Approximately one in five women has their labor induced in the United States.1 Labor induction can be lengthy and involve an extended latent phase, which increases the risk of complications including postpartum hemorrhage, chorioamnionitis, and endometritis.2,3 Developing strategies to decrease the length of induction to delivery would likely have a large population effect. The Foley catheter has been shown to be a safe, successful, and economic means of inducing labor4,5 and has been used with additional induction agents in hopes of decreasing the total time to delivery. Oxytocin is occasionally used in conjunction with an intracervical Foley catheter for this reason.
Prior studies are mixed on the effectiveness of adding oxytocin to a Foley catheter for ripening and initiation of induction,6–8 and parity appeared to play a role in the negative primary outcomes for at least two of the trials.6,8 The current study was performed to evaluate whether the addition of oxytocin to an intracervical Foley catheter at the initiation of labor induction will increase the rate of delivery within 24 hours compared with Foley followed by oxytocin and whether parity is an effect modifier.
MATERIALS AND METHODS
This was a multicenter, randomized trial conducted in parallel in nulliparous and multiparous women at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania, and Christiana Care Hospital in Newark, Delaware. Thomas Jefferson University Hospital serves a mostly urban population and some of the surrounding suburban areas, whereas Christiana Care Hospital serves as the major tertiary referral center in Delaware, treating urban, suburban, and rural populations. Institutional review board approval was obtained from Christiana Care Hospital, which served as the review board of record for both institutions. The trial was registered on ClinicalTrials.gov before enrollment (NCT02273115).
Women scheduled for labor induction between 24 and 42 weeks of gestation were approached as outpatients or on admission to labor and delivery and were offered participation in the study. Those who desired enrollment were included if they were at least 18 years old; had a singleton, live, nonanomalous vertex fetus; an admission Bishop score less than 6; and an intracervical Foley catheter could be placed. Premature prelabor rupture of membranes was not an exclusion criterion for the trial. Women were not eligible if they had regular painful contractions, placenta or vasa previa, placenta abruption (known or suspected), antepartum bleeding of unknown etiology, nonreassuring fetal tracing (category III tracing, minimal variability with decelerations, or late decelerations occurring with greater than 50% of contractions), more than one prior cesarean delivery, prior classic cesarean delivery, prior T-shaped hysterotomy, or a history of myomectomy. Women were also excluded if another ripening agent was used before Foley catheter placement. Any other contraindication to vaginal delivery (eg, active herpes infection) was also an exclusion criterion. Women were consented before Foley catheter placement.
After written consent was obtained, an intracervical Foley catheter was placed and inflated with 60 mL normal saline and taped on traction to the inner thigh. Depending on study site, a 16-French, 30-mL balloon, 75-mL Foley balloon, or Cook double-balloon catheter was placed. At one study site, it was the preference of the labor and delivery unit to use nonlatex equipment whenever possible. For this reason, the Cook double-balloon catheter was used; however, only the single uterine balloon was inflated to 60 mL, essentially acting as a large-volume silicone catheter. The second site initially used latex 16-French, 30-mL Foley catheters inflated to 60 mL. There were three Foley balloon ruptures that occurred at this site, and enrollment was halted until a Foley catheter approved for larger volumes could be obtained. A 20-French, 75-mL Foley catheter inflated to 60 mL was instituted and enrollment was continued. Patients were randomized to either a Foley catheter with oxytocin infusion (started within 60 minutes of Foley catheter placement) or a Foley catheter followed by oxytocin. In the Foley and oxytocin group, the oxytocin infusion at both sites was started at 2 milliunits/min and increased by 2 milliunits/min after 30 minutes with a maximum of 40 milliunits/min as tolerated by the mother and fetus. In the Foley followed by oxytocin group, oxytocin infusion was not started until the Foley had been expelled spontaneously or had remained in place for at least 12 hours. If the patient in the Foley followed by oxytocin group was in active labor after Foley catheter expulsion and did not require further augmentation as determined by her obstetric provider, oxytocin was not administered.
Foley catheters were removed after 12 hours if spontaneous expulsion did not occur before then, and a Bishop score was obtained. The remainder of the induction process was left up to the individual providers, including the timing of amniotomy and the administration of further ripening agents if desired. Replacement of a Foley catheter was not allowed.
