Vol 93, No 10 (2022)
Research paper
Published online: 2022-04-06

open access

Page views 4148
Article views/downloads 713
Get Citation

Connect on Social Media

Connect on Social Media

Interleukin-6 bedside test in detecting chorioamnionitis in women with preterm premature rupture of fetal membranes

Tamer E. El-Ghazaly1, Ibrahim A. Abdelazim12, Amal Elshabrawy1
Pubmed: 35419796
Ginekol Pol 2022;93(10):835-841.

Abstract

Objectives: About 30–80% of preterm deliveries following preterm premature rupture of fetal membranes (PPROM) are complicated by histological chorioamnionitis. To evaluate the accuracy of Interleukin-6 (IL-6) bedside test in detecting chorioamnionitis in women with PPROM.
Material and methods: One hundred and ten (110) pregnant women with PPROM > 24 and < 34 weeks’ gestation, admitted for conservative management were included in this study. Participants were examined on admission using sterile speculum examination for assessment of IL-6 in the cervico-vaginal secretions using the IL-6 bedside test. The IL-6 bedside test was repeated for all participants once termination of pregnancy (TOP) decided. After TOP, placenta, umbilical cord, and fetal membranes samples were examined for histologic detection of chorioamnionitis (gold standard). The histological results were compared with IL-6 bedside test results to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis in women with PPROM.
Results: The IL-6 bedside test had 98.6% sensitivity, 94.7% specificity, 97.3% positive predictive value (PPV), 97.3% negative predictive value (NPV) and 97.3% overall accuracy in detecting chorioamnionitis. The sensitivity, specificity, NPV and overall accuracy of IL-6 bedside test (98.6%, 94.7%, 97.3%, and 97.3%; respectively) were significantly higher than the clinical and laboratory parameters of chorioamnionitis (65.3%, 57.9%, 46.8%, and 62.7%; respectively) (p = 0.04, 0.02, 0.001 and 0.03; respectively).
Conclusions: The IL-6 bedside test is an accurate, non-invasive bedside test with 98.6% sensitivity, 94.7% specificity, 97.3% PPV, 97.3% NPV, and 97.3% overall accuracy in detecting chorioamnionitis. The IL-6 bedside test had significantly higher sensitivity, specificity, NPV, and overall accuracy than the clinical and laboratory parameters of chorioamnionitis.

ORIGINAL PAPER / OBSTETRICS

Ginekologia Polska

2022, vol. 93, no. 10, 835–841

Copyright © 2022 PTGiP

ISSN 0017–0011, e-ISSN 2543–6767

DOI 10.5603/GP.a2022.0027

Interleukin-6 bedside test in detecting chorioamnionitis in women with preterm premature rupture of fetal membranes

Tamer E. El-Ghazaly1Ibrahim A. Abdelazim12Amal Elshabrawy1
1Department of Obstetrics, and Gynaecology, Ain Shams University, Cairo, Egypt
2Ahmadi Hospital, Kuwait Oil Company, Ahmadi, Kuwait
ABSTARCT
Objectives: About 3080% of preterm deliveries following preterm premature rupture of fetal membranes (PPROM) are complicated by histological chorioamnionitis. To evaluate the accuracy of Interleukin-6 (IL-6) bedside test in detecting chorioamnionitis in women with PPROM.
Material and methods: One hundred and ten (110) pregnant women with PPROM > 24 and < 34 weeks’ gestation, admitted for conservative management were included in this study. Participants were examined on admission using sterile speculum examination for assessment of IL-6 in the cervico-vaginal secretions using the IL-6 bedside test. The IL-6 bedside test was repeated for all participants once termination of pregnancy (TOP) decided. After TOP, placenta, umbilical cord, and fetal membranes samples were examined for histologic detection of chorioamnionitis (gold standard). The histological results were compared with IL-6 bedside test results to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis in women with PPROM.
Results: The IL-6 bedside test had 98.6% sensitivity, 94.7% specificity, 97.3% positive predictive value (PPV), 97.3% negative predictive value (NPV) and 97.3% overall accuracy in detecting chorioamnionitis. The sensitivity, specificity, NPV and overall accuracy of IL-6 bedside test (98.6%, 94.7%, 97.3%, and 97.3%; respectively) were significantly higher than the clinical and laboratory parameters of chorioamnionitis (65.3%, 57.9%, 46.8%, and 62.7%; respectively) (p = 0.04, 0.02, 0.001 and 0.03; respectively).
Conclusions: The IL-6 bedside test is an accurate, non-invasive bedside test with 98.6% sensitivity, 94.7% specificity, 97.3% PPV, 97.3% NPV, and 97.3% overall accuracy in detecting chorioamnionitis. The IL-6 bedside test had significantly higher sensitivity, specificity, NPV, and overall accuracy than the clinical and laboratory parameters of chorioamnionitis.
Key words: Interleukin-6; bedside test; Chorioquick®; Chorioamnionitis; preterm premature rupture of fetal membranes
Ginekologia Polska 2022; 93, 10: 835841

