJODVWVOHVVWKDQZHHNV
and prevent bacterial adhesion. DQGLVXVXDOO\SUHVHQWLQRIFRPPRQFROGFDVHV2
Objective To assess the clinical improvement in acute cough Children suffer from the common cold an average
in children with a common cold taking erdosteine vs. a placebo. of 6-8 times per year and coughing is a frequent
Methods We conducted a double-blind, randomized, controlled complaint by parents who take their child to visit the
WULDODWWKH3XEOLF+HDOWK&HQWHURI*HGRQJWHQJHQ<RJ\DNDUWD
doctor.,Q,QGRQHVLDRISDWLHQWVLQSULPDU\
ZLWKFKLOGUHQVHOHFWHGE\DFRQVHFXWLYHVDPSOLQJPHWKRG
Research subjects were randomized by computer program into two KHDOWKFHQWHUVDQGRIRXWSDWLHQWVYLVLWGRFWRUV
treatment groups, those receiving erdosteine therapy and those due to the common cold, which makes it one of the
UHFHLYLQJDSODFHER%RWKJURXSVZHUHPRQLWRUHGIRUGD\V$ PRVWFRPPRQKHDOWKFRPSODLQWV,Q<RJ\DNDUWDWKH
scoring system was used to assess the improvement of acute cough prevalence of the common cold in children below
symptoms and analyzed by chi-square test.
\HDUV RI DJH LV D \HDU ,QGRQHVLDQ +HDOWK
Results No significant differences in basic characteristics, cough
VHYHULW\ RU HQYLURQPHQW ZHUH IRXQG DPRQJ WKH FKLOGUHQ 0LQLVWU\
ZLWKFRPPRQFROGLQWKHWZRJURXSV$IWHUGD\VRIWUHDWPHQW %RWK LQ YLWUR DQG LQ YLYR H[SHULPHQWV KDYH
no significant difference in clinical improvement of acute cough shown that erdosteine increases mucociliary clear-
was found between the erdosteine (65 subjects improved out of DQFHDFWVDVDQDQWLR[LGDQWDQGSUHYHQWVEDFWHULDO
DQGSODFHERJURXSVDQGUHVSHFWLYHO\
3
adhesion. 5-9 One study reported that in 158 children
Conclusion Erdosteine was not more effective than the placebo aged 2-12 years old with acute lower respiratory tract
for treatment of acute cough in children with common cold. LQIHFWLRQDFXWHFRXJKV\PSWRPVLPSURYHGLQ
[Paediatr Indones. 2011;51:111-5].

Keywords: common cold, cough, erdosteine,

children From the Department of Child Health, Gadjah Mada University Medical
6FKRRO<RJ\DNDUWD,QGRQHVLD

Reprint request to<HQQ\0''HSDUWPHQWRI&KLOG+HDOWK*DGMDK

0DGD 8QLYHUVLW\ 0HGLFDO 6FKRRO -DODQ .HVHKDWDQ 1R <RJ\DNDUWD
,QGRQHVLD7HO)D[(PDLO
[email protected]

Paediatr Indones, Vol. 51, No. 2, March 2011 ‡111

Yenny et al: Randomized controlled trial of erdosteine for acute cough in children with colds

