Induction of labor in the United States has reached an all time high, with 1 in 5 pregnant women receiving induction of labor.1 An important contribution to this rising rate has been elective induction of labor. However, elective induction of labor results in an increase in cesarean delivery and healthcare costs.2–4 Furthermore, a recent report revealed that nulliparous patients with unfavorable cervices undergoing preinduction cervical ripening followed by oxytocin induction of labor are nearly 4 times more likely to have a cesarean delivery than their counterparts in spontaneous labor.5
The Bishop score is a commonly used method to predict vaginal delivery in women who undergo induction of labor. The original report by Bishop found that multiparous women who have a score of more than 9 are more likely to deliver vaginally.6 The American College of Obstetricians and Gynecologists has recently stated that women who have induction of labor with a score of more than 8 have a similar rate of vaginal delivery as those women who enter spontaneous labor.7 However, the ability of the Bishop score to predict vaginal delivery in a mixed population of patients has recently been challenged.8,9
Fetal fibronectin is an extracellular matrix protein found in high concentrations in the amniotic fluid and in the fetal membranes at the choriodecidual interface. It is not normally found in appreciable amounts in cervicovaginal secretions from 22–37 weeks, but is commonly present in patients with prematurely ruptured membranes and in symptomatic patients at risk for premature delivery.10 The ability of fetal fibronectin to predict shorter intervals to delivery, be it preterm10–12 or term,13–17 has been extensively evaluated. Because the concentration of cervicovaginal fetal fibronectin increases at term, studies suggest that it may be useful in predicting the onset of spontaneous labor14,15,17 as well as successful induction of labor.13,16
In an effort to find an objective and reliable predictor of successful induction of labor in women with an unfavorable cervix, we examined delivery route and the presence of fetal fibronectin in the cervicovaginal secretions of nulliparous women undergoing preinduction cervical ripening with the intracervical Foley catheter.
MATERIALS AND METHODS
Before initiation of the study protocol, institutional review board approval was obtained. This study was conducted at Christiana Hospital, Christiana Care Health System, Newark, Delaware, from November 2000 through July 2003. Women aged older than 18 years, nulliparous, with singleton gestation in the vertex presentation between 36 0/7 weeks and 41 6/7 weeks, and a Bishop score 7 or less were recruited into the study. Indication for induction was as per the physician diagnosis in the chart. Women were excluded from the study if they had ruptured membranes before obtaining a fetal fibronectin sample, placenta previa, or abruptio placenta. Due to the concerns of obtaining a false positive test, women who had had a digital examination, intercourse, or transvaginal ultrasound examination within the 24 hours preceding admission were excluded.
Fetal fibronectin specimens were obtained before digital examination for Bishop score assignment. Using a sterile speculum examination, a Dacron (E.I. du Pont de Nemours and Company, Wilmington, DE) polyester fiber swab was placed into the external cervical os and another into the posterior vaginal fornix for 10–15 seconds. Specimens were analyzed by standard quantitative immunoassay (Adeza Biochemical, Sunnyvale, CA) using 50 ng/mL or more as a positive test. This assay was performed per the manufacturer’s specifications and was systematically internally and externally validated throughout the duration of the study. Providers were blinded to the results of both the vaginal and cervical fetal fibronectin specimens.
After specimen collection, Bishop score was assigned by the examining physician. Once the Bishop score was determined to be 7 or less, the participant underwent a standardized protocol for the induction of labor by cervical ripening with a 16-French Foley catheter as previously described.12 No other ripening agent or use of concomitant oxytocin was allowed during the period of preinduction cervical ripening. After spontaneous extrusion of the Foley bulb, oxytocin was begun at 1 to 2 mIU/min and increased by 1 mIU every 20 minutes as per a standardized protocol.