The primary outcome was the time from Foley catheter placement to delivery at 24 hours or less. Prespecified secondary outcomes were time to Foley expulsion, change in Bishop score, the need for additional ripening, analgesia during Foley use, time to second stage, delivery within 12 hours, total time to delivery, duration of oxytocin use, mode of delivery, tachysystole (greater than five contractions in 10 minutes averaged over 30 minutes), chorioamnionitis (at least one maternal fever 100.4°F or greater with at least one additional clinical sign of maternal tachycardia, fetal tachycardia, uterine tenderness, or purulent or foul-smelling vaginal discharge), postpartum hemorrhage (greater 500 mL for vaginal deliveries or greater than 1,000 mL for cesarean delivery), and severe maternal morbidity (uterine rupture, intensive care unit admission, or maternal death). Indications for cesarean delivery were collected, and arrest disorders (both dilation and descent) and failed induction were defined using criteria from the Eunice Kennedy Shriver National Institute of Child Health and Human Development joint statement on “Preventing the First Cesarean Delivery.”9 Neonatal secondary outcomes included weight, 5-minute Apgar score less than 7, neonatal intensive care unit admission, and neonatal intensive care unit length of stay. All newborns of women diagnosed with chorioamnionitis were admitted to the neonatal intensive care unit for evaluation.
Study data were collected and managed using Research Electronic Data Capture hosted at Christiana Care Health System.10 Research Electronic Data Capture is a secure, web-based application designed to support data capture for research studies. Randomization was performed in a one-to-one computer-generated manner in random block sizes (four, six, and eight) and was stratified by center. The randomization sequence was then uploaded into Research Electronic Data Capture and was no longer available to the investigators or research personnel. A randomization sequence was generated separately for nulliparous and multiparous women and these groups were analyzed separately. Randomization occurred after Foley catheter placement, when the physician who just placed the Foley contacted study personnel by phone for randomization and allocation.
Baseline demographic and clinical characteristics were summarized by randomization assignment using counts and percentages or mean, medians, standard deviations, and ranges. Randomization groups (Foley and oxytocin compared with Foley followed by oxytocin) were compared with respect to outcomes using Kruskal-Wallis tests for continuous variables and χ2 or Fisher exact tests for categorical variables. The distribution of time to delivery was estimated using the Kaplan-Meier method. All analyses were performed separately for nulliparous and multiparous women using SAS 9.4. The P values for all hypotheses were two-sided, and statistical significance was set at P<.05.
Baseline estimates of the 24-hour delivery rate for nulliparous (53%) and multiparous (68%) women were obtained from the previous trial performed by Pettker et al6 to calculate the sample size. Nulliparous and multiparous populations were analyzed separately. To detect an increase in total delivery rate within 24 hours of Foley placement by 20% (eg, from 53% to 73% in nulliparous women) with an α of 0.05 and 80% power for each parity group, 91 nulliparous women and 68 multiparous women would be required per treatment group. Total recruitment was set at 200 nulliparous and 150 multiparous women to account for potential dropouts.
A total of 607 women were screened for participation from January 2015 through July 2016. After initial screening exclusions and declinations, 323 women were randomized, including 184 nulliparous women and 139 multiparous women (Fig. 1).11 There was one postrandomization exclusion of a multiparous women randomized to the Foley and oxytocin group because she had not had a Foley placed. There were no withdrawals or patients lost to follow-up. Because an upcoming change in institution affiliation was anticipated for the principal investigator and there was less than expected dropout, the decision was made among all coinvestigators to cease enrollment after 90% recruitment was achieved. A total of 90 nulliparous and 71 multiparous women were allocated to a Foley catheter with concurrent oxytocin. A total of 94 nulliparous and 67 multiparous women were allocated to the control group of a Foley catheter only for cervical ripening with oxytocin infusion to follow.
There were no notable differences in groups with respect to baseline characteristics (Tables 1 and 2). Gestational age at induction was similar in all groups; 2% of nulliparous women and 8% of multiparous women were less than 36 weeks of gestation at the time of induction. Foley catheter type was similar in all groups.