of the erdosteine group by the 5th day of therapy, as cigarette smoke or mosquito repellant during the
FRPSDUHGWRLQWKHSODFHERJURXS$QRWKHU VWXG\$GGLWLRQDOWKHUDS\RISDUDFHWDPRODWDGRVDJH
VWXG\RIFKLOGUHQDJHG\HDUVZLWKDFXWHORZHU RIPJNJHYHU\KRXUVZDVJLYHQIRUGD\VLIWKH
respiratory tract infection showed statistically sig- subject had fever. School was defined as children’s
nificant improvement in symptoms in 59.8% in the enrollment status in kindergarten. Mother’s education
erdosteine group after 7 days of the therapy compared is shown as the level completed.
WRLQWKHSODFHERJURXS3 11 Common cold was diagnosed in children using
Erdosteine is widely prescribed by physicians. WKH$$3*XLGHOLQHVWKDWGHILQHWKHFRQGLWLRQDV
However, there is little data on its effectiveness in having cough and cold with fluid and clear secretions
acute upper respiratory tract infections, especially RUPXFRSXUXOHQWGLVFKDUJHIRUOHVVWKDQGD\VZLWKRU
common colds in children. Therefore, this study aims ZLWKRXWPLOGIHYHUoC), good general condition and
to assess the effectiveness of erdosteine on clinical QRDEQRUPDOLWLHVRQFKHVWH[DPLQDWLRQ12$FXWHFRXJK
improvement of acute cough symptoms in children ZDVGHILQHGDVDFRXJKODVWLQJIRUGD\VZLWKWRWDO
\HDUVROGZLWKWKHFRPPRQFROGLQ,QGRQHVLD FOLQLFDOFRXJKVFRUH•&RXJKVFRUHLPSURYHPHQWZDV
defined as a decrease in the total clinical cough score,
while no improvement was a persistence or increase in
Methods the total cough score (Table 1).
3DWLHQW FRPSOLDQFH WR WUHDWPHQW DQG DGYHUVH
We performed a randomized, double-blind, con- drug effects were taken as secondary outcomes.
WUROOHG WULDO LQ WKH 3XEOLF +HDOWK &HQWHU 3+& RI $GYHUVHGUXJHIIHFWVZHUHGHILQHGDVWKHXQH[SHFWHG
*HGRQJWHQJHQ<RJ\DNDUWDIURP$XJXVWXQWLO effects related to the drug during the treatment.
$SULO :H LQFOXGHG FKLOGUHQ DJHG Drug compliance was defined as fulfilling the drug
PRQWKVZLWKFRPPRQFROG”GD\VZLWKWRWDOFRXJK administration schedule and no missed dosages
VFRUH•Table 1), good nutritional state, and who during the entire treatment course. Compliance was
GLGQRWUHFHLYHPXFRO\WLFVH[SHFWRUDQWVDQWLWXVVLYHV FKHFNHGDW3+&ZKHQSDWLHQWVUHWXUQHGIRUFRQWURO
antihistamines or corticosteroid therapy before the YLVLWVZLWKWKHERWWOHVWRVHHLI!RIWKHGUXJVKDG
VWXG\HQUROOPHQW:HH[FOXGHGWKRVHZLWKDFXWHRWLWLV been taken by the patients. Dropout was defined as
media, heart disease, cough preceded by choking, the parents’ refusal to continue the study, inability
lower respiratory tract symptoms (tachypnea, dyspnea, to reestablish contact with parents, or the child’s
rhonchi, wheezing, stridor, crepitation, asymmetric condition worsening and requiring hospitalization.
breathing sounds, or chest wall retractions), and $SK\VLFLDQDW3+&ZDVWUDLQHGWRVHOHFWVXEMHFWV
IDPLO\SDWLHQW KLVWRU\ RI DVWKPD DOOHUJLF UKLQLWLV diagnosed with the common cold who met the
XUWLFDULDDQGIRRGGUXJDOOHUJLHV inclusion criteria through history taking and physical
Subjects fulfilling the criteria were computer H[DPLQDWLRQ7KHNDSSDYDOXHZDVIRUDJUHHPHQW
randomized into 2 groups after determining the sample EHWZHHQ UHVHDUFKHU DQG 3+& SK\VLFLDQ $ WUDLQHG
VL]H6XEMHFWVUHFHLYHGHLWKHUHUGRVWHLQHPJNJGD\ QXUVH DW 3+& ILOOHG UHVHDUFK IRUPV H[SODLQHG WR
or placebo dry syrup in 2 divided doses daily for 6 days. parents how to fill the drug compliance forms, and set
,IWKHVXEMHFWYRPLWHGZLWKLQKRXURIWDNLQJWKH WKHIROORZXSDSSRLQWPHQW$WUDLQHGSKDUPDF\DVVLV
syrup, another dose was given. Erdosteine and placebo
preparations were stable up to 7 days and similar in
package, flavor and color. Table 1. Cough clinical score
Disease duration was measured starting from Secretions Sleep at night
WKH ILUVW GD\ RI FRXJK DQGRU FROG XQWLO WKH ILUVW 0. Cough without mucous 0. Good
GD\RIWKHUDS\DW3+&0LOGIHYHUZDVGHILQHGDVD 1. Cough with mucous 1. Awaken once due to
cough
WHPSHUDWXUH RI ƒ& ERWK EHIRUH DQG GXULQJ WKH
2. Cough till vomit 2. Awaken > once due to
study. Risk factors were defined as a history of common cough
FROGH[SRVXUHDWKRPHRUVFKRROZLWKLQWKHSDVWZHHN 3. Child cannot sleep due
DQGVXEMHFWV·H[SRVXUHWRH[RJHQRXVVWLPXODQWVVXFK to cough

