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International Journal of Gynecology and Obstetrics 132 (2016) 165–169

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International Journal of Gynecology and Obstetrics

journal homepage: www.elsevier.com/locate/ijgo

CLINICAL ARTICLE

Predicting outcomes of emergency cerclage in women with cervical


insufficiency using inflammatory markers in maternal blood and
amniotic fluid
Eun Young Jung a, Kyo Hoon Park a,⁎, Sung Youn Lee a, Aeli Ryu a, Jung Kyung Joo a, Jeong Woo Park b
a
Departments of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
b
Department of Obstetrics and Gynecology, Inje University College of Medicine, Ilsan-Paik Hospital, Gyeonggi, Korea

a r t i c l e i n f o a b s t r a c t

Article history: Objective: To identify inflammatory markers in maternal blood and amniotic fluid that can predict outcomes of
Received 25 February 2015 emergency cerclage in women with cervical insufficiency. Methods: This retrospective cohort study included
Received in revised form 10 July 2015 patients at 18–24 weeks of pregnancy who underwent amniocentesis before receiving emergency cerclage for cer-
Accepted 16 October 2015 vical insufficiency between August 2004 and August 2013 at a university teaching hospital in South Korea. Total
and differential white blood cell counts were measured during amniocentesis. Amniotic fluid was cultured and an-
Keywords:
alyzed for the presence of interleukin (IL)-6 and IL-8. The primary outcome measure was spontaneous preterm de-
Amniotic fluid
Cervical insufficiency
livery (SPTD) at less than 32 weeks of pregnancy following cerclage placement. Results: Of 37 patients, 18 (49%)
Emergency cerclage experienced SPTD at less than 32 weeks of pregnancy. These patients were found to have significantly more ad-
Interleukin-8 vanced cervical dilatation at presentation, as well as higher mean neutrophil–lymphocyte ratios (NLRs) and higher
Neutrophil-to-lymphocyte ratio IL-6 and IL-8 levels in amniotic fluid in comparison with those who did not experience SPTD at less than 32 weeks
of pregnancy. In a multivariable analysis, a high NLR and high amniotic fluid IL-8 levels showed a significant cor-
relation with the occurrence of SPTD at less than 32 weeks of pregnancy (P = 0.032). Conclusion: Pre-operative
NLR and amniotic fluid IL-8 levels may be important markers for predicting emergency cerclage outcomes in
women with cervical insufficiency.
© 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

1. Introduction small numbers of patients [8] and have not included important variables
such as amniotic-fluid culture results and white blood cell (WBC) counts
Although acute cervical insufficiency is relatively rare, accounting for [7]. Moreover, these studies have not examined the use of maternal
less than 0.5% of all pregnancies, in the absence of intervention it has a blood inflammatory markers as less invasive predictors [6]. Maternal
number of devastating outcomes associated with extreme preterm birth systemic inflammatory biomarkers in peripheral blood, such as WBC
[1,2]. Emergency cerclage placement is often the only hope for prolonging counts and C-reactive protein (CRP), have been reported to reflect
pregnancy for patients with this condition, resulting in fetal salvage rates infection/inflammation resulting from subclinical chorioamnionitis in
of 46%–100% [3–5]. However, despite the importance of this procedure, women with preterm labor or preterm premature rupture of mem-
information on predictors of success in women undergoing emergent branes [11,12]. Importantly, recent studies have demonstrated that the
cerclage, especially using non-invasive methods, remains limited. blood neutrophil–lymphocyte ratio (NLR), which reflects systemic in-
Intrauterine infection and/or inflammation are associated with a poor flammation, is an independent diagnostic and prognostic factor of sub-
prognosis following emergency cerclage [6–9], and their prenatal diag- clinical inflammatory diseases, including preterm labor and gestational
nosis is particularly important because they may increase the risk of diabetes [13,14]. However, little information is available on whether
long-term handicap in preterm infants who survive [10]. Therefore, nu- these systemic inflammatory biomarkers are related to adverse out-
merous studies have focused on discovering biomarkers for this condi- comes in patients undergoing emergency cerclage for cervical insuffi-
tion, finding that the levels of interleukin (IL)-1, IL-6, and IL-8 in the ciency. The present study aimed to identify inflammatory markers in
amniotic fluid can be used to predict the success of emergency cerclage maternal blood and amniotic fluid, and to assess their effectiveness in
in patients [6–8]. However, these studies have been limited by very predicting outcomes of emergency cerclage for cervical insufficiency.

