• pISSN: 2085-1545

• eISSN: 2339-093X
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Comparison between Insulin-like Growth Factor Binding Protein-1 Level and Bishop Score as Predictor of Successful ...

RESEARCH ARTICLE
Comparison between Insulin-like Growth Factor Binding Protein-1
Level and Bishop Score as Predictor of Successful Labor Induction in
Full Term Pregnancy with Preeclampsia
Nurul Setiyorini1, Ratnasari Dwi Cahyanti 2
1
Resident of Obstetrics and Gynecology Department, Medical Faculty, Diponegoro University, Semarang, Indonesia
2
Staff of Obstetrics and Gynecology Department, Medical Faculty, Diponegoro University, Semarang, Indonesia
*corresponding author, email: dr.noeroelanindita@gmail.com

ABSTRACT
Introduction: preeclampsia/eclampsia contributed to 30% of maternal mortality in RSUP Dr. Kariadi. Pre-induction bishop score assessment is a
standard for cervical maturity estimation. Other predictors currently being developed, including insulin-like growth factor binding protein-1 (IGFBP-1).
However, there is no cut-off point for IGFBP-1 examination in full term pregnancy, especially with preeclampsia and its complications. Objective: to
find IGFBP-1 levels and Bishop Score differences in preeclampsia women with induction labor.
Methods: this prospective observational cohort study was conducted in preeclampsia women with gestational age ≥37 weeks planned labor induction at
Obstetrics and Gynecology Ward RSUP Dr. Kariadi Semarang and networking hospital during study period (n=66). History taking, physical examination,
proteinuria, cervical mucus IGFBP-1, and bishop score calculation was performed. Statistical analysis was performed with paired-t test, followed by ROC
for cut-off value of successful induction prediction, and logistic regression to determine confounding variables effect on IGFBP-1 levels.
Results: The average Bishop score of 66 subjects was 2.5±1.81 and 2.6±1.8 for women who deliver ≤24 labor and in labor for ≤12 hours, respectively.
Although the bishop score was higher in the successful labor group, there was no significant difference between groups. Mean IGFBP-1 value was 8.29±5.033
mcg/L with median value of 10.8 mcg/L. Successful induction had significant higher IGFBP-1 levels with area-under-curve (AUC) 0.76 and 8.145 cutoff
value (p=0.002, RR=5.1).
Conclusion: IGFBP-1 level with cutoff point 8.145 can be used as predictor of successful labor induction in term pregnancy with preeclampsia.

Keywords: preeclampsia, labor induction, insulin-like growth factor binding protein-1, Bishop Score

ABSTRAK
Pendahuluan: preeklamsia/eklampsia menyebabkan 30% mortalitas maternal di RSUP Dr. Kariadi. Pemeriksaan skor bishop sebelum
induksi persalinan merupakan standar untuk memperkirakan maturasi serviks. Saat ini, banyak prediktor lain yang sedang diteliti,
temasuk insulin-like growth factor binding protein-1 (IGFBP-1), namun belum ada cut-off point pemeriksaan IGFBP-1 pada kehamilan aterm
dengan preeklamsia dan komplikasi preeklamsia. Tujuan: untuk mengetahui perbedaan kadar IGFBP-1 dan skor bishop pada pasien
preeclampsia yang menjalani induksi persalinan.
Metode: penelitian kohort prospektif observasional ini dilakukan pada pasien preeklamsia dengan usia kehamilan ≥37 minggu yang
direncanakan menjalani induksi persalinan di Bangsal Obstetri dan Ginekologi RSUP Dr. Kariadi Semarang dan RS jejaring selama
periode penelitian (n=66). Anamesis, pemeriksaan fisik, proteinuria, IGFBP-1 lendir serviks, dan skor bishop dilakukan pengukuran.
Analisis statistik dilakukan dengan uji T-berpasangan, diikuti perhitungan ROC untuk mengetahui nilai cut off prediksi keberhasilan
induksi, dan regresi logistik untuk menentukan efek variabel perancu terhadap kadar IGFBP-1.
Hasil: Dari 66 subjek, rerata skor bishop adalah 2,5±1,81 dan 2,6±1,8 pada wanita yang bersalin ≤24 jam dan inpartu ≤12 jam, secara
berurutan. Meskipun skor bishop didapatkan lebih tinggi pada kelompok berhasil induksi, namun tidak didapatkan perbedaan bermakna
dengan kelompok gagal induksi. Rerata kadar IGFBP-1 adalah 8,29±5,033 mcg/L dengan median sebesar 10,8 mcg/L. Keberhasilan
induksi diketahui memiliki kadar IGFBP-1 yang lebih tinggi dengan area dibawah kurva (AUC) sebesar 0,76 dan nilai cut off sebesar
8,145 (p=0,002, RR=5,1).
Kesimpulan: IGFBP-1 dengan nilai cut-off 8.145 dapat digunakan sebagai predictor keberhasilan induksi persalinan pada kehamilan
aterm wanita degan preeklamsia

Keywords: preeklampsia, induksi persalinan, insulin-like growth factor binding protein-1, skor bishop

INTRODUCTION Indonesia or about 5.3%, with no significant decrease

Nowadays, preeclampsia is still the top three in the last two decades (Wibowo et al., 2016). In RSUP
cause of maternal and fetal morbidity and mortality, dr. Kariadi, preeclampsia/eclampsia contributed to
with 128,273 annual incidence of preeclampsia in 30% of maternal mortality in 2016 (Anonim, 2016)
Copyright @ 2020 Authors. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-
ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-nc-sa/4.0/), which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original author and source are properly cited.