Corresponding author:

Ibrahim A. Abdelazim

Department of Obstetrics, and Gynaecology, Ain Shams University, Cairo, Egypt

e-mail: dr.ibrahimanwar@gmail.com

Received: 12.03.2021 Accepted: 21.02.2022 Early publication date: 6.04.2022

This article is available in open access under Creative Common Attribution-Non-Commercial-No Derivatives 4.0 International (CC BY-NC-ND 4.0) license, allowing to download articles and share them with others as long as they credit the authors and the publisher, but without permission to change them in any way or use them commercially.

INTRODUCTION

The preterm premature rupture of fetal membranes rupture (PPROM) is one of the common problems in obstetrics [1]. It occurs in approximately 35% of all pregnancies [2–4], and accounts for 3040% of preterm deliveries (PTDs) [5]. About 3080% of PTDs following PPROM are complicated by histological chorioamnionitis [5].

Management of PPROM should be conservative if PPROM occurs before 34 weeks’, while pregnancy should be terminated (labor should be induced) if PPROM occurs34 weeks’ [1].

PPROM usually associated with prematurity, and infections morbidities, and 524% of the neonates delivered after PPROM suffer from neonatal sepsis [6, 7].

Conservative management of PPROM may reduce the risk of prematurity but entails risk of an intrauterine infection (IUI) [2, 3].

Maternal clinical and blood parameters have limited accuracy in detection of an ongoing fetal and/or IUI [8, 9].

Although, the amniotic fluid (AF) IL-6 (interleukin 6) at 745 pg/mL threshold had 93% sensitivity, 91% specificity in detection of AF inflammation [10]. AF sampling is an invasive procedure, and unsuitable for daily routine [11, 12].

Currently, there is no accurate, non-invasive test available for detection of IUI, and Kayem et al. [13] suggested the vaginal IL-6 as non-invasive test for detection of AF and/or IUI. The AF IL-6 is good predictor of fetal inflammatory response, and histologic funisitis [14].

IL-6 bedside test is a new IL-6 based test with the potential to detect IL-6 at three different thresholds for diagnosing chorioamnionitis [5]. Therefore, this study designed to evaluate the accuracy of the IL-6 bedside test in detecting chorioamnionitis in women with PPROM.

Objectives

To evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis in women with PPROM (primary outcome).

To compare the accuracy of IL-6 bedside test in detecting chorioamnionitis to the clinical and laboratory parameters of chorioamnionitis (secondary outcome).

MATERIAL AND METHODS

This prospective comparative double blinded study was conducted from February 2019 till August 2020, after approval by the ethical committee of the Obstetrics and Gynecology department (OB_9012_18), and registration as clinical trial (ACTRN12619000191190).

One hundred and ten (110) women with PPROM > 24 and < 34 weeks gestation, were included in this study after informed consent in accordance with the Declaration of Helsinki to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis in women with PPROM.

Inclusion criteria include women between 2040 years old, presented with PPROM > 24 and < 34 weeks, and admitted for conservative management.

Women < 24 or > 34 weeks, not sure of dates, on antibiotic, severe oligohydramnios, fetal anomaly, fetal death, multiple pregnancies, non-reassuring cardiotocography (CTG), PTD, vaginal bleeding, active labor, suspicious of chorioamnionitis (clinical or laboratory), and refused to participate and/or give consent were excluded from this study.

