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A randomized trial of Foley Bulb for Labor Induction in Premature Rupture of Membranes in Nulliparas (FLIP)
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A randomized trial of Foley Bulb for Labor Induction in Premature Rupture of Membranes in Nulliparas (FLIP) Jennifer M. H. Amorosa, MD; Joanne Stone, MD; Stephanie H. Factor, MD, MPH; Whitney Booker, MD; Meredith Newland; Angela Bianco, MD
BACKGROUND: In premature rupture of membranes (PROM), the risk of chorioamnionitis increases with increasing duration of membrane rupture. Decreasing the time from PROM to delivery is associated with lower rates of maternal infection. The American College of Obstetricians and Gynecologists suggests that all women with PROM who do not have a contraindication to vaginal delivery have their labor induced instead of being managed expectantly. Although the use of oxytocin for labor induction has been demonstrated to decrease the time to delivery compared with expectant management, no studies have evaluated the effectiveness of cervical ripening with a Foley bulb to additionally decrease the time to delivery. OBJECTIVE: To determine whether simultaneous use of an intracervical Foley bulb and oxytocin decreases time from induction start to delivery in nulliparous patients with PROM compared with the use of oxytocin alone. STUDY DESIGN: A randomized trial was conducted from August 2014 to February 2016 that compared the use of concurrent Foley bulb/oxytocin vs oxytocin alone in nulliparous patients 34 weeks’ gestational undergoing labor induction for PROM. Our primary outcome was time from induction to delivery. Secondary outcomes were mode of delivery, tachysystole, chorioamnionitis, postpartum hemorrhage, Apgar scores,
P
remature rupture of membranes (PROM) or rupture of membranes before the onset of labor affects 8% of pregnancies.1 The risk of chorioamnionitis increases with increasing duration of membrane rupture, and multiple studies have demonstrated that decreasing the time from PROM to delivery is associated with lower rates of maternal infection.2-5 Therefore, the American College of Obstetricians and Gynecologists suggests that all women with PROM who do not have a contraindication to vaginal delivery have their labor induced instead of being managed
Cite this article as: Amorosa JMH, Stone J, Factor SH, et al. A randomized trial of Foley Bulb for Labor Induction in Premature Rupture of Membranes in Nulliparas (FLIP). Am J Obstet Gynecol 2017;:. 0002-9378/$36.00 ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2017.04.038
and admission to the neonatal intensive care unit. RESULTS: A total of 128 women were randomized. Baseline characteristics were similar between groups. We found no difference in induction-to-delivery time between women induced with concurrent Foley bulb/oxytocin vs oxytocin alone (median time 13.0 hours [interquartile 10.7, 16.1] compared with 10.8 hours [interquartile range 7.8, 16.6], respectively, P ¼ .09). There were no significant differences in mode of delivery, rates of postpartum hemorrhage, chorioamnionitis, or epidural use. Both groups had similar rates of tachysystole as well as total oxytocin dose. There were no differences in neonatal birth weight, Apgar scores, cord gases, or admissions to the neonatal intensive care unit. CONCLUSION: This is the first randomized trial to compare concurrent Foley bulb/oxytocin vs oxytocin alone in nulliparous patients undergoing induction of labor for PROM. We found no difference in time from induction to delivery in patients induced with concurrent Foley bulb/oxytocin vs oxytocin alone. In nulliparous patients with PROM, this study suggests that addition of a Foley bulb to oxytocin does not decrease the time from induction start to delivery. Key words: Foley bulb, induction of labor, labor induction, nulliparous, premature rupture of membranes, PROM
expectantly.6 Although the use of oxytocin for labor induction has been demonstrated to decrease the time to delivery compared with expectant management, no studies have evaluated the effectiveness of cervical ripening with the use of a Foley bulb to additionally decrease the time to delivery. The use of 2 induction agents concurrently compared with the use of one has been demonstrated to decrease time to delivery in pregnant women without PROM. Connolly et al7 in their study of women undergoing induction found a decreased time to delivery among women receiving concurrent Foley bulb and oxytocin compared with sequential Foley bulb followed by oxytocin. In a 4-arm study of women undergoing induction, Levine et al8 compared time to delivery among women assigned to 4 different induction protocols: (1) concurrent Foley bulb and misoprostol; (2) concurrent Foley bulb
and oxytocin; (3) misoprostol alone; and (4) Foley bulb alone. The groups with concurrent administration of 2 agents had shorter time to delivery than the groups with sequential administration of agents. The use of concurrent Foley bulb and oxytocin has never been studied in women with PROM. The purpose of this study was to determine whether simultaneous use of an intracervical Foley bulb inflated to 60 cc and oxytocin decreases the time from induction start to delivery in nulliparous patients with PROM compared with the use of oxytocin alone.
