Objective
The purpose of this study was to determine whether the maximum time for cervical ripening (from 24-12 hours) would influence the efficacy of a transcervical Foley catheter and to compare efficacy to that of a prostaglandin E 2 vaginal insert.
Study Design
Three hundred ninety-seven women were assigned randomly to (1) Foley catheter left in place for a maximum of 24 hours, (2) Foley catheter left in place for a maximum of 12 hours, or (3) prostaglandin E 2 controlled-release vaginal insert. Primary outcome was vaginal delivery within 24 hours.
Results
There were no differences in vaginal delivery rates. The proportion of women who achieved vaginal delivery in 24 hours was lower in the 24-hour Foley catheter group than in the other 2 groups (24-hour Foley catheter, 21.0%; 12-hour Foley catheter, 59.8%; vaginal prostaglandin E 2 , 48.5%; P < .0001).
Conclusion
Cutting the ripening time with a Foley catheter by one-half increases the proportion of women who deliver vaginally within 24 hours and yields efficacy similar to that of prostaglandin E 2 vaginal insert.
Despite the fact that induction of labor is an increasingly common obstetric intervention, achievement of a vaginal delivery in a reasonably short time for a woman with an unfavorable cervix who requires induction remains a great challenge facing obstetricians today.
More than 40 years have passed since the state of the cervix has been recognized as having a major influence on the success of attempts to induce labor ; artificial cervical ripening has now become an integral part of the induction process in women whose cervices are initially unfavorable for induction. A great amount of research has been directed to the development of either pharmacologic agents or mechanical devices that are capable of accelerating cervical ripening, although no single method has proved to be “ideal” to meet the needs of both the practitioner and the patient.
In 1977, Calder et al claimed that the contribution of a transcervical Foley catheter that was used for extraamniotic prostaglandin E 2 (PGE 2 ) to the ripening effect on the cervix was “minor,” because it was much slower in action than prostaglandin. Although subsequently several investigators found mechanical ripening with transcervical Foley catheter balloon to be at least as effective as pharmacologic methods of ripening, the concept of a slow ripening process that is associated with transcervical catheters has been revived more recently in 2 reviews and a metaanalysis . Indeed, notwithstanding a weak strength of evidence, clinical trials that have compared mechanical methods with locally applied prostaglandin suggest that women who are allocated to the Foley catheter arms were more likely to not achieve vaginal delivery within 24 hours.
Time is an important consideration when a method of cervical ripening is chosen. A lengthy ripening process most likely overburdens already busy antenatal wards, contributes to increased health care costs, and is associated with lower satisfaction rates with the birthing experience. When cervical ripening is undertaken with prostaglandin, the maximal time for ripening that takes place before formal induction is started is rigorously established in accordance with the manufacturer recommendations. Conversely, no consensus exists on the time limitation for exposure to extraamniotic Foley catheter balloon, and considerable heterogeneity in mechanical ripening protocols is found in trial reports. If spontaneous expulsion of the transcervical catheter does not occur, some practitioners remove the device after an arbitrary time limit (varying between 6 and 24 hours in different series), whereas other practitioners wait until extrusion without predicted time limit. To date, we have not been able to identify any published study that has addressed the issue of adequate balloon ripening time.
The purposes of this study are 2-fold: (1) to determine whether cutting the ripening time (from 24-12 hours) would influence the efficacy of a transcervical Foley catheter, and (2) to compare efficacy results with those of locally applied PGE 2 , which is the main pharmacologic agent that currently is used to ripen unfavorable cervices. For the latter purpose, we chose prostaglandin in the form of a controlled-release vaginal insert, which has gained a widespread use in clinical practice and has never been compared with mechanical methods of ripening.
Materials and Methods
Patients with unfavorable cervices who were scheduled to undergo labor induction between July 2008 and June 2010 at the Obstetrics Department of University of Insubria, Varese, Italy, were screened for study inclusion. All recruited women had a singleton gestation, vertex presentation, Bishop score ≤6, intact membranes, gestational age ≥34 weeks, and reassuring fetal heart tracing on admission. Women with antepartum bleeding, intrauterine fetal death, previous uterine scars, known allergy to latex, placenta previa, or any other contraindication to vaginal delivery were excluded. All the participants gave written informed consent; Institutional Review Board approval had been obtained before the beginning of the study.