The diagnosis of PPROM was based on patient’s history of water gush, confirmed by visualization of amniotic fluid (AF) pooling from the cervical canal during sterile speculum examination, positive nitrazine, AmnioQuick Duo test [1, 15], and amniotic fluid index (AFI)5 cm using trans-abdominal ultrasound (TAS) [16].

The gestational age of participants was calculated from the first day of last menstrual period (LMP) and confirmed by early ultrasound scan (≤ 20 weeks gestation) [16].

Participants were subjected to general, and abdominal examinations, abdominal ultrasound, sterile speculum examination for detection of AF pooling, and assessment of IL-6 in the cervico-vaginal secretions (CVS) using the non-invasive IL-6 bedside test (Chorioquick®, Biosynex SA, Strasbourg, France) on admission [5]. During the conservative treatment, studied women received two doses dexamethasone [12 mg intramuscularly 12 hours apart (for induction of fetal lung maturity)], and antibiotics according to ACOG recommendations (intravenous ampicillin 2 g, and erythromycin 250 mg every 6 h for 48 h, followed by oral amoxicillin 250 mg, and erythromycin 333 mg every 8 h for 5 days). One-gram Azithromycin single dose is an alternative to erythromycin if unavailable or poorly tolerated [17].

Participants were also subjected to laboratory tests for detection of chorioamnionitis twice weekly, and fetal wellbeing assesment using; fetal movements count, non-stress tests daily, and TAS weekly to detect AF volume, fetal growth, and umbilical artery Doppler during the conservative treatment [18].

Short term tocolysis (beta-mimetics or calcium channel blockers) were given for participants who developed uterine contraction before the two dexamethasone doses (after exclusion of chorioamnionitis) [18].

The clinical signs, and laboratory parameters of chorioamnionitis include maternal fever, maternal tackycardia, uterine tenderness, maternal leucocytosis, positive C reactive proteins, and procalcitonin [18].

IL-6 bedside test was performed for all participants on admission and repeated once termination of pregnancy (TOP) or induction of labor decided [16] (Fig. 1).

Figure 1. The IL-6 bedside test results in relation to histologic examination of the placenta, umbilical cord, and fetal membranes; FN False negative; FP False positive; IL-6 Interleukin-6; PPROM Preterm premature ruptured fetal membranes; TN True negative; TP True positive

Management of PPROM should be conservative if PPROM occurs before 34 weeks, while pregnancy should be terminated (labor should be induced) if PPROM occurs34 weeks [1].

The conservative treatment was discontinued, and pregnancy was terminated by induction of labor for studied participants before 34 weeks with either development of chorioamnionitis or spontaneous labor pains (Fig. 2).

Figure 2. Indications of TOP, and the clinical and lab. parameters of chorioamnionitis in relation to histologic examination of the placenta, umbilical cord, and fetal membranes; FN False negative; FP False positive; Lab. Laboratory; PPROM Preterm premature ruptured fetal membranes; TN True negative; TOP Termination of pregnancy; TP True positive

IL-6 bedside test is a new IL-6 based test to detect chorioamnionitis and has the potential to detect IL-6 in CVS at three different thresholds [IL-6 low (0.1 ng/mL), IL-6 medium (0.25 ng/mL), and IL-6 high (5 ng/mL)] [5].

The IL-6 bedside test was considered positive with the presence of two distinct lines; one at level of C zone (control zone), and another line at level of T zone (test zone), (even of weak intensity) at any of threshold indicators and was considered negative with no visible lines at T zone at any of threshold indicators [5].

The decision of TOP or induction of labor based on the clinical and laboratory parameters of chorioamnionitis was taken by the consultant on-call who was blinded to IL-6 bedside test results. Within 48 hours after delivery, placenta, umbilical cord, and fetal membranes samples were examined for detection of chorioamnionitis (gold standard) by histology specialist who was blinded to IL-6 bedside test results (double blinded).

Presence of inflammatory cells in the samples (placenta, umbilical cord, and fetal membranes) in form of multiple (≥ 5) foci of polymorph nuclear leukocytes (PNLs) in the subchorionic fibrin indicates grade 2 inflammation (gold standard for culture-proven AF infection, and chorioamnionitis) [19].

