Keywords
obstetrics - misoprostol - complications of labor and delivery - induced labor
Palavras-chave
obstetrícia - misoprostol - complicações do trabalho de parto - trabalho de parto
induzido
Introduction
Labor induction is one of the most performed obstetric interventions and refers to
techniques of stimulation of the uterine contractions that will lead to labor.[1] According to the World Health Organization (WHO), in an assessment of maternal perinatal
health, 9.6% of births worldwide need to be induced.[2]
The decision to induce labor is made when the continuity of pregnancy is associated
with increased maternal or fetal risk, and there is no contraindication to vaginal
delivery.[1] Successful induction of labor depends on the maturity of the cervix, which is generally
assessed using the Bishop index, the best predictor of success for vaginal birth nowadays.[3] Several techniques for cervical ripening and labor induction are evaluated with
the aim of reducing the cesarean section rates, with the available mechanical and
pharmacological options.[4]
The main mechanical methods are: artificial rupture of membranes (amniotomy), membrane
sweeping, and cervical dilators (laminaria and Krause method).[5] Pharmacological methods include prostaglandins (PGE2: dinoprostone or PGE1: misoprostol),
selective modulators of progesterone receptors, oxytocin, and nitric oxide (NO) donating
compounds.[6]
[7]
Misoprostol, a synthetic analogue of prostaglandin E1, has been used for labor induction
since the 1990s and has a plasma half-life of less than one hour when administered
vaginally.[8]
[9] It has been shown to be an effective stimulator of the myometrium of the gravid
uterus by several studies. The use of misoprostol for induction of labor is still
off label. This drug was initially approved by the FDA in an oral form (Cytotecs, Pfizer) to
reduce the risk of ulcers induced by non-steroidal anti-inflammatory drugs (NSAIDs).
However, this medication has been used for the past 30 years in the third trimester
of pregnancy for cervical ripening and labor induction, being orally, vaginally, rectally,
and sublingually applied, in high or low dose regimens, although the ideal route of
use is still unknown. The doses initially used for induction of labor were empirical
and ranged from 25 µg every 3 to 6 hours, to 200 µg in a single dose intravaginally
or orally.[10]
Thus, as labor induction rates increase, it is of clinical importance to clearly determine
the different variables that influence the safety and effectiveness of methods for
inducing labor in pregnant women. As the appropriate doses of misoprostol for preparation
and induction of labor in pregnant women with live fetuses are not well established,
in the proposed study, the primary objective was to determine the predictive criteria
for the success of labor induction with the use of misoprostol in pregnant women at
the Otto Cirne Maternity Hospital of the Hospital das Clínicas of UFMG. Our secondary
objective was to determine the rates of vaginal or cesarean delivery, mean duration
of induction, interval of misoprostol administration, the main causes of induction
of labor, and indications for operative delivery.
Methods
A descriptive observational study of retrospective analysis was performed, with a
review of the clinical records of pregnant women admitted for labor induction at the
Otto Cirne Maternity of the Hospital das Clínicas of UFMG from January 2017 to December
2018.
Data were collected through the analysis of electronic and physical records of patients
admitted for delivery. Pregnant women candidates for cervical ripening underwent maternal
and fetal evaluation, confirming the absence of contraindications to induction of
labor and vaginal delivery. The gestational age of all patients was determined by
date of last menstruation or earlier ultrasound, anamnesis, and clinical examination.
The inclusion criteria in this study were patients followed-up at our service, with
medical and obstetric indications for the labor induction with misoprostol in live
fetuses. Exclusion criteria were based on our primary design, which was to study misoprostol
labor induction in women with live fetuses. Therefore, in addition to the exclusion
of women hospitalized for induction with a dead fetus on admission, induction with
oxytocin without the use of misoprostol and women who had the induction initiated
by legal interruption were also excluded, since fetal vitality and the newborn's outcome
were not important and limiting factors of conduct for the obstetrician in these situations.
