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Foley Plus Oxytocin Compared With Oxytocin for Induction After Membrane Rupture: A Randomized Controlled Trial

Mackeen, A., Dhanya, MD, MPH; Durie, Danielle, E., MD; Lin, Monique, MD; Huls, Christopher, K., MD; Qureshey, Emma, MD; Paglia, Michael, J., MD, PhD; Sun, Haiyan, MS; Sciscione, Anthony, DO

doi: 10.1097/AOG.0000000000002374
Contents: Original Research
Correction

OBJECTIVE: To evaluate the use of a transcervical Foley catheter plus oxytocin infusion compared with oxytocin infusion alone for labor induction and cervical ripening in women 34 weeks of gestation or greater with prelabor rupture of membranes.

METHODS: This is a randomized, multicenter trial of women with a live, singleton gestation at 34 weeks of gestation or greater with prelabor rupture of membranes, an unfavorable cervical examination (less than 2 cm or 80% effaced), and no contraindication to labor. Participants were randomly allocated to a transcervical Foley catheter inflated to 30 cc with concurrent oxytocin infusion or oxytocin infusion alone. Oxytocin administration was standardized across sites. The primary study outcome was interval from induction to delivery. To detect a 2.5-hour difference in the interval from induction to delivery, we required outcome data on 194 women, assuming 80% power and a two-tailed α of 5%. Analysis was by intent to treat.

RESULTS: We enrolled 201 women: 93 were allocated to Foley and 108 to oxytocin. Demographics were similar between the groups. Time to delivery was not significantly different between groups: in the Foley group, it was 13.9 hours (±6.9 SD) compared with 14.4 hours (±7.9 SD) in the oxytocin group (P=.69). There were more cases of clinical chorioamnionitis (8% compared with 0%, P<.01) in the Foley group compared with the oxytocin group. There were no differences for other infectious morbidities or any other variable studied.

CONCLUSION: In patients with prelabor rupture of membranes, the use of a transcervical Foley catheter in addition to oxytocin does not shorten the time to delivery compared with oxytocin alone, but may increase the incidence of intraamniotic infection.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01973036.

The use of a transcervical Foley catheter does not shorten the time to delivery for women with an unfavorable cervix undergoing oxytocin labor induction after membrane rupture.

Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine and Biostatistics Core, Geisinger, Danville, Pennsylvania; the Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Lehigh Valley Health Network, Allentown, Pennsylvania; the University of Colorado School of Medicine, Aurora, Colorado; the University of Arizona College of Medicine, Phoenix at Banner University Medical Center, Phoenix, Arizona; and Christiana Care Health System, Newark, Delaware.

Corresponding author: A. Dhanya Mackeen, MD, MPH, 100 N Academy Avenue, Danville, PA 17822; email: admackeen@geisinger.edu.

Both Geisinger and Lehigh Valley Health Network received small internal grants to assist with the conduct of the study at those individual sites. The internal grant at Geisinger was also applied for the statistical analyses for the entire study.

Financial Disclosure The authors did not report any potential conflicts of interest.

Presented at the 37th Annual Meeting of the Society for Maternal-Fetal Medicine, January 23–28, 2017, Las Vegas, Nevada.

The authors thank Natacha Antunes, Kristina Blessing, Ana Bodea Braescu, Dr Kendra Gray, Vicki Greenberg, Carrie Kitto, Dr Sandra Madueke-Laveaux, Gloria Mullen, Dr Roger Packard, Dr Trevor Quinor, Rachel Rodel, Duane Shaffer, Mallory Snyder, and Mary Sobotor for assisting with the conduct of the study at the individual study sites; and the resident, research, and labor and delivery staff at all participating institutions.

Each author has indicated that he or she has met the journal's requirements for authorship.

