Vaginal misoprostol and cervical ripening balloon for

induction of labor in late-term pregnancies

Abstract

Aim: The aim of this study was to compare vaginal misoprostol with the Cook cervical ripening
balloon (CCRB) for induction of labor in late-term nulliparous women.

Methods: This open, quasi-experimental, prospective study included 109 nulliparous women
with late-term pregnancies and Bishop scores < 7. Fifty-five women were allocated to receive
vaginal misoprostol 25 mcg and 54 received the CCRB to induce labor. The primary outcome
was the time until delivery. Secondary outcomes included time to the onset of labor and obstetric
and perinatal outcomes.

Results: Women in the misoprostol group experienced shorter time until delivery (25.41 h vs
31.26 h; P < 0.01) and in a greater percentage gave birth within the first 24 h. Time to active
stage of labor was 19.5 h and 23.8 h (P < 0.01) for misoprostol and the CCRB, respectively.
There were no differences in the rates of cesarean section or post-partum anemia. Additionally,
there were no differences in rates of tachysystolia, intrapartum fever, or meconium. Perinatal
outcomes, post-partum pH, Apgar scores, and neonatal admissions were similar in the two
groups.

Conclusion: Misoprostol 25 mcg reduces labor induction time compared with the CCRB with
similar safety in late-term pregnancies.

Key words: balloon catheter, cervical ripening, labor induction, misoprostol, perinatal outcomes.

Introduction

Post-term pregnancy is defined as a pregnancy that extends to 42 +0 weeks of gestation or 294

days from the first day of the last menstrual period. The majority of post-term pregnancies have
no known cause, but women at highest risk are those with a previous post-term pregnancy. Other
causes, such as advanced maternal age, nulliparity, previous cesarean section, male fetuses, and
obesity, have been involved.

Post-term pregnancies are associated with increased fetal and

neonatalmorbidityandmortality.Thesefetuses are at higher risk of fetal macrosomia, meconium
aspiration syndrome, dysmaturity, neonatal acidemia, umbilical cord compression due to
oligohydramnios, abnormal antepartum or intrapartum fetal heart rate patterns, and stillbirth. 9
14 Maternal morbidity is also increased due to labor dystocia, severe perineal lacerations related
to macrosomia, operative vaginal delivery, infection, post-partum hemorrhage, and higher
cesarean section rates. For these reasons, induction of labor is recommended in late-term
pregnancies, defined as one that has reached 41 +0 41 +6 weeks of gestation, in order to reduce
post-term pregnancies and to avoid related adverse outcomes. Present evidence reveals that
elective labor induction is associated with a reduced risk of intrapartum meconium, low perinatal
morbidity/mortality rates, and higher satisfaction expressed by women 1620 without increasing
the risk of cesarean section.

For pregnant women with unfavorable Bishop scores, defined as <7, cervical ripening is
necessary before inducing labor. Prostaglandin E1 (PGE1) or E2 (PGE2), misoprostol and
dinoprostone, as well as mechanical methods, such as the Cook cervical ripening balloon
(CCRB), are the most common options for cervical ripening. Although prostaglandins are
associated with a shorter induction time, especially PG1, mechanical methods have advantages,
such as a decreased risk of both uterine tachysystolia and systemic adverse effects caused by
prostaglandins.

The present study was designed to compare the effectiveness and safety of vaginally
administered misoprostol with the CCRB for onset of labor in a homogeneous group of
nulliparous women with late-term pregnancies.

Methods

This survey was conducted as an open prospective quasi-experimental cohort study and was
approved by the institutional review board of the Reina Sofia Hospital, Crdoba, Spain
(Reference 24323/07/2015). All of the procedures were in accordance with the Helsinki
Declaration of 1975. Over the 6-month period from July 2015 to January 2016, 109 women were
recruited to compare vaginally administered misoprostol 25 mcg (Misofar, Bial Laboratories)
and the CCRB (Cook, Inc.) as methods of induction of labor for late-term pregnancy.
Nulliparous pregnant women between 41 +0 and 42 +0 weeks of gestation according to last
menstrual period or first trimester ultrasound, with Bishop score < 7, were included. Exclusion
criteria included premature rupture of membranes, multiple gestation, personal history of
previous cesarean section, major uterine surgery, absence of fetal well-being, previous
childbirths, chorioamnionitis or an active infection in the birth canal, metrorrhagia, and non-
cephalic presentation.

After admission, women could choose misoprostol or the CCRB as an induction method.
Misoprostol 25 mcg tablets were administered vaginally every 4 h up to a maximum of four
tablets. The CCRB was inserted bimanually into the cervical canal; both the intrauterine and
intravaginal balloons were filled with 50 mL glucosaline solution and left in place for up to 24 h.

Pregnancies with abnormal cardiotocography, onset of the active stage of labor, and the
presence of regular uterine contractions (three to five every 10 min) were excluded. If labor did
not initiate within 24 h of beginning the protocol, oxytocin was administered at increasing doses
to stimulate regular contractions.