Furthermore, women with contraindications to induction of labor or vaginal delivery
were also excluded, as established in the HC-UFMG Obstetrics Protocol: history of
previous uterine rupture, history of gynecological surgery on the uterine body (such
as intramural myomectomy), active genital herpes, total placenta previa or vasa previa,
cord prolapse, anomalous fetal presentations (except in fetal descent), macrosomia
with estimated fetal weight greater than 4 kg, invasive cervical cancer, patient's
refusal, non-reassuring fetal pattern, anomalous pelvis, some fetal congenital anomalies
such as neural tube and/or abdominal wall closure defects with good neonatal prognosis,
and fetal tumors that determine fetal-pelvic disproportion. Women who had used oxytocin
after misoprostol and whose fetuses died during hospitalization were not excluded
from this study.
Data collected from medical records were: age, parity, gestational age at admission
and at delivery, days of hospitalization, maternal morbidity, induction indication,
uterine height on admission, Bishop index on admission, total number of misoprostol
tablets used, total number of doses of misoprostol used, analgesia, obesity according
to the body-mass index (BMI), use of oxytocin during induction, maximum dose of oxytocin,
type of delivery, time of delivery after beginning of induction, indication of operative
delivery, Apgar index at birth (first minute) and Apgar after 5 minutes, fetal condition
at birth (alive or dead), newborn weight, amniorrhexis, and clear fluid appearance,
considered in admission and during labor. Maternal morbidity and indication for induction
were described according to the medical records but for analysis purposes, groups
were defined as described below.
Regarding maternal morbidity, as pregnant women admitted to the Hospital das Clínicas
are primarily considered “High Risk” (∼60%), around 85 different comorbidities were
identified and divided into 8 groups: no comorbidities, hypertensive disorders, diabetes,
mental disorders, heart disease, kidney disorders, infectious diseases, and “other”:
cholestasis, asthma, obesity, myasthenia gravis, thrombophilia, hypothyroidism, hearing
loss, anemia, rheumatic fever, factor XI deficiency, congenital deafness, dermatopolymyositis,
autoimmune thrombocytopenia, coagulopathy, Crohn disease, rheumatoid arthritis, adrenal
adenoma, Cushing syndrome, isoimmunization, neoplasm, previous history of thrombosis,
drug use, liver transplantation, systemic lupus erythematosus (SLE), epilepsy, myomatosis,
pheochromocytoma, cholelithiasis, need for cerclage in pregnancy, alcoholism, Graves
ophthalmopathy, hyperthyroidism, idiopathic thrombocytopenic purpura (ITP), antiphospholipid
antibody syndrome (APLS), pituitary adenoma, sickle cell trait, smoking during pregnancy,
maternal hydrocephalus, Hodgkin lymphoma, Von Willerbrand disease, ascites, vitiligo,
pulmonary hypertension, isthmus-cervical incompetence, Turner syndrome, and history
of bariatric surgery.
One point to be raised would be the lack of consensus on the concept of successful
induction of labor. For example, for successful induction, the National Institute
for Health and Clinical Excellence (NICE) considers achieving a vaginal delivery within
24 hours.[11] However, the WHO considers the rate of cesarean sections as an indicator of success.[2] And the Society of Obstetricians and Gynecologists of Canada (SOGC) considers vaginal
delivery between 24 and 48 hours of induction as a success.[9] Other authors add “uncomplicated vaginal delivery,” or “reaching the active phase
of labor.”[3] In our study, labor induction was considered successful when non-operative vaginal
delivery occurred, without the use of forceps or vacuum extractor. Procedures with
absence of uterine contractions, changes in the cervix, or complications during labor
culminating in a cesarean section were considered as unsuccessful labor inductions.
The hospital chosen for the research was the Otto Cirne Maternity of UFMG's Hospital
das Clínicas (UFMG-HC). This is a general, public, university hospital, which is a
reference center in highly complex care for the Unified Health System of Minas Gerais
(UHS/MG), with a monthly average of 190 births at the time of this study. The UFMG-HC
protocol for misoprostol use determines a maximum dose of 275 mcg divided into 8 doses,
as follows: 1 tablet of 25 mcg via the vaginal route every 4 hours in the first 5
doses, and 2 tablets of 25 mcg via vaginal (50 mcg) every 6 hours on the sixth, seventh,
and eighth doses. Therefore, data was collected considering the number of doses, ranging
from 1 to 8 doses; but the total number of pills inserted can range from 1 to 11 pills.
