Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial

doi:10.1016/S0140-6736(16)00084-2

The Lancet

Volume 387, Issue 10028, 16–22 April 2016, Pages 1619-1628

, , , , , , , , , , , , , , , , , , , …

https://doi.org/10.1016/S0140-6736(16)00084-2 Get rights and content

Summary

Background

Labour is induced in 20–30% of all pregnancies. In women with an unfavourable cervix, both oral misoprostol and Foley catheter are equally effective compared with dinoprostone in establishing vaginal birth, but each has a better safety profile. We did a trial to directly compare oral misoprostol with Foley catheter alone.

Methods

We did an open-label randomised non-inferiority trial in 29 hospitals in the Netherlands. Women with a term singleton pregnancy in cephalic presentation, an unfavourable cervix, intact membranes, and without a previous caesarean section who were scheduled for induction of labour were randomly allocated to cervical ripening with 50 μg oral misoprostol once every 4 h or to a 30 mL transcervical Foley catheter. The primary outcome was a composite of asphyxia (pH ≤7·05 or 5-min Apgar score <7) or post-partum haemorrhage (≥1000 mL). The non-inferiority margin was 5%. The trial is registered with the Netherlands Trial Register, NTR3466.

Findings

Between July, 2012, and October, 2013, we randomly assigned 932 women to oral misoprostol and 927 women to Foley catheter. The composite primary outcome occurred in 113 (12·2%) of 924 participants in the misoprostol group versus 106 (11·5%) of 921 in the Foley catheter group (adjusted relative risk 1·06, 90% CI 0·86–1·31). Caesarean section occurred in 155 (16·8%) women versus 185 (20·1%; relative risk 0·84, 95% CI 0·69–1·02, p=0·067). 27 adverse events were reported in the misoprostol group versus 25 in the Foley catheter group. None were directly related to the study procedure.

Interpretation

In women with an unfavourable cervix at term, induction of labour with oral misoprostol and Foley catheter has similar safety and effectiveness.

Funding

FondsNutsOhra.

Section snippets

Background

Induction of labour is an obstetric intervention that artificially initiates the process of effacement of the cervix, dilatation, uterine contractions, and eventually delivery of the baby. It aims to end the pregnancy through vaginal delivery, when continuation of the pregnancy could jeopardise the condition of the mother or her baby, and delivery ought to improve outcomes compared with continuing pregnancy. 25% of women in high-resource settings have labour induced.1, 2, 3, 4, 5 In women with

Study design and participants

We did this open-label, non-inferiority trial in six tertiary-care and 23 secondary-care hospitals collaborating in the Dutch consortium for women's health research.

We enrolled women with a vital singleton pregnancy in cephalic presentation, intact membranes, a gestational age of 37 weeks or more, and an unfavourable cervix (Bishop score <6), scheduled for induction of labour. We excluded women with known hypersensitivity to any of the products used, age younger than 18 years, a history of

Results

Between July 18, 2012, and Oct 10, 2013, we deemed 2316 women eligible, of whom 1859 consented to participate. We randomly assigned 932 women to misoprostol and 927 to Foley catheter (figure 1). 14 women were excluded from the intention-to-treat analyses, including two who did not meet the eligibility criteria: each had a history of caesarean section and no vaginal examination before randomisation. We believe that these women were enrolled by mistake by the treating physician. At the interim

Discussion

In this randomised trial, we found that, in women with an unfavourable cervix at term, induction of labour with oral misoprostol was not inferior to Foley catheter in terms of safety and effectiveness. The composite of post-partum haemorrhage and asphyxia did not occur significantly more often after induction of labour with oral misoprostol than with Foley catheter, and the individual components of the outcome were also similar. The proportion of patients who had caesarean section was similar

References (22)