Materials and Methods This was a single-center, nonblinded, randomized clinical trial in which we compared the efficacy of Foley bulb plus oxytocin vs oxytocin alone in patients with PROM. The study was approved by the Icahn School of Medicine at Mount Sinai Medical Center’s Institutional
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Review Board and was registered with the clinical trials registry (ClinicalTrials. gov #NCT02098421). Women age 18 and older with a viable cephalic singleton gestation of 34 weeks’ gestational age or greater who presented with PROM between August 2014 and February 2016 were evaluated for participation by labor floor providers. Patients were eligible for participation if their cervix was dilated less than 3 cm or, if the primary provider wished to defer the initial cervical examination because of ruptured membrane status, the patient was having contractions less than 3 times every 10 minutes. Patients were ineligible to participate if they had a multifetal gestation, a known anomalous fetus, a fetus with malpresentation, a latex allergy, unexplained vaginal bleeding or contraindication to vaginal delivery (such as a placenta previa), had received latency antibiotics, had had previous uterine surgery (including previous cesarean delivery or myomectomy), or were in spontaneous labor (regular uterine contractions with cervical change). If eligible patients indicated that they were interested in hearing more about the study, they were approached by a member of the research team, who explained the study and obtained informed consent from agreeable patients. Once the patient consented to participate in the study, participants were randomized to receive either concurrent Foley bulb and oxytocin or oxytocin alone. The randomization envelopes were prepared before the start of the study by the use of a random numbers generator from OpenEPi, Version 3 (http://www.OpenEpi.com). Cards allocating patients to either “oxytocin plus Foley” or “oxytocin alone” were placed in sequentially numbered, sealed opaque envelopes. After signing consent, participants were given the next ordered envelope. Patients in the Foley bulb and oxytocin group had a 16-F, 30-cc Foley bulb inserted digitally or under direct visualization with the aid of a sterile speculum. The Foley was threaded through the internal cervical os and filled with 60 mL of normal saline. The
FIGURE 1
Study enrollment, allocation, and analysis Enrollment
Approached (n=144)
Declined to participate (n=16)
Randomized (n=128)
Allocation Pitocin + Foley group (n=62): ♦ Received allocated intervention (n=61) ♦
Pitocin Only group (n=66): ♦ Received allocated intervention (n=65)
1 person treated off protocol
♦
1 person treated off protocol
Follow-Up Lost to follow-up (n=0)
Lost to follow-up (n=0)
Analysis Analyzed (n=61) ♦ Excluded from analysis (n=1): one paƟent <18 yo inadvertently recruited
Analyzed (n=66)
Flow chart demonstrating patient recruitment through analysis. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
diameter of the Foley balloon with this volume of saline is w4 cm. The catheter of the Foley bulb was then taped to the patient’s thigh under tension. Oxytocin was started within 1 hour of Foley bulb placement. In the oxytocin alone group, oxytocin was started as soon as possible after consent was obtained. In both groups, oxytocin was titrated according to our institution’s standard induction protocol in which the oxytocin infusion is started at 2 mU/ min. This dose is doubled every 30 minutes to a maximum dose of 16 mU/min (2e4e8e16) and then may be increased by 2 mU/min every 30 minutes to a maximum dose of 30 mU/min or until regular uterine contractions occur. Fetal heart rate and contraction patterns are monitored continuously in all patients receiving oxytocin. Further labor
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management was at the discretion of the private provider. Demographic characteristics, pregnancy history, labor course, delivery data, and neonatal outcomes were collected via patient interview and/or chart review by the study team. After each delivery, the fetal heart rate tracing was reviewed for periods of tachysystole (>5 uterine contractions in 10 minutes, averaged over 30 minutes). The primary outcome measure was time from start of induction to delivery. Secondary outcomes included mode of delivery, tachysystole, chorioamnionitis, postpartum hemorrhage, neonatal Apgar scores, and admission to the neonatal intensive care unit (NICU). The sample size was estimated a priori based on the primary outcome. We assumed a normal distribution of
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TABLE 1
Baseline demographics Characteristics Maternal age, y mean (SD)
Foley þ oxytocin n ¼ 61 (%) 30.4 (5.3)
Oxytocin alone n ¼ 66 (%) 29.5 (6.3)
Maternal age category, y 18e19
2 (4)
4 (6)
20e29
21 (34)
24 (36)
30e39
35 (57)
35 (53)
40e49
3 (5)
3 (5)
3 (5)
1 (2)
18.5 and <25 (healthy weight)
35 (57)
46 (71)
25 to < 30 (overweight)
Maternal prepregnancy BMI <18.5 (underweight)
16 (26)
11 (17)
30 to < 35 (obese)
3 (5)
1 (2)
35 (morbidly obese)
4 (7)
6 (9)
Gestational age at delivery, median (IQR)
39.3 (38.1, 40.0)
39.2 (38.0, 40.0)
34w0d-36w6d
8 (13)
7 (11)
37w0d-41w6d
53 (87)
59 (89)
Estimated fetal weight at initiation of study, g mean (SD) Small-for-gestational age (<2500 g) Normal (2500 and 4500 g) Large-for-gestational age (>4500)
3359.5 (322.56) 0 58 (100) 0
3316.4 (300.01) 0 66 (100) 0
Original Research
induction to delivery times with a mean induction to delivery time of 16.0 9 hours with oxytocin based on previously published data.4,9-11 We estimated that 57 women would be needed in each group for 80% power to detect a 30% difference in mean induction to delivery time for the 2 groups using a 2-tailed ttest and an a of 0.05. We chose to use a 30% difference as one that would be generally accepted as clinically significant. A modified intention-to-treat approach was used for the analysis, which included all participants who were 18 years or older at the time of induction. One participant was younger than 18 years but was inadvertently enrolled and randomized and was excluded from this modified intention-to-treat analysis. The primary outcome, time from the start of induction to delivery, was analyzed with Kaplan-Meier analysis and the Wilcoxon rank sum test. Secondary outcomes were compared with the c2 test, Fisher exact test, Student t test, and Wilcoxon ranksum, as appropriate. SAS, version 9.4 (SAS Institute Inc, Cary, NC) was used for the analysis. A P value of .05 was considered significant.
Race White
32 (52)
39 (59)
Black
6 (10)
9 (14)
Asian
9 (15)
8 (12)
American Indian/Alaskan
0
0
Pacific Islander/Hawaiian
0
0
Results
Ethnicity Hispanic/Latina
11 (18)
12 (18)
Non-Hispanic/Latino
42 (69)
53 (80)
Married
45 (74)
46 (70)
Single
13 (21)
14 (21)
2 (3)
6 (9)
Private
46 (75)
42 (64)
Medicaid or self-pay
15 (25)
24 (36)
Marital status
Domestic partner Insurance status
Time from rupture to induction start, h median (IQR)
5.5 (3.8, 8.7)
Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
5.5 (4.2, 9.1) (continued)
A total of 128 women were enrolled from August 2014 to February 2016 (Figure 1). Of these, 62 women were assigned to receive Foley bulb plus oxytocin, and 66 were assigned to receive oxytocin alone. Of the 62 patients randomized to the Foley bulb plus oxytocin group, one was excluded from the analysis because she was younger 18 years of age. Of the remaining 61 patients in the Foley bulb plus oxytocin group, 53 received both the Foley bulb and the oxytocin per protocol (ie, initiated less than 1 hour apart, and 8 received both the Foley bulb and the oxytocin but initiated at greater than 1 hour apart). Of the 66 patients assigned to receive oxytocin alone, 65 received the oxytocin per protocol, and 1 had a Foley bulb placed per personal provider decision. The 2 groups were similar with regard to baseline characteristics, including age,
