Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 94e97

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Original Article

Fetal fibronectin is more valuable than ultrasonographic examination of the cervix or Bishop score in predicting successful induction of labor Dilek Uygur, A. Seval Ozgu-Erdinc*, Ruya Deveer, Hakan Aytan, M. Tamer Mungan Zekai Tahir Burak Women Health Care, Research and Education Hospital, Ankara, Turkey

a r t i c l e i n f o

a b s t r a c t

Article history: Accepted 4 June 2014

Objective: To compare fetal fibronectin (fFN) assessment, ultrasound parameters, and Bishop score in the prediction of successful induction of labor at term when cervix is unfavorable. Materials and Methods: Seventy-three nulliparous women undergoing labor induction at term with Bishop score less than 5 were enrolled in this study. Successful labor induction was defined as vaginal delivery occurring within 24 hours of initiation of induction. fFN obtained from vaginal secretion was measured by immunoassay. Results: Patients who delivered within 24 hours (n ¼ 33) differed significantly from the remaining patients by a positive fFN (84.8% vs. 15.2%, p ¼ 0.002). The mean cervical length or Bishop scores were not statistically different between women who delivered vaginally before 24 hours of induction and those who did not (28.9 mm vs. 27.9 mm, p ¼ 0.468 and 3.3 vs. 3.2, p ¼ 0.928, respectively). Binary logistic regression analysis showed only the fFN immunoassay to be an independent statistically significant predictor of vaginal delivery within 24 hours of induction (odds ratio 6.168; 95% confidence interval 1.897e20.059; p ¼ 0.002). A positive fibronectin assay had a sensitivity and specificity of 84.9% and 50%, respectively. Conclusions: In cases with unfavorable cervix, presence of vaginal fFN predicts the success of labor induction. Copyright © 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/ 4.0/).

Keywords: Bishop score fetal fibronectin labor induction prediction transvaginal sonography

Introduction The incidence of caesarean section following labor induction when the cervix is unfavorable has been reported to be between 22% and 24% [1,2]. Currently, the only method in practice to predict whether an induced labor will result in successful vaginal delivery is preinduction Bishop score [3]. However, the specificity of the Bishop score among patients with transitional (6e9) or low (5) scores is poor. Although many of these patients can deliver easily, such low scores have been associated with high rates of prolonged labor and caesarean section [4]. Therefore, more sensitive selection criteria are needed with regard to induction of labor. Transvaginal ultrasound examination of the cervix has been reported to be a simple and reproducible examination for the

* Corresponding author. Zekai Tahir Burak Women's Health Care, Training and Education Hospital, Talatpasa Bulvari, Ankara 06230, Turkey. E-mail address: [email protected] (A.S. Ozgu-Erdinc).

prediction of successful labor induction [5]. However, the results of previous comparative studies are contradictory [5e10]. Recently, increasing attention has been focused on the presence of fetal fibronectin (fFN) in the cervical secretions. fFN is a glycoprotein involved in the adhesion of cells present in the extracellular matrix of decidua basalis, adjacent to the intervillous space [11]. When delivery is imminent, fFN enters into cervical and vaginal secretions, and therefore may become detectable. fFN has been reported to be an indicator for premature delivery and can be used as a complementary test to confirm the clinical diagnosis of premature rupture of fetal membranes [12e15]. There are also studies reporting correlation between fFN presence and successful labor induction at term pregnancies [16e19]. However, its role in predicting successful induction has been less clear. This prospective study was designed to compare the presence of fFN in cervicovaginal secretions with ultrasound parameters or Bishop score in predicting successful labor induction when the cervix is unfavorable.

http://dx.doi.org/10.1016/j.tjog.2014.06.009 1028-4559/Copyright © 2016, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