After TOP, the IL-6 bedside test results and the clinical and laboratory parameters of chorioamnionitis were compared to histologic examination of the samples (gold standard) to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis in women with PPROM (primary outcome) (Fig. 1 and 2).

While the secondary outcome measures the accuracy of IL-6 bedside test in detecting chorioamnionitis compared to the clinical and laboratory parameters of chorioamnionitis.

Sample size justification

The required sample size was calculated from previous studies [14, 20], and using G Power software version 3.17 for sample size calculation, setting α-error probability at 0.05, power (1-β error probability) at 0.95%, and effective sample size (w) at 0.5. An effective sample110 women was needed to produce statistically acceptable figure.

Statistical analysis

Collected data were statistically analyzed using Statistical Package for Social Sciences (SPSS): computer software version 20 (Chicago, IL, USA). Numerical variables were presented as mean and standard deviation (± SD), while categorical variables were presented as number (n) and percentage (%). Chi-square test (x2) was used for analysis of qualitative variables. Sensitivity: proportional detection of individuals with the disease of interest in the population. Specificity: proportional detection of individuals without the disease of interest in the population. Positive predictive value (PPV): proportion of all individuals with positive tests, who have the disease. Negative predictive value (NPV): proportion of all individuals with negative tests, who are non-diseased.

RESULTS

One hundred and ten (110) women with PPROM > 24 and < 34 weeks ‘gestation, were included in this study to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis. The mean maternal age of the participants, parity, body mass index (BMI), gestational age at recruitment, gestational age at TOP, and duration of the conservative treatment were presented in Table 1.

Table 1. Demographic data of the studied women and indications of TOP

Variables

Studied participants (number 110)

Maternal age [years]

29.6 ± 5.2

Parity

3.1 ± 2.4

Previous miscarriage

25/110 (22.7%)

BMI [kg/m2]

26.7 ± 9.7

Smoking

32/110 (29.1%)

Previous history of PPROM

17/110 (15.5%)

Gestational age at recruitment [weeks]

28.3 ± 2.6

Gestational age at TOP [weeks]

32.5 ± 4.3

Duration of conservative treatment [weeks]

4.2 ± 1.7

Indications of TOP

Clinical and lab. parameters of chorioamnionitis

Spontaneous labor pains

At 34 weeks gestation

63/110 (57.3%)

35/110 (31.8%)

12/110 (10.9%)

BMI body mass index; Lab. Laboratory; PPROM Preterm premature rupture of fetal membranes; TOP Termination of pregnancy; Data presented as mean ± SD (standard deviation) and number and percentage (%)

About 25/110 (22.7%) of participants had previous history of miscarriage, 32/110 (29.1%) were smokers, and 17/110 (15.5%) had previous history of PPROM. Regarding the indications of TOP, in 63/110 (57.3%) of participants the pregnancy was terminated due to clinical and laboratory parameters of chorioamnionitis, in 35/110 (31.8%) due to spontaneous labor pains, and in 12/110 (10.9%) at 34 weeks gestation (Tab. 1 and Fig. 2).

After TOP, the IL-6 bedside test results, and the clinical and laboratory parameters of chorioamnionitis were compared to histologic examination of the placenta, umbilical cord, and fetal membranes samples (gold standard).

The clinical and laboratory parameters of chorioamnionitis were TP (true positive) in 47/72 (65.3% = sensitivity), FP (false positive) in 16 cases, while they were TN (true negative) in 22/38 (57.9 = specificity), and FN (false negative) in 25 cases (Fig. 2).

The clinical and laboratory parameters of chorioamnionitis had 65.3% sensitivity, 57.9% specificity, 74.6% PPV, 46.8% NPV and 62.7% overall accuracy in detecting chorioamnionitis (Tab. 2).