Prelabor rupture of membranes (PROM) complicates between 3% and 19% of all pregnancies and 8–10% of pregnancies at term.1 Of those with term PROM, approximately 40% will not spontaneously enter labor by 24 hours.2 Multiple studies have demonstrated that prolongation of latency greater than 24 hours is associated with increased incidence of chorioamnionitis and neonatal sepsis.1–3 Results from the largest randomized trial to date of expectant management compared with labor induction in women with term PROM demonstrated that expectant management was associated with a significantly increased incidence of clinical chorioamnionitis, postpartum fever, and longer neonatal length of stay (LOS) in the neonatal intensive care unit compared with induction of labor with oxytocin.2 Expedient delivery appears to be the optimal management strategy for women with term PROM.

In the setting of PROM, oxytocin and prostaglandins have similar efficacy4 and a transcervical Foley catheter may result in a shorter time to delivery without increased risk of infectious morbidity compared with misoprostol.5,6 However, evidence comparing a Foley catheter with oxytocin in PROM is limited. Two smaller studies examined the efficacy of a Foley catheter (with or without concurrent oxytocin) in the setting of PROM and found no difference in time to delivery or infectious morbidity compared with oxytocin.7,8 A concern with mechanical cervical ripening in the setting of PROM is increased risk of intraamniotic infection and other infection morbidity, which is not increased when membranes are intact.9 Although the Foley catheter has been established as safe and effective in women with intact membranes, its efficacy has not been established in women with PROM.

Oxytocin is not the method of choice for cervical ripening in women with intact membranes and an unfavorable cervix, so we hypothesized that it is unlikely to be the optimal choice in women with ruptured membranes and an unfavorable cervix. The objective of this study was to assess whether cervical ripening with a Foley catheter plus oxytocin decreases the interval to delivery and associated complications compared with oxytocin alone in women at 34 weeks of gestation or greater with PROM.

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MATERIALS AND METHODS

This trial was conducted as a multicenter, randomized controlled investigation in accordance with the published Consolidated Standards of Reporting Trials guidelines10 with full institutional review board approval at four institutions: Geisinger (Danville and Wilkes-Barre, Pennsylvania), Lehigh Valley Health Network (Allentown, Pennsylvania), Banner University Medical Center (Phoenix, Arizona), and Christiana Care Health System (Newark, Delaware). Women with a live, singleton gestation at 34 weeks of gestation or greater with PROM, an unfavorable cervical examination (less than 2 cm or 80% effaced), and no contraindication to labor were approached for study participation. Obstetric care providers on labor and delivery performed cervical examinations and assessments for PROM. Women who experienced PROM before 34 weeks of gestation were eligible for this study if they did not meet any exclusion criteria once they were eligible for labor induction at 34 weeks of gestation. Women had to spontaneously rupture membranes at least 60 minutes before starting induction. Spontaneous rupture of membranes was defined as a clinical history with the presence of at least two of the following four criteria: pooling, ferning, Nitrazine, or oligohydramnios. In the absence of a clinical history, ultrasonographically diagnosed oligohydramnios and pooling were necessary for the diagnosis of rupture of membranes. Oligohydramnios was defined as a total amniotic fluid index less than 5 cm or a maximum vertical pocket less than 2 cm. Additionally, the fetus had to be cephalic and the mother English-speaking with a plan for vaginal delivery. Maternal exclusion criteria included those in active labor and those with suspected intraamniotic infection, abruption or significant hemorrhage, latex allergy, greater than one prior cesarean delivery, any contraindication to vaginal delivery, or human immunodeficiency virus or acquired immunodeficiency syndrome. Active labor was defined as contractions more frequent than every 5 minutes (or 12 contractions or greater in 1 hour) associated with 1 cm or greater cervical change. In the absence of 1 cm or greater cervical change after 2 hours, patients with contractions could be included in the study. Fetal exclusion criteria were multifetal gestations, lethal fetal anomalies, intrauterine fetal demise, and category II or III fetal heart rate tracings.

Women who met the previously mentioned requirements were invited to participate; those who gave written informed consent were enrolled and randomized. Randomization was based on a one-to-one computer-generated schema in random-sized blocks stratified by multiparity or primiparity, preterm or term gestation, and hospital site. The randomization schema was created by Geisinger and maintained through a Microsoft Access database at each individual site.