D. Uygur et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 94e97

Material and methods This study was conducted at Zekai Tahir Burak Women's Health Care, Training and Education Hospital. A total of 73 women undergoing labor induction at term were enrolled in this prospective study. The study protocol was approved by the Ethics Committee of the Hospital. The inclusion criteria were as follows: nulliparity, singleton pregnancy, gestational age between 37 weeks and 42 weeks, cephalic presentation, Bishop score of 5 or less, and no clinical evidence of regular contraction. Women with coexisting obstetric conditions such as ruptured membranes, vaginal bleeding, or any contraindication to vaginal birth were not included. The date of the confinement was calculated according to the duration of amenorrhea and checked by an ultrasound examination performed before 20 weeks of gestation. The sample was obtained from the posterior vaginal fornix with a Dacron swab and tested for fFN by a qualitative fast-reacting immunoassay with the positive cutoff value set at 50 ng/mL or greater (Maya Biomedical, Istanbul, Turkey), analyzed, and evaluated at the bedside. Specimens were combined with an antihuman fibronectinegold colloid conjugate, and passed through a membrane containing a monoclonal antibody specific for fFN. A visible colored spot within 5 minutes indicates a positive result. Digital cervical examination was performed and the Bishop score was assigned [3]. After the digital examination, transvaginal ultrasonographic examination of the cervix was performed using the General Electric Logic 200 ultrasound machine equipped with a 6.5-MHz transvaginal transducer. Sonography was performed by one of the first three authors. Cervical length was measured from the internal ostium to the external ostium, the furthest points at which the cervical walls were juxtaposed [20]. Because the compression may artificially lengthen the cervical measurement, care was taken not to compress the cervix with the endovaginal probe. Wedging or funneling, defined as any triangled“V or U pattern”dat the area of the internal ostium with its apex anywhere along the cervical canal, was measured longitudinally [20]. The patient was subsequently managed according to the standard induction protocol of the unit. Intravenous oxytocin administration was started at 2 mU/min and increased every 15 minutes by 2 mU/min to a maximum of 20 mU/min. Cervical ripening agents were not used at all. Clinicians involved in the patients care were blind to the result of the fFN assay. The main outcome parameter was defined as successful labor induction occurring within 24 hours. The Statistical Program for Social Sciences (SPSS) 17.0 for Windows software was used for the calculations (SPSS Inc., Chicago, IL, USA). The normally distributed data are presented as the mean (standard deviation) for baseline and descriptive statistics, whereas the non-normally distributed data are presented as the median and range. Data with a normal distribution were analyzed using the unpaired t test. The ManneWhitney U test was used to analyze non-normally distributed data. The accuracy of each test was evaluated separately and a multiple binary logistic regression model was generated to identify variables that were significantly associated with the outcome of interest. All p values were calculated as two tailed and p value less than 0.01 was accepted as statistically significant. Results The indications for induction of labor were as follows: postdate pregnancy (n ¼ 45), pregnancy-induced hypertension (n ¼ 3), nonreassuring testing (n ¼ 7), oligohydramnios (n ¼ 18). The mean gestation age at induction was 41 weeks (range 37e42 weeks).