112‡Paediatr Indones, Vol. 51, No. 2, March 2011

Yenny et al: Randomized controlled trial of erdosteine for acute cough in children with colds

tant gave either erdosteine or placebo according to the treatment and placebo groups. Before treatment,
randomized list along with other drugs prescribed by cough severity of total score 2-3 was not significantly
WKHGRFWRU$OOSDUWLFLSDQWVSDUHQWVSK\VLFLDQQXUVH GLIIHUHQWEHWZHHQWKHWUHDWPHQWDQGSODFHER
and pharmacy assistant were blinded to the content JURXSV3
of the research drugs. On the 6 th day of follow-up, no significant
3DWLHQWVZHUHH[DPLQHGRQWKHGD\RIHQUROOPHQW difference in clinical improvement of cough symptoms
and the 6th day of treatment, using the same clinical between the two groups was observed. In the
cough scoring scale. Secondary outcomes were also erdosteine group, 92.9% improved and in the placebo
evaluated, including drug side effects and dropping JURXSLPSURYHG3 Table 3). During
out of the therapy regimen. the course of treatment, no side effects were reported
The Ethics Committee of Faculty of Medicine, H[FHSW E\ RQH SDUWLFLSDQW LQ WKH HUGRVWHLQH JURXS
*DGMDK 0DGD 8QLYHUVLW\ <RJ\DNDUWD ,QGRQHVLD who suffered from vomiting but did not require
approved this study. Informed consent was obatained hospitalization.
from parents.
Table 2. Characteristics of subjects.
Effectiveness of the erdosteine compared to
placebo was predicted to be 25%, based on data Characteristic Erdosteine Placebo
n=70 n=70
obtained from previous studies on acute cough. Age (months)
%\WDNLQJDQDOSKD DQGHVWLPDWLQJDSDWLHQW 12 – 35, n (%) 36 (51.4) 36 (52.2)
ORVVVDPSOHVL]HZDVFDOFXODWHGDVZLWKSRZHU 36 - 60 34 (48.6) 34 (47.8)
Data was presented in tabulation form with means Weight (kg)
and standard deviations. Numerical data was then 10-12, n (%) 33 (47.1) 36 (52.2)
grouped into categories and converted to percentages. 13-15 20 (28.6) 18 (26.1)
16-19 17 (24.3) 16 (21.7)
Chi square test was used to assess differences between Illness duration, days, n (%)
erdosteine and placebo in acute cough improvement. 1-3 57 (81.4) 57 (82.6)
Multivariate logistic regression was used to assess and 4-5 13 (18.6) 13 (17.4)
Gender, n (%)
identify other factors influencing cough improvement.
Boys 37 (52.9) 38 (55.1)
Subjects who dropped out or were lost on follow up
Girls 33 (47.1) 32 (44.9)
were included, since this was an intention to treat
Initial cough score, n (%)
analysis. We used a confidence interval of 95% and 2-3 66 (94.3) 66 (95.7)
performed doubled data entry and statistical analysis 4-5 4 (5.7) 4 (4.3)
ZLWK6WDWD Mother’s education, n (%)
Primary school 10 (14.3) 7 (10.1)
Junior high school 27 (38.6) 38 (55.1)
Senior high school 28 (40.0) 22 (31.9)
Results College 5 (7.1) 3 (2.9)
School, n(%)
2XWRISDWLHQWVZKRYLVLWHG3+&VXEMHFWV Yes 40 (57.1) 53 (76.8)
ZHUH HQUROOHG RXU VWXG\ $OO VXEMHFWV GLYLGHG LQWR No 30 (42.9) 17 (23.2)
WZRJURXSVRIHDFKWKHWUHDWPHQWJURXSDQGWKH Smoke exposure, n (%)
placebo group. One participant in the placebo group Yes 48 (68.6) 54 (78.3)
dropped out because they were unable to be contacted No 22 (31.4) 16 (21.7)
(Figure 1). We did an intention to treat analysis and Common cold exposure, n (%)
therefore included subject who dropped out. Yes 37 (52.9) 39 (56.5)
Demographic characteristics of participants No 33 (47.1) 31 (43.5)
are shown in Table 2. There were no significant Fever, n (%)
Yes 25 (35.7) 31 (44.9)
differences in subjects’ age, weight, gender, duration
No 45 (64.3) 39 (55.1)
of the disease, initial cough score, mothers’ education,
Compliance, n (%)
KLVWRU\RIVPRNHH[SRVXUHKLVWRU\RIFRPPRQFROG Yes 59 (84.3) 57 (82.6)
H[SRVXUH IHYHU RU GUXJ FRPSOLDQFH EHWZHHQ WKH No 11 (15.7) 13 (17.4)