Table 2. Accuracy of the IL-6 bedside test in detecting chorioamnionitis compared to clinical and lab. parameters of chorioamnionitis

Variables

IL-6 bedside test

Clinical and lab. parameters

p-value

Sensitivity (TP ÷ TP + FN) X 100

71 ÷ 71 + 1 = 98.6%

47 ÷ 47 + 25 = 65.3%

0.04*

Specificity (TN ÷ TN FP) X 100

36 ÷ 36 + 2 = 94.7%

22 ÷ 22 + 16 = 57.9%

0.02*

PPV (TP ÷ TP + FP) X 100

71 ÷ 71 + 2 = 97.3%

47 ÷ 47 + 16 = 74.6%

0.1

NPV (TN ÷ TN + FN) X 100

36 ÷ 36 + 1 = 97.3%

22 ÷ 22 + 25 = 46.8%

0.001*

Accuracy (TP + TN ÷ TP + TN + FP + FN) X 100

71 + 36 ÷ 71 + 36 + 2 + 1 = 97.3%

47 + 22 ÷ 47 + 22 + 16 + 25 = 62.7%

0.03*

*Significant difference. Chi-square test (x2) was used for statistical analysis. Data presented as number and percentage (%); FN False negative; FPFalse positive; IL-6 — Interleukin-6; Lab. Laboratory. NPV Negative predictive value; PPV Positive predictive value; TN True negative; TP True positive

The IL-6 bedside test was TP (true positive) in 71/72 (98.6% = sensitivity), FP (false positive) in 2 cases, while it was TN (true negative) in 36/38 (94.7% = specificity), and FN (false negative) in 1 case (Fig. 1).

The IL-6 bedside test had 98.6% sensitivity, 94.7% specificity, 97.3% PPV, 97.3% NPV, and 97.3% overall accuracy in detecting chorioamnionitis (Tab. 2).

The IL-6 bedside test sensitivity, specificity, NPV and overall accuracy (98.6%, 94.7%, 97.3%, and 97.3%; respectively) were significantly higher than the clinical and laboratory parameters of chorioamnionitis (65.3%, 57.9%, 46.8%, and 62.7%; respectively), (p = 0.04, 0.02, 0.001 and 0.03; respectively) (Tab. 2).

DISCUSSION

The PPROM occurs in approximately 35% of all pregnancies [2–4], and accounts for 3040% of PTDs [5]. About 3080% of PTDs following PPROM are complicated by histologic chorioamnionitis [5]. PPROM usually associated with prematurity, and infections morbidities, and 524% of the neonates delivered after PPROM suffer from neonatal sepsis [6, 7]. Currently, there is no accurate, non-invasive test available for detection of IUI [13].

IL-6 bedside test is a new IL-6 based test to detect chorioamnionitis and has the potential to detect IL-6 in CVS at three different thresholds [IL-6 low (0.1 ng/mL), IL-6 medium (0.25 ng/mL), and IL-6 high (5 ng/mL)] [5].

Therefore, one hundred and ten (110) women with PPROM > 24 and < 34 weeks, were included in this study to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis compared to the gold standard (histologic examination of the placenta, umbilical cord, and fetal membranes) as primary outcome.

While the secondary outcome measures the accuracy of IL-6 bedside test in detecting chorioamnionitis compared to the clinical and laboratory parameters of chorioamnionitis.

The mean maternal age of participants was 29.6 ± 5.2 years, mean gestational age at recruitment was 28.3 ± 2.6 weeks`, mean gestational age at TOP was 32.5 ± 4.3 weeks`, and mean duration of conservative treatment was 4.2 ± 1.7 weeks`. About 25/110 (22.7%) of participants had previous history of miscarriage, 32/110 (29.1%) were smokers, and 17/110 (15.5%) had previous history of PPROM.

Assefa et al. [21] found women with history of abortion had higher risk (3.06 times) to develop PROM (premature rupture of membranes) than those with no history of abortion. Zhou et al. [22] also found an increased risk of PPROM < 28 weeks of pregnancy in those with history of recurrent abortions (OR 2.75).

Assefa et al. [21] found women with history of PROM had higher odds (44.5) of developing PROM compared to others with no history of PROM. Similarly, Choudhary et al. and Emechebe et al. [23, 24] found that the previous PROM was significant risk factor for recurrent PROM.

Regarding the indications of TOP, in 63/110 (57.3%) of participants the pregnancy was terminated due to clinical and laboratory parameters of chorioamnionitis, in 35/110 (31.8%) due to spontaneous labor pains, and in 12/110 (10.9%) at 34 weeks.