2. Materials and methods


⁎ Corresponding author at: Department of Obstetrics and Gynecology, Seoul National
University Bundang Hospital, 82, Gumi-ro 173 Beon-gil, Bundang-gu, Seongnam,
463–707, Korea. Tel.: +82 31 787 7252; fax: +82 31 787 4054. This retrospective cohort study included consecutive patients who
E-mail address: pkh0419@snubh.org (K.H. Park). underwent emergency cerclage following a diagnosis of cervical

http://dx.doi.org/10.1016/j.ijgo.2015.07.011
0020-7292/© 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

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166 E.Y. Jung et al. / International Journal of Gynecology and Obstetrics 132 (2016) 165–169

insufficiency at Seoul National University Bundang Hospital (Seongnamsi, or a tendency towards an association with SPTD at less than 32 weeks of
South Korea) between August 1, 2004 and August 31, 2013. The inclusion pregnancy in the univariate analysis (P b 0.1) were then further analyzed
criteria were singleton gestation; presence of a live fetus at between using a logistic regression model to select independent predictors of this
18 + 1 weeks and 24 + 6 weeks of gestation; transabdominal amniocen- outcome. In the logistic regression model, continuous indicators were
tesis conducted prior to cerclage to evaluate the microbiologic and in- transformed into dichotomous variables for the purposes of prediction
flammatory status of the amniotic cavity, and/or to reduce tension in or decision, and receiver-operating characteristic (ROC) curves were
the amniotic cavity; maternal blood drawn at the time of amniocentesis used to identify the best cut-off values for dichotomization. A ROC-
to determine the WBC count and CRP level; and intact amniotic mem- curve analysis was used to display the relationship between the sensitiv-
branes. The exclusion criteria were major congenital anomalies, prophy- ity (true-positive rate) and false-positive rates, and to select the best cut-
lactic cerclage early in the pregnancy, clinical chorioamnionitis, preterm off values for the NLR, amniotic fluid IL-6, and amniotic fluid IL-8 levels in
labor, preterm premature rupture of membranes, vaginal bleeding, and predicting SPTD at less than 32 weeks of pregnancy. The cerclage-to-
multiple gestations. Patients with healthy singleton pregnancies who delivery interval was assessed with a Kaplan–Meier analysis and was
underwent genetic amniocentesis between 16 + 3 and 18 + 6 weeks compared between the groups using a log-rank test. Cox proportional
of pregnancy at the same hospital during the same period, and who deliv- hazards modeling was used to examine the relationship between the
ered at term, were included as a control cohort for the amniotic-fluid cy- cerclage-to-delivery interval and the results of the analyses of the poten-
tokine study. The primary outcome measure was spontaneous preterm tial biomarkers after adjusting for other prognostic variables. Participants
delivery (SPTD) at less than 32 completed weeks of pregnancy. An addi- who underwent delivery preterm for either maternal or fetal indications
tional analysis of SPTD at less than 37 weeks of pregnancy was performed. were included in this analysis, with a censoring time equal to the
Written informed consent for the collection and use of amniotic-fluid cerclage-to-delivery interval. The correlation analysis was performed
samples was obtained from all study subjects. The local ethics committee using the Spearman rank correlation test. P b 0.05 was considered
at Seoul National University Bundang Hospital approved the study statistically significant.
(project number B-1311/228-010).
Cervical insufficiency was defined as painless cervical dilatation of at
least 1 cm with exposed fetal membranes without contractions of the 3. Results
uterus; this was determined by visual evaluation during a sterile specu-