Sains Medika, Vol. 10, No. 2, July - December 2020 : 59-66 59

• pISSN: 2085-1545
• eISSN: 2339-093X
Setiyorini, et al.
therefore need more appropriate management.
Management of preeclampsia includes both
active and expectative management. Active management
is done by immediate delivery once pregnancy reaches
aterm (Wibowo et al., 2016). In preeclampsia which not
been in labor yet, induction of labor becomes an option
for pregnancy termination (National Collaborating
Centre for Women’s and Children’s Health, 2010; the
American College of Obstetricians and Gynecologists,
2013). However, before induction of labor is performed,
a number of examinations are performed in order to
estimate successful induction. Bishop Score currently a
standard to estimate cervical maturation. Several studies
have shown that cervical maturity is a major predictor
of successful labor induction compared to other factors
assessed in the Bishop score. Bishop score is a simple
and easy examination; however, it is a subjective
scoring with high inter- and intra-observer variability
with low predictive value to assess induction outcome
(Benediktsdottir, Eggebø and Salvesen, 2015).
Considering that cervical maturity factor plays
an important role in the successful induction of
labor, several studies have been developed to obtain
an easier and objective predictor to predict successful
labor induction. One of them is Insulin-like Growth
Factor Binding Protein 1 (IGFBP-1). IGFBP-1 will
be found in cervical secretions, its presence in the
cervical mucus will shows decidual activation and
opening of the internal uterine ostium (Rahkonen,
2010; Benediktsdottir, Eggebø and Salvesen, 2015;
Kosinska-Kaczynska et al., 2015). Previous study
found that IGFBP-1 had a specificity value of 93%
compared with 83% predictive value of Bishop Score
in predicting premature labor (Conde-Agudelo et al.,
2011). However, there are no cut-off points of IGFBP-
1 in full term pregnancy, especially with preeclampsia
and its complications.
This study was aimed to analyze the comparison
between IGFBP-1 levels in cervical mucus and Bishop’s
score to predict the success of labor induction in full
term pregnancy with preeclampsia.
METHODS
Design, Time and Place
This was an observational study with prospective
cohort design. The subjects were women, gestational age
≥37 weeks, with preeclampsia or severe preeclampsia
who attend and planned for labor induction treated
in the Obstetrics and Gynecology Ward at RSUP dr.
Kariadi Semarang and networking hospitals during
the study period that met the criterias. The study was
conducted in March-May 2017. This study has been
60
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approved by institutional etchics (No. 84/EC/FK-
RSDK/III/2017) comittee prior sampling and data
collection.
Sample
Singleton, head presentation, intrauterine
preeclampsia pregnancy with gestational age ≥37 weeks,
without labor sign, and willing participate in the study
by signing the informed consent. The minimum sample
size required in this study was 64 people. Sampling was
done with consecutive sampling.
Data collection
Primary data obtained from patient’s history,
physical examination, proteinuria, Insulin-like Growth
Factor Binding Protein 1 level prior induction. Secondary
data was taken from patient medical record to complete
primary data.
Data Analysis
Data was analyzed using SPSS software.
Comparison was done by paired T-test if data was
normally distributed. ROC test was performed to
determine cut off value of successful induction
prediction, and logistic regression test to find the
effect of confounding variables. Data was presented
by frequency, percentage, picture and table.
RESULTS
Subject Characteristic
Average maternal age was 29.8±6.05 years, with
43.9% of the subject belong to 20-30 years age categories.
Majority of participants are multiparity (74.2%) with
overweight BMI categories (54.5%). Highest blood
pressure category comprises 60.6% of PE group. The
fetal weight estimation categories were <3500 gram or
80.3% with birth weight <3500 gram in 75.8%.
Labor Induction
The succession rate of labor induction was
shown in Table 1.