SL Kjos et al.
Insulin-requiring diabetes in pregnancy: a randomized trial of active induction of labor and expectant management
Am J Obstet Gynecol
(1993)
L Sanchez-Ramos et al.
Expectant management versus labor induction for suspected fetal macrosomia: a systematic review
Obstet Gynecol
(2002)
K Broekhuijsen et al.
Immediate delivery versus expectant monitoring for hypertensive disorders of pregnancy between 34 and 37 weeks of gestation (HYPITAT-II): an open-label, randomised controlled trial
Lancet
(2015)
M Jozwiak et al.
Foley catheter versus vaginal prostaglandin E2 gel for induction of labour at term (PROBAAT trial): an open-label, randomised controlled trial
Lancet
(2011)
AA Hussain et al.
Elective induction for pregnancies at or beyond 41 weeks of gestation and its impact on stillbirths: a systematic review with meta-analysis
BMC Public Health
(2011)
M Boulvain et al.
Elective delivery in diabetic pregnant women
Cochrane Database Syst Rev
(2001)
ACOG Practice Bulletin No 107: induction of labor
Obstet Gynecol
(2009)
CM Huisman et al.
Cervical ripening in the Netherlands: a survey
Obstet Gynecol Int
(2013)
Z Alfirevic et al.
Oral misoprostol for induction of labour
Cochrane Database Syst Rev
(2014)
GJ Hofmeyr et al.
Vaginal misoprostol for cervical ripening and induction of labour
Cochrane Database Syst Rev
(2010)

WHO recommendations for induction of labour

Cited by (93)