lum examination. Emergency cerclage was offered to patients with cer- Of the 42 patients who fulfilled the inclusion criteria, failed cerclage
vical insufficiency and was performed using the McDonald technique during rescue cerclage placement occurred in four patients, and one had
under spinal anesthesia. For patients with advanced cervical dilatation no amniotic fluid available for IL measurement, leaving 37 participants
and bulging membranes, amnioreduction was performed to decrease suitable for evaluation. Of the patients included in the present study, the
intra-amniotic-fluid pressure and, if necessary, an inflated number-16 time of cerclage ranged from 18 + 3 weeks to 24 + 6 weeks of pregnancy.
Foley catheter was used to push the amniotic membranes back into Positive amniotic-fluid cultures were obtained from 4 (11%) individuals.
the uterine cavity during suture placement. All patients received pro- The microorganisms isolated from the amniotic-fluid samples included
phylactic antibiotics. After the cerclage procedure, all patients were con- Ureaplasma urealyticum (from four patients) and Mycoplasma hominis
tinuously monitored using a tocodynamometer for at least 2 hours. (present in three patients). Polymicrobial invasion was present in three
Tocolytics were used at the discretion of the attending obstetrician if of the four cases. SPTDs at less than 32 weeks of pregnancy and less
regular uterine contractions developed. Prenatal corticosteroids were than 37 weeks of pregnancy occurred in 18 (49%) and 26 (70%) patients,
administered to patients with cervical insufficiency at 24–34 weeks of respectively. The control cohort enrolled 18 patients.
pregnancy to enhance fetal lung maturity. Prenatal corticosteroids and Table 1 shows the baseline demographic and clinical characteristics
antibiotics were administered following amniocentesis. of the study and control cohorts. Amniotic fluid IL-6 and IL-8 levels
Before cerclage placement, transabdominal amniocentesis was per- were significantly higher in the cerclage group than in the control
formed to obtain amniotic fluid using an aseptic technique with ultra- group (P b 0.001). The control group was older and had a significantly
sound guidance. The amniotic fluid was cultured for aerobic bacteria, lower length of pregnancy at the time of amniocentesis (P b 0.001).
anaerobic bacteria, and genital mycoplasma, and was analyzed to The demographic and clinical characteristics of the study population
make a WBC count according to a previously described method [15]. when stratified according to SPTD following cerclage placement at both
The remaining amniotic fluid was centrifuged at 1500 g at 4 °C for 10 less than 32 weeks of pregnancy and less than 37 weeks of pregnancy
minutes; the supernatant was aliquoted and immediately stored at are shown in Table 2. Patients who experienced SPTD at less than
− 70 °C until assayed. IL-6 and IL-8 in the stored amniotic fluid were 32 weeks of pregnancy had significantly more advanced cervical dilata-
measured using an enzyme-linked immunosorbent assay human tion (P = 0.012) at presentation, a higher mean NLR (P = 0.017), and
DuoSet Kit (R&D System, Minneapolis, MN, USA). All samples were higher amniotic fluid IL-6 (P = 0.036) and IL-8 (P = 0.020) levels than
measured in duplicate. The calculated intra- and inter-assay coefficients those who did not deliver spontaneously at less than 32 weeks of preg-
of variation were each lower than 10%. nancy. However, no significant associations were found between SPTD
Maternal blood was collected immediately after amniocentesis at less than 32 weeks of pregnancy and maternal age, parity, duration
for determining the WBC counts and CRP levels. The maternal blood
total and differential WBC counts were determined using an automated Table 1
hemocytometer (XE-2100; Sysmex, Tokyo, Japan). The CRP level was Clinical characteristics of the study and control cohorts.a