In table 1 we found that the majority of
subjects were delivered <24 hours (77.3%) and 15
(22.7%) subjects failed to perform vaginal delivery
and underwent per abdominal delivery instead. Forty-
nine subjects managed to achieve labor within 12 hours.
Two subjects achieve labor in >12 hours but underwent
successful vaginal delivery within 24 hours.
Bishop’s Score
The mean Bishop’s score of all study subjects
was 2.4 ± 1.71, the median was 2, the minimum score
Sains Medika, Vol. 10, No. 2, July - December 2020 : 59-66
Table 1 .The Succession of Labor Induction (n=66)
Table 1 .The Succession of Labor Induction (n=66) • pISSN: 2085-1545
Table 1The .The Succession
Success of Laborof Labor Induction (n=66)
Induction n (%) • eISSN: 2339-093X
The Success ofinLabor
http://jurnal.unissula.ac.id/index.php/sainsmedika
Delivery 24 Induction n (%)
Table 1The .The Succession
Success of hours
ofinbetween
Labor Labor Induction (n=66)
Induction n (%)
- Yes Delivery
Comparison 24 hours
Insulin-like Growth Factor Binding Protein-1 Level and Bishop Score as Predictor of Successful ...
51 (77.3)
Table 1The .The
-- Success Delivery
Succession
Yes in 24
of hours
Labor Induction (n=66) 51
No of Labor Induction
Table 1 .The Succession of Labor Induction (n=66) 15n(77.3)
(%)
(22.7)
-- Yes No 51
15 (77.3)
(22.7)
Delivery in 1224 hours
The- Success No inofLabor
Labor hours
Induction 15n(22.7)
(%)
-- Labor Yes
Yes in  12 hours 51
49 (77.3)
(74.2)
Delivery in 24 hours
-- Yes No in  12 hours
Labor
No 49
15
17 (74.2)
(22.7)
(25.8)
-- Yes Yes
No
51
49
17
(77.3)
(74.2)
(25.8)
-- No Labor in  12 hours 15
No 17 (22.7)
(25.8)
- Yes 49 (74.2)
Table 2. TheLabor in Score
Bishop’s 12 hours
Based on the Successful labor and stage 1 parturition Induction
Table 2.-- TheNo Bishop’s Score Based on the Successful labor and stage 1 parturition Induction
Yes 17
49 (25.8)
(74.2)
Table 2. The Bishop’s Score Based on the Successful labor and stage 1 parturition Induction
- No Bishop Score 17 (25.8) p¥
Table 2. The Bishop’s Score Based on the Successful Bishop
labor Score
and
Mean±SD; Median (min-max)stage 1 parturition Induction p¥
Table 2. The Bishop’s Score Based Bishop
on the Successful
Mean±SD; Score
Medianlabor and stage 1 parturition Induction
(min-max) p¥
Table 2. DeliveryDelivery in 24hours
The Bishop’s Score Based on the Successful labor and stage 1 parturition Induction
Mean±SD; Median (min-max)
- Yes in 24hours 2.5±1.81; 2 (0-6)
Bishop Score 0.5
p¥
-Delivery Yes
No in 24hours 2.5±1.81;
2.1±1.30; 2 (0-6)
(1-5) 0.5
-
-- Yes Mean±SD; Median
2.5±1.81; 2 (min-max)
Labor Noin  12 hours 2.1±1.30; 2 (0-6)
Bishop Score (1-5) 0.5
p-¥
Delivery
-Labor in 24hours
Noin  12 hours 2.1±1.30; 2 (1-5) -
-- Yes Mean±SD; Median
2.6±1.80; (min-max)
Yes 2.5±1.81; 2 2 (0-6)
(0-6) 0.4
0.5
-Labor in  12 hours
Delivery
- Yes No in 24hours
No 2.6±1.80;
2.1±1.30; 2
2.1±1.41; 2 (0-6)
(0-5)
(1-5) 0.4
--
-- No Yes
Yes 2.6±1.80;
2.5±1.81; 2
2.1±1.41; 2 (0-5)
(0-6)
(0-6) 0.4
0.5-
SD= Standard Labor
- No Noin  12 hours
deviations; Min=Minimum; Max= 2.1±1.41; Maximum2 (0-5)
SD= Standard - 2.1±1.30; 2 (1-5) --
- Yesdeviations; Min=Minimum; Max= 2.6±1.80; Maximum2 (0-6) 0.4
SD= Standard Labor
- No in 
deviations;
12 Min=Minimum;
hours Max= Maximum
2.1±1.41; 2 (0-5) -
- Yes 2.6±1.80; 2 (0-6) 0.4
TableStandard
SD= 3. IGFB-1 Level andMin=Minimum;
Success of LaborMax= Induction
Table 3. -IGFB-1 No deviations;
Level and Success of Labor Induction
Maximum2 (0-5)
2.1±1.41; -
Table 3. IGFB-1
SD= Standard deviations; Min=Minimum; Level and Success of Labor
Table 3. IGFB-1 Induction
Max=
LevelMaximum
and Success
IGFBP of Labor
LevelInduction p¥
Induction Success Criteria IGFBP Level p¥
Table 3. IGFB-1 Induction Level and Success
Success Criteriaof Labor Induction Mean±SB; Median (min-max)
Mean±SB; IGFBPMedianLevel(min-max) p¥
Delivery
InductioninSuccess 24 hours
Criteria
Table 3. IGFB-1 in 24 Mean±SB; Median (min-max)
- YesLevel
Delivery andhours
Success of Labor Induction 9.34±4.729;
IGFBP 11.13 (0.01-25.93)
Level 0,002
p¥
Delivery
-Induction Yes
No in 24
Success hours
Criteria 9.34±4.729;
4.73±4.494; 11.13
3.60 (0.01-25.93)
(0.02-11.26) 0,002
Mean±SB; Median (min-max)
--Labor Yes
No in  12 hours
