Keywords
labor induction - cervical Foley - cervical ripening - rupture of membranes - PPROM
Preterm premature rupture of membranes (PPROM) complicates 3% of pregnancies.[1] Intrauterine infection is a significant risk among patients with premature membrane
rupture with an estimated incidence of 15 to 25%.[2] Moreover, preterm neonates have been well documented to have higher rates early-onset
sepsis than term infants. Induction of labor is recommended between 34 and 36 6/7 weeks' gestation following preterm membrane rupture, but the optimal induction method
has not yet been established.[3]
[4] Combination cervical ripening with mechanical and pharmacological agents shortens
time to delivery compared with single-agent induction methods in term pregnancies
with intact membranes.[5]
[6]
[7]
[8] The Foley catheter, however, has a theoretical risk of introducing infection in
ruptured membranes. While studies have examined balloon-related infectious morbidity
in term membrane rupture,[9]
[10]
[11]
[12] infectious morbidity in preterm membrane rupture has not been established. Thus,
the study objective was to evaluate effectiveness and safety of the balloon catheter
for induction in preterm membrane rupture and determine whether balloon catheter for
cervical ripening reduces time to delivery or cesarean section rate compared with
oxytocin alone in this preterm population.
Materials and Methods
Screening and Recruitment
After approval from the institutional review board at Christiana Care Health Services
(Newark, DE, CCC no.: 38169), we conducted a retrospective cohort study on all patients
18 years and older diagnosed with PPROM between 240/7 and 366/7 weeks' gestation from January 2005 to October 2018 at our academic tertiary care
hospital. Women were included if they met the diagnosis of PPROM by clinical assessment
and findings on exam including pooling of amniotic fluid, positive nitrazine test,
visible ferns, and/or oligohydramnios on ultrasound, as described by the American
College of Obstetricians and Gynecologists.[11] Gestational age was estimated using date of last menstruation, confirmed by sonogram
per standard criteria.[12] For pregnancies conceived with artificial reproductive technology, the date of embryo
transfer was used.
Patients with an unfavorable cervical examination (≤2-cm dilation), no contraindication
to labor and undergoing labor induction were analyzed. Individuals were excluded if
they presented in active labor, had clinical or objective signs of intra-amniotic
infection, had nonreassuring fetal heart rate tracing, or any other indication for
immediate delivery. Pregnancies with fetal anomalies, multiple gestation, and unknown
rupture time were excluded from the analysis.
Statistical Analysis
Continuous variables were calculated as median (interquartile range). The data were
then tested for normality using the Shapiro–Wilk test and Student's t-test or Mann–Whitney U test were then used as appropriate. Categorical variables
were calculated as proportions and compared using the chi-square test. Time to delivery
was analyzed using multivariable linear regression model with prespecified adjustment
for cervical dilation at induction and nulliparity.
Results
A total of 260 participants were included: 109 in the combination Foley catheter and
oxytocin group (Foley/oxytocin) and 151 in the oxytocin alone group. Demographic characteristics
were similar between the two groups ([Table 1]). Unadjusted time to delivery was significantly longer in the combination Foley/oxytocin
group (Foley/oxytocin: 20.35 hours vs. oxytocin alone: 14.7 hours, p < 0.001, [Table 2]). The unadjusted rate of cesarean delivery was higher in the combination Foley/oxytocin
group (Foley/oxytocin: 16.5% vs. oxytocin alone: 7.3%, p = 0.03).