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TABLE 1
Baseline demographics (continued) Foley þ oxytocin n ¼ 61 (%)
Characteristics
Oxytocin alone n ¼ 66 (%)
Time from rupture to oxytocin, h median (IQR) Bishop score, median (IQR)
5.6 (3.8, 9.0)
5.5 (4.2, 9.1)
3 (1, 4)
3 (1, 4)
Dilation, cm 0
13 (21)
14 (29)
1-2
47 (77)
35 (71)
3e4
1 (2)
0
BMI, body mass index; IQR, interquartile range. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
TABLE 2
Maternal outcomes Foley þ oxytocin n ¼ 61 (%)
Characteristic
Oxytocin alone n ¼ 66 (%)
P value
Primary outcome Induction to delivery, h 13.0 (10.7, 16.1)
10.8 (7.8, 16.6)
.09a
Normal vaginal delivery
36 (59)
43 (65)
.91b
Cesarean delivery
18 (30)
16 (24)
Forceps assisted
4 (7)
4 (6)
Vacuum assisted
3 (5)
3 (5)
Arrest of descent
3 (5)
2 (3)
.67b
Arrest of dilation
11 (18)
8 (12)
.35c
4 (7)
5 (8)
1.00b
Postpartum hemorrhage
5 (8)
2 (3)
.26b
Chorioamnionitis
6 (10)
3 (5)
.31b
Endometritis
2 (3)
2 (3)
1.00b
Epidural use
61 (100)
64 (97)
.50b
7 (11)
8 (12)
.89c
median (IQR) Secondary outcomes Mode of delivery
Reasons for cesarean delivery
Nonreassuring fetal heart tracing
Other delivery-related outcomes Tachysystole Max dose of oxytocin, mU/min median (IQR)
12.0 (8.0, 18.0)
12.0 (8.0, 18.0)
.74a
Total dose of oxytocin, mL median (IQR)
237.5 (102.5, 431.5) 222.8 (78.0, 438.0)
Meconium
4 (7)
.75b
6 (9)
Analyzed with Wilcoxon rank sum test; Analyzed with the Fisher exact test; Analyzed with the c test. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017. a
b
c
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.83a
2
prepregnancy body mass index, estimated fetal weight, and gestational age (Table 1). All of the women were nulliparous and the median Bishop’s score was similar in the 2 groups.3 Both groups had been ruptured for approximately the same length of time before the start of the induction. In addition, both groups had been ruptured for similar lengths of time before oxytocin was started. There was no difference in induction-to-delivery time between women induced with a combination of the Foley bulb plus oxytocin when compared with those induced with oxytocin alone (median time 13.0 hours [interquartile range {IQR} 10.7, 16.1] compared with 10.8 hours [IQR 7.8, 16.6], respectively, P ¼ .09) (Table 2; Figure 2). The log rank test indicates that there is no difference between the curves in time from the start of induction to delivery in the 2 groups. Consistent with that finding, the curves cross. When only women who followed the assigned protocol were analyzed, there was also no difference in induction-todelivery time between the 2 groups. There were also no differences in mode of delivery, rates of postpartum hemorrhage, chorioamnionitis, endometritis, or epidural use. Both groups had similar rates of tachysystole, and the total and maximum doses of oxytocin were similar between both groups (Table 2). There was no difference in time from start of induction to delivery between the 2 groups when the data were stratified by the maternal characteristic of prepregnancy body mass index (Table 3). In women who delivered vaginally, those receiving oxytocin alone had shorter mean time to delivery than those in the combination group (10.6 hours [IQR 7.1, 14.2] vs 13.2 hours (IQR 10.8, 15.9), whereas there was no difference in those who delivered by cesarean delivery. In patients who started the induction at 0 cm dilation, there was a significantly longer median time from start of induction to delivery in the Foley bulb plus oxytocin group compared with the oxytocin alone group (15.4 hours [IQR
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Original Research
FIGURE 2
Kaplan-Meier time curve for start of induction to delivery
There was no significant difference in time from induction start to delivery in nulliparous patients with PROM who were induced by the use of either a combination of concurrent foley bulb plus oxytocin vs oxytocin alone. PROM, premature rupture of membranes. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
13.2, 17.5] in the Foley bulb plus oxytocin group vs 11.8 hours [IQR 9.4, 14.2] in the oxytocin alone, P ¼ .02). There were no differences in neonatal birth weight, Apgar scores, or admission to the neonatal intensive care unit (Table 4). Umbilical cord gases were similar in the 2 groups.
Comment There was no difference in the time from start of induction until delivery in
patients with PROM who were induced with a combination of a Foley bulb plus oxytocin vs oxytocin alone. Although no significant differences were observed in mode of delivery, labor complications, or maternal adverse outcomes such as chorioamnionitis and postpartum hemorrhage, twice as many patients in the Foley plus oxytocin group had a postpartum hemorrhage or delivery affected by chorioamnionitis. However, this study was not powered to
specifically address these outcomes, and the overall numbers were small. In addition, no differences were found in adverse neonatal outcomes such as admission to the NICU, cord gas values, or Apgar scores. Among patients who started their induction at 0 cm dilation, patients who were induced with a combination of Foley bulb plus oxytocin had a significantly longer time to delivery than those who received oxytocin alone; however, the number of
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TABLE 3
Median time and IQR in hours from start of induction to delivery by maternal characteristics Characteristic
Foley þ oxytocin, median hours (IQR)
n
Oxytocin alone, median hours (IQR)
N
P valuea
Mode of delivery Vaginal
43
13.2 (10.8, 15.9)
50
10.6 (7.1, 14.2)
.02
Cesarean delivery
18
12.3 (10.5, 17.0)
16
16.0 (9.8, 18.2)
.57
0
13
15.4 (13.2, 17.5)
14
11.8 (9.4, 14.2)
.02
1e2
47
12.0 (10.1, 15.9)
35
11.0 (8.2, 17.7)
.86
3
7.0 (5.2, 15.9)
1
18.5 and <25
35
13.0 (10.8, 15.2)
46
10.8 (7.2, 16.7)
.14
25 to <30
16
12.2 (10.2, 16.3)
11
11.3 (8.7, 16.6)
.86
7
18.5 (11.3, 21.1)
7
10.7 (5.9, 15.1)
.15
Dilation
Maternal prepregnancy BMI <18.5
30þ
6.1
1.0
BMI, body mass index; IQR, interquartile range. a
Analyzed with the Wilcoxon Rank Sum test. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
patients in this group was very small. A subgroup analysis of the patients who began their induction at 0 cm dilation showed similar doses of total oxytocin whether they received oxytocin alone or oxytocin with concurrent Foley balloon. To our knowledge, there have been no previous studies specifically comparing the concurrent use of oxytocin and Foley bulb with oxytocin alone for labor induction in patients with PROM. There have been other studies that compared other dual agent inductions in PROM. Our finding that concurrent Foley and oxytocin compared with oxytocin alone did not shorten induction times is similar to the results of a study by Tan et al,12 in which concurrent dinoprostone and oxytocin was compared against induction with oxytocin alone in term PROM patients. They randomized 116 term, nulliparous patients with PROM to receive either 3 mg of dinoprostone pessary plus oxytocin vs a placebo plus oxytocin. There was no significant difference in time from induction to delivery between the 2 groups. Similar to our study, there also were no significant differences in mode of delivery and rates of postpartum hemorrhage. There were also no differences in Apgar scores and NICU admissions.