The following variables were recorded: maternal age, gestational age, previous
childbirths, body mass index, Bishop score, misoprostol doses, type of anesthesia, hours until the
onset of active stage of labor and delivery, presence of uterine tachysystolia, intrapartum fever
(>38C), maternal hemoglobin, meconium, type of delivery and reasons for operative delivery,
oxytocin use, birthweight, pH, and Apgar score at 5 min. Maternal and newborn complications,
including neonatal intensive care unit admissions, were also recorded.

Statistical analysis

For the sample calculation, GRANMO 7.11 was used, developed by the URLEC consortium. We
used an risk of0.05anda riskof0.20inabilateralcontrast,resulting in a sample of 76 women for
each group to detect a difference 0.2 units, assuming a proportion of 0.5 and a loss rate of 1%.
 Data were analyzed using the G-Stat 2.0 free statistical software (Glaxo Smith Kline).
The Students t-test was used for comparisons between quantitative variables and the 2 -test or
Fishers test were used for qualitative variables. A P-value < 0.05 was considered statistically
significant.

Results

A total of 109 nulliparous pregnant women were included. Of them, 54 chose the CCRB method
for labor induction while the other 55 opted for vaginal misoprostol. No significant differences in
clinical baseline parameters were observed between the two groups (Table 1).

The main outcome, time until delivery, was shorter in the misoprostol group. Women in
the misoprostol group experienced less time until delivery (25.4 h vs 31.3 h; P = 0.006) and in a
greater percentage gave birth within the first 24 h (Table 2). Also, women in the misoprostol
group started the active stage of labor faster than those in the CCRB group
(19.5hvs23.9h,respectively;P<0.01).

Women in the CCRB group required more oxytocin than those in the misoprostol group
(5.9 mUI vs 3.3 mUI, respectively; P = 0.007). No differences were
observed in the rates of uterine tachysystolia, intrapartum fever, or presence of
meconium. There were also no differences in perinatal outcomes (Table 2), type of
delivery, rates of cesarean section, or incidence of anemia (Table 3). Outcomes of labor
induction and operative rates and indications are given in Table 3. Intrapartum
complications included five cases of uterine atony requiring treatment, four in the
misoprostol group and one in the CCRB group.

Discussion

Labor induction refers to the artificial initiation of labor before its spontaneous onset
using a set of techniques to stimulating uterine contractions with the purpose of a vaginal
delivery. One of the most frequent indications for labor induction is late-term pregnancy.
There are two types of labor-inducing agents:(i) pharmacological ,such as prostaglandins
(PGE1 and PGE2);and(ii)mechanical, such as Foleys catheter and the CCRB. Among
prostaglandins, vaginal misoprostol (PGE1) has proved to be a better alternative than
dinoprostone (PGE2) regarding effectiveness, safety, and cost. 24 Results from the
present study suggest that for late-term gestations, misoprostol is very effective and it
was not associated with an increased rate of uterine hyperstimulation, cesarean section, or
neonatal admissions. These data appear to be consistent with previous reports from other

authors, including Lawani et al., 23 Hofmeyr et al., 25 and Ozkan et al.

In our study, we did not observe an increased incidence of uterine tachysystolia or

cardiotocography abnormalities in the misoprostol group. However, some reports suggest
that the main adverse effect of prostaglandins is an increased prevalence of uterine
tachysystolia, which may originate from abnormal fetal heart rate, resulting in
nonreassuring fetal status and increased rate of cesarean sections and instrumental
deliveries. In this sense, a recent study by Jozwiak et al. 27 showed a decreased risk of
uterine tachysystolia and reduced maternal systemic effects with the CCRB when
compared with prostaglandins.

In accordance with a recent study by Mackeen et al., the present series did not
observe a higher incidence of chorioamnionitis or intrapartum fever associated with the
use of mechanical methods; however, in a systematic review by Mozurkewich et al., 29
an increased rate of infection with mechanical methods was suggested.
 In our study, misoprostol was associated with a shorter time until delivery with an
increased likelihood of giving birth within the first 24 h compared with the CCRB and
shorter elapsed time from administration until the onset of the active stage of labor. In
other reports, misoprostol has also been related to a shorter induction time and a higher
frequency of vaginal deliveries within the first 12 h compared with dinoprostone and
mechanical methods.

Controversy exists regarding the cost-effectiveness of both mechanical and

pharmacological methods to induce labor. In this sense, misoprostol seems to be more
effective than the CCRB, taking into account the current low cost of four tablets of
misoprostol and those of the CCRB (4.5-fold higher), as well as the lack of differences
observed regarding the type of delivery, complications, duration of hospital stay, and the
anesthesia required. However, other reports are not consistent with our findings. Gelber
and Sciscione suggested that mechanical methods are an alternative just as effective as
other methods of labor induction with additional benefits, such as low cost, very few
adverse and systemic effects, and low risk of uterine hyperstimulation.

The limitations of this study include the limited number of patients included, the
lack of randomization, and the fact that, in this open study, the women could select the
method that they preferred, biasing the final results. In conclusion, although further
studies solving the present limitations are needed, it appears that 25-mcg misoprostol
tablets administered vaginally every 4 h are safe, effective, and reduce labor induction
time in lateterm nulliparous pregnant women when compared with the CCRB.

Disclosure
The authors report that they have no conflicts of interest either with the information
included in this manuscript or with the devices and drugs used in this study