Keywords
labor induction - misoprostol - oxytocin - cesarean sections
Palavras-chave
indução de parto - misoprostol - ocitocina - parto cesárea
Introduction
Labor induction is any procedure that stimulates uterine contraction before labor
begins naturally.[1]
[2] It is indicated when the maternal/fetal associated risks with the pregnancy are
higher than the maternal/fetal associated risks of early delivery.[3] The most common causes of labor induction are prolonged gestation (> 42 weeks),
preeclampsia, and premature rupture of membranes.[3]
For the induction of labor, it is necessary to administer labor inducers. The main
mechanical methods are the following: artificial rupture of membranes (amniotomy),
breast stimulation, cervical dilators (Hegar dilators and laminaria tents), and digital
sweeping in the lower segment.[4] Pharmacological methods include the use of oxytocin and synthetic prostaglandins.[1]
[2]
Misoprostol is a synthetic prostaglandin E1 (PGE1) analogue that acts as an inducer
of the ripening process, thus favoring dilation and causing uterine contractions.[5] It is indicated for labor induction in cases of unfavorable uterine cervix (Bishop
score < 6).[6] Misoprostol can be administered via the vaginal,[7] oral,[8] and sublingual[9] routes, with the vaginal route being the preferred one. However, misoprostol has
contraindications, such as previous cesarean delivery, previous uterine surgery, placenta
previa, asthma, coronary disease, and cephalopelvic disproportion.[10] The risks associated with labor induction using misoprostol are uterine hyperstimulation
with hypertonia, tachysystole, and uterine rupture.[11]
The objective of this study was to evaluate pregnant women submitted to induction
of labor through vaginal 25-µg tablets of misoprostol and the maternal outcomes in
a tertiary hospital in the Southeast of Brazil.
Methods
A retrospective cohort study was conducted between November 2014 and August 2016 in
a maternity in the Southeast of Brazil. The sample comprised pregnant women with indication
for labor induction with vaginal misoprostol. The inclusion criteria were singleton
pregnancy with live fetus, gestational age > 40 weeks, and premature rupture of membranes > 34
weeks in the absence of signs of maternal infection. The exclusion criteria were previous
uterine scar, cephalopelvic disproportion, and abnormal presentations. The study was
approved by the Research Ethics Committee (CAAE: 62832016.7.0000.5145), and informed
consent was obtained from the participants.
Labor induction was performed with 25-µg tablets of misoprostol in pregnant women
with Bishop scores < 6. The drug was inserted in the posterior vaginal fornix at a
dosage of 1 tablet every 6 hours for a maximum period of 48 hours (200 µg = 8 tablets).
In the cases in which labor was initiated, oxytocin was administered by a continuous
infusion pump at an initial rate of 12 mL/h and increasing to 196 mL/h. In cases of
absence of labor, induction was deemed unsuccessful after eight tablets were inserted
in the vagina of a pregnant woman with an intact amniotic sac and without changes
in the uterine cervix. In cases of premature rupture of membranes, induction was deemed
unsuccessful after four tablets were inserted and no changes occurred in the uterine
cervix.
The dependent variables of this study were mode of delivery (vaginal or cesarean section),
amniotic sac condition (intact or ruptured), number of tablets used (one to eight
tablets), and duration of labor (time in hours between the beginning of induction
and delivery). The control variables were maternal age and parity. The women selected
for the study were recruited through a search in the computerized medical record system
(Soul MV, MV Informática Nordeste Ltda, Recipe, PE, Brazil) of one of our institutions
using the term misoprostol 25 µg as the search filter. Subsequently, an active search on the medical records obtained
from the previous search to collect the relevant data on the procedure was conducted.
The data were entered into an Excel 2010 spreadsheet (Microsoft Corp., Redmond, WA,
USA), and the statistical analyses were performed using the IBM SPSS statistics software,
version 23.0 (IBM Corp., Armonk, NY, USA). We considered vaginal deliveries as successful
inductions of labor, and the absence of uterine contractions/uterine cervix modifications
or any intercurrence during the labor culminating with cesarean section was considered
as unsuccessful induction of labor.