Participants were randomly allocated to oxytocin infusion alone or to a Foley catheter with concurrent oxytocin infusion. Allocation was not concealed. All women received an intravenous oxytocin infusion that was standardized across sites. Oxytocin was started at a dose of 2 milliunits/min and increased by 2 milliunits/min every 30 minutes to achieve an adequate contraction pattern, as per the institution's definition, to a maximum dose of 30 milliunits/min. For women randomized to Foley, a 16-French latex Foley catheter with a 30-cc balloon was introduced past the internal cervical os into the lower uterine segment using a sterile speculum and ring forceps or sterile vaginal examination with or without a sterile Foley guidewire. The balloon was inflated with 30 cc sterile water or saline, pulled back until taut, and the Foley was taped to the inside of the maternal thigh under tension. If the initial attempt at Foley placement was not successful, the obstetric care provider could attempt to reintroduce the catheter within 1 hour of the first attempt. If the second attempt remained unsuccessful, oxytocin infusion was continued. Catheter checks were performed hourly by traction. If the Foley had not been expelled within 12 hours, it was deflated and removed.

Timing of anesthesia administration, use of fetal scalp electrodes, and intrauterine pressure catheters were at the discretion of the treating team. Antibiotics were administered as per evidence-based indications for group B streptococci prophylaxis or clinically suspected intraamniotic infection.11 Cesarean delivery was performed at the managing team's discretion for maternal or fetal indications. If the patient was not in labor after 24 hours, the management was per the discretion of the attending physician.

Outcomes data were either documented in an ongoing fashion by the labor and delivery team or abstracted from the medical records by research personnel not involved with data analysis. Data were abstracted by the individual sites and recorded on the study case report form, which was sent to the primary site for centralized data entry. Data entry was double-checked. The primary outcome was the interval from induction to delivery. The start of the induction was either the time the Foley catheter was inserted or the time the oxytocin was started, whichever occurred first. Linear regression was used to adjust for body mass index {BMI, calculated as weight (kg)/(height [m])2}, delivery mode, and stratification variables. Secondary outcomes included interval from induction to vaginal delivery, interval from induction to delivery excluding those with PROM before 34 weeks of gestation, cesarean delivery rate, rate of vaginal delivery within 12 and 24 hours, indication for cesarean delivery, infection complications (eg, clinically suspected chorioamnionitis, endometritis, and maternal sepsis), maternal LOS (from admission to discharge and delivery to discharge), and neonatal outcomes (eg, 5-minute Apgar score less than 5, neonatal infectious evaluation and diagnosis of sepsis, LOS, neonatal intensive care unit admission, and neonatal intensive care unit LOS). Chorioamnionitis was defined as temperature 38°C (or 100.4°F) or greater with at least two of the following: uterine tenderness, maternal tachycardia (heart rate 100 beats per minute or greater), fetal tachycardia (heart rate 160 beats per minute or greater), foul odor of the amniotic fluid, or maternal leukocytosis (greater than 15,000 cells/mL3).12 To ensure that our results would be more generalizable, we also planned to analyze our data using a less stringent definition of chorioamnionitis, that is, maternal temperature plus one of the aforementioned criteria. Because preterm PROM is associated with increased risk of intraamniotic infection, we planned to exclude all those who were hospitalized with preterm PROM before 34 0/7 weeks of gestation from the analysis of chorioamnionitis. At the conclusion of our study, a new definition for suspected intraamniotic infection arose, so we assessed our data with regard to this definition as well. Suspected intraamniotic infection was defined as temperature 39°C or greater (or temperature 38°C or greater sustained for 30 minutes) with one additional finding: fetal tachycardia, purulent cervical drainage, or maternal leukocytosis.13 Endomyometritis was defined as temperature 38°C or greater plus one of the following: fundal tenderness, maternal tachycardia, purulent cervical discharge, and no other source of fever.