Membrane rupture is associated with prostaglandin release locally at the site of the membrane—this mechanism alone is enough to trigger labor onset in most patients, as 60% will go into labor within 24 hours and 95% within 72 hours.1,13 It is plausible that the prostaglandin release thought to be stimulated by the Foley balloon is not necessary as perhaps the optimal physiologic amount already is released at time of membrane rupture. There are several limitations to this study. First, 17 of 66 patients in the oxytocin-alone group did not have a
cervical examination before the start of their oxytocin because of provider preference. It is possible that this subset of patients had a more favorable Bishop score than the other patients enrolled in the study and could have skewed the results to shorter induction times in the oxytocin alone group as a whole. This is unlikely however, as we compared the patients who had an initial examination in the oxytocin alone group vs those who did not have an initial examination and found similar total times from induction start to delivery. In the 49 women who had a cervical examination
TABLE 4
Neonatal outcomes Characteristics
Foley þ oxytocin n ¼ 61 (%)
Oxytocin alone n ¼ 66 (%)
P value
Birth weight, g, mean (SD)
3163.6 (457.5)
3101.8 (500.5)
.47a
1-minute Apgar score, median (IQR)
9 (9, 9)
9 (9, 9)
.14b
5-minute Apgar score, median (IQR)
9 (9, 9)
9 (9, 9)
.18b
Admission to the NICU
4 (7)
8 (12)
.37c
Cord gas pH, mean (SD)
7.25 (0.06)
7.25 (0.07)
.77a
IQR, interquartile range; NICU, neonatal intensive care unit. Analyzed with the Student t test; b Analyzed with the Wilcoxon rank-sum test; c Analyzed with the Fisher exact test. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
a
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ajog.org before the start of their oxytocin, the median time from the start of induction to delivery was 11.0 hours (IQR 8.4 hours, 16.6 hours). In the 17 women who did not have a cervical examination before the start of their oxytocin, the median time form the start of induction to delivery was 10.8 hours (IQR 6.1 hours, 14.3 hours). There was no statistical difference in these times based on the Wilcoxon rank sum test (P ¼ .44). Second, there is a potential for selection bias in our study—we do not have data available to compare the women with PROM who participated in our study with all women with PROM at our institution. Another potential imitation of the study has to do with institutionspecific protocols. Our oxytocin protocol for labor induction may vary from other institutions and our protocol is to fill Foley bulbs to 60 cc, whereas other institutions may use other standard volumes. This study used a sample size calculation that was based on the assumption that times from the start of induction to delivery would be normally distributed. The times from the start of induction to delivery observed in this study were not normally distributed. This study found that patients induced with a combination of Foley and oxytocin had a nonstatistically significant longer time from induction start to delivery. A larger study may have found that increase in time actually was statistically significant. This study, on its own, suggests that the addition of Foley does not decrease time from the start of induction to delivery, which was the clinically relevant outcome we were studying. Based on the results of this study, the addition of Foley is not recommended to shorten induction times in patients with PROM.
OBSTETRICS
Many obstetrical providers question whether the introduction of the Foley bulb in patients with PROM may increase rates of maternal complications such as infection and postpartum hemorrhage. Although twice as many patients in the Foley plus oxytocin group had their delivery complicated by either chorioamnionitis or postpartum hemorrhage in this study, the overall numbers were small, and the difference did not meet statistical significance. A much larger study would be needed to address these specific questions. We found no difference in time from induction to delivery in nulliparous patients with PROM who were induced either using a combination of concurrent Foley bulb plus oxytocin versus oxytocin alone. These findings address a frequently asked question about whether there is utility in using Foley bulbs to assist with cervical ripening in patients with PROM in an effort to shorten the duration of labor induction. This study suggests that Foley bulbs should not be used in induction of labor for PROM in nulliparous patients, as no additional benefit is conferred. n References 1. Gunn GC, Mishell DR Jr, Morton DG. Premature rupture of the fetal membranes. A review. Am J Ostet Gynecol 1970;106:469-83. 2. Seaward PG, Hannah ME, Myhr TL, et al. International Multicentre Term Prelabor Rupture of Membranes Study: evaluation of predictors of clinical chorioamnionitis and postpartum fever in patients with prelabor rupture of membranes at term. Am J Ostet Gynecol 1997;177:1024-9. 3. Soper DE, Mayhall CG, Froggatt JW. Characterization and control of intraamniotic infection in an urban teaching hospital. Am J Ostet Gynecol 1996;175:304-9. discussion 309-10. 4. Hannah ME, Ohlsson A, Farine D, et al. Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. N Engl J Med 1996;334:1005-10.
Original Research
5. Dare MR, Middleton P, Crowther CA, Flenady VJ, Varatharaju B. Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). Cochrane Database Syst Rev 2006;(1):CD005302. 6. ACOG Committee on Practice Bulletins— Obstetrics. ACOG Practice Bulletin No. 107: induction of labor. Obstet Gynecol 2009;114: 386-97. 7. Connolly KA, Kohari KS, Rekawek P, et al. A randomized trial of Foley balloon induction of labor trial in nulliparas (FIAT-N). Am J Ostet Gynecol 2016;215:392.e1-6. 8. Levine L, Downes K, Elovitz M, Parry S, Sammel M, Srinivas S. Mechanical and pharmacologic methods of labor induction. Obstet Gynecol 2016;128:1357-64. 9. 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. 10. Sanchez-Ramos L, Chen AH, Kaunitz AM, Gaudier FL, Delke I. Labor induction with intravaginal misoprostol in term premature rupture of membranes: a randomized study. Obstet Gynecol 1997;89:909-12. 11. Carbone JF, Tuuli MG, Fogertey PJ, Roehl KA, Macones GA. Combination of Foley bulb and vaginal misoprostol compared with vaginal misoprostol alone for cervical ripening and labor induction: a randomized controlled trial. Obstet Gynecol 2013;121: 247-52. 12. 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. 13. Grant JM, Keirse MJNC. Prelabour rupture of the membranes at term. In: Chalmers L, Enkin M, Keirse MJNC, eds. Effective care in pregnancy and child birth, Vol. 2. Child birth. Oxford: Oxford University Press; 1989:112-7.