Among nulliparous women, the overall rate of delivery within 24 hours of Foley placement was 64% in the Foley with concurrent oxytocin compared with 43% in women who received a Foley catheter alone for cervical ripening followed by oxytocin (Table 3; P=.003). The relative risk for delivery within 24 hours was 1.51 (95% confidence interval [CI] 1.14–2.00). Nulliparous women in the concurrent group also had a shorter median interval from induction initiation to delivery of 5.2 hours (20.9 compared with 26.1 hours, P<.001). There was no difference in mode of delivery between induction methods for women (Table 3). When censoring cesarean delivery, the rate of vaginal delivery within 24 hours of Foley placement remained significantly higher in the concurrent group (75% compared with 50%, P=.006). The most common indications for cesarean delivery were arrest of dilation (53%) in the concurrent Foley and oxytocin group and nonreassuring tracing in the Foley followed by oxytocin group (40%). Although overall indication for cesarean delivery was not different, cesarean delivery for arrest of dilation was more common in the Foley and oxytocin group for nulliparous women (53% compared with 23%, P=.005). The total duration of oxytocin infusion was 6.1 hours longer in nulliparous women receiving both a Foley catheter and oxytocin for labor induction (18.4 compared with 12.3 hours, P<.001). There was no statistically significant increase in maternal or neonatal complications for women receiving Foley and oxytocin infusion compared with Foley followed by oxytocin alone (Table 4).
Multiparous women had an overall rate of delivery within 24 hours of 87% in the concurrent oxytocin group compared with 72% in women who received Foley followed by oxytocin (Table 5; relative risk 1.22, 95% CI 1.02–1.45). The median total time to delivery was also shorter in the concurrent Foley and oxytocin group by 3.7 hours (14.9 compared with 18.6 hours, P=.013) (Fig. 2). There was no difference in mode of delivery between randomization groups (Table 5). When censoring cesarean delivery, vaginal delivery within 24 hours of Foley placement occurred at a significantly higher rate in the concurrent group (92% compared with 23%, P=.004). The indication for cesarean delivery was not different in either induction method. The total duration of oxytocin infusion was longer in women receiving both Foley catheter and oxytocin for labor induction by 4 hours (13.1 compared with 9.1 hours, P<.001). There was no difference in the rate of maternal or neonatal complications, including tachysystole, meconium staining, or hemorrhage between groups (Table 6).
Uterine rupture did not occur in this study and there were no maternal deaths. The only study patient admitted to an intensive care unit was admitted there for diabetes insipidus.
Labor induction with Foley catheter and concurrent oxytocin shortens the time to delivery and increases the rate of delivery within 24 hours compared with cervical ripening with a Foley catheter followed by oxytocin. This is true for both nulliparous and multiparous women. Similar to a prior study, the Foley Balloon Induction of Labor Trial in Nulliparas by Connelly et al7 also had a reduction in time to delivery for nulliparous women who received simultaneous oxytocin with Foley catheter for induction compared with Foley alone. The time difference was slightly shorter than the one found in this trial (approximately 3 compared with 5 hours). Although the initial trial by Pettker et al6 found no benefit in adding concurrent oxytocin for increasing delivery within 24 hours, that trial also did not power the primary outcome for parity. Findings in this trial and the Foley Balloon Induction of Labor Trial in Nulliparas differ slightly from the Foley or Misoprostol for the Management of Induction trial, which compared four different methods of cervical ripening (Foley, misoprostol, Foley and oxytocin, Foley and misoprostol).8 Initially a 3-hour benefit was seen for Foley and oxytocin compared with Foley alone, but this was no longer significant after adjusting for parity.8
Unlike in the Foley Balloon Induction of Labor Trial in Nulliparas,7 indications for cesarean delivery did not differ by induction method.
There may be additional benefits to using concurrent oxytocin and Foley. There was a lower rate of chorioamnionitis in women who received the combined method; however, the difference was not statistically significant. A much larger study would be required to adequately assess this finding.
Significant safety concerns arose for Foley catheter inductions using standard balloon sizes (30 mL) and larger volumes during the course of this trial. Three different Foley catheter balloons ruptured after inflation to 60 mL. No complications resulted from these Foley catheter ruptures, but there is a possibility of having retained fragments of latex that would require removal. Several studies show that larger balloon volumes during Foley catheter induction decrease time to delivery,12–14 and because commercially available catheters can accommodate larger volumes (60–80 mL), these should be used to prevent intrauterine catheter ruptures if a larger volume is desired.