Initially, we compared the maternal variables of the pregnant women with those of
the women who progressed to cesarean delivery using the unpaired Student t-test and Fisher exact test. Then, we performed a stepwise regression analysis to
identify the factors present at the beginning of induction that could be used as predictors
of successful induction. Subsequently, we compared the women that exhibited these
characteristics with those who did not. In all of the analyses, the level of significance
(p) was set at 5%.
Results
The study included 412 pregnant women with indication for labor induction. The majority
of patients (51%) were aged between 20 and 30 years. In 244 patients (59.2%), 1 or
2 tablets of misoprostol were sufficient to achieve the expected effect, and 117 patients
(28.4%) required 3 or 4 tablets. Regarding the Bishop score before labor induction,
241 patients (58.5%) had a score between 2 and 3, and 171 patients (41.5%) had scores
between 4 and 5.
In our sample, 197 (47.8%) patients required oxytocin after induction with misoprostol
for labor progression, and 215 patients (52.2%) did not need it. The induction of
labor led to 69% of normal deliveries, and 31% of women progressed to cesarean delivery.
The indications for cesarean section were the following: unsuccessful induction (10.9%);
fetal bradycardia (10.7%); placental abruption (0.7%); secondary arrest of dilation
(7.8%); and secondary arrest of descent (1.7%). The distribution of women according
to the time (in hours) elapsed between the beginning of induction and delivery was
the following: 12% between 4 and 7 hours; 18% between 8 and 11 hours; 17% between
12 and 15 hours; 13% between 16 and 19 hours; 23% between 20 and 29 hours; and 16% > 30
hours of induction.
[Table 1] shows the maternal outcomes of the pregnant women submitted to induction of labor
with misoprostol that progressed to vaginal delivery (successful induction) or cesarean
delivery (unsuccessful induction). The variables previous deliveries, parity, Bishop
score, number of misoprostol tablets, time of induction, use of oxytocin, and previous
vaginal delivery were associated with successful labor induction.
Table 1
Comparison between the maternal variables according to successful (vaginal birth)
and unsuccessful (cesarean section) labor inductions with misoprostol
|
Successful vaginal birth
(n = 285)
|
Cesarean section
(n = 127)
|
|
|
Mean
|
SD
|
Mean
|
SD
|
p
|
|
Age (years)
|
24.7
|
6.2
|
24.2
|
6.0
|
0.45
|
|
Number of previous deliveries
|
2.0
|
1.4
|
1.6
|
0.9
|
0.001
|
|
Parity
|
0.9
|
1.2
|
0.3
|
0.8
|
< 0.001
|
|
Number of previous miscarriages
|
0.1
|
0.4
|
0.2
|
0.5
|
0.06
|
|
Bishop score
|
3.5
|
1.1
|
2.8
|
0.8
|
< 0.001
|
|
Number of misoprostol tablets
|
2.3
|
1.5
|
3.6
|
2.4
|
< 0.001
|
|
Time of induction (hours)
|
16.5
|
9.9
|
23.6
|
13.9
|
< 0.001
|
|
N/n
|
%
|
N/n
|
%
|
p
|
|
Ruptured amniotic sac
|
103/285
|
36%
|
40/127
|
31%
|
0.37
|
|
Use of oxytocin
|
151/285
|
53%
|
46/127
|
36%
|
0.002
|
|
Previous vaginal birth
|
130/285
|
46%
|
23/127
|
18%
|
< 0.001
|
|
Successful vaginal birth
|
144/285
|
51%
|
27/127
|
21%
|
< 0.001
|
Abbreviation: SD, standard deviation.
The stepwise regression analysis showed that only Bishop scores of 4 and 5 ([Table 2]) and previous vaginal delivery ([Table 3]) were independent factors with statistical significance in the prediction of successful
vaginal labor induction with misoprostol (β = 0.23, p < 0.001, for Bishop scores of 4 and 5, and β = 0.22, p < 0.001, for previous vaginal delivery).