Women satisfaction on choosing the cervical ripening method: Oral misoprostol versus balloon catheter
2023, European Journal of Obstetrics and Gynecology and Reproductive Biology: X
Induction of labor concerns about 29 % of women in Unites States and 33 % in Europe. Among the various methods for cervical ripening, the efficacy and safety profiles of oral misoprostol and balloon catheter are comparable, but data in the literature on maternal satisfaction during induction of labor are few. The objective of this study was to assess the satisfaction of women who chose the method of cervical ripening, i.e. either balloon catheter or oral misoprostol, for induction of labor.
This retrospective study asked women who had undergone induction of labor between February 1, 2020 and February 28, 2021. After receiving verbal and written information, the choice of method between oral misoprostol and balloon catheter was left to the patient’s free appreciation. Satisfaction was assessed by means of a questionnaire distributed to all women during their stay in the maternity unit. The principal assessment criterion was based on women’ inclination to choose the same cervical ripening method if induction of labor were to prove necessary in a future pregnancy, and their willingness to recommend this method to a friend. Univariate analyses were conducted using Student’s t-test, Chi-2 test or Fisher’s exact test.
On 575 women eligible for analysis, 365 (63.5 %) of these women replied to the satisfaction questionnaire. Of this number, 236 (64.7 %) chose cervical ripening by balloon catheter, and 129 (35.3 %) by oral misoprostol. No significant difference was found between the two groups: 68.2 % of women in the balloon catheter group would opt for the same method of cervical ripening if it proved necessary in a future pregnancy and 64.7% would recommend it to a pregnant friend, versus 65.9 % and 63.6 % in the oral misoprostol group, respectively. Women were overall pleased to be able to choose their method of cervical ripening: 90.5 % of patients in the balloon catheter group and 95.3 % in the oral misoprostol group
When women choose the method of cervical ripening, satisfaction is overall good, irrespective of the method, whether by balloon catheter or misoprostol.
The influence of various induction methods on adverse outcomes in small for gestational age neonates: A secondary analysis of the PROBAAT 1 and 2 trials
2023, European Journal of Obstetrics and Gynecology and Reproductive Biology
To evaluate the safety aspects of different induction methods in pregnancies with small-for-gestational-age neonates.
This was a secondary analysis of two previously reported multicenter, randomized controlled trials conducted in the Netherlands. In the original trials, women were randomized to either a 30 cc Foley catheter, vaginal prostaglandin E2 (PROBAAT-1) or oral misoprostol (PROBAAT-2). A total of 425 patients with a term, singleton pregnancy in cephalic presentation with an indication for labor induction and a small-for-gestational-age neonate were included in this secondary analysis. Our primary outcome was a composed adverse neonatal outcome of Apgar score < 7 after 5 min and/or a pH in the umbilical artery < 7.05 and/or NICU admission. Secondary outcomes were mode of birth, operative birth for fetal distress and pH < 7.10 in the umbilical artery. For these outcome measures, multivariate as well as bivariate analyses were performed.
An adverse neonatal outcome occurred in 4.7 % (10/214) induction with a Foley catheter, versus 12.8 % (19/149) after misoprostol (RR 0.36; 95 % CI 0.17–0.76) and 4.7 % (3/64) after Prostaglandin E2 (RR 0.98; 95 %CI 0.28–3.51).
For individual components of the composed outcome of adverse events, a difference was found between a Foley catheter and misoprostol for Apgar score < 7 at 5 min (0.5 % versus 3.4; RR 0.14; 95 %CI 0.02–1.16) and NICU admission (1.9 % versus 6.1 %; RR 0.31; 0.10–0.97). No differences were found for mode of birth.
For women who gave birth to a small-for-gestational-age neonate, a Foley catheter is probably a safer induction method compared to oral misoprostol.
Intracervical Foley catheter plus intravaginal misoprostol compared to intravaginal misoprostol-only for cervical ripening: A systematic review and meta-analysis
2023, European Journal of Obstetrics and Gynecology and Reproductive Biology
To compare the combination of intracervical Foley catheter and intravaginal misoprostol administration versus intravaginal misoprostol administration-only for cervical ripening. The Medline, EMBASE, ClinicalTrials.gov, PROSPERO, Scopus, and Cochrane Collaboration databases were searched systematically. Randomized controlled trials that included patients with a singleton viable fetus who underwent induction of labor that required cervical ripening with an unfavorable cervix (Bishop ≤ 6) were eligible for inclusion. Primary outcomes was time to delivery and rate of cesarean delivery. Thirteen trials with 2978 subjects met the inclusion criteria. There was no difference in the incidence of cesarean delivery between the two groups (RR, 0.90; 95 % CI, 0.72–1.14; I² = 69 %). The combination group resulted in comparable time to delivery (MD −2.50 h; 95 % CI 0.38, −5.38; I² = 97 %), shorter time to vaginal delivery (MD −3.49 h; 95 % CI −4.89, −2.09; I² = 81 %), lower risk of neonatal intensive care unit (NICU) admission (RR 0.72, 95 % CI 0.58–0.90, I² = 0 %), meconium-stained fluid (RR 0.48, 95 % CI 0.31–0.73, I² = 28 %), and tachysystole with fetal heart trace changes (RR 0.49, 95 % CI 0.27–0.86, I² = 43 %), compared with intravaginal misoprostol-only group. There was no statistical difference in rates of terbutaline use, endometritis or chorioamnionitis between the two groups. The combination of intravaginal misoprostol with intracervical Foley catheter for cervical ripening is not associated with shorter time to delivery. However, the combination group shows significant difference in shorter time to vaginal delivery, NICU admission, meconium-stained fluid, and tachysystole with fetal heart trace changes.