Paediatr Indones, Vol. 51, No. 2, March 2011 ‡113

Yenny et al: Randomized controlled trial of erdosteine for acute cough in children with colds

Eligibility assessment
In our study, there was a significant difference
(not recorded) among children that attended kindergarten between
WKH WZR JURXSV 3 +RZHYHU DIWHU PXOWL
Randomized
(n = 140) variate regression analysis, we found that children
attending kindergarten did not strongly correlate to
Erdosteine group Group Placebo group
treatment between the groups (Table 4).
(n = 70) allocation (n = 70) By the 3rd day of treatment, there was impro-
YHPHQWLQV\PSWRPVLQWKHHUGRVWHLQHJURXS
Vomiting Follow-up Dropped out
(n = 1) at 6 days (n = 1) and in the placebo group (98.6%), however they were
not significantly different. (Figure 2)
Included in Analysis Included in
intention to treat analysis intention to treat analysis
(n = 70) (n = 70)

Discussion
Figure 1. Consort diagram Our findings differed from those of two previous studies
by Titti et al., and Balli et al.112QHH[SODQDWLRQFRXOG
Table 3. Improvement of acute cough symptoms. be that their studies were on subjects with acute lower
Erdosteine Placebo P respiratory tract infections, which are more likely to be
n = 70 n = 70 caused by bacteria. For their purposes, erdosteine was
Cough score prescribed along with antibiotics. The anti-adhesive
improvement
Yes, n (%) 65 (92.9) 62 (88.6) 0.382*
effect of erdosteine prevents bacterial adhesion to the
No, n (%) 5 (7.1) 8 (11.4) respiratory tract and synergizes with the antibiotic
Side effects effects, influencing outcomes.13$QRWKHUGLIIHUHQFHLV
Yes, n (%) 1(1.4) - 0.319* in the nature of cough receptors in the upper and lower
No, n (%) 69(98.6) 69 (100)
respiratory tracts. The upper tract is mechanosensitive,
:UKIPKſECPVKH2XCNWG
while lower tract is chemosensitive. In vitro studies
Table 4. Multivariate logistic regression analysis for showed no correlation between concentrations of
QVJGTHCEVQTUVJCVOC[KPƀWGPEGVJGKORTQXGOGPVQH QLWULWHR[LGHDQG,/DQGQDVDOVHFUHWLRQVRIFRPPRQ
the acute cough symptoms. cold patients, while IL-8 levels significantly increased
Factors P RR 95% CI in symptomatic patients.15,16 Erdosteine significantly
Good drug compliance 0.790 1.020 0.880-1.183 reduced the production of tumor necrosis factor-Į
Illness duration (1-3 days) 0.856 0.986 0.844-1.152 (TNF-A) and interleukin-1B,6 (IL-1B,6) in alveolar
Initial cough score (2-3) 0.713 0.986 0.913-1.064
School (Yes)19 0.013 0.744 0.585-1.946 macrophages.17,18
Smoke exposure (Yes) 0.196 0.876 0.716-1.072 Children under five years of age who attended
VFKRRORUNLQGHUJDUWHQKDYHEHHQVKRZQWRKDYHD
higher chance of having a common cold compared to
Improvement on cough symptoms
KOHOR Erdostein Plasebo
100 Day 1 87,1 91,4 those staying at home.19 We found a significant differ-
98 Day 2
Day 3
91,4
91,4
94,3
98,6
98,6 97,1
ence among children attending kindergarten between
96 97,1
Day 4 90,0 97,1 the erdosteine and placebo groups.
Proportion