Table 2
Stepwise regression analysis to predict the success of labor induction with misoprostol
according to Bishop score
|
Bishop score between 4 and 5
(n = 171)
|
Bishop score between 2 and 3
(n = 241)
|
|
|
Mean
|
SD
|
Mean
|
SD
|
p*
|
|
Age (years)
|
25.0
|
6.1
|
24.3
|
6.1
|
0.23
|
|
Number of previous births
|
2.1
|
1.4
|
1.7
|
1.1
|
0.001
|
|
Parity
|
0.9
|
1.3
|
0.5
|
1.0
|
0.001
|
|
Number of previous miscarriages
|
0.2
|
0.4
|
0.2
|
0.5
|
0.96
|
|
Bishop score
|
4.4
|
0.5
|
2.5
|
0.5
|
< 0.001
|
|
Number of misoprostol tablets
|
1.8
|
1.2
|
3.3
|
2.1
|
< 0.001
|
|
Time of induction (hours)
|
13.2
|
8.1
|
22.6
|
12.3
|
< 0.001
|
|
N/n
|
%
|
N/n
|
%
|
p
**
|
|
Ruptured amniotic sac
|
85/171
|
50%
|
58/241
|
24%
|
< 0.001
|
|
Use of oxytocin
|
75/171
|
44%
|
122/241
|
51%
|
0.19
|
|
Previous vaginal birth
|
82/171
|
48%
|
71/241
|
29%
|
< 0.001
|
|
Successful vaginal birth
|
144/171
|
84%
|
141/241
|
59%
|
< 0.001
|
Abbreviation: SD, standard deviation.
Notes: *p value obtained using the unpaired Student t-test; **p value obtained using the Fisher exact test.
Table 3
Stepwise regression analysis to predict the success of labor induction with misoprostol
according to previous vaginal delivery
|
Previous vaginal birth
(n = 153)
|
No previous vaginal birth
(n = 259)
|
|
|
Mean
|
SD
|
Mean
|
SD
|
p*
|
|
Age (years)
|
28.4
|
5.8
|
22.3
|
5.1
|
< 0.001
|
|
Number of previous births
|
3.1
|
1.3
|
1.1
|
0.4
|
< 0.001
|
|
Parity
|
1.9
|
1.2
|
0.0
|
0.0
|
< 0.001
|
|
Number of previous miscarriages
|
0.2
|
0.5
|
0.1
|
0.4
|
0.13
|
|
Bishop score
|
3.6
|
1.0
|
3.2
|
1.0
|
< 0.001
|
|
Number of misoprostol tablets
|
2.6
|
1.9
|
2.7
|
1.9
|
0.39
|
|
Time of induction (hours)
|
17.3
|
11.8
|
19.5
|
11.6
|
0.07
|
|
N/n
|
%
|
N/n
|
%
|
p
**
|
|
Ruptured amniotic sac
|
42/153
|
27%
|
101/259
|
39%
|
0.02
|
|
Use of oxytocin
|
72/153
|
47%
|
125/259
|
48%
|
0.84
|
|
Bishop score > 6
|
82/153
|
54%
|
89/259
|
34%
|
< 0.001
|
|
Successful vaginal birth
|
130/153
|
85%
|
155/259
|
60%
|
< 0.001
|
Abbreviation: SD, standard deviation.
Notes: *p value obtained using the unpaired Student t-test; **p value obtained using the Fisher exact test.