In our study, the dose of misoprostol used was in accordance with the American College
of Obstetricians and Gynecologists (ACOG) guidelines, which recommends a misoprostol
dosage of 25 mcg every 3 to 6 hours (50 mcg every 6 hours may be appropriate in some
situations).[5]
This research project was approved by the UFMG Research Ethics Committee (CAAE 06358919.7.0000.5149–Number
3.278.259, April 23rd, 2019) and does not present any conflict of interests.
As for the descriptive analysis, data from all patients were initially collected and
recorded in Excel (Microsoft CO. Redmond, WA, USA). The statistical software R (R
Foundation for Statistical Computing, Vienna, Austria) was used to set up a database
and perform the statistical analyses. Data related to categorical variables were analyzed
in frequency tables, which have both absolute and relative frequency. For the numerical
variables, the measures of central tendency used were the mean and median; as measures
of variation, we used the standard deviation (SD), the minimum value, the maximum
value, and in some cases the limits of the 95% confidence intervals (95% CI) of the
average.
The analyzes of the quantitative variables with the response variable (non-operative
delivery) were performed using box plots[12] and the non-parametric statistical Mann-Whitney test,[13] also known as the unpaired Wilcoxon test, using the wilcox.test function in R. As
for the qualitative variables, the analyzes were performed using bar graphs and the
Yates chi-square test, with the chisq.test function in R.[14]
In a second step, multivariate logistic regression analysis was performed, aiming
to create a predictive statistical model. Multivariate (or multiple) analyzes were
performed using logistic regression techniques, with the glm function in R, which
generates a final equation that can be used for future predictions, in addition to
saying how much each variable influences (increases or decreases) the probability
of occurrence of the event of the response variable.[14] We used the backward variable selection method, also known as variable elimination.[13] The final significance level chosen was 0.01 and not 0.05, due to how this selection
method causes a possible underestimation bias of p-values. It is noteworthy that regardless of the result of the bivariate analyses,
all variables entered the first model. Finally, the quality of the predictions of
the models was evaluated through sensitivity, specificity, percentage of correct answers,
and false positives and negatives.
Results
We selected 1065 patients hospitalized for labor induction at the Hospital das Clínicas
of UFMG from January 2017 to December 2018. Among those, 84 pregnant women hospitalized
with fetal failure and 104 pregnant women whose induction was not performed with the
aid of misoprostol were excluded. The final analyzed sample contains 873 patients.
No patient refused to undergo the induction process after medical advice and clarification
of doubts ([Fig. 1]).
Fig. 1 Flowchart of patients selected for the study.
[Table 1] shows the mean age of patients, Bishop score on admission, number of misoprostol
doses used in total, time of delivery after induction onset, Apgar score at birth
and gestacional age at delivery.
Table 1
Characterization of patients regarding mean age, Bishop score on admission, total
number of misoprostol doses, time of delivery after induction onset, Apgar score at
birth, and gestational age at delivery
|
Mean
|
95% CI of the mean
|
Minimum – maximum
|
|
Age (years)
|
27.66 ± 6.83 (27)
|
(27.21; 28.12)
|
13–48
|
|
Bishop index at admission
|
1.59 ± 1.32 (1)
|
(1.50; 1.68)
|
1–6
|
|
Total number of misoprostol doses
|
3.59 ± 2.26 (3)
|
(3.44; 3.74)
|
1–10
|
|
Delivery time after beginning of induction (hours)
|
21.22 ± 13.30 (18.25)
|
(20.33; 22.10)
|
1–109
|
|
Apgar index at birth
|
7.85 ± 1.88 (8)
|
(7.72; 7.97)
|
0–10
|
|
Gestational age at delivery
|
N (%)
|
|
Birth < 37 weeks
|
99 (11.4)
|
|
Birth 37–41 weeks and 6 days
|
773 (88.5)
|
|
Birth ≥ 42 weeks)
|
1 (0.1)
|
|
Total
|
873 (100)
|
Abbreviations: 95% CI, 95% confidence interval.
The body mass index (BMI) of the participants was also evaluated; however, for only
139 of the participants was this information present in the medical record. Thus,
we obtained a sample mean equal to 31.8, sample standard deviation equal to 6.69 and
median equal to 31. Regarding the number of previous vaginal deliveries, 53.15% of
the pregnant women had no previous vaginal delivery, approximately 25% of the patients
had one previous vaginal birth, 12.03% had two previous vaginal deliveries, and almost
5% had 3 or more previous deliveries. [Table 2] characterizes the patients regarding maternal morbidity, with 59.22% of the pregnant
women having some comorbidity.
