Associated with approximately 20% of all live births, induction of labor is a common obstetric procedure in the United States. Moreover, its frequency has increased tremendously, with the rate of induction in the United States rising twofold, from 9.5 to 20.6% of all births, between 1990 and 2003.1 It is generally recognized that induction is associated with increased complications when compared with spontaneous labor, including prolonged labor, cesarean delivery, and chorioamnionitis. Although this change in the rate of induction should be examined critically, it is still important that we refine our techniques of induction with respect to safety, efficacy, and cost-effectiveness.
Preinduction cervical ripening with the transcervical Foley catheter is a proven and effective method. Barnes first used a rubber balloon filled with water for induction in 1861,2 representing the first application of this technique, and over 100 years later Embry and Mollison3 described its use in a large number of patients. Since the 1980s copious studies have proven the transcervical Foley catheter as an effective induction agent in improving the initial cervical examination and in achieving vaginal delivery rates comparable to other induction techniques, including vaginal prostaglandins.4–11 Furthermore, the Foley catheter technique has not been associated with an increased risk of uterine rupture.12
It is common practice to use the transcervical Foley catheter with simultaneous low-dose oxytocin administration under the assumption that this combination results in improved induction outcomes. Some studies have shown increased effectiveness when the Foley technique is combined with pharmacologic agents,13 whereas others have not.6–14 Indeed, there is evidence that decidual prostaglandin production is increased by oxytocin, which is a potential method of further augmenting induction.15 Studies comparing transcervical Foley catheter to other induction techniques are heterogeneous in their use of adjuvant oxytocin and do not provide support for an advantage to simultaneous oxytocin. While single-arm studies have speculated on and evaluated the improved efficacy of transcervical Foley catheter and oxytocin,16,17 we are unaware of any randomized clinical trial evaluating in a prospective fashion whether this is true (MEDLINE database from January 1950 to March 2008 searched using MeSH terms “labor, induced” and “Oxytocin” and keywords “Foley” or “balloon”).
The use of oxytocin, particularly long-duration use, is associated with increased risks of pain, hemorrhage, hyperstimulation, and uterine rupture, and oxytocin may require the use of more resources, including more intensive fetal monitoring and nursing. As a result, oxytocin use should be limited to indicated and efficacious ends. This trial seeks to justify the use of simultaneous oxytocin with transcervical Foley catheter, with the hypothesis that oxytocin does improve induction outcome in the setting of transcervical Foley catheter ripening without increasing the risks.
PARTICIPANTS AND METHODS
A prospective, randomized study of 200 women with singleton pregnancies presenting to Columbia University Medical Center for induction of labor was conducted from November 1, 2003, to October 31, 2005. The institutional review board of Columbia University Medical Center approved this study comparing transcervical Foley catheter ripening only (control) to transcervical Foley catheter ripening with low-dose oxytocin (treatment). Before initiation of the study, random one-to-one allocation was performed using a random number generating table with allocations written on premade allocation cards, specifying “oxytocin” or “no oxytocin,” sorted in blocks of eight and placed into sequentially numbered, sealed, opaque envelopes. After obtaining written consent and confirming entry into the study by a staff physician, each patient was assigned by that physician a treatment group by selection of the next consecutive envelope.
Patients eligible for the study were those presenting and admitted for induction as determined by their primary obstetric provider, with fetuses in cephalic presentation, at a gestational age greater than 23 weeks. Exclusion criteria included any condition precluding vaginal delivery, estimated fetal weight more than 4,500 g, a previous attempt at ripening or induction during the pregnancy, clinically significant cervical or vaginal infection, chorioamnionitis, human immunodeficiency virus, hepatitis B or C, unexplained vaginal bleeding, low-lying placenta, abnormal cervical anatomy or cervical cerclage, or latex allergy. We did not exclude patients with only one previous cesarean delivery presenting for trial of labor.
All women were given transcervical Foley catheter, placed by a resident or attending member of the physician staff. Patients were placed in the dorsal lithotomy position in stirrups in the delivery bed. A sterile vaginal speculum was used to visualize the cervix, and the cervix and vaginal apex was cleansed with povidone-iodine solution. Using sterile ring forceps, a 20 F, 30-mL Foley was introduced and fed through the cervix. The Foley balloon was filled with 30 mL of normal saline once it was above the internal os. Proper placement of the Foley was confirmed with digital or ultrasound examination in all cases. The end of the catheter was taped to the side of the patient’s leg, without traction.