Discussion
Misoprostol is considered the standard method for obtaining cervical maturity and,
currently, for inducing labor. It is believed that 25 µg of this drug administered
vaginally is the ideal dosage for pregnant women with viable fetuses.[12]
[13]
We found a higher incidence of cases of induced labor with misoprostol among pregnant
women between 20 and 30 years of age, which is similar to the data found in the literature.[14] Maternal age can influence the unsuccessful labor induction due to: the less robust
vasculature and an insufficient hemodynamic demand during pregnancy;[15] the gradual decrease in myometrial contraction function;[16] and the higher incidence of medical comorbidities in advanced maternal age.[17] Regardless of parity, advanced maternal age (≥ 35 years) is independently associated
with an increased risk of cesarean section following labor induction (adjusted odds
ratio [OR]: 2.29; 95% confidence interval [95%CI]: 1.64–3.20; p < 0.001).[18]
Successful labor induction with misoprostol occurred in the majority of the pregnant
women (59.2%) with a low dose of this drug (25 µg to 50 µg). This result is consistent
with the findings reported by Tsikouras et al,[19] which confirmed the safety and efficacy of 50 µg of misoprostol in inducing labor
in low-risk and postterm pregnant women (> 40 weeks), as well as in women with an
unfavorable cervix (Bishop score ≤ 6). A lower dose of misoprostol is also associated
with a lower incidence of adverse effects on the mother and fetus, such as tachysystole,
uterine hyperstimulation and fetal metabolic acidosis.[20]
According to some protocols, PGE1 is administered to promote cervical ripening as
the first step in the labor induction of pregnant women with unfavorable uterine cervices.
Prostaglandin E1 alone initiates labor, and oxytocin is obviously needed for the conduction
of labor.[21] In our study, 197 pregnant women (47.8%) required oxytocin after induction with
misoprostol to continue labor.
Brusati et al[22] evaluated the efficacy of 25 µg of sublingual misoprostol in inducing labor in single
births. They found that vaginal birth occurred within 24 hours in 78% of multiparous
women and in 65% of nulliparous women. In our study, not only parity, but also the
Bishop score, the amount of misoprostol administered, the time of induction, the use
of oxytocin, and prior vaginal births were all associated with the successful induction
of labor.
Many studies have shown that, when compared with expectant management, induced labor
in cases of full-term pregnancy is associated with a reduction in perinatal mortality.[23]
[24]
[25] The traditional method for predicting whether labor will be induced successfully
in cases of vaginal birth is the presence of a favorable cervix, as determined by
the Bishop score. In the past, some studies demonstrated that the Bishop score rarely
predicted the success of induced labor.[26]
[27]
[28] Recently, a review of the Cochrane Library, which included 234 patients, compared
the Bishop score to the assessment of cervix length by transvaginal ultrasound to
determine the success of induced labor.[29] According to this review, there is no clear superiority of one method over another
to assess the pre-induction of the cervix for the following post-natal outcomes: vaginal
birth (OR: 1.07; 95%CI: 0.92–1.25); cesarean section (OR: 0.81; 95%CI: 0.49–1.34);
and admission to a neonatal intensive care unit (OR: 1.67; 95%CI: 0.41–6.71). Our
study used a stepwise regression analysis to identify the pre-induction factors that
could be used as predictors of a successfully induced labor. We found that a Bishop
score between 4 and 5 and previous vaginal birth were independent factors with statistical
significance in the prediction of a successful vaginal birth.
The most common indication for cesarean section was unsuccessful induction (10.9%).
According to a study by Pajak et al[30], 12% of post term pregnant women had unsuccessful labor induction with misoprostol
50 µg every 12 hours (maximum: 150 µg). A total of 18% of the pregnant women required
8 to 11 hours between the start of labor and delivery. Sharami et al[31] obtained an average of 13.2 hours in a group of 633 primigravidae who received a
50-µg vaginal dose of misoprostol. Santo et al[32] used 25 µg of misoprostol placed in the posterior vaginal fornix and found an average
time between induction and the start of the active phase of labor of 10 hours and
20 minutes, while labor lasted for an average of 15 hours and 35 minutes.
One limitation of our study is the fact that it is a retrospective study. In addition,
we did not evaluate the influence of body mass index on the success of induced labor.
However, this study included 412 patients who were duly monitored until the end of
labor, which enabled the proper assessment of the maternal outcomes.
Conclusion
The present study concluded that successful labor induction with misoprostol occurred
in the majority of the pregnant women with a low dose of this drug. Higher Bishop
scores and previous vaginal deliveries were the best predictors of vaginal delivery
when 25 µg of misoprostol was administrated vaginally.