Table 2
Maternal morbidity
|
|
Frequency
|
|
Groups
|
n
|
%
|
|
No comorbidities
|
356
|
40.8%
|
|
Hypertensive disorders
|
317
|
36.3%
|
|
Others
|
205
|
23.5%
|
|
Diabetes
|
127
|
14.6%
|
|
Infectious diseases
|
59
|
6.8%
|
|
Mental disorders
|
21
|
2.4%
|
|
Kidney disorders
|
21
|
2.4%
|
|
Heart diseases
|
20
|
2.3%
|
|
Total participants
|
873*
|
–
|
Note: *Patients could have more than one comorbidity, so the sum of the number of pregnant
women in each group is greater than 873, which is the total number of participants.
[Table 3] shows the delivery outcome. It is clear that most patients who participated in the
survey had non-operative vaginal delivery, which corresponds to just over 72%. The
second most common type of delivery was the cesarean operation with almost 23% of
the cases, followed by the forceps vaginal delivery, with approximately 4% of the
deliveries, and finally the extraction vacuum vaginal delivery, which had just under
1% of the cases.
Table 3
Childbirth outcome
|
Frequency
|
|
Type of delivery
|
n
|
%
|
|
Cesarean delivery
|
199
|
22.8%
|
|
Vaginal delivery
|
632
|
72.4%
|
|
Vaginal delivery by forceps
|
34
|
3.9%
|
|
Vaginal delivery by vacuum extractor
|
8
|
0.9%
|
|
Total
|
873
|
100%
|
The time of delivery after the beginning of induction was also evaluated, which was
timed from the insertion of the first misoprostol tablet until the birth of the newborn.
We observed that 67.81% of the patients delivered within 24 hours and 26.92% delivered
within 12 hours of the beginning of induction as an outcome. A considerable amount
also presented delivery from 24 to 36 hours after the beginning of induction, approximately
18%. Only 4% gave birth 48 hour after the start of induction. The total average time
of delivery after beginning of induction was 21.22 hours, with a sample deviation
equal to 13.3. The smallest value identified was equal to 1 and the largest value
equal to 109 hours. With the 95% confidence interval of the mean, we found a lower
limit of 20.33 and an upper limit of 22.10. With the analysis of [Table 4], we can see the main indications for labor induction, the main reason being hypertensive
disorders, which affected approximately 37.46% of the patients. Antepartum amniorrhexis
was the second most recurrent reason, found in 23.02% of the participants. Gestational
age (18.33%) was the third most recurrent reason for labor induction, and comorbidities
related to diabetes also had a significant frequency, in approximately 12.6% of the
patients. The other indications occurred in a maximum of 10% of the patients. As each
patient could have more than one reason for induction, the sum of frequencies in [Table 5] is not equal to the total number of participants.
Table 4
Indication of labor induction
|
Frequency
|
|
Indication
|
n
|
%
|
|
Hypertensive disorders
|
327
|
37.5%
|
|
Gestational age ≥ 41 weeks
|
160
|
18.3%
|
|
Antepartum amniorrhexis
|
201
|
23%
|
|
Diabetes
|
110
|
12.6%
|
|
Fetal indication
|
87
|
10%
|
|
Fetal malformations
|
57
|
6.5%
|
|
Others
|
55
|
6.3%
|
|
Severe maternal comorbidity
|
32
|
3.7%
|
|
Infectious diseases
|
29
|
3.3%
|
|
Total of participants
|
873
|
–
|
Notes: Fetal malformations: fetal heart disease, trisomy 13, trisomy 18, cystic adenomatoid
malformation of the lung (MAC) type II, Dandy-Walker syndrome. Fetal indication: fetal
macrosomia, intrauterine growth restriction (IUGR), fetal flow centralization, fetus
large for gestational age (LGA), oligohydramnios, pelvic presentation, polyhydramnios.