measured with a latex-enhanced turbidimetric immunoassay (Denka Variable Cerclage cohort Control cohort P value
Seiken, Tokyo, Japan) and an automated analyzer (Toshiba 200FR; (n = 37) (n = 18)
Toshiba, Tokyo, Japan). The NLR was defined as the absolute neutrophil Maternal age, y 31.8 ± 3.2 35.2 ± 3.9 b0.001
count divided by the absolute lymphocyte count. Clinical and histologic Duration of pregnancy at 21.4 ± 1.4 17.3 ± 0.7 b0.001
chorioamnionitis was diagnosed according to previously described amniocentesis, wk
Duration of pregnancy at delivery, wk 30.8 ± 7.0 38.6 ± 1.3 b0.001
definitions [12,16].
Amniotic fluid IL-6 level, ng/mL 11.33 ± 19.67 0.27 ± 0.29 b0.001
Statistical analyses were performed using SPSS for Windows version Amniotic fluid IL-8 level, ng/mL 4.40 ± 4.62 0.38 ± 0.35 b0.001
20.0 (IBM, Armonk, NY, USA). The Shapiro–Wilk test was conducted to Cervical length assessed by 38.6 ± 7.6
test the normal distribution of the data. A univariate analysis was per- ultrasound, mm
formed using the Student t test, Mann–Whitney U test, Fisher exact Abbreviation: IL, interleukin.
test, or χ2 test, as appropriate. Variables showing a significant correlation a
Values are given as mean ± SD unless indicated otherwise.

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Table 2
Demographic and clinical characteristics of the study population.a

Characteristics Delivery at b32 weeks Delivery at ≥32 weeks P values Delivery at b37 weeks Delivery at ≥37 weeks P values
of pregnancy of pregnancy of pregnancy of pregnancy
(n = 18) (n = 19) (n = 26) (n = 11)

Age, y 31.4 ± 2.4 32.2 ± 3.8 0.461 31.6 ± 2.5 32.4 ± 4.5 0.421
≥35 3 (17) 4 (21) 1.000 4 (15) 3 (27) 0.403
b35 15 (83) 15 (79) 22 (85) 8 (73)
Nulliparous patient 11 (61) 6 (32) 0.103 13 (50) 4 (36) 0.495
Duration of pregnancy at cerclage, wk 21.6 ± 1.8 21.4 ± 1.1 0.425 21.6 ± 1.6 21.3 ± 1.1 0.300
Cervical dilatation at presentation, cm 3 (1–5) 2 (1–8) 0.072 3 (1–6) 2 (1–8) 0.019
≥3 14 (78) 7 (37) 0.012 18 (69) 3 (27) 0.018
b3 4 (22) 12 (63) 8 (31) 8 (73)
Maternal WBC count, ×103/mm3 11.08 ± 2.98 10.09 ± 2.60 0.327 10.71 ± 2.96 10.27 ± 2.50 0.756
Serum CRP, g/L 0.0062 ± 0.0087 0.0076 ± 0.0075 0.271 0.0069 ± 0.0076 0.0071 ± 0.0093 0.481
Maternal blood NLR 5.68 ± 2.36 4.32 ± 1.76 0.017 5.43 ± 2.40 3.92 ± 0.79 0.040
Amniotic fluid WBC counts, cells/mm3 200.22 ± 597.27 21.26 ± 36.24 0.988 149.46 ± 499.40 11.09 ± 10.11 0.935
Amniotic fluid IL-6 levels, ng/mL 17.98 ± 25.90 5.04 ± 7.38 0.036 15.19 ± 22.37 2.20 ± 3.45 0.005
Amniotic fluid IL-8 levels, ng/mL 12.51 ± 25.85 3.070 ± 3.28 0.020 10.06 ± 21.75 1.99 ± 2.19 0.011
Positive amniotic fluid cultures 3 (17) 1 (5) 0.340 4 (15) 0 (0) 0.296
Use of tocolytics 11 (61) 8 (42) 0.330 15 (58) 4 (36) 0.295
Use of corticosteroids 7 (39) 3 (16) 0.151 9 (35) 1 (9) 0.224
Use of antibiotics 18 (100) 19 (100) 26 (100) 11 (100)
Histologic chorioamnionitisb 17/18 (94) 1/6 (17) 0.001 18/24 (75) 0/0 (0)
Clinical chorioamnionitis 3 (17) 0 (0) 0.105 3 (12) 0 (0) 0.540
Duration of pregnancy at delivery, wk 24.2 ± 3.1 37.0 ± 2.0 b0.001 27.6 ± 5.9 38.4 ± 0.9 b0.001