Navali et al. [25] studied 199 women with PPROM at 29.6 ± 3.4 weeks` gestation, and found the most frequent indications for TOP were reaching 34 weeks, spontaneous labor pains, and chorioamnionitis (most common maternal complication). In addition, Eleje et al. [5] found 3080% of PTDs following PPROM were complicated by chorioamnionitis.

In this study, the IL-6 bedside test had 98.6% sensitivity, 94.7% specificity, 97.3% PPV, 97.3% NPV and 97.3% overall accuracy in detecting chorioamnionitis in women with PPROM.

In addition, the sensitivity, specificity, NPV, and overall accuracy of the IL-6 bedside test (98.6%, 94.7%, 97.3%, and 97.3%; respectively) were significantly higher than the clinical and laboratory parameters of chorioamnionitis (65.3%, 57.9%, 46.8%, and 62.7%; respectively) (p = 0.04, 0.02, 0.001 and 0.03; respectively).

Musilova et al. [26] found strong positive correlation between vaginal, and AF IL-6 concentrations, and they found that higher vaginal IL-6 was associated with microbial invasion of AF, and microbial-associated intra-amniotic inflammation.

A vaginal IL-6 of 2500 pg/mL threshold had 53% sensitivity, 89% specificity, 63% PPV, 85% NPV, in detection of AF microbial invasion, while it had 74% sensitivity, 91% specificity, 67% PPV and 94% NPV in detection of intra-amniotic inflammation, and 100% sensitivity, 90% specificity, 57% PPV, and 100% NPV in detection of microbial associated intra-amniotic inflammation [26].

Eleje et al. [5] found the IL-6 bedside test had 97.5% sensitivity, 87.9% specificity, and 93.2% accuracy in diagnosing chorioamnionitis in women with PROM, and it had 100% sensitivity, 91.3% specificity, and 95.8% overall accuracy in diagnosing chorioamnionitis in women with PPROM (< 37 weeks).

Abdelazim et al. [20] found the IL-6 in CVS had 90.7% sensitivity, 91.0% specificity, 87.5% PPV, 93.4% NPV, and 90.9% overall accuracy in detecting chorioamnionitis.

Chaemsaithong et al. [10] found the AF IL-6 at 745 pg/mL threshold had 93% sensitivity, 91% specificity and a positive likelihood ratio of 10 in detecting AF inflammation.

This study concluded that the IL-6 bedside test is an accurate, non-invasive bedside test with 98.6% sensitivity, 94.7% specificity, 97.3% PPV, 97.3% NPV, and 97.3% overall accuracy in detecting chorioamnionitis. The IL-6 bedside test had significantly higher sensitivity, specificity, NPV, and overall accuracy than the clinical and laboratory parameters of chorioamnionitis.

Abdelazim et al. [20] also concluded that the IL-6 in CVS is a sensitive, non-invasive marker in detecting neonatal infection, and chorioamnionitis.

In addition, Musilova et al. [26] concluded that vaginal IL-6 is a rapid, non-invasive, and inexpensive test for detecting intra-amniotic inflammation and/or microbial-associated intra-amniotic inflammation with good specificity, and NPV.

The high accuracy of the IL-6 bedside test in detecting chorioamnionitis in this study can be explained by the ability of IL-6 bedside test to detect IL-6 in CVS at three different thresholds [IL-6 low (0.1 ng/mL), IL-6 medium (0.25 ng/mL), and IL-6 high (5 ng/mL)].

This study was the first prospective comparative double blinded study (consultant decided TOP, and histopathologist) conducted to evaluate the accuracy of IL-6 bedside test in detecting chorioamnionitis in women with PPROM.

Women refused to participate and/or give consent, and shipping of kits from the manufacturer to the study place were the limitations faced during the study.

The accuracy of IL-6 bedside test in diagnosing chorioamnionitis should be confirmed in future studies including the neonatal outcome following chorioamnionitis.

CONCLUSIONS

The IL-6 bedside test is an accurate, non-invasive bedside test with 98.6% sensitivity, 94.7% specificity, 97.3% PPV, 97.3% NPV, and 97.3% overall accuracy in detecting chorioamnionitis. The IL-6 bedside test had significantly higher sensitivity, specificity, NPV, and overall accuracy than the clinical and laboratory parameters of chorioamnionitis.