Table 5
Indication of surgical delivery
|
|
Frequency
|
|
|
Indication
|
n
|
%
|
Total %
|
|
Acute fetal distress
|
84
|
34.9%
|
9,6%
|
|
Induction failure
|
46
|
19.1%
|
5.3%
|
|
Maternal exhaustion
|
24
|
10%
|
2.8%
|
|
Cephalo-pelvic disproportion
|
24
|
10%
|
2.8%
|
|
Secondary arrest of dilation
|
21
|
8.7%
|
2.4%
|
|
Cesarean on request
|
8
|
3.3%
|
0.9%
|
|
Placental abruption
|
8
|
3.3%
|
0.9%
|
|
Macrosomy
|
5
|
2.1%
|
0.6%
|
|
Not informed
|
4
|
1.7%
|
0.5%
|
|
Acute fetal distress and maternal exhaustion
|
3
|
1.2%
|
0.3%
|
|
Pelvic presentation
|
2
|
0.8%
|
0.2%
|
|
Maternal heart disease
|
2
|
0.8%
|
0.2%
|
|
Twin pregnancy
|
2
|
0.8%
|
0.2%
|
|
IUGR with altered doppler
|
1
|
0.4%
|
0.1%
|
|
Induction failure and fetal macrosomia
|
1
|
0.4%
|
0.1%
|
|
HELLP syndrome
|
1
|
0.4%
|
0.1%
|
|
Provenance of hands
|
1
|
0.4%
|
0.1%
|
|
Fetal risk of intrapartum vaginal death
|
1
|
0.4%
|
0.1%
|
|
Acute fetal distress and breech presentation
|
1
|
0.4%
|
0.1%
|
|
Acute fetal distress and induction failure
|
1
|
0.4%
|
0.1%
|
|
Acute fetal distress and secondary arrest of dilation
|
1
|
0.4%
|
0.1%
|
|
Total
|
241
|
100%
|
27.6%
|
Abbreviations: IUGR, intrauterine growth restriction; HELLP, hemolysis, elevated liver enzymes,
and low platelets. Notes: Induction failure: absence of labor after insertion of 8 doses of misoprostol or
11 tablets. Acute fetal distress: described in medical record as “persistent fetal
bradycardia,” “non reassuring fetal state “, “late deceleration in CTG” and “prolonged
deceleration in CTG.” The number of operative vaginal deliveries is 42 (4,8%); antepartum
c-sections, 50 (5,7%); intrapartum c-sections, 149 (17%).
[Table 5] refers to the indication for operative delivery (cesarean section or instrumentalized
vaginal delivery, with the use of forceps or vacuum extractor). The most recurrent
indications are related to the group of acute fetal distress (34.85%), already presented,
as well as induction failure (19.09%), cephalopelvic disproportion (CPD, 9.96%), and
maternal exhaustion (9.96%).
The logistic regression analysis considering the outcome “nonoperative delivery” was
performed. To adjust the final model, the database was first divided into a training
base and a test base, the first having 70% of all observations (611) and the second
30% (262). Then, the selection of variables was made using the training base and following
the backward method, in which the variables are extracted one by one. The equation
for the probability of non-operative delivery is presented as [supplementary material]. The percentage of success of the predictive model in both the test base and the
training base was 79.1%. This gave us confidence that there was no overfitting of
the data, and the final result considered the entire database. However, although the
original database contains 873 patients, as the records of some patients had missing
values for some variables, 856 patients remained for evaluation of the model's prediction,
as shown in [Table 6].
Table 6
Logistic regression forecast results for non-operative childbirth: final template
for admission and hospitalization variables
|
Type of delivery
|
Template (Expected Response)
|
|
|
(Response observed)
|
Operative delivery
|
Non-operative delivery
|
Total
|
|
Operative delivery
|
84
|
149
|
233
|
|
Non-operative delivery
|
30
|
593
|
623
|
|
Total
|
114
|
742
|
856
|
Notes: sensitivity = 95.2%; specificity = 36.1%; hit percentage = 79.1%; false positives = 20.1%;
false negatives = 26.3%.
In another template for nonoperative delivery, we chose to consider only the variables
available at the time of patient's admission. The equation for the probability of
non-operative delivery is presented as [supplementary material]. It is important to note that the three variables in common in the two results above
(age, previous normal births, and gestational age at admission) have almost identical
coefficients in the two models, indicating the robustness of the results. The percentage
of accuracy of the predictive model was 73% in the test base and 76% in the training
base, also not indicating a very big difference that could indicate an overfitting
of the model to the data. Thus, the final results considered the entire database.