Author and article information From the Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai Hospital, New York, NY. Received March 4, 2017; accepted April 24, 2017. The authors report no conflict of interest. Corresponding author: Jennifer M. H. Amorosa, MD. [email protected]
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A randomized trial of Foley Bulb for Labor Induction in Premature Rupture of Membranes in Nulliparas (FLIP) Jennifer M. H. Amorosa, MD; Joanne Stone, MD; Stephanie H. Factor, MD, MPH; Whitney Booker, MD; Meredith Newland; Angela Bianco, MD
BACKGROUND: In premature rupture of membranes (PROM), the risk of chorioamnionitis increases with increasing duration of membrane rupture. Decreasing the time from PROM to delivery is associated with lower rates of maternal infection. The American College of Obstetricians and Gynecologists suggests that all women with PROM who do not have a contraindication to vaginal delivery have their labor induced instead of being managed expectantly. Although the use of oxytocin for labor induction has been demonstrated to decrease the time to delivery compared with expectant management, no studies have evaluated the effectiveness of cervical ripening with a Foley bulb to additionally decrease the time to delivery. OBJECTIVE: To determine whether simultaneous use of an intracervical Foley bulb and oxytocin decreases time from induction start to delivery in nulliparous patients with PROM compared with the use of oxytocin alone. STUDY DESIGN: A randomized trial was conducted from August 2014 to February 2016 that compared the use of concurrent Foley bulb/oxytocin vs oxytocin alone in nulliparous patients 34 weeks’ gestational undergoing labor induction for PROM. Our primary outcome was time from induction to delivery. Secondary outcomes were mode of delivery, tachysystole, chorioamnionitis, postpartum hemorrhage, Apgar scores,
P
remature rupture of membranes (PROM) or rupture of membranes before the onset of labor affects 8% of pregnancies.1 The risk of chorioamnionitis increases with increasing duration of membrane rupture, and multiple studies have demonstrated that decreasing the time from PROM to delivery is associated with lower rates of maternal infection.2-5 Therefore, the American College of Obstetricians and Gynecologists suggests that all women with PROM who do not have a contraindication to vaginal delivery have their labor induced instead of being managed
Cite this article as: Amorosa JMH, Stone J, Factor SH, et al. A randomized trial of Foley Bulb for Labor Induction in Premature Rupture of Membranes in Nulliparas (FLIP). Am J Obstet Gynecol 2017;:. 0002-9378/$36.00 ª 2017 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2017.04.038
and admission to the neonatal intensive care unit. RESULTS: A total of 128 women were randomized. Baseline characteristics were similar between groups. We found no difference in induction-to-delivery time between women induced with concurrent Foley bulb/oxytocin vs oxytocin alone (median time 13.0 hours [interquartile 10.7, 16.1] compared with 10.8 hours [interquartile range 7.8, 16.6], respectively, P ¼ .09). There were no significant differences in mode of delivery, rates of postpartum hemorrhage, chorioamnionitis, or epidural use. Both groups had similar rates of tachysystole as well as total oxytocin dose. There were no differences in neonatal birth weight, Apgar scores, cord gases, or admissions to the neonatal intensive care unit. CONCLUSION: This is the first randomized trial to compare concurrent Foley bulb/oxytocin vs oxytocin alone in nulliparous patients undergoing induction of labor for PROM. We found no difference in time from induction to delivery in patients induced with concurrent Foley bulb/oxytocin vs oxytocin alone. In nulliparous patients with PROM, this study suggests that addition of a Foley bulb to oxytocin does not decrease the time from induction start to delivery. Key words: Foley bulb, induction of labor, labor induction, nulliparous, premature rupture of membranes, PROM
expectantly.6 Although the use of oxytocin for labor induction has been demonstrated to decrease the time to delivery compared with expectant management, no studies have evaluated the effectiveness of cervical ripening with the use of a Foley bulb to additionally decrease the time to delivery. The use of 2 induction agents concurrently compared with the use of one has been demonstrated to decrease time to delivery in pregnant women without PROM. Connolly et al7 in their study of women undergoing induction found a decreased time to delivery among women receiving concurrent Foley bulb and oxytocin compared with sequential Foley bulb followed by oxytocin. In a 4-arm study of women undergoing induction, Levine et al8 compared time to delivery among women assigned to 4 different induction protocols: (1) concurrent Foley bulb and misoprostol; (2) concurrent Foley bulb
and oxytocin; (3) misoprostol alone; and (4) Foley bulb alone. The groups with concurrent administration of 2 agents had shorter time to delivery than the groups with sequential administration of agents. The use of concurrent Foley bulb and oxytocin has never been studied in women with PROM. The purpose of this study was to determine whether simultaneous use of an intracervical Foley bulb inflated to 60 cc and oxytocin decreases the time from induction start to delivery in nulliparous patients with PROM compared with the use of oxytocin alone.
Materials and Methods This was a single-center, nonblinded, randomized clinical trial in which we compared the efficacy of Foley bulb plus oxytocin vs oxytocin alone in patients with PROM. The study was approved by the Icahn School of Medicine at Mount Sinai Medical Center’s Institutional
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Review Board and was registered with the clinical trials registry (ClinicalTrials. gov #NCT02098421). Women age 18 and older with a viable cephalic singleton gestation of 34 weeks’ gestational age or greater who presented with PROM between August 2014 and February 2016 were evaluated for participation by labor floor providers. Patients were eligible for participation if their cervix was dilated less than 3 cm or, if the primary provider wished to defer the initial cervical examination because of ruptured membrane status, the patient was having contractions less than 3 times every 10 minutes. Patients were ineligible to participate if they had a multifetal gestation, a known anomalous fetus, a fetus with malpresentation, a latex allergy, unexplained vaginal bleeding or contraindication to vaginal delivery (such as a placenta previa), had received latency antibiotics, had had previous uterine surgery (including previous cesarean delivery or myomectomy), or were in spontaneous labor (regular uterine contractions with cervical change). If eligible patients indicated that they were interested in hearing more about the study, they were approached by a member of the research team, who explained the study and obtained informed consent from agreeable patients. Once the patient consented to participate in the study, participants were randomized to receive either concurrent Foley bulb and oxytocin or oxytocin alone. The randomization envelopes were prepared before the start of the study by the use of a random numbers generator from OpenEPi, Version 3 (http://www.OpenEpi.com). Cards allocating patients to either “oxytocin plus Foley” or “oxytocin alone” were placed in sequentially numbered, sealed opaque envelopes. After signing consent, participants were given the next ordered envelope. Patients in the Foley bulb and oxytocin group had a 16-F, 30-cc Foley bulb inserted digitally or under direct visualization with the aid of a sterile speculum. The Foley was threaded through the internal cervical os and filled with 60 mL of normal saline. The