Acknowledgments

Authors are grateful to Doctor Thierry Paper (CEO and President of Biosynex, SA) to supply the IL-6 bedside test (Chorioquick®) kits freely for this study (Doctor Thierry Paper was not involved in any part of this study and/or analysis of the data). The authors are also grateful to women agreed and gave consent to participate in this study.

Conflict of interest

Authors declare no conflict of interests in relation to this study.

REFERENCES

  1. Abdelazim IA, Shikanova S, Karimova B, et al. Diagnostic accuracy of insulin-like growth factorbinding protein-1/alpha-fetoprotein (amnioquick duo) in ruptured fetal membranes. SN Comprehensive Clinical Medicine. 2020; 2(12): 28342839, doi: 10.1007/s42399-020-00600-w.
  2. Mercer B. Preterm premature rupture of the membranes. Obstet Gynecol. 2003; 101(1): 178193, doi: 10.1016/s0029-7844(02)02366-9, indexed in Pubmed: 12517665.
  3. Mercer BM, Goldenberg RL, Meis PJ, et al. The Preterm Prediction Study: prediction of preterm premature rupture of membranes through clinical findings and ancillary testing. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol. 2000; 183(3): 738745, doi: 10.1067/mob.2000.106766, indexed in Pubmed: 10992202.
  4. Sae-Lin P, Wanitpongpan P. Incidence and risk factors of preterm premature rupture of membranes in singleton pregnancies at Siriraj Hospital. J Obstet Gynaecol Res. 2019; 45(3): 573577, doi: 10.1111/jog.13886, indexed in Pubmed: 30537150.
  5. Eleje GU, Ukah CO, Onyiaorah IV, et al. Diagnostic value of Chorioquick for detecting chorioamnionitis in women with premature rupture of membranes. Int J Gynaecol Obstet. 2020; 149(1): 98105, doi: 10.1002/ijgo.13095, indexed in Pubmed: 31907923.
  6. Bond DM, Middleton P, Levett KM, et al. Planned early birth versus expectant management for women with preterm prelabour rupture of membranes prior to 37 weeks’ gestation for improving pregnancy outcome. Cochrane Database Syst Rev. 2017; 3: CD004735, doi: 10.1002/14651858.CD004735.pub4, indexed in Pubmed: 28257562.
  7. Drassinower D, Friedman AM, Običan SG, et al. Prolonged latency of preterm prelabour rupture of membranes and neurodevelopmental outcomes: a secondary analysis. BJOG. 2016; 123(10): 16291635, doi: 10.1111/1471-0528.14133, indexed in Pubmed: 27245741.
  8. Higgins RD, Saade G, Polin RA, et al. Chorioamnionitis Workshop Participants. Evaluation and Management of Women and Newborns With a Maternal Diagnosis of Chorioamnionitis: Summary of a Workshop. Obstet Gynecol. 2016; 127(3): 426436, doi: 10.1097/AOG.0000000000001246, indexed in Pubmed: 26855098.
  9. Stepan M, Cobo T, Musilova I, et al. Maternal serum c-reactive protein in women with preterm prelabor rupture of membranes. PLoS One. 2016; 11(3): e0150217, doi: 10.1371/journal.pone.0150217, indexed in Pubmed: 26942752.
  10. Chaemsaithong P, Romero R, Korzeniewski SJ, et al. A rapid interleukin-6 bedside test for the identification of intra-amniotic inflammation in preterm labor with intact membranes. J Matern Fetal Neonatal Med. 2016; 29(3): 349359, doi: 10.3109/14767058.2015.1006620, indexed in Pubmed: 25758618.
  11. Combs CA, Gravett M, Garite TJ, et al. ProteoGenix/Obstetrix Collaborative Research Network. Amniotic fluid infection, inflammation, and colonization in preterm labor with intact membranes. Am J Obstet Gynecol. 2014; 210(2): 125.e1125.e15, doi: 10.1016/j.ajog.2013.11.032, indexed in Pubmed: 24274987.
  12. Romero R, Miranda J, Chaemsaithong P, et al. Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2015; 28(12): 13941409, doi: 10.3109/14767058.2014.958463, indexed in Pubmed: 25190175.