All patients received an intravenous line and basal intravenous fluids. To those randomly assigned to receive oxytocin, the infusion of oxytocin was initiated at 1 milliunit/minute and increased 1 milliunit/min every 15 minutes to a maximum of 10 milliunits/min and titrated to achieve acceptable contraction rates without tachysystole. Thus, not all patients necessarily received this maximal dosing. Patients and providers were not blinded to oxytocin use.
Removal of the Foley balloon occurred with spontaneous expulsion or after 24 hours of attempted ripening. Labor and delivery was managed according to routine obstetric and institutional protocols, according to the primary caregiver. If further ripening was necessary, no explicit guidelines for second-line ripening agent were proscribed. Oxytocin was continued or started (in the case of the control group) as indicated. All patients had continuous fetal heart rate and uterine activity monitoring.
Our primary outcome was the proportion of deliveries achieved within 24 hours of transcervical Foley catheter placement. Secondary outcomes measured were proportion of vaginal deliveries within 24 hours of transcervical Foley catheter placement, overall proportion of vaginal deliveries, duration of ripening, and time interval from transcervical Foley catheter placement to delivery. We also investigated rates of adverse outcomes (chorioamnionitis, hemorrhage) and analgesia use. Given the clear differences in the literature between nulliparous and multiparous patients in induction outcome, we specified a priori that we would conduct a subgroup analysis dividing the subjects into these two groups.
Sample size was calculated based on our primary outcome for nulliparous and multiparous patients combined. A sample size calculation was not performed for the subgroup analysis. Review of our institutional data on inductions demonstrated that our proportion of deliveries within 24 hours was approximately 60%. We calculated that we would need 90 patients in each arm to detect a 20% (60% compared with 80%) difference in the rate of deliveries within 24 hours, with an alpha of 0.05 and power of 80%, using two-tailed tests. To account for dropouts, we aimed to recruit a total of 200 patients.
Statistical analysis was performed by SAS (SAS Institute Inc., Cary, NC) using χ2 test or Fisher exact test (for categorical variables), and Student t test or Mann-Whitney U test (for continuous variables), where appropriate. Categorical variables were also analyzed for relative risk (RR), with 95% confidence intervals (CIs). Statistical significance was set at P<.05. Data were analyzed in an intent-to-treat manner.
A total of 200 women were randomly assigned to the control and treatment arms, with 100 in each group. At the termination of the study, we had complete data for 183 patients (92 patients in the Foley plus oxytocin group and 91 patients in the Foley only group); analysis was limited to this group of patients. We could not account for 17 assigned patients—data sheets and/or medical records could not be retrieved—and thus their characteristics and outcomes were not available for analysis. Figure 1 presents a flowchart of the trial. The Foley was successfully inserted in all patients, although it was not tolerated (and removed shortly after insertion) in one patient who was in the Foley only group.
Demographic and baseline information is provided in Table 1. Our patients were on average aged approximately 28 years, with pregnancies of 39 weeks gestational age. The only maternal characteristics with significant differences were prevalence of diabetes and gestational age. However, there were two outliers for gestational age, and when excluding those or using a nonparametric test, there was not a significant difference. In addition, the difference was small, on the order of a few days, and not judged to be clinically significant. The percentages of nulliparous patients were comparable to the literature studying induction techniques. Bishop scores, which were available in 165 patients (83 control, 82 treatment), were comparable between groups, and the overwhelming majorities were indeed “unfavorable” by any criteria. Nulliparous patients had higher (4.16±2.28) Bishop scores compared with multiparous patients (3.11± 1.77) (P=.001). There was no statistically significant difference in group B streptococci status between our two main study groups.
There was no difference in the proportion of deliveries in 24 hours, our primary outcome, between Foley with oxytocin and Foley only (RR 1.08, 95% CI 0.86–1.35; Table 2). The number of patients needed to treat with oxytocin to provide benefit of delivery in less than 24 hours for one patient is 21. There was also no difference between these two groups in proportions of vaginal deliveries in 24 hours (RR 1.04, 95% CI 0.76–1.41) or cesarean deliveries (RR 0.92, 95% CI 0.60–1.43), and no difference in the duration of ripening (time to Foley removal) and time to delivery (Table 2).
There were no differences in clinically relevant complications during induction or labor and delivery (Table 3). The rate of chorioamnionitis was 7% for both groups. There were also no significant differences in neonatal characteristics and outcomes.
Notably, there were differences in the analgesia requirements for patients during Foley ripening (Table 4). Patients who received oxytocin during Foley ripening, compared with controls receiving Foley only, more often requested analgesic relief (RR 1.77, 95% CI 0.98–3.18), mostly in the form of epidurals (RR 2.60, 95% CI 1.21–5.56). Use of analgesia during labor was not different between treatment and control groups (overall RR 0.96, 95% CI 0.91–1.01; epidural RR 1.00, 95% CI 0.93–1.07) (Table 4).