94 94,3
Day 5 92,9 97,1
92 Day 691,4 92,9 88,6 92,9
92,9
Systematic review studies show that cough medi-
91,4
90 91,4 90,0
88,6
cine is not recommended as first-line therapy for acute
88
86
87,1 cough in children. When used, patients require
Day 1 Day 2 Day 3 Day 4 Day 5 Day 6 routine monitoring and the drug must be discontinued
Erdosteine Placebo LI QR LPSURYHPHQW RFFXUV ZLWKLQ WKH H[SHFWHG WLPH
period.23&OLQLFLDQVQHHGWRH[SODLQWKHDSSURSULDWHXVH
Figure 2. Improvement of cough over 6 days with of cough medicines to parents and encourage them to
PQUKIPKſECPVFKHHGTGPEG
2KPRGTEGPVCIGQH bring their children back if coughing does not subside
subjects between erdosteine and placebo group.
to look for possible alternative causes.

114‡Paediatr Indones, Vol. 51, No. 2, March 2011

Yenny et al: Randomized controlled trial of erdosteine for acute cough in children with colds

$ OLPLWDWLRQ RI WKLV VWXG\ ZDV WKDW WKHUH ZDV QHXWURSKLOV3KDUPDFRO

some subjectivity to the quantitative scoring of cough 7LWWL*/L]]LR$7HUPLQL&1HJUL3)D]]LR60DQFLQL&
severity. Total cough scores were measured at home $FRQWUROOHGPXOWLFHQWHUSHGLDWULFVWXG\LQWKHWUHDWPHQW
by parents and there was no kappa test for agreement of acute respiratory tract diseases with the aid of a new
between parents and doctors in assessing coughs. VSHFLILFFRPSRXQGHUGRVWHLQH,36(,WDOLDQ3HGLDWULF6WXG\
In conclusion, we observed that erdosteine had (UGRVWHLQH,QW-&OLQ3KDUPDFRO7KHU
no effect on clinical improvement of cough symptoms %DOOL)%HUJDPLQL%&DOLVWUX3&LRIX(3'RPHQLFL5'RURV
in upper respiratory tract illnesses compared to the G, et al. Clinical effects of erdosteine in the treatment of acute
placebo. This study may form the basis for future UHVSLUDWRU\ WUDFW GLVHDVH LQ FKLOGUHQ ,QW - &OLQ 3KDUPDFRO
research. 7KHU
7RODQ5: 1JX\HQ015KLQRYLUXVLQIHFWLRQ>FLWHGRQ
Acknowledgments -XQH@$YDLODEOHIURPKWWSZZZHPHGLFLQHFRP
UKLQRYLUXVWRSLFKWP
:HWKDQN'U(QG\3DU\DQWR3UDZLURKDUWRQR7DUL7XUQHU0' %UDJD3&=XFFRWWL7'DO6DVVR0'%DFWHULDODGKHVLYHQHVV
and all research assistants. We also stated that authors had no effects of the SH metabolite of erdosteine (mucoactive
conflict of interest. drug) plus clarithromycin versus clarithromycin alone. J
&KHPRWKHU
&KDQJ$%7KHSK\VLRORJ\RIFRXJK3HGLDWU5HV5HYLHZV
References
=KX = 7DQJ :/ *ZDOWQH\ -0 (OLDV -$ 5KLQRYLUXV