Planned sample size for this investigation was based on detecting a clinically significant difference in the induction-to-delivery interval. Data from several published sources comparing the use of oxytocin in this clinical setting were used for the sample size estimation. A mean of 11.6±6.2 hours for the oxytocin group was assumed.14–17 We were required to collect outcome data on 194 women, assuming 80% power and 5% significance to detect a 2.5-hour difference in the induction to delivery time between the groups using a two-sided two-sample equal-variance t test. The sample size calculation further assumed one interim analysis (for the data safety monitoring board) using the O'Brien-Fleming spending function. The significance level was set at .003 and .049 at the first and final analyses, respectively. Analysis was by intention to treat. An as-treated analysis was also performed. Proportional data were compared with the χ2 or Fisher exact test as appropriate. Continuous data were compared with either the Student t test or the Wilcoxon rank-sum test if data were not normally distributed. All data are expressed as means and SDs unless otherwise noted. Analysis of covariance was used to assess differences between treatment modality groups adjusted for important covariates (stratification factors, BMI, and cesarean delivery). Kaplan-Meier curve analysis was performed to assess the time to delivery censored for cesarean delivery. Statistical significance was defined as two-sided P<.05. Statistical analyses were performed with SAS 9.4.

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RESULTS

From March 2014 to July 2016, we randomized 201 women, 93 to Foley (88 received Foley) and 108 to oxytocin (113 received oxytocin alone; Fig. 1). Demographic and antenatal characteristics were similar between groups (Table 1). There were 46 participants enrolled at Geisinger, 84 at Lehigh Valley Health Network, 49 at Banner University Medical Center, and 22 at Christiana Care Health System. The most common reason for Foley catheter removal was spontaneous expulsion (84%).

Fig 1

Fig 1

Table 1

Table 1

Approximately 44% of women in both groups received antibiotics during labor: group B streptococci prophylaxis was the most common indication (Foley 64% compared with oxytocin 73%, P=.35). The use of epidural anesthesia was also similar between the two groups (Foley 88% compared with oxytocin 95%, P=.06). Ten patients experienced PROM before 34 weeks of gestation.

Although the average induction time was shorter in the Foley group as compared with the oxytocin group (Table 2), this difference of approximately 0.4 hours is neither clinically nor statistically significant. As planned, we performed an adjusted linear regression analysis and there remained a nonsignificant shorter time to delivery of 0.9 hours (95% CI −2.8 to 1.0; P=.35) in those who were treated with Foley as compared with oxytocin when adjusting for preterm, parity, hospital site, BMI, and cesarean delivery. An as-treated analysis was performed and revealed a mean time to delivery of 6.9 hours (SD 12.7) for the 88 patients treated with Foley and 7.9 hours (SD 12.6) for the 113 patients treated with oxytocin (P=.59). The overall proportion of women delivered within 12 and 24 hours was similar between the Foley and oxytocin groups (Table 3). No significant differences were noted between study groups with respect to mode of delivery or indications for cesarean delivery (Table 3). The mean time to delivery did not differ significantly between treatment groups when assessing only multiparous women (11.6 hours [±5.7 SD] Foley compared with 11.9 hours [±6.1 SD] oxytocin, P=.87); the same was true for nulliparous women (15.5 hours [±7.3 SD] Foley compared with 15.7 hours [±8.4 SD] oxytocin, P=.88). In a Kaplan-Meier analysis, no significant differences were noted between women receiving Foley compared with oxytocin with respect to time to delivery (Fig. 2).

Table 2

Table 2

Table 3

Table 3

Fig 2

Fig 2

Except for chorioamnionitis, there were no differences for other delivery outcomes, other infection morbidities, or any other outcome studied, including endometritis and neonatal sepsis (Table 3). The rate of intrauterine pressure catheter placement (36% Foley compared with 32% oxytocin, P=.54) and vaginal examinations (6.8 Foley compared with 6.2 oxytocin, P=.06) did not differ between groups. Although there was a significantly higher rate of fetal scalp electrode use in the Foley group (28% compared with 13% oxytocin, P<.01), logistic regression analysis showed that fetal scalp electrode use was not related to chorioamnionitis, regardless of definition used (P=.37). As planned, we applied several definitions of chorioamnionitis and intraamniotic infection; regardless of the definition used, there were significantly more cases of infection in those who were treated with Foley as compared with those who were treated with oxytocin (Table 4). Those with suspected intraamniotic infection had an induction-to-delivery interval that was 9 hours longer than those without suspected infection. Although we initially planned to analyze these data excluding those with PROM before 34 weeks of gestation, none of those 10 patients had chorioamnionitis, so we kept them in the analysis.