Taking into consideration that the records of some patients had missing values for
some variables, 871 patients remained for evaluation of the template's prediction,
as shown in [Table 7].
Table 7
Logistic regression prediction results for non-operative childbirth: final template
for admission variables only
|
Type of delivery
|
Template (expected response)
|
|
|
(Response observed)
|
Operative delivery
|
Non-operative delivery
|
Total
|
|
Operative delivery
|
56
|
185
|
241
|
|
Non-operative delivery
|
33
|
597
|
630
|
|
Total
|
89
|
782
|
871
|
Notes: sensitivity = 94.8%; specificity = 23.2%; hit percentage = 75.7%; false positives = 23.7%;
false negatives = 37.1%.
Discussion
The aim of this study was to determine the predictive criteria for success in labor
induction with the use of misoprostol, in addition to determining the rates of vaginal
birth or cesarean operation, mean duration of induction, interval of misoprostol administration,
the main causes of labor induction, and indication of operative delivery.
The association between cesarean operation and induction is reinforced by daily obstetric
practice, and it is a common belief that induction of labor increases the risk of
cesarean operation. However, using the appropriate comparison group, studies show
that induction of labor is actually associated with a small decrease in this risk.[15] The labor induction rate between the years 2017 and 2018 at Hospital das Clínicas
of UFMG was 27.8%, and the cesarean rate was 37.87% in the total number of deliveries
performed.[16] Of the induced deliveries, we had a rate of caesarean section of 22.79% found in
the study, which is significantly lower than the total group of patients monitored
in our hospital.
This finding is in line with what is registered in the literature, and in a meta-analysis
the cesarean rate was quite variable between the compared trials, with an overall
trend of reduction with vaginal misoprostol (34 trials, RR (Relative Risk) 0.95, 95%
CI (Confidence Interval) 0, 87 to 1.03).[17]
Regarding the time of delivery after the start of induction, we observed that almost
70% of the patients delivered within 24 hours, and approximately 27% delivered within
12 hours of the start of induction.
A randomized clinical trial demonstrated a higher proportion of women who delivered
within 12 hours and within 24 hours using misoprostol combined with mechanical dilation
using a Foley tube.[18]
The American College of Obstetricians and Gynecologists (ACOG) suggests that the appropriate
dosage of misoprostol is 25 mcg every 3 to 6 hours (or 50 mcg every 6 hours, in some
situations), the SOGC recommends 50 mcg orally with a glass of water or 25 mcg vaginally
every 4 hours, while WHO recommends 25 mcg of oral misoprostol every 2 hours or 25
mcg of misoprostol vaginally every 6 hours for labor induction.[9] In our study, the dose of misoprostol used is in accordance with the ACOG, and proved
to be adequate with satisfactory results.
A review on labor induction showed that the success of induction with vaginal birth
increases with gestational age.[3] In our study, the most frequent types of pregnancies in the sample are those considered
early term and full term, with 37.57% and 33.33% of the situations respectively, which
may have influenced the best outcome.
In a prospective observational study, the main cause of induction was pregnancy ≥
41 weeks, 29.8%, 17.9% with antepartum amniorrhexis, elective induction in 9.5% of
the cases, followed by preeclampsia in 8.5% of cases, 8.1% with oligohydramnios, severe
maternal morbidity in 7.7%, diabetes in 3.8%, severe fetal morbidity in 3.3%, and
other causes < 2%.[19] In our study, however, the main reason for induction were the hypertensive disorders,
which affected approximately 37.46% of the patients. Followed by antepartum amniorrhexis
in 23.02% of the participants. Gestational age was the third most recurrent reason
for labor induction, in 18.33% of the patients, and comorbidities related to diabetes
also had a significant frequency, in approximately 12.6% of the patients. The other
indications occurred in 10% of the patients at most. This difference in relation to
the literature may have occurred because the Hospital das Clínicas of UFMG is a high-risk
referral unit.