This investigation was conducted as a randomized trial to compare 3 protocols of preinduction cervical ripening. Once the decision to induce labor was made, women who wished to participate in the study were recruited. Random assignment was ensured by the use of a computer-generated block randomization list with a block size of 30 and a 1:1:1 allocation for each arm of the study.
In 2 of the 3 groups, a transcervical Foley catheter was to be used. The cervix was visualized with a sterile speculum and cleansed with a povidone-iodine solution. Under direct visualization, an 18-F Foley catheter was inserted into the endocervical canal. Once the catheter was past the internal os, the catheter balloon was filled with 50 mL of saline solution and pulled snugly against the internal os. The external end of the device was taped without tension to the medial aspect of the woman’s thigh. After completion of the device placement, patients underwent continuous fetal heart rate monitoring for 30 minutes and then were allowed to ambulate. The first group (24-hour Foley catheter group) had the Foley catheter left in place for a maximum of 24 hours since the initial placement; the second group (12-hour Foley catheter group) followed a protocol that limited exposure to the balloon catheter for a maximum of 12 hours. In both groups, the Foley catheter was removed for the following reasons: (1) the maximal time allowed for cervical ripening to take place was elapsed; (2) spontaneous rupture of membranes occurred; (3) the balloon was expelled spontaneously; (4) patients entered the active phase of labor (defined as at least 4 uterine contractions in a 30-minute interval with a totally effaced cervix and a cervical dilation ≥3 cm), or (5) fetal distress was suspected.
The third group underwent cervical ripening with a dinoprostone 10-mg controlled-release vaginal insert. The drug was placed high in the vaginal fornix, and the patients were monitored for uterine activity and fetal heart rate for at least 1 hour and then allowed to ambulate, with fetal heart rate tracing every 6 hours or until painful contractions ensued. Primary reasons for discontinuation of the PGE 2 insert included completion of the 24-hour dosing period, onset of active labor, uterine contractile abnormalities, or nonreassuring fetal heart rate patterns that prompted clinical intervention.
For women who did not enter spontaneous labor during the ripening process, formal induction with amniotomy and intravenous oxytocin commenced once the catheter was expelled/removed or 1 hour had elapsed since removal of the vaginal dinoprostone insert. Oxytocin was administered with a standard dose regimen in all patients. The induction protocol at our institution specifies the start of oxytocin at 5 mIU/min with an increase incrementally by 5 mIU/min every 15 minutes to achieve 7 contractions in 15 minutes or up to a maximum infusion of 30 mIU/min.
Once the woman was in active labor, routine intrapartum management was carried out by the staff members in charge of the Labor and Delivery Unit. Oxytocin was initiated for the augmentation of labor during the first stage if the cervix remained unchanged on 2 consecutive pelvic examinations that were conducted 2 hours apart and when the second stage of labor was longer than 2 hours in nulliparous women and 1 hour in multiparous women.
Tachysystole was identified when there were >5 contractions per 10 minutes for at least 20 minutes. Hypertonus was defined as a single contraction that lasted at least 2 minutes. Hyperstimulation syndrome was defined as the presence of tachysystole or hypertonus associated with an abnormal fetal heart rate pattern. Failed induction was diagnosed when women did not progress into the active phase of labor, despite adequate contraction patterns, after amniotomy, and a minimum of 4 hours of oxytocin infusion. Failure to progress was defined as unchanged cervical dilation in a 4-hour interval, despite oxytocin augmentation or no descent after 1 hour.
All outcome data were obtained concurrent with patient care and recorded by the investigators team. The primary outcome measure was vaginal delivery within 24 hours of the initiation of ripening. Other outcome variables included improvement in the Bishop score after ripening, cesarean delivery rates, ripening-to-delivery interval, oxytocin administration, epidural request, and neonatal outcomes.