FIGURE 1
Study enrollment, allocation, and analysis Enrollment
Approached (n=144)
Declined to participate (n=16)
Randomized (n=128)
Allocation Pitocin + Foley group (n=62): ♦ Received allocated intervention (n=61) ♦
Pitocin Only group (n=66): ♦ Received allocated intervention (n=65)
1 person treated off protocol
♦
1 person treated off protocol
Follow-Up Lost to follow-up (n=0)
Lost to follow-up (n=0)
Analysis Analyzed (n=61) ♦ Excluded from analysis (n=1): one paƟent <18 yo inadvertently recruited
Analyzed (n=66)
Flow chart demonstrating patient recruitment through analysis. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
diameter of the Foley balloon with this volume of saline is w4 cm. The catheter of the Foley bulb was then taped to the patient’s thigh under tension. Oxytocin was started within 1 hour of Foley bulb placement. In the oxytocin alone group, oxytocin was started as soon as possible after consent was obtained. In both groups, oxytocin was titrated according to our institution’s standard induction protocol in which the oxytocin infusion is started at 2 mU/ min. This dose is doubled every 30 minutes to a maximum dose of 16 mU/min (2e4e8e16) and then may be increased by 2 mU/min every 30 minutes to a maximum dose of 30 mU/min or until regular uterine contractions occur. Fetal heart rate and contraction patterns are monitored continuously in all patients receiving oxytocin. Further labor
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management was at the discretion of the private provider. Demographic characteristics, pregnancy history, labor course, delivery data, and neonatal outcomes were collected via patient interview and/or chart review by the study team. After each delivery, the fetal heart rate tracing was reviewed for periods of tachysystole (>5 uterine contractions in 10 minutes, averaged over 30 minutes). The primary outcome measure was time from start of induction to delivery. Secondary outcomes included mode of delivery, tachysystole, chorioamnionitis, postpartum hemorrhage, neonatal Apgar scores, and admission to the neonatal intensive care unit (NICU). The sample size was estimated a priori based on the primary outcome. We assumed a normal distribution of
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TABLE 1
Baseline demographics Characteristics Maternal age, y mean (SD)
Foley þ oxytocin n ¼ 61 (%) 30.4 (5.3)
Oxytocin alone n ¼ 66 (%) 29.5 (6.3)
Maternal age category, y 18e19
2 (4)
4 (6)
20e29
21 (34)
24 (36)
30e39
35 (57)
35 (53)
40e49
3 (5)
3 (5)
3 (5)
1 (2)
18.5 and <25 (healthy weight)
35 (57)
46 (71)
25 to < 30 (overweight)
Maternal prepregnancy BMI <18.5 (underweight)
16 (26)
11 (17)
30 to < 35 (obese)
3 (5)
1 (2)
35 (morbidly obese)
4 (7)
6 (9)
Gestational age at delivery, median (IQR)
39.3 (38.1, 40.0)
39.2 (38.0, 40.0)
34w0d-36w6d
8 (13)
7 (11)
37w0d-41w6d
53 (87)
59 (89)
Estimated fetal weight at initiation of study, g mean (SD) Small-for-gestational age (<2500 g) Normal (2500 and 4500 g) Large-for-gestational age (>4500)
3359.5 (322.56) 0 58 (100) 0
3316.4 (300.01) 0 66 (100) 0
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induction to delivery times with a mean induction to delivery time of 16.0 9 hours with oxytocin based on previously published data.4,9-11 We estimated that 57 women would be needed in each group for 80% power to detect a 30% difference in mean induction to delivery time for the 2 groups using a 2-tailed ttest and an a of 0.05. We chose to use a 30% difference as one that would be generally accepted as clinically significant. A modified intention-to-treat approach was used for the analysis, which included all participants who were 18 years or older at the time of induction. One participant was younger than 18 years but was inadvertently enrolled and randomized and was excluded from this modified intention-to-treat analysis. The primary outcome, time from the start of induction to delivery, was analyzed with Kaplan-Meier analysis and the Wilcoxon rank sum test. Secondary outcomes were compared with the c2 test, Fisher exact test, Student t test, and Wilcoxon ranksum, as appropriate. SAS, version 9.4 (SAS Institute Inc, Cary, NC) was used for the analysis. A P value of .05 was considered significant.
Race White
32 (52)
39 (59)
Black
6 (10)
9 (14)
Asian
9 (15)
8 (12)
American Indian/Alaskan
0
0
Pacific Islander/Hawaiian
0
0
Results
Ethnicity Hispanic/Latina
11 (18)
12 (18)
Non-Hispanic/Latino
42 (69)
53 (80)
Married
45 (74)
46 (70)
Single
13 (21)
14 (21)
2 (3)
6 (9)
Private
46 (75)
42 (64)
Medicaid or self-pay
15 (25)
24 (36)
Marital status
Domestic partner Insurance status
Time from rupture to induction start, h median (IQR)
5.5 (3.8, 8.7)
Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
5.5 (4.2, 9.1) (continued)
A total of 128 women were enrolled from August 2014 to February 2016 (Figure 1). Of these, 62 women were assigned to receive Foley bulb plus oxytocin, and 66 were assigned to receive oxytocin alone. Of the 62 patients randomized to the Foley bulb plus oxytocin group, one was excluded from the analysis because she was younger 18 years of age. Of the remaining 61 patients in the Foley bulb plus oxytocin group, 53 received both the Foley bulb and the oxytocin per protocol (ie, initiated less than 1 hour apart, and 8 received both the Foley bulb and the oxytocin but initiated at greater than 1 hour apart). Of the 66 patients assigned to receive oxytocin alone, 65 received the oxytocin per protocol, and 1 had a Foley bulb placed per personal provider decision. The 2 groups were similar with regard to baseline characteristics, including age,
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TABLE 1
Baseline demographics (continued) Foley þ oxytocin n ¼ 61 (%)
Characteristics
Oxytocin alone n ¼ 66 (%)
Time from rupture to oxytocin, h median (IQR) Bishop score, median (IQR)
5.6 (3.8, 9.0)
5.5 (4.2, 9.1)
3 (1, 4)
3 (1, 4)
Dilation, cm 0
13 (21)
14 (29)
1-2
47 (77)
35 (71)
3e4
1 (2)
0
BMI, body mass index; IQR, interquartile range. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