Our primary outcome was the rate of vaginal delivery. For the purpose of analysis, women who underwent operative vaginal delivery were not differentiated from those who had a spontaneous vaginal delivery. Based on our previously published experience with the Foley catheter, we estimated that to obtain a power of 80% and an alpha error of 0.05, we calculated a total of 236 (118 in each group) women would need to be enrolled to detect a 50% (33% to 16.5%) reduction in cesarean delivery rate.
Categorical variables were evaluated using a χ2 test or Fisher exact test when appropriate. Continuous variables were analyzed using a Student t test with unequal variance or Wilcoxon rank sum test if these data were not normally distributed per the Shapiro-Wilk test for normality. All statistical analysis was performed using STATA 7.0 (Stata Corporation, College Station, TX) on a Pentium (Intel Corporation, Santa Clara, CA)–based computer.
A total of 285 women gave informed consent and enrolled in our study. Of these, 44 participants were excluded because of error in specimen collection or processing (n = 12), spontaneous rupture of membranes while placing the Foley (n = 4), unable to place Foley (n = 4), multiparity (n = 6), or Bishop score more than 7 (n = 18). Among the remaining 241, 43.2% had a positive cervical fetal fibronectin test, and 24.5% had a positive vaginal fetal fibronectin test. Good correlation was noted between vaginal and cervical specimens (r = 0.63). Only 1 woman had a positive vaginal fetal fibronectin and a negative cervical specimen. The rate of vaginal delivery was 54.4% for the active cohort.
Antenatal patient characteristics were similar between women who were fetal fibronectin–positive and those who were fetal fibronectin–negative (Table 1). Women whose vaginal fetal fibronectin swab was positive were further in gestation (fetal fibronectin–positive 40.45 weeks compared with fetal fibronectin–negative 39.9 weeks, P < .01) when compared with those whose swab was negative. Similarly, women whose vaginal and cervical specimens were fetal fibronectin–positive had a slightly higher Bishop score, although these differences were small (Table 1).
Labor management and delivery characteristics are presented in Table 2. There was no statistically significant difference between groups with respect to mode of delivery or indications for cesarean delivery. Although the rate of vaginal delivery was slightly higher among women whose fetal fibronectin sample was positive (cervical fetal fibronectin–positive 55.8% compared with fetal fibronectin–negative 53.3%, P = .70; vaginal fetal fibronectin–positive 57.6% compared with fetal fibronectin–negative 53.3%, P = .56), these differences were not statistically significant. To reach statistical significance based on these differences, an excess of 8,000 women in both groups would have been required.
However, women who were positive for cervical fetal fibronectin seemed to respond more favorably to induction than women negative for cervical fetal fibronectin. Women whose cervical fetal fibronectin was positive were quicker to extrude their intracervical Foley catheter, have a shorter duration of oxytocin exposure, and require lower doses of oxytocin when compared with women with a negative cervical fetal fibronectin. Women with a positive vaginal specimen were quicker to extrude their Foley catheter, but did not otherwise differ from their negative counterparts.
Neonatal outcomes are presented in Table 3. Women who had a positive vaginal fetal fibronectin had a neonate with greater birth weight when compared with those who did not. This finding is in keeping with the fact that these women were further in gestation then their fetal fibronectin–negative counterparts. No differences in any other neonatal outcomes could be detected.
In 1990, the rate of induction of labor in the United Sates was 9.5%; in 1998 the rate rose to 19.4%, with individual hospitals reporting rates as high as 40%.1 Considerable variation exists in induction practices across region, ethnicity, and educational background. Those most likely to be induced are non-Hispanic white, with more than 12 years education, private insurance, early prenatal care, and in a community hospital setting.1
Although the rate of obstetrically and medically indicated induction has changed very little over the past decade, there has been 15-fold increase in the rate of elective induction.1 This increase seems greatest in nulliparous patients, irrespective of cervical status. This may reflect patient and physician convenience, improved antenatal surveillance, medical–legal concerns, and increasing concern about risks of postterm pregnancy. Despite these concerns, the literature has consistently shown that elective induction of nulliparous women results in an increased rate of cesarean delivery and increased morbidity and cost.13–15
There is a clear need for an objective, reliable method to time and predict successful vaginal delivery in nulliparous women who are induced. Among the potential markers that have been studied are Bishop score, transvaginal sonography and fetal fibronectin.