Planned sample size for this investigation was based on the detection of a clinically significant increase in vaginal delivery that was achieved within 24 hours when maximum ripening time is cut from 24-12 hours. Previously published institutional data from inductions with a transcervical Foley catheter indicated a vaginal delivery rate in 24 hours of 37.4%. A review of studies that compared different forms of locally applied prostaglandin reports a vaginal delivery rate within 24 hours with the vaginal insert that is approximately 20% higher (55.1%). Under this scenario, we assumed that reducing the Foley catheter ripening time to 12 hours would allow the achievement of a rate of vaginal delivery within 24 hours that would be similar to that observed with PGE 2 vaginal insert. With an alpha score of .025 (with Bonferroni’s inequality to adjust alpha for a comparison among 3 groups) and a beta score of .20, a sample size of 126 women per group would be required to detect a 20% increase (37.4-57.4%) in the proportion of women who deliver vaginally within 24 hours. Sample size was calculated with a 2-tailed test in G*Power 3 software. To account for a protocol violation rate of 5%, 132 patients were enrolled in each arm of the study.
Statistical analysis of outcomes data was performed with GraphPad (version 5; GraphPad Software, San Diego CA). Normality testing (D’Agostino and Pearson test) was performed to determine whether data were sampled from a Gaussian distribution. One-way analysis of variance and Kruskal-Wallis test were performed to compare groups of continuous parametric and nonparametric variables, respectively. The chi-square test was used to analyze proportions. Analysis of the proportions of women who remained undelivered over time was performed by plotting Kaplan-Meier survival curves. A probability value of < .05 was used as the cut-point for significance.
Results
A total of 397 women were enrolled in this investigation and were allocated to 1 of 3 interventions groups. Flow of participants through the randomized clinical trial is displayed in Figure 1 . The Foley catheter was not placed successfully in 1 woman, who was assigned randomly to the 12-hour Foley catheter group, had a closed cervix that did not admit the ripening device. Three patients who were allocated to the 24-hour Foley catheter group did not have the catheter successfully placed because of rupture of membranes during catheter insertion (n = 2), and the device spontaneously fell out soon after 2 attempts of placement (n = 1). In all cases of catheter insertion failure, the patients received a PGE 2 vaginal insert for cervical ripening. None of these women were excluded, and an intent-to-treat analysis was performed.
The demographics and baseline characteristics of the participants were comparable between groups ( Table 1 ). Table 2 shows the details of the ripening and labor induction outcomes. The proportion of women who achieved vaginal delivery within 24 hours was significantly higher in the 12-hour Foley catheter group and in the PGE 2 vaginal insert group than in the 24-hour Foley catheter group. Sixty patients (45.1%) in the 24-hour Foley catheter group, 71 patients (53.8%) in the 12-hour Foley catheter group, and 87 patients (65.9%) in the PGE 2 vaginal insert group went into active labor during the ripening process, without any additional intervention (vaginal insert group vs both Foley catheter groups; P < .05). The mean time from initiation of ripening to delivery (either vaginal or cesarean) and to vaginal delivery was significantly longer in the 24-hour Foley catheter group than in the other 2 groups. Oxytocin for induction/augmentation of labor and epidural analgesia were administered more frequently when a transcervical catheter was used than when a sustained release dinoprostone vaginal insert was administered for cervical ripening. The vaginal insert was removed because of uterine hypertonus without fetal heart rate changes in 1 patient; uterine hyperstimulation syndrome occurred in 8 cases (6.1%). No case of uterine hypercontractility occurred in either of the 2 Foley catheter groups. The rate of cesarean delivery for abnormal fetal heart rate tracings that occurred during the ripening process was higher in the vaginal insert group than in the Foley catheter groups; however, the difference reached statistical significance only vs the 12-hour Foley catheter ( Table 2 ). When an “as-treated” analysis was performed, the finding of our study remained unchanged; the only exception was the rate of cesarean delivery for fetal heart rate changes that occurred while the ripening agent was in situ that were significantly higher in the vaginal insert group than in either of the Foley catheter groups.