This study has several strengths. By powering the study for parity, we were able to detect a difference in the primary outcome, where mixing nulliparous and multiparous women may have yielded a negative result. The population is generalizable given it was multicentered and enrolled women from urban, suburban, and rural areas who were cared for by both midwives and obstetricians in academic and private practices. Management after Foley expulsion was also left to the discretion of the obstetrician, simulating the care that would occur outside of trial conditions.
Limitations include the fact that this study was not blinded. Different catheters were in use during the course of the trial, but all were inflated to 60 mL, which should make any differences minimal if present at all, and catheter type was not different between groups. The primary outcome and safety were not powered for subgroups such as premature prelabor rupture of membranes and vaginal birth after cesarean delivery, and nonsignificant differences in secondary outcomes also may be the result of lack of statistical power.
The rate of labor induction has significantly increased over the previous decades and is not expected to decrease in the near future given the increase in maternal morbidities. Innovative ways of inducing labor are going to be required to meet the increased demand on labor and delivery units. Combination methods such as a Foley catheter and oxytocin induction should be considered to increase delivery rates within 24 hours and decrease total time to delivery.
1. Martin JA, Hamilton BE, Osterman MJ, Curtin SC, Matthews TJ. Births: final data for 2013. Natl Vital Stat Rep 2015;64:1–65.
2. Rouse DJ, Weiner SJ, Bloom SL, Varner MW, Spong CY, Ramin SM, et al. Failed labor induction: toward an objective diagnosis. Obstet Gynecol 2011;117:267–72.
3. Simon CE, Grobman WA. When has an induction failed? Obstet Gynecol 2005;105:705–9.
4. Sciscione AC, Bedder CL, Hoffman MK, Ruhstaller K, Shlossman PA. The timing of adverse events with Foley catheter preinduction cervical ripening; implications for outpatient use. Am J Perinatol 2014;31:781–6.
5. Alfirevic Z, Keeney E, Dowswell T, Welton NJ, Medley N, Dias S, et al. Methods to induce labour: a systematic review, network meta-analysis and cost-effectiveness analysis. BJOG 2016;123:1462–70.
6. Pettker CM, Pocock SB, Smok DP, Lee SM, Devine PC. Transcervical Foley catheter with and without oxytocin for cervical ripening: a randomized controlled trial. Obstet Gynecol 2008;111:1320–6.
7. Connolly KA, Kohari KS, Rekawek P, Smilen BS, Miller MR, Moshier E, et al. A randomized trial of Foley balloon induction of labor trial in nulliparas (FIAT-N). Am J Obstet Gynecol 2016;215:392.e1–6.
8. Levine LD, Downes KL, Elovitz MA, Parry S, Sammel MD, Srinivas SK. Mechanical and pharmacologic methods of labor induction: a randomized controlled trial. Obstet Gynecol 2016;128:1357–1364.
9. Spong CY, Berghella V, Wenstrom KD, Mercer BM, Saade GR. Preventing the first cesarean delivery: summary of a joint Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, and American College of Obstetricians and Gynecologists Workshop. Obstet Gynecol 2012;120:1181–93.
10. Harris PA, Taylor R, Thielke R, Payne J, Gonzalez N, Conde JG. Research electronic data capture (REDCap)—a metadata-driven methodology and workflow process for providing translational research informatics support. J Biomed Inform 2009;42:377–81.
11. Schulz KF, Altman DG, Moher D; CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Obstet Gynecol 2010;115:1063–70.
12. Delaney S, Shaffer BL, Cheng YW, Vargas J, Sparks TN, Paul K, et al. Labor induction with a Foley balloon inflated to 30 mL compared with 60 mL: a randomized controlled trial. Obstet Gynecol 2010;115:1239–45.
13. Levy R, Kanengiser B, Furman B, Ben Arie A, Brown D, Hagay ZJ. A randomized trial comparing a 30-mL and an 80-mL Foley catheter balloon for preinduction cervical ripening. Am J Obstet Gynecol 2004;191:1632–6.
© 2017 by The American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.
14. Kashanian M, Nazemi M, Malakzadegan A. Comparison of 30-mL and 80-mL Foley catheter balloons and oxytocin for preinduction cervical ripening. Int J Gynaecol Obstet 2009;105:174–5.