We stratified the outcomes data by parity, dividing each study group into nulliparous (Table 5) and multiparous (Table 6) subgroups, as specified a priori. For the nulliparous subgroup, there were no statistically significant differences between treatment and control groups in proportions of overall (RR 0.97, 95% CI 0.68–1.40, number needed to treat for harm 66) or vaginal deliveries in 24 hours (RR 0.87, 95% CI 0.52–1.45) or cesarean delivery rate (RR 0.96, 95% CI 0.59–1.57) (Table 5). There were also no differences in nulliparas in the mean times between Foley insertion and delivery between the control and the oxytocin group. However, the increased use of analgesia during induction associated with oxytocin was noted in nulliparas (RR 1.91, 95% CI 0.97–3.76).
Results were different for the multiparous subgroup (Table 6). In this subgroup, we did see a higher proportion of patients delivered in 24 hours in the Foley plus oxytocin group (RR 1.33, 95% CI 1.06–1.67, number of patients needed to treat with oxytocin to provide benefit 5), as well as an average 4-hour difference in the interval to delivery. The proportion of vaginal deliveries in 24 hours was marginally higher for the Foley plus oxytocin group (RR 1.38, 95% CI 0.98–1.92), and there was no difference in cesarean delivery rate (RR 0.63, 95% CI 0.24–1.62). Finally, in contrast to the nulliparous subgroup, there were no differences in analgesia use during induction for the multiparous patients (RR 0.82, 95% CI 0.21–3.20).
Overall, the addition of oxytocin does not affect the likelihood of delivery in 24 hours, shorten the duration of induction, or affect the vaginal delivery rate. Additionally, there is an increased use of analgesia during ripening by patients receiving oxytocin. Given the risks of oxytocin, as well as the increased use of resources involved in oxytocin administration, this should cause us to think more about the use of oxytocin as an adjuvant in Foley ripening.
In producing a significantly shorter mean time to delivery and producing a higher rate of deliveries in 24 hours, without significant effects on analgesia use, the use of adjuvant oxytocin may be justified in multiparous patients in some situations. The proportion of vaginal deliveries in 24 hours was clinically different, although not statistically significant. This may have been due to an inadequate sample size to detect this difference. These results, although part of an a priori subgroup analysis, should be interpreted cautiously, because our study was not designed to test the hypothesis that there were differences among multiparous or nulliparous patients. Nevertheless, the discrepancies observed between subgroups reinforces the differences in induction ease and success between nulliparous and multiparous patients. In light of this evidence, however, we are led to question whether nulliparous and multiparous patients, in general, should be subjected to the same induction protocols or techniques. The results of this trial would suggest that the two sets of patients should be treated differently in terms of the transcervical Foley catheter ripening technique.
The safety of the Foley catheter method of induction is reinforced by this report. The rate of chorioamnionitis was 7% overall, which is not different from studies of other induction techniques. However, given the low number of patients undergoing trial of labor after a previous cesarean delivery, this trial is unable to assess the safety of Foley ripening in inducing these patients.
There are several limitations to this study. First, there were a small number of patients that could not be accounted for at the end of the study. This represented less than 10% of the study population, the proportion was distributed equally between the two study groups, and thus we do not believe this affected our results.
Secondly, medication exposure was not blinded in this study; thus patients and providers were aware of the administration of oxytocin. As a result, interpretation of the results regarding requests for analgesia during ripening may be viewed with some skepticism, because it is possible that the knowledge of oxytocin administration may have influenced the patient or provider to perceive a higher need for pain control. Notably, the overall use of analgesia by our study patients was high, but characteristic of the patients induced at our institution.
Finally, as with most clinical trials, our study may be limited in generalizability or external validity. Our low-dose oxytocin regimen is specific and may differ from those of other institutions. Also, we chose to use a 30-mL Foley balloon, and recent evidence suggests that a larger balloon may further improve the efficacy of the technique.18 Finally, the demographic characteristics of the patients in this study may be different from those not in large urban environments like our own.
Nevertheless, our study provides ample evidence to support the use of transcervical Foley catheter ripening without oxytocin. This suggests that, when this method is favored, it may be appropriate for outpatient use, or other settings requiring less intensive surveillance or nursing. It also may favor its use in patients whom we wish to limit exposure to oxytocin, particularly patients desiring a trial of labor after a prior cesarean delivery.
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