Abbreviations: WBC, white blood cell; CRP, C-reactive protein; NLR, neutrophil–lymphocyte ratio; IL, interleukin.
a
Values are given as the mean ± SD, number (percentage), number/number of patients available for evaluation (percentage), or median (range), unless indicated otherwise.
b
Data for histologic evaluation of the placenta were available for 24 (65%) of the 37 study participants because it was the policy at the study institution that placentas were only sent for
histopathologic examination in cases of preterm delivery.

of pregnancy at the time of cerclage, maternal WBC counts, serum CRP of pregnancy. The sensitivities of the cut-off values of at least 4.7 for
levels, and amniotic-fluid WBC counts. Similar results were obtained the NLR and at least 4.0 ng/mL for the amniotic fluid IL-8 level, which
for the secondary endpoint of SPTD at less than 37 weeks of pregnancy. were identified as the optimal thresholds, were 67% and 67%, respec-
NLRs were not correlated with cervical dilatation, or amniotic fluid IL-6 tively, and the specificities were 79% and 79%, respectively. The area
and IL-8 levels. Cervical dilatation was found to be significantly correlat- under the curves for the NLR and amniotic fluid IL-8 level did not differ
ed with amniotic fluid IL-6 levels (r [correlation coefficient] = 0.456, P = significantly (P N 0.99).
0.005) but not with amniotic fluid IL-8 levels (r = 0.290, P = 0.082). Kaplan–Meier estimates of the cerclage-to-delivery interval for a
Amniotic fluid IL-6 and IL-8 levels were significantly correlated with NLR of at least 4.7 or less than 4.7, an amniotic fluid IL-6 level of at least
each other (r = 0.806, P b 0.001). 4.1 ng/mL or less than 4.1 ng/mL, an amniotic fluid IL-8 level of at least
Based on the criteria of producing a P value of less than 0.1 in the uni- 4.0 ng/mL or less than 4.0 ng/mL, and a cervical dilatation of at least
variate analyses, the following variables were assessed in the multivariate 3 cm or less than 3 cm are shown in Fig. 2. Comparisons made between
logistic regression analysis as being predictors associated with SPTD at the groups using log rank tests were significant (NLR of at least 4.7,
less than 32 weeks of pregnancy following cerclage: cervical dilatation, P = 0.001; amniotic fluid IL-6 level of at least 4.1 ng/mL, P = 0.032; am-
NLR, and amniotic fluid IL-6 and IL-8 levels. In this model, all continuous niotic fluid IL-8 level of at least 4.0 ng/mL, P = 0.027; and cervical dilata-
predictors were entered as dichotomous variables using the cut-off values tion of at least 3 cm, P = 0.046). The Cox proportional modeling
derived from the ROC curves. The optimal cut-off values for NLR, performed indicated that, after being controlled for high amniotic fluid
amniotic fluid IL-6 level, and amniotic fluid IL-8 level were at least 4.7, IL-6 or IL-8 levels and advanced cervical dilatation, the NLR results had
at least 4.1 ng/mL, and at least 4.0 ng/mL, respectively. Based on previous a significant relationship with the cerclage-to-delivery interval (hazard
reports [17,18], the variable of advanced cervical dilatation was dichoto- ratio: 4.00; 95% confidence interval; 1.60–10.02, P = 0.003).
mized to shorter than 3 cm and at least 3 cm (consistent with the cut-
off value derived from the ROC curve of the present study data). Owing
to the levels of IL-6 and IL-8 in the amniotic fluid being highly correlated,
Table 3
two separate models were constructed, with each model consisting of Logistic regression models of the potential predictors of spontaneous preterm delivery at
high amniotic fluid IL-8 (Model I) or high amniotic fluid IL-6 (Model II) less than 32 weeks of pregnancy.a
levels in addition to a high NLR and advanced cervical dilatation. Only a
Predictor Odds 95% Confidence P value
high NLR and high amniotic fluid IL-8 level showed a significant correla- ratio interval
tion with SPTD at less than 32 weeks of pregnancy (Table 3). A combina-
Model I
tion of NLR (cut-off, 4.7) and amniotic fluid IL-8 level (cut-off, 4.0 ng/mL)
High neutrophil–lymphocyte ratio 6.62 1.18–37.27 0.032
showed a sensitivity of 44.4% (8/18), a specificity of 94.7% (18/19), a pos- Advanced cervical dilatation 5.76 0.91–36.63 0.064
itive predictive value of 88.9% (8/9), and a negative predictive value of High amniotic fluid interleukin-8 level 6.62 1.18–37.27 0.032
64.3% (18/28) in predicting SPTD at less than 32 weeks of pregnancy fol- Model II
High neutrophil-lymphocyte ratio 6.06 1.18–31.13 0.031
lowing cerclage. The positive- and negative-likelihood ratios were 8.44
Advanced cervical dilatation 4.33 0.79–23.76 0.092
(1.17–60.94) and 0.59 (0.38–0.90), respectively. High amniotic fluid interleukin-6 level 3.00 0.59–15.32 0.187
Fig. 1 displays the ROC curves for NLR and amniotic fluid IL-8 levels a
Each of the study variables was dichotomized: high neutrophil-lymphocyte ratio
in predicting SPTD at less than 32 weeks of pregnancy following (≥4.7 vs b4.7), advanced cervical dilatation (≥3 cm vs b3 cm), high amniotic fluid inter-
cerclage. Both curves were above the 45° line, indicating a significant leukin-8 level (≥4.0 ng/mL vs b4.0 ng/mL ), and high amniotic fluid interleukin-6 level
correlation between these parameters and SPTD at less than 32 weeks (≥4.1 ng/mL vs b4.1 ng/mL).