Table 4

Table 4

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DISCUSSION

In patients with PROM, the use of a transcervical Foley catheter in addition to oxytocin does not shorten the time to delivery compared with oxytocin alone, but may increase the incidence of intraamniotic infection.

A few studies have evaluated the efficacy and safety of the Foley catheter in the setting of PROM with mixed results: one noted a significantly shorter time to delivery with the Foley catheter compared with misoprostol6; the randomized controlled trial found similar induction to delivery times and rates of infection morbidity.5

A retrospective study comparing a Foley catheter (with or without oxytocin) with oxytocin alone showed no difference in infection morbidity between groups.18 A recent randomized trial comparing Foley plus oxytocin and oxytocin only in the setting of PROM in nulliparous women also found a nonsignificant difference in time to delivery without any statistically significant difference in chorioamnionitis. This smaller study differed from ours in several ways. They did not mandate cervical examination before randomization (and the cervix was not examined in 17 patients who were randomized and analyzed); the Foley catheter was inflated to 60 cc, and their oxytocin protocol differed from ours. Likely the 128 patients included in their study were not sufficient to find a statistically significant difference in chorioamnionitis, although twice as many patients in the Foley plus oxytocin group had chorioamnionitis compared with the oxytocin alone group (10% compared with 5%, P=.31). Lastly, they did not define their diagnosis of chorioamnionitis.8

Strengths of our study were several. This was a multicenter randomized controlled trial with a diverse patient population. We applied a computerized randomization database stratified by hospital site, parity, and preterm status. All patients had an initial cervical examination before consideration for inclusion in the study. All four sites applied the same oxytocin protocol. Data entry was double-checked for accuracy. The chorioamnionitis definition was standardized and based on objective data. Charts of all identified cases of chorioamnionitis were reconfirmed by the site principal investigator.

This study also had some limitations. We calculated that 194 women were required to detect a difference in delivery time of 2.5 hours between the two groups. However, the difference in delivery interval in our group was only 0.4 hours, neither statistically nor clinically significant. Some debate about the appropriate primary outcome for labor induction and cervical ripening studies. We opted to assess the time from induction to delivery (without excluding cesarean delivery) because we felt time to delivery (regardless of mode) was the most applicable outcome in clinical practice. There were no significant differences in the incidence of cesarean delivery between the groups. We also assessed time to vaginal delivery and vaginal delivery within 12 and within 24 hours. Given our initial assumptions for power calculation, this study has 70% power to detect a difference of 2.5 hours for the 155 patients who delivered vaginally.

We were not able to assess whether any particular aspect of Foley catheter use increases the risk of chorioamnionitis, for example, method of insertion, length of time with the Foley in place, or whether there is a technique that could be applied to decrease the risk of infection, for example, cervical preparation with Betadine before catheter insertion. Although we had hoped to assess histopathologic examination as a secondary outcome, we did not dictate that placental pathology be sent in all participants because this was not the primary aim of the study. Only one third of the placentas in our study were sent for pathologic evaluation.

The fact that clinical intraamniotic infection differed between treatment groups should make us question whether use of a Foley catheter is appropriate in those with ruptured membranes. A post hoc power analysis was done showing that we had 81% power to show a difference in chorioamnionitis based on the strict definition we used (ie, maternal fever plus two criteria).

In conclusion, transcervical Foley plus oxytocin infusion does not significantly shorten the interval to delivery as compared with oxytocin infusion alone for labor induction in women at 34 weeks of gestation or greater with PROM. Additionally, the Foley catheter may increase the risk of chorioamnionitis.

