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

Sains Medika, Vol. 10, No. 2, July December 2020 : 59-66 Copyright @ 2020 Authors. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercialShareAlike 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. RESEARCH ARTICLE

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.

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 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.

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. Fortynine 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       is also shown in figure 1.

IGFBP-1 Serum Level
The mean IGFBP-1 serum level of all subjects was 8.29 ± 5.033 μg/L, with median 10.80 μg/L, was 0 and the maximum was 6. Table 2 shows that the Bishop score of groups who deliver < 24 hours was higher than women who deliver >24 hours, however the difference was not significant, p = 0.5. Subject who reach labor in < 12 hours have higher Bishop's score than subject who reach labor in >12 hours, the difference was not significant (p = 0.4). Comparison of Bishop score based on successful induction of labor minimum value 0.01 μg/L and maximum value 25.93 μg/L. IGFBP-1 serum levels based on successful labor induction are shown in Table 3.       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)

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. 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      in preeclampsia, which reported average induction age of 26 years, and insignificant as a predictor of successful induction (Frass, Shuaib and Al-harazi, 2011). Another study reported successful induction in >90% of 18-35 age group (Vogel, Souza and Gülmezoglu, 2013).
Approximately 78% of subjects had a BMI<30 with mean BMI 27.5 ± 3.75. Based on BMI factor, we could not find significant correlation with induction of labor. This result was consistent with study reported a successful induction on subjects with BMI<30 and not correlate significantly with successful of labor induction (Lubena, 2015;Guerra et al., 2017). Different results was obtained on different study in 2009 which reported that BMI of <30 was a significant factor for successful labor induction (Pevzner et al., 2017).
Other studies reported several other significant factors for labor induction, such as estimated fetal weight and parity. A study stated that fetal weight <3500 grams was a significant factor for successful labor induction (Chung et al., 2015). Meanwhile, our study found similar finding which 78.4% of the subjects with fetal weight <3500 grams could achieve stage 2