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168 E.Y. Jung et al. / International Journal of Gynecology and Obstetrics 132 (2016) 165–169

biomarkers resulted in a specificity of 94.7%, suggesting that a negative


test result with this combination can effectively identify patients who
will benefit from emergency cerclage.
The major study finding that NLR has independent predictive value for
clinical outcomes of emergency cerclage for cervical insufficiency sug-
gests that systemic subclinical inflammation, irrespective of whether
intra-amniotic infection/inflammation is present, may play a role in the
pathogenesis of SPTD in this setting. Similarly, in previous studies, Kim
et al. found that NLRs may be a predictive marker of impending preterm
delivery, especially in the context of normal CRP levels and placental in-
flammatory response [14,19]. In contrast to NLRs, pre-cerclage CRP levels
demonstrated poor predictive value for SPDT outcomes in the present
study. This finding is consistent with data from previous reports demon-
strating that serum CRP levels on the postoperative day (as opposed to
before cerclage) predicted the occurrence of very-preterm birth in
women that had undergone indicated or rescue cervical cerclage [8,20].
Although the results of the present study cannot explain the discrep-
ancy between NLRs and CRP levels, these data suggest that the NLR is
superior to the CRP level in predicting SPTD following emergency
Fig. 1. Receiver-operating characteristics curves for maternal blood NLR and AF IL-8 levels
in predicting spontaneous preterm delivery at less than 32 weeks of pregnancy following cerclage. Consequently, the NLR should be considered an effective pre-
emergency cerclage. NLR: AUC 0.728; SE 0.087, P = 0.018; AF IL-8: AUC 0.722, SE 0.085, dictor of success in women undergoing rescue cerclage, particularly in
P = 0.021. Abbreviations: NLR, neutrophil–lymphocyte ratio; IL, interleukin; AF, amniotic centers with limited resources owing to determining NLRs being simple,
fluid; AUC, area under the curve; SE, standard error. non-invasive, and inexpensive.
The present study found that elevated pre-operative IL-6 and IL-8
4. Discussion levels in the amniotic fluid were associated, according to the bivariate
analysis, with an increased chance of SPTD at less than 32 weeks of preg-
The present study demonstrated that high pre-operative NLRs and nancy following emergency cerclage. These findings confirm those of
amniotic fluid IL-8 levels were significantly associated with an adverse previous reports [7,8] and are not unexpected; once an intra-amniotic in-
pregnancy outcome following emergency cerclage. This association flammatory response to infection occurs (reflected in elevated amniotic
persisted after adjustment for important predictors such as cervical di- fluid IL-6 or IL-8 levels), appropriate treatments (e.g., antibiotic therapy,
latation and amniotic fluid IL-6 levels. Moreover, combining these two rescue cerclage) after the onset of symptoms may not prevent preterm