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Thirty-five women (47.9%) had vaginal deliveries and in 33 (94.3%) of these women, vaginal deliveries were within the 24 hours of labor induction. Thirty-eight women (52.1%) underwent caesarean section. Table 1 presents the obstetric characteristics of the 73 women. The mean birth weight was 3401 g. The mean duration of labor was 9.5 hours (range 2.25e29 hours). In 48 of the 73 women (65.8%) included in the study, the fFN assessment gave a positive result. Patients who succeeded to vaginal delivery within 24 hours (n ¼ 28) differed significantly from the remaining patients (n ¼ 5) by a positive fFN (84.8% vs. 15.2%, p ¼ 0.002). The caesarean section rate was higher in patients with negative fFN results, with 18 of 25 (72%) requiring caesarean section in the group with negative results, compared with 20 of 48 (41.7%) requiring caesarean section in the group with positive results (p ¼ 0.014). A positive fibronectin assay had a sensitivity, specificity, positive predictive value, and negative predictive value of 84.9%, 50%, 58.3%, and 80%, respectively, for prediction of the induction success. There was no statistically significant difference in cervical funneling between women who delivered vaginally before 24 hours of induction and those who did not (30% vs. 12.1%, p ¼ 0.09). Neither the mean cervical length (28.9 mm vs. 27.9 mm, p ¼ 0.468) nor the Bishop score (3.3 vs. 3.2, p ¼ 0.928) between women who delivered vaginally before 24 hours of induction and others was different. A binary logistic regression model was constructed, which included Bishop score, fFN immunoassay, cervical length, and funneling (Table 2). Stepwise multiple regression analysis showed only the fFN immunoassay to be an independent statistically significant predictor of vaginal delivery within 24 hours of induction (odds ratio 6.168; 95% confidence interval 1.897e20.059; p ¼ 0.002). Discussion In our study, we have confirmed the importance of fFN as a predictive marker for delivery within 24 hours of labor induction, whereas the presence of funneling or cervical length measurements by transvaginal ultrasound and Bishop score failed to predict successful labor induction. fFN has been proposed as a new tool for cervical evaluation before labor induction [17,18]. Our results are in agreement with those of Ahner et al [16] and Garite et al [18]. Ahner et al [16] reported the presence of fFN in the cervicovaginal secretions of term deliveries to yield a high probability of success for induction [16]. They also concluded that in the case of a woman with fibronectinnegative cervicovaginal secretions and unfavorable cervix score, induction of labor should not be attempted. Garite et al [18], in a study that included 73 nulliparous women with low Bishop scores,

Table 1 Characteristics of the study population (N ¼ 73). Maternal age (y), mean ± SD (range) Nulliparous (n) BMI (kg/m2), mean ± SD (range) Gestational weeks, mean ± SD (range) Education (high school or university), n (%) Birth weight (g), mean ± SD (range) Bishop score, mean ± SD Cervical length (mm), mean ± SD (range) Funneling present, n (%) Positive fFN assay, n (%) Vaginal delivery within 24 h, n (%) Sex, male, n (%)

23.3 ± 4.5 (17e34) 73 28.1 ± 3.3 (21.9e36.3) 40.7 ± 0.9 (38e42.5) 44 (60.3) 3401 ± 390 (2370e4300) 3.3 ± 1.4 28.4 ± 5.8 (14e48) 16 (21.9) 48 (65.8) 33 (45.2) 37 (50.7)

BMI ¼ body mass index; fFN ¼ fetal fibronectin; SD ¼ standard deviation.

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D. Uygur et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 94e97

Table 2 Results of logistic regression analysis in the prediction of the vaginal delivery within 24 hours of induction. Variable

Odds ratio

95% Confidence interval

p

Bishop score Cervical length Funneling Fibronectin

0.971 0.967 0.246 6.168

0.657e1.437 0.879e1.064 0.064e0.952 1.897e20.059

0.885 0.490 0.042 0.002

found that the presence of cervicovaginal fFN predicted successful induction of labor, independent of Bishop score. However, Reis et al [21] reported only obstetric history and digital examination to predict vaginal delivery accurately within 24 hours and were independently associated with labor duration. However, these authors could not find a predictive value of fFN and ultrasound measurements [21]. Similarly, Sciscione et al [22] also reported that fFN could not predict vaginal delivery in nulliparous women requiring preinduction cervical ripening. Furthermore, Droulez et al [23] in a prospective study, which included 234 patients, showed that the only variables to be independently associated with a successful induction were Bishop score, parity, and age of the patient. No significant association was found between the presence of cervical fibronectin and the section rate. In addition, Ojutiku et al [24] and Roman et al [25] reported that fFN is not helpful for prediction of inducibility at term (Table 3). Theoretically, assessment of the cervix with transvaginal ultrasonography could give more accurate information than digital examination because the supravaginal portion of the cervix usually comprises about 50% of cervical length. In addition, effacement is difficult to evaluate in a closed cervix. However, a limited number of publications report divergent results. Some of these studies have focused on the relationship of cervical length and Bishop score with duration of latent phase but not with mode of delivery [20]. Boozarjomehri et al [20] found that ultrasound cervical length is correlated with only the latent phase of labor. Ware and Raynor [6] showed that the predictive value of cervical length for labor duration was comparable to that of the Bishop score. Gabriel et al [7] found that labor was shorter among women with a cervical length of less than 26 mm. By contrast, the logistic regression model of Gonen et al [26] found that only the Bishop score and