Table 1
Maternal and pregnancy characteristics by labor induction method
|
Combination Foley, Pitocin (n = 109)
|
Pitocin only (n = 151)
|
p-Value
|
|
Maternal age (y), median, IQR
|
30.0 [25.0; 36.0]
|
30.9 [27.0; 35.0]
|
0.90
|
|
Black race, n (%)
|
26 (23.9)
|
47 (31.1)
|
0.21
|
|
Hispanic ethnicity, n (%)
|
20 (18.3)
|
26 (17.2)
|
0.87
|
|
Nulliparous, n (%)
|
68 (62.4)
|
64 (42.4)
|
0.002
|
|
Indication for induction
|
|
≥34 weeks' gestation
|
103 (94.5)
|
141 (93.4)
|
0.22
|
|
Clinical chorioamnionitis
|
5 (4.6)
|
7 (4.6)
|
|
NRFHT
|
1 (0.92)
|
3 (2.0)
|
|
Cervical dilation ≤ 1 cm at Induction, n (%)
|
79 (72.5)
|
34 (22.5)
|
<0.001
|
|
Group B Streptococcus positive status, n (%)
|
13 (11.9)
|
27 (17.9)
|
0.22
|
|
Magnesium sulfate for fetal neuroprotection, n (%)
|
9 (8.3)
|
12 (7.9)
|
1.0
|
|
Betamethasone administration, n (%)
|
30 (27.5)
|
34 (22.5)
|
0.38
|
|
Tocolysis administration, n (%)
|
10 (9.2)
|
14 (9.3)
|
1.0
|
|
Maternal comorbidities, n (%)
|
|
History of preterm birth
|
3 (2.8)
|
11 (7.3)
|
0.16
|
|
History of LEEP
|
1 (0.9)
|
1 (0.7)
|
1.0
|
|
History of short cervix
|
2 (1.8)
|
5 (3.3)
|
0.70
|
|
Gestational diabetes
|
11 (10.1)
|
9 (6.0)
|
0.24
|
|
Gestational hypertension
|
5 (4.6)
|
9 (6.0)
|
0.78
|
|
Asthma
|
11 (10.1)
|
24 (15.9)
|
0.20
|
|
Maternal thyroid disease
|
7 (6.4)
|
7 (4.6)
|
0.58
|
|
IVF pregnancy, n (%)
|
5 (4.6)
|
2 (1.3)
|
0.13
|
|
Tobacco use in pregnancy, n (%)
|
16 (14.7)
|
22 (14.6)
|
1.0
|
Abbreviations: IQR, interquartile range; IVF, in vitro fertilization; LEEP, loop electrosurgical
excision procedure; NRFHT, nonreassuring fetal heart tracing.
Table 2
Labor outcome by labor induction method
|
Combination Foley, Pitocin (n = 109)
|
Pitocin only (n = 151)
|
Unadjusted p-value
|
Adjusted p-value
|
|
Cesarean delivery, n (%)
|
18 (16.5)
|
11 (7.3)
|
0.03
|
0.06
|
|
Operative delivery, n (%)
|
4 (3.7)
|
4 (2.6)
|
0.72
|
–
|
|
Unadjusted time to delivery, h, median, IQR
|
20.35 [12.4; 26.3]
|
14.7 [7.51; 21.34]
|
<0.001
|
0.23
|
|
Clinical intra-amniotic infection and inflammation, n (%)
|
9 (8.3)
|
14 (9.3)
|
0.83
|
–
|
|
Suspected placental abruption, n (%)
|
5 (4.6)
|
7 (4.6)
|
1.0
|
–
|
|
Endometritis, n (%)
|
2 (1.8)
|
0 (0.0)
|
0.18
|
–
|
|
Wound infection, n (%)
|
0 (0.0)
|
0 (0.0)
|
–
|
–
|
Abbreviation: IQR, interquartile range.
Statistical adjustments were made for a cervical dilation less than 1 cm at induction
initiation and nulliparity; there was a trend toward higher rates of cesarean delivery
in the combination Foley/oxytocin group (Foley/oxytocin: 16.5% vs. oxytocin alone:
7.3%, p = 0.06, [Table 2]).
No differences in length of labor were detected after adjusting for cervical dilation
at induction and nulliparity (p = 0.5). There were no differences in clinical chorioamnionitis rates between the
two groups (Foley/oxytocin: 8.3% vs. oxytocin alone: 9.3%, p = 0.83). Furthermore, no significant differences were found in maternal and neonatal
outcomes between the two groups ([Table 3]). There were no significant differences in survival or neonatal outcomes. Rates
of intraventricular hemorrhage and necrotizing enterocolitis did not differ between
the two groups. Rate of neonatal deaths, sepsis, and Apgar at 5 minutes were similar
between the two groups.