9.34±4.729;
4.73±4.494;
IGFBP 11.13 (0.01-25.93)
3.60Level
(0.02-11.26) 0,002
p¥
Delivery
Induction
-Labor in 24
Success
No in  12 hours hours
Criteria 4.73±4.494;Median
3.60 (0.02-11.26)
-- Yes Mean±SB;
9.26±4.811; (min-max)
11,11 (0.01-25.93)
(0.01-25.93) 0,01
Yes 9.34±4.729; 11.13 0,002
-Labor
Delivery
Yes
No in 
in 12
24hours
hours 9.26±4.811;
5.49±4.722; 11,11
4.81 (0.01-25.93)
(0.02-11.26) 0,01
-
- No 4.73±4.494; 3.60 (0.02-11.26)
-- No Yes
Yes 9.26±4.811;
9.34±4.729; 11,11
5.49±4.722;11.13 (0.01-25.93)
(0.01-25.93)
4.81 (0.02-11.26) 0,01
0,002
-
SD=Standard Labor
- No No in  12 hours
Deviation; Min=Minimum; Max= Maximum 5.49±4.722; 3.604.81 (0.02-11.26)
(0.02-11.26) -
SD=Standard - Deviation; Min=Minimum; Max= Maximum 4.73±4.494;
- Yes 9.26±4.811; 11,11 (0.01-25.93) 0,01
SD=Standard
Table 4. Area Labor
- No in  Curve
Deviation;
Under Min=Minimum;
12 hoursand cut-off value Max= Maximum
of Bishop score and4.81
5.49±4.722; IGFBP-1 level in labor ≤ 12 hours -
(0.02-11.26)
Table 4. Area - YesUnder Curve and cut-off value of Bishop 9.26±4.811;
score and11,11 (0.01-25.93)
IGFBP-1 level in labor ≤ 12 hours0,01
SD=Standard
Table 4. Area Table
- Deviation;
4.
Under
No Area Curve Min=Minimum;
Under Curve
and and
cut-off value Max=
cut-off
of Maximum
value
Bishop of Bishop
score
5.49±4.722; score
and and
IGFBP-1
4.81 IGFBP-1
level level
(0.02-11.26) in labor
inp labor ≤ 12≤hours
12 hours - value
Predictor Area Under ROC Curve (CI 95%) cut-off
Predictor
SD=Standard
Bishop Deviation;
score Area Under
Min=Minimum; ROCMaximum
0.56Max=
(0.41 Curve
s/d (CI 95%)
0.710) p
0.4 cut-off 1.5value
Table 4. Area
Predictor Under Curve and cut-off
Area value
Under of Bishop
ROC Curvescore
(CI and
95%)IGFBP-1 level in p labor ≤ 12 hourscut-off
Bishop
IGFBP score level 0.56
0.70(0.41
(0.56s/d
s/d0.710)
0.85) 0.4
0.01 1.5value
8.145
TableBishop
4. Area
IGFBP score
Under Curve and cut-off value
level 0.56
0.70(0.41
of s/d 0.710)
Bishop
(0.56 score and IGFBP-1 level 0.01 0.4labor ≤ 12 hours8.145
in 1.5
Predictor Area Under ROCs/d Curve0.85)
(CI 95%) p cut-off value
IGFBP level 0.70 (0.56 s/d 0.85) 0.01 8.145
TableBishop
5. IGFBP-1
Predictor score Level and occurrence 0.56 (0.41
of labor s/d
inand 0.710)
≤Curve
12 hours 0.4 1.5value
Table Area Under
5. IGFBP-1 ROC
Level (CI 95%)
occurrence p
of labor in ≤ 12 hours cut-off
Table 5. IGFBP-1
IGFBP level Level and occurrence of labor
0.70 in s/d
(0.56 ≤ 120.85)
hours 0.01 8.145
TableBishop
5. IGFBP-1 score Level and occurrence 0.56 (0.41
of labor ins/d
≤ 120.710)
hours 0.4 1.5
Labor in 12 hours
IGFBP
IGFBP Level (g/L) level Labor 0.70
in (0.56
12in s/d
hours 0.85) p* 0.01
Relative Risk (RR) 8.145
Table 5. IGFBP-1
IGFBP Level Level
(g/L) and occurrence
No ofin
Labor labor ≤ 12 hours p*
Yes
12 hours Relative Risk (RR)
IGFBP < 8.145 Level (g/L) No
11 (47.83%) Yes
12 (52.17%) p*
0.003 Relative
3.4 (1.5Risk (RR)
to 8.1)
Table 5. < IGFBP-1 8.145 Level and occurrence No ofin
11 (47.83%) labor
12in ≤ 12 hours 0.003
Yes
(52.17%) 3.4 (1.5 to 8.1)
Labor 12 hours
IGFBP 
< 8.145 Level (g/L)
8.145 6 (13.95%)
11 (47.83%) 37 12 (86.05%)
(52.17%) p*
0.003 Relative
3.4 (1.5Risk (RR)
to 8.1)
2
 8.145 6 (13.95%)
No in 12
Labor 37 hours
(86.05%)
Yes
* test
IGFBP 
< 8.145 Level (g/L)
8.145 6 (13.95%)
11 (47.83%) 37 12 (86.05%)
(52.17%) p*
0.003 Relative
3.4 (1.5Risk (RR)
to 8.1)
*2 test No Yes
was2 0 and the
* test maximum was 6. Table 2 shows that the is also shown in figure 1.
< 8.145 8.145 6 (13.95%)
11 (47.83%) 12 37 (52.17%)
(86.05%) 0.003 3.4 (1.5 to 8.1)
Bishop score of groups who deliver < 24 hours was
2
* testthan
higher  8.145 women who deliver6 >24 (13.95%) 37 (86.05%) IGFBP-1 Serum Level
hours, however
the difference was not significant, p = 0.5. Subject
*2 test The mean IGFBP-1 serum level of all subjects
who reach labor in < 12 hours have higher Bishop’s was 8.29 ± 5.033 μg/L, with median 10.80 μg/L,
score than subject who reach labor in >12 hours, the minimum value 0.01 μg/L and maximum value 25.93
difference was not significant (p = 0.4). Comparison μg/L. IGFBP-1 serum levels based on successful labor
of Bishop score based on successful induction of labor induction are shown in Table 3.