parity, not cervical length, significantly correlated with vaginal delivery and duration of labor. In this study, binary logistic regression analysis showed only the fFN immunoassay to be an independent statistically significant predictor of vaginal delivery within 24 hours of induction. Although it is widely accepted that induction, particularly in the presence of an unripe cervix, increases the risk of caesarean delivery, the overall 58.8% rate among nulliparous women with fFNnegative assessment appears to be higher than expected. An important conclusion of this study is that in the presence of negative fFN, induction of labor should not be attempted without prior cervical ripening. One important feature of our study was the inclusion of a homogenous group of patients with regard to parity. Nulliparous women with Bishop score of 5 or less were chosen as a study group on the basis of previous publications [4,18], which suggested that such patients have higher caesarean section rates for failed inductions or failed labor progression. There are limited data on the value of the Bishop score in predicting success of induction among nulliparous patients, but it is clear that failed inductions, especially among patients with low Bishop score, are more common in nulliparous than in multiparous patients [27]. In addition, among patients where the cervix is closed clinically, a question remains whether ultrasonographic cervical assessment is useful in predicting successful labor induction or not. To our knowledge, this is the first study comparing fFN assay, Bishop score, and ultrasound examination of cervix in the assessment of successful labor induction among term nulliparous patients with unfavorable cervix. In this study, cervical ripening agents were not used for induction of labor. Randomized controlled studies using different cervical ripening agents are required to assess the correlation of fFN positivity and duration of cervical ripening. Accurate identification of patients who are likely to respond to labor induction will help to reduce the caesarean sections due to failed induction. Our data have confirmed the importance of fFN, as positive fFN assessment predicts response to induction more accurately than transvaginal ultrasound assessment or Bishop score when the cervix is unfavorable. More importantly, this result was seen in a homogenous study population of nulliparous patients with low Bishop score who are at highest risk for failed inductions and sections.

Table 3 Predicting the success of induction of labor (a comparison of previous studies). Author, Year [reference no.]

Journal

Population

Outcome

Ahner et al, 1995 [16]

Am J Obstet Gynecol

Blanch et al, 1996 [17]

Am J Obstet Gynecol

Garite et al, 1996 [18]

Am J Obstet Gynecol

64 women scheduled for induction of labor at term 103 patients undergoing induction of labor at term 160 term patients undergoing labor induction

Ojutiku et al, 2002 [24]

Eur J Obstet Gynecol Reprod Biol Am J Obstet Gynecol

33 nulliparous women undergoing induction of labor for postdates 134 women undergoing labor induction at term

Positive fFN yields a high probability of success for induction fFN score is equivalent to Bishop score in its predictive value for ease of labor induction fFN predicts which patients will have shorter and easier inductions of labor and lower cesarean section rates fFN is not a useful test for inducibility at term

Ultrasound Obstet Gynecol Obstet Gynecol

106 pregnant women with a Bishop score  5 undergoing labor induction 241 nulliparous women undergoing preinduction cervical ripening 234 women undergoing induction of labor

Reis et al, 2003 [21]

Roman et al, 2004 [25] Sciscione et al, 2005 [22] Droulez et al, 2008 [23] fFN ¼ fetal fibronectin.

J Gynecol Obstet Biol Reprod (Paris)

fFN and ultrasound measurements failed to predict accurately the outcome of induced labor. Only obstetric history and digital examination accurately predicted vaginal delivery within 24 h fFN assessment showed no significant correlation with induction failure fFN does not predict vaginal delivery fFN does not predict vaginal delivery

D. Uygur et al. / Taiwanese Journal of Obstetrics & Gynecology 55 (2016) 94e97

Conflicts of interest The authors have no conflicts of interest relevant to this article. Acknowledgments

[13]

[14] [15]

The authors wish to thank Michael Jones and Professor Meral Beksac for revising the article.

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