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REFERENCES

1. Gunn GC, Mishell DR Jr, Morton DG. Premature rupture of the fetal membranes. A review. Am J Obstet Gynecol 1970;106:469–83.
2. Hannah ME, Ohlsson A, Farine D, Hewson SA, Hodnett ED, Myhr TL. Induction of labor compared with expectant management for prelabor rupture of membranes at term. TERMPROM Study Group. N Engl J Med 1996;334:1005–10.
3. Induction of labor. ACOG Practice Bulletin No. 107. American College of Obstetricians and Gynecologists. Obstet Gynecol 2009;114:386–97.
4. Ten Eikelder ML, Mast K, van der Velden A, Bloemenkamp KW, Mol BW. Induction of labor using a Foley catheter or misoprostol: a systematic review and meta-analysis. Obstet Gynecol Surv 2016;71:620–30.
5. Kruit H, Tihtonen K, Raudaskoski T, Ulander VM, Aitokallio-Tallberg A, Heikinheimo O, et al. Foley catheter or oral misoprostol for induction of labor in women with term premature rupture of membranes: a randomized multicenter trial. Am J Perinatol 2016;33:866–72.
6. Mackeen AD, Walker L, Ruhstaller K, Schuster M, Sciscione A. Foley catheter vs prostaglandin as ripening agent in pregnant women with premature rupture of membranes. J Am Osteopath Assoc 2014;114:686–92.
7. Wolff K, Swahn ML, Westgren M. Balloon catheter for induction of labor in nulliparous women with prelabor rupture of the membranes at term. A preliminary report. Gynecol Obstet Invest 1998;46:1–4.
8. Amorosa JMH, Stone J, Factor SH, Booker W, Newland M, Bianco A. A randomized trial of Foley bulb for labor induction in premature rupture of membranes in nulliparas (FLIP). Am J Obstet Gynecol 2017;217:360.e1–7.
9. McMaster K, Sanchez-Ramos L, Kaunitz AM. Evaluation of a transcervical Foley catheter as a source of infection: a systematic review and meta-analysis. Obstet Gynecol 2015;126:539–51.
10. Schulz KF, Altman DG, Moher D; for the CONSORT Group. CONSORT 2010 statement: updated guidelines for reporting parallel group randomized trials. Obstet Gynecol 2010;115:1063–70.
11. Use of prophylactic antibiotics in labor and delivery. Practice Bulletin No. 120. American College of Obstetricians and Gynecologists. Obstet Gyencol 2011;117:1472–83.
12. Tita AT, Andrews WW. Diagnosis and management of clinical chorioamnionitis. Clin Perinatol 2010;37:339–54.
13. Higgins RD, Saade G, Polin RA, Grobman WA, Buhimschi IA, Watterberg K, et al. Evaluation and management of women and newborns with a maternal diagnosis of chorioamnionitis: summary of a workshop. Obstet Gynecol 2016;127:426–36.
14. Sanchez-Ramos L, Bernstein S, Kaunitz AM. Expectant management versus labor induction for suspected fetal macrosomia: a systematic review. Obstet Gynecol 2002;100:997–1102.
15. Wing DA, Paul RH. Induction of labor with misoprostol for premature rupture of membranes beyond thirty-six weeks gestation. Am J Obstet Gynecol 1998;179:94–9.
16. Zeteroğlu S, Engin-Ustün Y, Ustun Y, Güvercinçi M, Sahin G, Kamaci M. A prospective randomized study comparing misoprostol and oxytocin for premature rupture of membranes at term. J Matern Fetal Neonatal Med 2006;19:283–7.
17. Tan PC, Daud SA, Omar SZ. Concurrent dinoprostone and oxytocin for labor induction in term premature rupture of membranes: a randomized controlled trial. Obstet Gynecol 2009;113:1059–65.
18. Cabrera IB, Quiñones JN, Durie D, Rust J, Smulian JC, Scorza WE. Use of intracervical balloons and chorioamnionitis in term premature rupture of membranes. J Matern Fetal Neonatal Med 2016;29:967–71.
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