TABLE 2
Maternal outcomes Foley þ oxytocin n ¼ 61 (%)
Characteristic
Oxytocin alone n ¼ 66 (%)
P value
Primary outcome Induction to delivery, h 13.0 (10.7, 16.1)
10.8 (7.8, 16.6)
.09a
Normal vaginal delivery
36 (59)
43 (65)
.91b
Cesarean delivery
18 (30)
16 (24)
Forceps assisted
4 (7)
4 (6)
Vacuum assisted
3 (5)
3 (5)
Arrest of descent
3 (5)
2 (3)
.67b
Arrest of dilation
11 (18)
8 (12)
.35c
4 (7)
5 (8)
1.00b
Postpartum hemorrhage
5 (8)
2 (3)
.26b
Chorioamnionitis
6 (10)
3 (5)
.31b
Endometritis
2 (3)
2 (3)
1.00b
Epidural use
61 (100)
64 (97)
.50b
7 (11)
8 (12)
.89c
median (IQR) Secondary outcomes Mode of delivery
Reasons for cesarean delivery
Nonreassuring fetal heart tracing
Other delivery-related outcomes Tachysystole Max dose of oxytocin, mU/min median (IQR)
12.0 (8.0, 18.0)
12.0 (8.0, 18.0)
.74a
Total dose of oxytocin, mL median (IQR)
237.5 (102.5, 431.5) 222.8 (78.0, 438.0)
Meconium
4 (7)
.75b
6 (9)
Analyzed with Wilcoxon rank sum test; Analyzed with the Fisher exact test; Analyzed with the c test. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017. a
b
c
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.83a
2
prepregnancy body mass index, estimated fetal weight, and gestational age (Table 1). All of the women were nulliparous and the median Bishop’s score was similar in the 2 groups.3 Both groups had been ruptured for approximately the same length of time before the start of the induction. In addition, both groups had been ruptured for similar lengths of time before oxytocin was started. There was no difference in induction-to-delivery time between women induced with a combination of the Foley bulb plus oxytocin when compared with those induced with oxytocin alone (median time 13.0 hours [interquartile range {IQR} 10.7, 16.1] compared with 10.8 hours [IQR 7.8, 16.6], respectively, P ¼ .09) (Table 2; Figure 2). The log rank test indicates that there is no difference between the curves in time from the start of induction to delivery in the 2 groups. Consistent with that finding, the curves cross. When only women who followed the assigned protocol were analyzed, there was also no difference in induction-todelivery time between the 2 groups. There were also no differences in mode of delivery, rates of postpartum hemorrhage, chorioamnionitis, endometritis, or epidural use. Both groups had similar rates of tachysystole, and the total and maximum doses of oxytocin were similar between both groups (Table 2). There was no difference in time from start of induction to delivery between the 2 groups when the data were stratified by the maternal characteristic of prepregnancy body mass index (Table 3). In women who delivered vaginally, those receiving oxytocin alone had shorter mean time to delivery than those in the combination group (10.6 hours [IQR 7.1, 14.2] vs 13.2 hours (IQR 10.8, 15.9), whereas there was no difference in those who delivered by cesarean delivery. In patients who started the induction at 0 cm dilation, there was a significantly longer median time from start of induction to delivery in the Foley bulb plus oxytocin group compared with the oxytocin alone group (15.4 hours [IQR
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FIGURE 2
Kaplan-Meier time curve for start of induction to delivery
There was no significant difference in time from induction start to delivery in nulliparous patients with PROM who were induced by the use of either a combination of concurrent foley bulb plus oxytocin vs oxytocin alone. PROM, premature rupture of membranes. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
13.2, 17.5] in the Foley bulb plus oxytocin group vs 11.8 hours [IQR 9.4, 14.2] in the oxytocin alone, P ¼ .02). There were no differences in neonatal birth weight, Apgar scores, or admission to the neonatal intensive care unit (Table 4). Umbilical cord gases were similar in the 2 groups.
Comment There was no difference in the time from start of induction until delivery in
patients with PROM who were induced with a combination of a Foley bulb plus oxytocin vs oxytocin alone. Although no significant differences were observed in mode of delivery, labor complications, or maternal adverse outcomes such as chorioamnionitis and postpartum hemorrhage, twice as many patients in the Foley plus oxytocin group had a postpartum hemorrhage or delivery affected by chorioamnionitis. However, this study was not powered to
specifically address these outcomes, and the overall numbers were small. In addition, no differences were found in adverse neonatal outcomes such as admission to the NICU, cord gas values, or Apgar scores. Among patients who started their induction at 0 cm dilation, patients who were induced with a combination of Foley bulb plus oxytocin had a significantly longer time to delivery than those who received oxytocin alone; however, the number of
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TABLE 3
Median time and IQR in hours from start of induction to delivery by maternal characteristics Characteristic
Foley þ oxytocin, median hours (IQR)
n
Oxytocin alone, median hours (IQR)
N
P valuea
Mode of delivery Vaginal
43
13.2 (10.8, 15.9)
50
10.6 (7.1, 14.2)
.02
Cesarean delivery
18
12.3 (10.5, 17.0)
16
16.0 (9.8, 18.2)
.57
0
13
15.4 (13.2, 17.5)
14
11.8 (9.4, 14.2)
.02
1e2
47
12.0 (10.1, 15.9)
35
11.0 (8.2, 17.7)
.86
3
7.0 (5.2, 15.9)
1
18.5 and <25
35
13.0 (10.8, 15.2)
46
10.8 (7.2, 16.7)
.14
25 to <30
16
12.2 (10.2, 16.3)
11
11.3 (8.7, 16.6)
.86
7
18.5 (11.3, 21.1)
7
10.7 (5.9, 15.1)
.15
Dilation
Maternal prepregnancy BMI <18.5
30þ
6.1
1.0
BMI, body mass index; IQR, interquartile range. a
Analyzed with the Wilcoxon Rank Sum test. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
patients in this group was very small. A subgroup analysis of the patients who began their induction at 0 cm dilation showed similar doses of total oxytocin whether they received oxytocin alone or oxytocin with concurrent Foley balloon. To our knowledge, there have been no previous studies specifically comparing the concurrent use of oxytocin and Foley bulb with oxytocin alone for labor induction in patients with PROM. There have been other studies that compared other dual agent inductions in PROM. Our finding that concurrent Foley and oxytocin compared with oxytocin alone did not shorten induction times is similar to the results of a study by Tan et al,12 in which concurrent dinoprostone and oxytocin was compared against induction with oxytocin alone in term PROM patients. They randomized 116 term, nulliparous patients with PROM to receive either 3 mg of dinoprostone pessary plus oxytocin vs a placebo plus oxytocin. There was no significant difference in time from induction to delivery between the 2 groups. Similar to our study, there also were no significant differences in mode of delivery and rates of postpartum hemorrhage. There were also no differences in Apgar scores and NICU admissions.