Sains Medika, Vol. 10, No. 2, July - December 2020 : 59-66 61

 Figure 1. Bishop score of study subjects based on successful labor induction (n=66). Panel A:
• pISSN: 2085-1545
Bishop score
• eISSN: 2339-093X based on labor  12 hours. Panel B: Bishop score based on delivery  24 hours
http://jurnal.unissula.ac.id/index.php/sainsmedika
Setiyorini, et al.

A p=0,4 B p=0,5

Figure 3. ROC Curve of the Bishop score and serum IGFBP-1

Figure1.1.Bishop
Figure Bishop score
score of
ofstudy
studysubjects based
subjects on successful
based on12 labor induction
successful (n=66). (n=66).
labor induction Panel A:Panel
BishopA:
level to predict labor hours (n=66)
score based on labor < 12 hours. Panel B: Bishop score based on delivery < 24 hours
Bishop score based on labor  12 hours. Panel B: Bishop score based on delivery  24 hours

A p=0,4 B p=0,5

A B
p=0,01 p=0,002

Figure 2.1.
Figure
Figure Serum IGFBP
Serum
2.Bishop level
IGFBP
score of (mg/L) of studyof
level subjects
study (g/L) subjects
studyon
based based on success
subjects based
successful of
onlabor
labor induction
success (n=66).
of (n=66).
induction labor PanelA:
induction
Panel A:
Serum IGFBP-1 level based on labor < 12 hours. Panel B: Serum IGFBP-1 level based on delivery < 24 jam
(n=66).
Bishop Panel A: Serum
score based IGFBP-1
on labor  12 level
hours.based
Panelon
B: labor 12 hours.
Bishop score Panel
based B: Serum
on delivery IGFBP-1
 24 hours
Figure 3. ROClevel based
Curve on Bishop
of the deliveryscore
 24and
jamserum IGFBP-1
level to predict labor 12 hours (n=66)

A B
p=0,01 p=0,002

Figure 1. Bishop score of study subjects based on successful labor induction (n=66). Panel A: Bishop
score based on labor < 12 hours. Panel B: Bishop score based on delivery < 24 hours

Figure 3. ROC Curve of the Bishop score and serum IGFBP-1 level to predict labor < 12 hours (n=66)
Figure 3. ROC Curve of the Bishop score and serum IGFBP-1
Figure 2. Serum IGFBP level
level(g/L) of study
to predict laborsubjects based
12 hours on success of labor induction
(n=66)
(n=66). Panel A: Serum IGFBP-1 level based on labor  12 hours. Panel B: Serum IGFBP-1
62 level based on deliverySains
 24Medika,
jam Vol. 10, No. 2, July - December 2020 : 59-66