Fig. 2. Kaplan–Meier estimates of the cerclage-to-delivery interval for (A) NLR of at least 4.7 or less than 4.7; (B) AF IL-6 level of at least 4.1 ng/mL or less than 4.1 ng/mL; (C) AF IL-8 level of
at least 4.0 ng/mL or less than 4.0 ng/mL; and (D) CD of at least 3 cm or less than 3 cm. NLR: median 21.29 days (95%CI 13.48–29.10) vs 112.58 days (95%CI 86.41–138.76), P = 0.001; AF IL-
6: median 41.25 days (95%CI 4.71–77.79) vs 96.88 days (95%CI 60.65–133.10), P = 0.032; AF IL-8: median 25.38 days (95%CI 7.07–43.68) vs 96.88 days (95%CI 58.08–135.67), P = 0.027;
CD: median 41.25 days (95%CI 0.00–97.43) vs 112.58 days (95%CI 86.95–139.22), P = 0.046. Abbreviations: NLR, neutrophil–lymphocyte ratio; AF, amniotic fluid; IL, interleukin; CD, cer-
vical dilatation; CI, confidence interval.

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The major limitations of the present study included its retrospective term delivery in preterm labour. Eur J Clin Invest 2011;41(7):773–80.
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which patients can benefit from rescue cerclage, and will need to be [16] Gibbs RS, Blanco JD, St Clair PJ, Castaneda YS. Quantitative bacteriology of amniotic
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In conclusion, the present study demonstrated that pre-operative [17] Terkildsen MF, Parilla BV, Kumar P, Grobman WA. Factors associated with success of
NLRs and amniotic fluid IL-8 levels are important biochemical markers emergent second-trimester cerclage. Obstet Gynecol 2003;101(3):565–9.
for predicting the outcome of emergency cerclage for cervical insuffi- [18] Fuchs F, Senat MV, Fernandez H, Gervaise A, Frydman R, Bouyer J. Predictive score
for early preterm birth in decisions about emergency cervical cerclage in singleton
ciency. The combined use of these markers can help in identifying preg- pregnancies. Acta Obstet Gynecol Scand 2012;91(6):744–9.
nancies with cervical insufficiency at a low risk for SPTD and assist [19] Kim MA, Lee YS, Seo K. Assessment of predictive markers for placental inflammatory
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Acknowledgments Perinat Med 2011;39(2):151–5.
[21] Grigsby PL, Novy MJ, Sadowsky DW, Morgan TK, Long M, Acosta E, et al. Maternal
azithromycin therapy for Ureaplasma intraamniotic infection delays preterm deliv-
This study was supported by a grant from the Korea Health Technol- ery and reduces fetal lung injury in a primate model. Am J Obstet Gynecol 2012;
ogy R&D Project, Ministry of Health and Welfare, Republic of Korea 207(6):475.e1.e14.
(Grant No. HI 14C1798). [22] Gravett MG, Adams KM, Sadowsky DW, Grosvenor AR, Witkin SS, Axthelm MK, et al.
Immunomodulators plus antibiotics delay preterm delivery after experimental
intraamniotic infection in a nonhuman primate model. Am J Obstet Gynecol 2007;
Conflict of interest 197(5):518.e1–8.
[23] Sakai M, Sasaki Y, Yoneda S, Kasahara T, Arai T, Okada M, et al. Elevated interleukin-8
in cervical mucus as an indicator for treatment to prevent premature birth and pre-
The authors have no conflicts of interest. term, pre-labor rupture of membranes: a prospective study. Am J Reprod Immunol
2004;51(3):220–5.
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