As for the indication of cesarean, in a study of labor induction with oxytocin, misoprostol,
or both, it was found that acute fetal distress played an important role in the indication
of cesarean, with 35.1% correlation rates, followed by CPD with 23.4%, and 16% of
induction failure.[20] In the present study, we found very similar results, with the most recurrent indications
related to the group of acute fetal distress (34.85%), with induction failure in second
place (19.09%), followed by CPD (9.96%), and maternal exhaustion (9.96%).
It should be noted that, in our study, these indications are not only for cesarean
section, but also instrumentalized vaginal delivery, in which case the main cause
was maternal exhaustion.
For induction to be successful, we generally take into account the maturity of the
cervix, which is assessed using the Bishop index, the best predictor of success for
vaginal birth nowadays.[3] A review that considered more than 40 articles correlated the Bishop index at the
beginning of induction with its outcome, concluding that it would be a poor predictor
and should not be used to decide whether or not to induce labor.[21] At the moment, however, this index remains the main tool for evaluating the uterine
cervix at the beginning of induction. Our model proposes to complement this index,
as it includes other variables that were not considered as predictors until now.
Regarding the logistic regression models found, for non-operative delivery, the model
showed that at the time of admission, the younger maternal age, more previous normal
deliveries, lower gestational age, and greater dilatation, all contribute for a higher
probability of this patient undergoing non-operative delivery, which confirms the
results in the literature. During hospitalization, the lower number of vaginal touches,
in addition to the occurrence of amniotomy, amniorrhexis (on admission or hospitalization),
and appearance of clear fluid, were related to a higher occurrence of non-operative
delivery.
For the models where the answer is non-operative delivery, the percentage of correct
answers was 79% (admission and hospitalization variables) and 76% (only admission
variables), which are considered high values. The percentages of false positives (35%
and 42%) and false negatives (21% and 21%) were less than 50% in both models. Sensitivity
was excellent in both models (95%), but specificity was low in both with 36% considering
all variables (admission and hospitalization) and 23% using only admission variables.
One of the reasons for this difference between sensitivity and specificity is the
fact that the models predicted more non-operative deliveries than the actual total.
Thus, it can be said that there was a “difficulty” of the models in identifying and
predicting operative deliveries.
Overall, both logistic regression models designed here had difficulty predicting the
least frequent outcome, which was operative deliveries (241 deliveries out of 873).
On the other hand, false positives and false negatives were always less than 50%,
and the percentage of correct answers was greater than 65%, indicating that the predictions
made by such models are always more likely to be right than wrong.
A strength of this study would be that the overall clinical volume of the studied
hospital and cesarean rates did not change significantly over the years spanning the
study period, making the confounding factor related to temporal trends less likely.
Another relevant point of this study was that we arrived at final models for predicting
childbirth, with both admission and hospitalization variables.
As this is a retrospective study with review of medical records, some of the necessary
patient data were not present in the medical records. Another important limitation
of this study is that, although we had statistical power to detect differences in
time from induction to delivery, for most outcomes—including cesarean operation, and
adverse maternal and neonatal outcomes—we did not have the statistical power to discern
potentially important differences between groups.
Conclusion
At admission, factors such as younger maternal age (age < 24 years), more previous
normal births, lower gestational age, and greater dilatation, were all associated
with a higher probability of undergoing non-operative delivery. During hospitalization,
fewer vaginal touches, amniotomy and amniorrhexis with clear fluid, and shorter labor
induction time were associated with a greater chance of non-operative delivery. However,
despite the percentage of false positives and false negatives being always below 50%
and that of correct answers being above 65%, the final models had difficulty predicting
the outcome “operative delivery” because it was less frequent.
Furthermore, in our study, labor induction with misoprostol had a 15% lower cesarean
incidence compared with the overall cesarean rate of our hospital in the study's period,
with most patients (almost 70%) giving birth in up to 24 hours after initiation of
induction, using up to 4 doses of the tablet.
The most recurrent indications for operative delivery and the main causes of labor
induction in this study were similar to those found in the literature, the second
differing only in the frequency and order of the results found, a fact that may have
occurred because the Hospital das Clínicas of UFMG is a high-risk reference unit.
Future studies in different environments, with a prospective design and analysis of
other factors are needed to assess replicability, generalization of these findings,
and improved prediction rates.