A B
p=0,01 p=0,002

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Comparison between Insulin-like Growth Factor Binding Protein-1 Level and Bishop Score as Predictor of Successful ...
Figure 4. ROCFigure ROC
curve of4.the curve
Bishop of the
score andBishop score andlevel
serum IGFBP-1
to predicted delivery in  24 hours
Table 3 shows that serum IGFBP-1 level in
women who deliver < 24 hours was significantly
higher than women who deliver >24 hours (p = 0.002).
Moreover, women who reach labor in < 12 hours have
significantly higher IGFBP-1 value than women who
reach labor in >12 hours (p = 0.01). Comparison of
serum IGFBP levels based on successful induction of
labor is also shown in Figure 2.
Bishop Score and Level of Serum IGFBP-1 as
Predictor Success of Labor Induction
Labor in <12 hours
The receiver operating characteristic (ROC)
curves of the Bishop’s score and serum IGFBP-1 levels
to assess labor <12 hours were shown in figure 3.
The area under ROC curve and the cut-off value
of the Bishop score and serum IGFBP levels to predict
labor < 12 hours are shown in table 4.
The area under ROC curve of the Bishop score
to predict the occurrence of labor in <12 hours was
0.56 (p = 0.4) and cut-off value of 1.5. The area under
ROC curve of IGFBP level was 0.70 (p = 0.01) with
cut-off value of 8.145. Based on this result, IGFBP-1
level can be used to predict labor <12 hours.
Based on table 5, majority of women with IGFBP-
1 serum level >8.145 mg/L (86.05%), performed labor in
< 12 hours (p = 0.003). The RR value was 3.4, meaning
that subjects with serum IGFBP-1 level <8.145 mg/L
had 3.4 fold risk of labor in >12 hours. Based on these
result, it can be concluded that serum IGFBP levels
can be used to predicted labor in < 12 hours.
Delivery in < 24 hours
The receiver operating characteristic (ROC)
curves of the Bishop score and serum IGFBP levels
to assessed delivery in < 24 hours are shown in Figure
Sains Medika, Vol. 10, No. 2, July - December 2020 : 59-66
• pISSN: 2085-1545
• eISSN: 2339-093X
serum IGFBP-1
to predicted level in < 24 hours
delivery
4.
Based on figures 4 and table 6, the area under
the ROC curve of the Bishop’s score able to predict
delivery in <24 h was 0.55 (p = 0.5), with a cut-off
value of 1.5. The area under the ROC curve of IGFBP
level was 0.76 (p=0.0021), with a cut-off value of 8.145.
Based on these result, we can concluded that serum
IGFBP-1 level can be used as a predictor of delivery
in <24 hours.
The distribution of serum IGFBP-1 based on the
occurrence delivery in <24 hours is shown in Table 7.
Based on table 7, majority of subject with serum
IGFBP-1 level >8.145 mg/L (90.70%) had delivery in
<24 hours (p<0.001). The RR score was 5.1, meaning
that subjects with serum IGFBP-1 level <8.145 mg/L
had 5.1 fold risk of delivery >24 hours. Based on these
results, we can concluded that serum IGFBP-1 level can
be used as a predictor of delivery in <24 hours.
Confounding Factors that Affect Delivery within
24 Hours
Table 8 shows that maternal age (p = 0.5), BMI
(0.9), blood pressure (p = 0.2), parity (0.3), Estimated
Fetal Weight or EFW (p = 0.7), Birth Weight or BW
(p = 1.0) were not significantly associated with the
delivery < 24 hours. Because there was no significant
confounding variable, the data analysis was not followed
by multivariate test.