Table 3
Neonatal outcomes by labor induction method
|
Combination Foley, Pitocin (n = 109)
|
Pitocin only (n = 151)
|
p-Value
|
|
Composite neonatal morbidity[a]
|
75 (68.8)
|
97 (64.2)
|
0.51
|
|
Birth weight (kg) median, IQR
|
2.31 [2.17; 2.79]
|
2.35 [2.25; 2.85]
|
0.22
|
|
Apgar score <7 at 5 min, n (%)
|
6 (5.5)
|
9 (6.0)
|
1.0
|
|
Female infant, n (%)
|
46 (42.2)
|
66 (43.7)
|
0.90
|
|
Infant death
|
1 (0.9)
|
0 (0.0)
|
0.42
|
|
NICU admission
|
74 (67.9)
|
96 (63.6)
|
0.51
|
|
NICU length of stay
|
9.3 [9.0; 9.0]
|
8.3 [9.0; 9.0]
|
0.28
|
|
Intraventricular hemorrhage
|
2 (1.8)
|
2 (1.3)
|
1.0
|
|
Necrotizing enterocolitis
|
–
|
–
|
|
|
Culture proven–presumed neonatal sepsis
|
5 (4.6)
|
11 (7.3)
|
0.44
|
Abbreviations: IQR, interquartile range; NICU, neonatal intensive care unit.
a Composite of neonatal death, NICU admission, Apgar < 7 at minute 5, necrotizing enterocolitis,
intraventricular hemorrhage, sepsis.
Notes: Data are presented as n (%) unless otherwise indicated. Categorical variables are compared with chi-square
and Fisher's exact tests and continuous variables are compared with Kruskal–Wallis
tests, unless otherwise indicated.
Discussion
Principal Findings
This study did not identify a difference in time to delivery between patients with
PPROM who received a combination of oxytocin and a Foley catheter versus oxytocin
alone. There were no differences in the cesarean delivery rate, chorioamnionitis rate,
or the rate of adverse neonatal outcomes.
Results in Context
The trials aimed at determining the optimal delivery timing in PPROM do not study
optimal methods of labor induction. The PPROMEXIL trial[12] did not compare prostaglandins and oxytocin, and subsequent follow-up trials[13]
[14] did not clearly specify the induction methods used. Among the various trials and
meta-analyses comparing methods of cervical ripening, none have studied patients with
preterm membrane rupture.
Amorosa et al compared oxytocin alone with a combination of a Foley catheter and oxytocin,[11] among patients ≥ 34 weeks with premature membrane rupture. Compared with oxytocin
alone, the Foley catheter and oxytocin immediately after the membrane rupture diagnosis
did not reduce the time from induction to birth; both groups also had similar caesarean
rates. However, a total of 15 patients were 340/7 to 366/7; the majority of patients recruited had PROM at term.
Mackeen et al included over 40 patients with PROM at ≥ 34 weeks and found that the
use of a transcervical Foley catheter in addition to oxytocin does not shorten the
time to delivery compared with oxytocin alone; however, they did find an increased
incidence of chorioamnionitis in the cohort who had a Foley catheter.[15] Currently, there are no data to support evidence-based recommendations regarding
the method of choice for labor induction following preterm membrane rupture.
Strengths and Limitations
Strengths and Limitations
A strength of our study is large number of diverse participants with an unfavorable
cervix at the time of induction. A weakness of our study is that the retrospective
analysis may introduce selection bias. However, demographic characteristics were similar
between the two groups. This was also a single-center study, and thus, the results
may not be generalizable to other centers with different labor management practices
and/or labor outcomes.
Conclusion
In patients with PROM, the use of a transcervical Foley catheter in addition to oxytocin
is not associated with a shorter time to delivery compared with oxytocin alone. However,
the use of a Foley catheter is not associated with an increased risk of chorioamnionitis.
A randomized prospective study is needed to confirm these findings.