+HLNNLQHQ 7 -DUYLQHQ $ 7KH FRPPRQ FROG /DQFHW stimulation of interleukin-8 in vivo and in vitro-role of NF-
kappa-B$P-3K\VLRO
+D\$':LOVRQ$)DKH\73HWHU7-7KHGXUDWLRQRIDFXWH .DXO36LQJK,7XUQHU5%(IIHFWRIQLWULFR[LGHRQUKLQRYLUXV
cough in pre-school children presenting to primary care: a UHSOLFDWLRQDQGYLUXVLQGXFHGLQWHUOHXNLQHODERUDWLRQ$P
SURVSHFWLYHFRKRUWVWXG\)DP3UDF -5HVSLU&ULW&DUH0HG
6DXQGHUV 15 7HQQLV 2 -DFREVRQ 6 *DQV 0 'LFN 37 <RRQ<--LQ+6<RQJ.6(XQ6+&KXQJ6/'HSUHVVDQW
3DUHQWV·UHVSRQVHVWRV\PSWRPVRIUHVSLUDWRU\WUDFWLQIHFWLRQ HIIHFWV RI DPEUR[RO DQG HUGRVWHLQH RQ F\WRNLQH V\QWKHVLV
LQWKHLUFKLOGUHQ&0$- granule enzyme release, and free radical production in rat
0DVVLH-&RXJKLQFKLOGUHQZKHQGRHVLWPDWWHU"3HGLDWU alveolar macrophages activated by lipopolysaccharide. J
5HV5HY 3KDUPDFRO7R[LF
,QGRQHVLDQ+HDOWK0LQLVWU\-DNDUWDS 6WDQHD9/6WDQFLX/$0HVVDJH6'(GZDUGV05*HUQ-(
2OLYLHUL''HO'RQQR0&DVDOLQL$'LSSROLWR5)UHJQDQ Johnston SL. Rhinovirus replication in human macrophages
*%$FWLYLW\RIHUGRVWHLQHRQPXFRFLOLDU\WUDQVSRUWLQSDWLHQWV induces NF-KB-dependent tumor necrosis factor alpha
DIIHFWHGE\FKURQLFEURQFKLWLV5HVS- SURGXFWLRQ-9LURO
+RVRH+.DLVH72KPRUL.,VRKDPD<.DL+7DNDKDPD 7XUQHU 5% 1HZ FRQVLGHUDWLRQV LQ WKH WUHDWPHQW DQG
.HWDO0XFRO\WLFDQGDQWLWXVVLYHHIIHFWVRIHUGRVWHLQH- SUHYHQWLRQ RI UKLQRYLUXV LQIHFWLRQV 3HGLDWU $QQ
3KDUP3KDUPDFRO
%UDJD 3& 'DO 6DVVR 0 6DOD 0) *LDQQHOOH 9 (IIHFW RI 6FKURHGHU . )DKH\ 7 2YHUWKHFRXQWHU PHGLFDWLRQV IRU
erdosteine and its metabolites on bacterial adhesiveness. acute cough in children and adults in ambulatory settings.
$U]QHLPLWWHO)RUVFKXQJ >&RFKUDQH UHYLHZ@ ,Q 7KH &RFKUDQH /LEUDU\ ,VVXH
+D\DVKL.,+RVRH+.DLVH72KPRUL.3URWHFWLYHHIIHFW 2[IRUG8SGDWH6RIWZDUH
of erdosteine against hypochlorous acid-induced acute lung 6FKURHGHU.)DKH\76KRXOGZHDGYLVHSDUHQWVWRDGPLQLVWHU
injury and lipopolysaccharide-induced neutrophilic lung over the counter cough medicine for acute cough? Systematic
LQIODPPDWLRQLQPLFH-3KDUP3KDUPDFRO UHYLHZ RI UDQGRPL]HG FRQWUROOHG WULDOV $UFK 'LV &KLOG
16.
'DO6DVVR0&XOLFL0%LDQFKL7)RQWL(%UDJD3&,QKLELWRU\ &KDQJ$%/DQGDX/,9DQ$VSHUHQ33*ODVJRZ1-5REHUWVRQ
effects of metabolite I of erdosteine on the generation of CF, Marchant JM, et al. Cough in children: definitions and
QLWULFR[LGHDQGSHUR[\QLWULWHFKHPLOXPLQHVFHQFHE\KXPDQ FOLQLFDOHYDOXDWLRQ0HG-$XVW

Paediatr Indones, Vol. 51, No. 2, March 2011 ‡115