DISCUSSIONS
Majority of the subject was on reproductive age
range between 20-34 years (48 subjects) with mean
age 29.8 ± 6.05 years. Induction was successful in 37
subjects (45.1% in 20-30 age group and 27.5% in 30-34
age group). This finding was similar to a study about the
effectiveness of misoprostol as a labor induction agent
63
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•Table
eISSN:6.2339-093X
The area under the ROC curve and the cut-off score of the Bishop score and serum IGFBP levels to
Table 6.delivery
predict The areainunder the ROC curve and the cut-off score of the Bishop
< 24 hours score and serum IGFBP levels to
http://jurnal.unissula.ac.id/index.php/sainsmedika
Setiyorini, et al. in < 24 hours
predict delivery
TablePredictor
6. The area under the Area ROC curve and theCurve score
cut-off (CI of the Bishop score and serum IGFBP levels to
Table 6. TheUnder ROC
area under the ROC curve 95%)
and the cut-off pscore of the BishopCut-off value
predict delivery in < 24 hours
Predictor Areaand
Under
Bishop Score score 0.55ROC
serum (0.41
IGFBPCurve
s/dlevels(CI
0.70) to95%) pin < 24 hours
predict delivery0.5 Cut-off
1.5value
Bishop Score
IGFBP-1 0.55 (0.62
(0.41 s/d 0.90)
0.70) 0.5 1.5
Predictor level Area Under0.76ROC Curve (CI 95%) 0.002
p 8.145
Cut-off value
IGFBP-1 level 0.76 (0.62 s/d 0.90) 0.002 8.145
Bishop Score 0.55 (0.41 s/d 0.70) 0.5 1.5
TableIGFBP-1 7. IGFBP-1 levelLevel and occurrence0.76of(0.62 s/d in
delivery 0.90)
≤ 12 hours 0.002 8.145
Table 7. IGFBP-1 Level and occurrence of delivery in ≤ 12 hours
Table 7. IGFBP-1 Level and occurrence of delivery in ≤ 12 hours
Delivery in 12 hours
TableIGFBP 7. IGFBP-1 Level (g/L) occurrence
Level and of delivery
Delivery in 12 Yes in ≤ 12 hours p*
hours Relative Risk (RR)
No
IGFBP Level (g/L) p* Relative Risk (RR)
- < 8,145 No
11 (47.83%)
Delivery in1212 Yes
(52.17%)
hours <0.001 5.1 (1.8 to 14.3)
IGFBP
-- < Level (g/L)
8,145 11 (47.83%) 12 (52.17%) p*
<0.001 Relative
5.1 (1.8Risk (RR)
to 14.3)
 8,145 No
4 (9.30%) Yes
39 (90.70%)
-- 
< 8,145 8,145 114(47.83%)
(9.30%) 1239 (90.70%)
(52.17%) <0.001 5.1 (1.8 to 14.3)
2
* test
*2 test -  8,145 4 (9.30%) 39 (90.70%)
Table 8. Confounding factors associated with successful labor
* 2
test8. Confounding factors Table 8. Confounding factors associated with successful labor
Table associated with successful labor
Confounding factors Delivery 24 hours
Table 8. Confounding Confounding factors
factors associated with successful
No labor Delivery 24 hours Yes p
nNo(%) nYes
(%) p
Confounding
Maternal Age factors Category n (%) Delivery 24 hours n (%)
-Maternal <20 Age Category 0 No
(0.0) 5 Yes
(9.8) p*
0.5
- 20-30 <20 n (%)
60(40.0)
(0.0) 23n (%)
5 (45.1)
(9.8) 0.5*
Maternal
- 30-34 20-30 Age Category 5
6 (33.3)
(40.0) 14
23 (27.5)
(45.1)
-- <20 35
30-34 50(26.7)
4 (0.0)
(33.3) 95(17.6)
14 (9.8)
(27.5) 0.5*
-BMI
- 20-30 35
Category 6
4 (40.0)
(26.7) 23 (45.1)
9 (17.6)
--BMI 30-34
< Category
25 5 (33.3)
3 (20.0) 14
13 (27.5)
(25.5) 0.9*
-- 35 25 – 29,9
< 25 4
9 (26.7)
3 (60.0)
(20.0) 9
27 (17.6)
13 (52.9)
(25.5) 0.9*
BMI
-  Category
2530
– 29,9 3 (20.0)
9 (60.0) 11 (21.6)
27 (52.9)
-Blood
- < 25
 30
Pressure Category 3
3 (20.0)
(20.0) 13
11 (25.5)
(21.6) 0.9*
--Blood 25
PE–Pressure
29,9 Category 9
7 (60.0)
(46.7) 27
33 (52.9)
(64.7) 0.2*
-- Severe