Membrane rupture is associated with prostaglandin release locally at the site of the membrane—this mechanism alone is enough to trigger labor onset in most patients, as 60% will go into labor within 24 hours and 95% within 72 hours.1,13 It is plausible that the prostaglandin release thought to be stimulated by the Foley balloon is not necessary as perhaps the optimal physiologic amount already is released at time of membrane rupture. There are several limitations to this study. First, 17 of 66 patients in the oxytocin-alone group did not have a
cervical examination before the start of their oxytocin because of provider preference. It is possible that this subset of patients had a more favorable Bishop score than the other patients enrolled in the study and could have skewed the results to shorter induction times in the oxytocin alone group as a whole. This is unlikely however, as we compared the patients who had an initial examination in the oxytocin alone group vs those who did not have an initial examination and found similar total times from induction start to delivery. In the 49 women who had a cervical examination
TABLE 4
Neonatal outcomes Characteristics
Foley þ oxytocin n ¼ 61 (%)
Oxytocin alone n ¼ 66 (%)
P value
Birth weight, g, mean (SD)
3163.6 (457.5)
3101.8 (500.5)
.47a
1-minute Apgar score, median (IQR)
9 (9, 9)
9 (9, 9)
.14b
5-minute Apgar score, median (IQR)
9 (9, 9)
9 (9, 9)
.18b
Admission to the NICU
4 (7)
8 (12)
.37c
Cord gas pH, mean (SD)
7.25 (0.06)
7.25 (0.07)
.77a
IQR, interquartile range; NICU, neonatal intensive care unit. Analyzed with the Student t test; b Analyzed with the Wilcoxon rank-sum test; c Analyzed with the Fisher exact test. Amorosa et al. Foley for labor induction in PROM (FLIP). Am J Obstet Gynecol 2017.
a
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ajog.org before the start of their oxytocin, the median time from the start of induction to delivery was 11.0 hours (IQR 8.4 hours, 16.6 hours). In the 17 women who did not have a cervical examination before the start of their oxytocin, the median time form the start of induction to delivery was 10.8 hours (IQR 6.1 hours, 14.3 hours). There was no statistical difference in these times based on the Wilcoxon rank sum test (P ¼ .44). Second, there is a potential for selection bias in our study—we do not have data available to compare the women with PROM who participated in our study with all women with PROM at our institution. Another potential imitation of the study has to do with institutionspecific protocols. Our oxytocin protocol for labor induction may vary from other institutions and our protocol is to fill Foley bulbs to 60 cc, whereas other institutions may use other standard volumes. This study used a sample size calculation that was based on the assumption that times from the start of induction to delivery would be normally distributed. The times from the start of induction to delivery observed in this study were not normally distributed. This study found that patients induced with a combination of Foley and oxytocin had a nonstatistically significant longer time from induction start to delivery. A larger study may have found that increase in time actually was statistically significant. This study, on its own, suggests that the addition of Foley does not decrease time from the start of induction to delivery, which was the clinically relevant outcome we were studying. Based on the results of this study, the addition of Foley is not recommended to shorten induction times in patients with PROM.
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Many obstetrical providers question whether the introduction of the Foley bulb in patients with PROM may increase rates of maternal complications such as infection and postpartum hemorrhage. Although twice as many patients in the Foley plus oxytocin group had their delivery complicated by either chorioamnionitis or postpartum hemorrhage in this study, the overall numbers were small, and the difference did not meet statistical significance. A much larger study would be needed to address these specific questions. We found no difference in time from induction to delivery in nulliparous patients with PROM who were induced either using a combination of concurrent Foley bulb plus oxytocin versus oxytocin alone. These findings address a frequently asked question about whether there is utility in using Foley bulbs to assist with cervical ripening in patients with PROM in an effort to shorten the duration of labor induction. This study suggests that Foley bulbs should not be used in induction of labor for PROM in nulliparous patients, as no additional benefit is conferred. n References 1. Gunn GC, Mishell DR Jr, Morton DG. Premature rupture of the fetal membranes. A review. Am J Ostet Gynecol 1970;106:469-83. 2. Seaward PG, Hannah ME, Myhr TL, et al. International Multicentre Term Prelabor Rupture of Membranes Study: evaluation of predictors of clinical chorioamnionitis and postpartum fever in patients with prelabor rupture of membranes at term. Am J Ostet Gynecol 1997;177:1024-9. 3. Soper DE, Mayhall CG, Froggatt JW. Characterization and control of intraamniotic infection in an urban teaching hospital. Am J Ostet Gynecol 1996;175:304-9. discussion 309-10. 4. Hannah ME, Ohlsson A, Farine D, et al. Induction of labor compared with expectant management for prelabor rupture of the membranes at term. TERMPROM Study Group. N Engl J Med 1996;334:1005-10.
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5. Dare MR, Middleton P, Crowther CA, Flenady VJ, Varatharaju B. Planned early birth versus expectant management (waiting) for prelabour rupture of membranes at term (37 weeks or more). Cochrane Database Syst Rev 2006;(1):CD005302. 6. ACOG Committee on Practice Bulletins— Obstetrics. ACOG Practice Bulletin No. 107: induction of labor. Obstet Gynecol 2009;114: 386-97. 7. Connolly KA, Kohari KS, Rekawek P, et al. A randomized trial of Foley balloon induction of labor trial in nulliparas (FIAT-N). Am J Ostet Gynecol 2016;215:392.e1-6. 8. Levine L, Downes K, Elovitz M, Parry S, Sammel M, Srinivas S. Mechanical and pharmacologic methods of labor induction. Obstet Gynecol 2016;128:1357-64. 9. 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. 10. Sanchez-Ramos L, Chen AH, Kaunitz AM, Gaudier FL, Delke I. Labor induction with intravaginal misoprostol in term premature rupture of membranes: a randomized study. Obstet Gynecol 1997;89:909-12. 11. Carbone JF, Tuuli MG, Fogertey PJ, Roehl KA, Macones GA. Combination of Foley bulb and vaginal misoprostol compared with vaginal misoprostol alone for cervical ripening and labor induction: a randomized controlled trial. Obstet Gynecol 2013;121: 247-52. 12. 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. 13. Grant JM, Keirse MJNC. Prelabour rupture of the membranes at term. In: Chalmers L, Enkin M, Keirse MJNC, eds. Effective care in pregnancy and child birth, Vol. 2. Child birth. Oxford: Oxford University Press; 1989:112-7.
Author and article information From the Division of Maternal Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Science, Mount Sinai Hospital, New York, NY. Received March 4, 2017; accepted April 24, 2017. The authors report no conflict of interest. Corresponding author: Jennifer M. H. Amorosa, MD. [email protected]
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