Bishop score alone, although traditionally used to evaluate cervical readiness for induction of labor, has been suggested to be inaccurate, subjective, and of questionable applicability to nulliparous women, especially in women with unfavorable cervical exams less than 5.16,17 Similarly, transvaginal ultrasonography for cervical length, cervical dilatation, and the presence of funneling, has shown conflicting results when used in women undergoing induction and does not seem to be an independent predictor of successful induction.18
Fetal fibronectin has been shown to predict successful vaginal delivery at term8,9; however, its role in predicting successful induction has been less clear. Blanche et al,11 in a study of 48 primparous women undergoing induction of labor at term, demonstrated that endocervical fetal fibronectin correlated with Bishop score, which correlated with decreased length of latent phase and decreased induction-to-delivery interval. This was not observed in multiparous patients in whom cervical dilatation was predictive. Garite et al,7 in a study that included 73 nulliparas with low Bishop scores, found that the presence of cervicovaginal fetal fibronectin predicted successful induction of labor, independent of Bishop score. These patients had a shorter induction-to-delivery interval, lower cesarean rates (although only statistically significant in the overall group), and fewer 2-day inductions. A meta-analysis of the literature available on fetal fibronectin as a predictor of term labor compared 8 reports; 5 relating to the spontaneous onset of labor and 3 addressing induction of labor. In all of the studies addressing induction of labor (n = 300), a positive fetal fibronectin was accompanied by a shorter interval to delivery in patients undergoing induction of labor with oxytocin, prostaglandin estradiol, or both. Two of 3 studies showed that women with a negative fetal fibronectin had higher rates of “unsuccessful” induction, resulting in higher incidence of operative or cesarean delivery.19
Our data partially supports these findings. As with others, we found that a positive cervical fetal fibronectin was associated with a shorter duration of cervical ripening, shorter induction time (oxytocin to delivery), and a lower maximal oxytocin requirement. When taken in aggregate, these findings suggest that such patients may be more biologically prepared for induction. In contrast, women with a positive vaginal fetal fibronectin sample were more likely to have a shorter duration of cervical ripening.
By comparison, the present study is unique in that we eliminated many variables that have confounded other studies. We designed a blinded, prospective, observational study in a specific subset of patients (nulliparas with unfavorable cervices), undergoing induction of labor by 1 method only (intracervical Foley catheter followed by oxytocin). Moreover, unlike other studies, we obtained both cervical and vaginal fetal fibronectin samples. Some may question the applicability of the current study due to its use of the Foley bulb for cervical ripening. It is worth noting that in previous studies, this method of cervical ripening has proved comparable to the commonly used prostaglandins preparations.12,20
Recently, Reis et al21 examined the role of clinical history, digital examination, fetal fibronectin, and cervical length in predicting successful induction at term. These data suggest higher parity, previous vaginal delivery, modified Bishop score (effacement and dilatation) 2 or greater, and cervical length 20 mm or greater positively correlate with vaginal delivery within 24 hours; however, the presence of fetal fibronectin had no positive predictive value (likelihood ratio 1.41, 95% confidence interval 0.9–2.2). Our data confirms and extends this finding in an exclusively nulliparous population with unfavorable cervices.
In conclusion, term nulliparas with a positive fetal fibronectin and an unfavorable cervix who undergo preinduction cervical ripening with the Foley catheter have lower oxytocin requirements and shorter induction times, but no reduction in cesarean delivery. Hence, this study does not support the use of outpatient fetal fibronectin sampling in nulliparas with unfavorable cervices to aid in the timing and success of induction of labor using the Foley catheter.
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