  13. Kayem G, Batteux F, Girard N, et al. Predictive value of vaginal IL-6 and TNFα bedside tests repeated until delivery for the prediction of maternal-fetal infection in cases of premature rupture of membranes. Eur J Obstet Gynecol Reprod Biol. 2017; 211: 814, doi: 10.1016/j.ejogrb.2017.01.013, indexed in Pubmed: 28160689.
  14. Kunze M, Klar M, Morfeld CA, et al. Cytokines in noninvasively obtained amniotic fluid as predictors of fetal inflammatory response syndrome. Am J Obstet Gynecol. 2016; 215(1): 96.e196.e8, doi: 10.1016/j.ajog.2016.01.181, indexed in Pubmed: 26829512.
  15. Abdelazim IA. Evaluation of the performance of the insulin-like growth factor-binding protein-1/alpha-fetoprotein test in diagnosing ruptured fetal membranes in pregnant women. J Perinatol. 2016; 36(1): 77, doi: 10.1038/jp.2015.180, indexed in Pubmed: 26707691.
  16. Abdelazim IA. Insulin-like growth factor binding protein-1 (Actim PROM test) for detection of premature rupture of fetal membranes. J Obstet Gynaecol Res. 2014; 40(4): 961967, doi: 10.1111/jog.12296, indexed in Pubmed: 24612210.
  17. Committee on Practice Bulletins-Obstetrics. ACOG practice bulletin no. 188: prelabor rupture of membranes. Obstet Gynecol. 2018; 131(1): e1e14, doi: 10.1097/AOG.0000000000002455, indexed in Pubmed: 29266075.
  18. Farghali M, Abdelazim I, Abdelrazek K. Delayed second twin delivery: benefits and risks. J Matern Fetal Neonatal Med. 2019; 32(10): 16261632, doi: 10.1080/14767058.2017.1413547, indexed in Pubmed: 29198155.
  19. Salafia CM, Weigi C, Silberman L. The prevalence and distribution of acute placental inflammation in uncomplicated term pregnancies. Obstet Gynecol. 1989; 30(1): 8484, doi: 10.1016/0020-7292(89)90252-x.
  20. Abdelazim I. Relation between interleukin-6 in the cervicovaginal fluid and subclinical chorioamnionitis in patients with preterm premature rupture of membranes. Asian Pacific Journal of Reproduction. 2013; 2(1): 3841, doi: 10.1016/s2305-0500(13)60113-x.
  21. Assefa NE, Berhe H, Girma F, et al. Risk factors of premature rupture of membranes in public hospitals at Mekele city, Tigray, a case control study. BMC Pregnancy Childbirth. 2018; 18(1): 386, doi: 10.1186/s12884-018-2016-6, indexed in Pubmed: 30268103.
  22. Zhou Q, Zhang W, Xu H, et al. Risk factors for preterm premature rupture of membranes in Chinese women from urban cities. Int J Gynaecol Obstet. 2014; 127(3): 254259, doi: 10.1016/j.ijgo.2014.06.020, indexed in Pubmed: 25200254.
  23. Choudhary M, Rathore S, Chowdhary J, et al. Pre and post conception risk factors in PROM. International Journal of Research in Medical Sciences. 2015: 25942598, doi: 10.18203/2320-6012.ijrms20150797.
  24. Charles JO, Charles AO. Poverty and patient abandonment in the University of Calabar Teaching Hospital (UCTH), Nigeria. Global Journal of Medical Sciences. 2003; 2(2), doi: 10.4314/gjms.v2i2.10128.
  25. Nazli N, Sanaz M, Saied N. indications of pregnancy termination in patients with preterm premature rupture of membranes and relationship between the latency of rupture and pregnancy outcomes . CJMB. 2020; 7(4): 564567, doi: 10.4324/9780429462023-66.
  26. Musilova I, Bestvina T, Hudeckova M, et al. Vaginal fluid interleukin-6 concentrations as a point-of-care test is of value in women with preterm prelabor rupture of membranes. Am J Obstet Gynecol. 2016; 215(5): 619.e1619.e12, doi: 10.1016/j.ajog.2016.07.001, indexed in Pubmed: 27402051.