PE30 PE 3
8 (20.0)
(53.3)
7 (46.7) 11
18 (21.6)
(35.3)
33 (64.7) 0.2*
Blood Pressure
- Severe PE Category 8 (53.3) 18 (35.3)
- PE Category
Parity 7 (46.7) 33 (64.7) 0.2*
- 1 Severe
-Parity PE
Category 8 (13.3)
2 (53.3) 18 (29.4)
15 (35.3) 0.3§
- ->1 1 2 (13.3)
13 (86.7) 15 (29.4)
36 (70.6) 0.3§
EFW - Category Parity
>1 Category 13 (86.7) 36 (70.6)
EFW - Category -<3500
1 2 (13.3)
13 (86.7) 15 (29.4)
40 (78.4) 0.3
0.7§
§

-- 3500 >1
<3500 13
13 (86.7)
2 (13.3)
(86.7) 36
11 (70.6)
(21.6)
40 (78.4) 0.7§
EFW
BW -Category Category 3500 2 (13.3) 11 (21.6)
BW --Category
§
<3500
<3500 13
12 (86.7)
(80.0) 40
38 (78.4)
(74.5) 0.7
1.0§
-- 3500 3500
<3500 2
3 (13.3)
12 (20.0)
(80.0) 11
38 (21.6)
13 (25.5)
(74.5) 1.0§
BW 2 Category
* Test - 3500 3 (20.0) 13 (25.5)
§*2 Test- <3500 12 (80.0) 38 (74.5) 1.0§
Fisher-Exact Test
§ - 3500 3 (20.0) 13 (25.5)
Fisher-Exact
2
Test
*preeclampsia,
in Test which reported average induction age (Lubena, 2015; Guerra et al., 2017). Different results
§
of 26 years, andTest
Fisher-Exact insignificant as a predictor of successful was obtained on different study in 2009 which reported
induction (Frass, Shuaib and Al-harazi, 2011). Another that BMI of <30 was a significant factor for successful
study reported successful induction in >90% of 18-35 labor induction (Pevzner et al., 2017).
age group (Vogel, Souza and Gülmezoglu, 2013). Other studies reported several other significant
Approximately 78% of subjects had a BMI<30 factors for labor induction, such as estimated fetal
with mean BMI 27.5 ± 3.75. Based on BMI factor, we weight and parity. A study stated that fetal weight
could not find significant correlation with induction of <3500 grams was a significant factor for successful
labor. This result was consistent with study reported a labor induction (Chung et al., 2015). Meanwhile, our
successful induction on subjects with BMI<30 and not study found similar finding which 78.4% of the subjects
correlate significantly with successful of labor induction with fetal weight <3500 grams could achieve stage 2

64 Sains Medika, Vol. 10, No. 2, July - December 2020 : 59-66


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Comparison between Insulin-like Growth Factor Binding Protein-1 Level and Bishop Score as Predictor of Successful ...
labor within 24 hours after induction, however, the
result was insignificant. Thirty-six (70.6%) of the 49
multiparity subjects underwent successful induction
compared to 15 (29.4%) subjects of nulliparity groups.
There were no significant differences between groups.
However, several other studies might found different
finding, which suggested that parity was a significant
factor for successful labor induction (Vogel, Souza
and Gülmezoglu, 2013; Chung et al., 2015; Guerra
et al., 2017).
One study reported that prolong first stage of
labor (more than 12 hours) doubles cesarean section
risk. In our study, we found 2 subjects with a labor
duration >12 hours who managed to achieve vaginal
delivery within 24 hours. Multiparity is still suspected
to be one of the causative factors.
Several studies either randomized controlled
trial/RCT or demographic studies, reported mixed
finding on successful induction in preeclampsia patient.
Studies in the United States reported incidence of
successful induction in term preeclampsia pregnancy
was 74%, while another reported significant induction
failure in preeclampsia group (Kim et al., 2010; Vogel,
Souza and Gülmezoglu, 2013; Roland, Warshak and
Defranco, 2017). Our study found that 33 subjects with
preeclampsia and 18 subjects with severe preeclampsia
underwent delivery within 24 hours. There was no
significant difference between groups so that the
classification of preeclampsia and severe preeclampsia
was not a predictor of successful labor induction.
Although there was inter- and intra-observer
variability, Bishop’s Score still currently serve as a
gold standard for successful labor prediction. Based
on Bishop’s score data, we found a significantly
higher score in patient with successful compared to
failed delivery (2.5±1.81 vs 2.1±1.41, respectively)
and in those who underwent labor within 12 hours
compared to >12 hours (2.6±1.8 vs 2.1±1.30). Although
the Bishop score was higher, we found no significant
difference between groups. This was in contrast with
previous studies which suggested that cervical maturity
is a critical determinant of successful labor induction
(Teixeira et al., 2012; Lubena, 2015).
The mean of IGFBP-1 level in this study was
8.29±5.033 mcg/L with median value of 10.8 mcg/L.
We found that levels of IGFBP-1 in successful delivery
was significantly higher with a cutoff IGFBP-1 value
8.145 (p = 0.002, RR 5.1). This finding was consistent
with preeclampsia theory, with increment of cervical
mucus IGFBP-1 level near-term. IGFBP-1 was the first
sign of chorionic and decidual adhesions detachment
(Kosinska-Kaczynska et al., 2015). The IGFBP-1 score
Sains Medika, Vol. 10, No. 2, July - December 2020 : 59-66
• pISSN: 2085-1545
• eISSN: 2339-093X
in this study was lower than those found in previous
study which reported a cutoff value of 10 mcg/L
(Weroha and Haluska, 2012; Kosinska-Kaczynska et
al., 2015).
In this study, all confounding factor was not
significantly correlated with successful labor induction,
hence, we could use cervical mucus IGFBP-1 level to
predict successful induction.
CONCLUSIONS
In this study, IGFBP-1 level with cut-off point
8,145 can be used as predictor of successful induction
of labor in term preeclampsia pregnancy. IGFBP-1 can
be considered as alternative modality management,
especially in preeclampsia patient who was planned to
undergo induction of labor. Future research is needed
to account other conditions such as serotonin and
premature rupture of membranes.
CONFLICT OF INTEREST
There is no conflict of interest in this
publication
ACKNOWLEDGMENT
We highly appreciate and thank the Obstetrics
and Gynecology Ward at RSUP dr. Kariadi Semarang’s
staffs during the samples collection.
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