Pain and satisfaction in women induced by vaginal dinoprostone, double balloon catheter and oral misoprostol
2022, Journal of Gynecology Obstetrics and Human Reproduction
The aim of this study was to evaluate the pain experience of women induced by intravaginal dinoprostone (Propess®), oral misoprostol (Angusta®) or double balloon catheter (Cook®).
This single-center prospective study was carried out in the obstetric gynecology department of the university hospital of Saint-Etienne from March 2018 to April 2021 in women requiring cervical ripening for the purpose of artificial labor induction.
We included 82 women in the oral misoprostol group, 35 in the vaginal dinoprostone group and 58 in the balloon group. The overall pain, assessed by a numerical scale from 0 to 10, was similar for the different methods of induction (p = 0.253). Pain at insertion was greater with the double balloon catheter compared to the vaginal dinoprostone (3.67 versus 5.75 p = 0.001). Pain in the 2 h prior to the delivery room was greater with vaginal dinoprostone and oral misoprostol compared with the double balloon catheter (7.91 and 7.4 versus 5.47 respectively, p = <0.0001). Women induced by balloon catheter would more often have preferred to be induced by another method compared to those induced by oral misoprostol or vaginal dinoprostone (p = 0.004). Adjusting for previous cesarian section, gestational age at delivery, need for oxytocin augmentation and indication for induction, women induced by balloon were five times more risk to prefer another induction method (OR 5.01 95% CI [1.09–23.03], p = 0.038). There was no significant difference in stress and overall experience of induction depending on the method.
In order to improve the women experience, information, consent and participation in the decisions and choices of their induction method are essential.
Association between the cervical sliding sign and successful induction of labor in women with an unfavorable cervix: A prospective observational study
2022, European Journal of Obstetrics and Gynecology and Reproductive Biology
Citation Excerpt :
Women who had cesarean delivery for fetal distress or reasons other than failure to progress in labor were excluded from final analysis. According to previous data [25–27], the rate of vaginal delivery within 24 h for IOL with unripe cervices (Bishop score ≤ 6) is approximately 50 %. Under the assumption of 90 % power and an alpha error of 0.05, we calculated we would need 154 patients to demonstrate a 50 % increase (from 50 % to 75 %) in the rate of the primary outcome in our study population.
To evaluate the role of the cervical sliding sign (CSS) in the prediction of the outcome of induction of labor (IOL).
Two-center prospective observational cohort study involving a non-consecutive series of uncomplicated singleton term pregnancies, planned for IOL, with a fetus in cephalic presentation and unfavorable cervix as defined by a Bishop score ≤ 6. The Bishop score was evaluated by transvaginal digital examination and the cervical length and CSS by transvaginal ultrasound. The presence of CSS was defined as the sliding of the anterior cervical lip on the posterior one under gentle pressure of the transvaginal probe. The primary outcome of the study was successful vaginal delivery within 24 h. The secondary outcome was the induction-to-active-labor time. The interobserver agreement for the CSS was also evaluated.
Over a period of 12 months, 179 women were included. The CSS was found in 86 (48.0 %) patients and was associated with an increased likelihood of vaginal delivery within 24 h (60/86 or 69.8 % vs 27/93 or 29.0 %, P < 0.001) and a shorter induction-to-active-labor time (954 ± 618 min vs 1416 ± 660 min, P < 0.001). Multivariable regression analysis showed that the CSS was an independent predictor of vaginal delivery within 24 h (aOR 5.37, 95 % CI 2.26–12.75) and shorter induction-to-active-labor time interval (HR 1.81, 95 % CI 1.19–2.74). The interobserver variability based on intraclass correlation coefficient for the CSS was excellent (ICC = 0.90).
In women undergoing IOL with an unfavorable cervix, the CSS is associated with a higher frequency of vaginal delivery within 24 h and a shorter induction-to-active-labor time.
Induction of labour with oral misoprostol versus vaginal misoprostol: A before-after study
2022, Gynecologie Obstetrique Fertilite et Senologie
Le déclenchement artificiel du travail représentait 22 % des accouchements en 2016 en France. Le misoprostol oral (Angusta®) a été commercialisé en France au dernier trimestre 2018. L’objectif de notre étude était de comparer l’efficacité et la tolérance du déclenchement artificiel du travail sur col défavorable par misoprostol oral par rapport au misoprostol vaginal.
Nous avons réalisé une étude rétrospective avant-après sur deux périodes de deux ans, incluant toutes les femmes ayant bénéficié d’un déclenchement artificiel du travail sur col défavorable avec enfant viable en présentation céphalique. L’antécédent de césarienne et la parité ≥ 4 étaient une contre-indication au déclenchement par misoprostol. Pendant la première période de 2 ans, le déclenchement était réalisé à J0 par 50 μg de misoprostol administré par voie vaginale répété si besoin après 6 heures. La maturation était poursuivie à J1 si besoin par 50 μg de misoprostol administré par voie vaginale toutes les 4 heures avec 3 prises maximum. Pendant la seconde période de 2 ans, les patientes recevaient deux comprimés de 25 μg de misoprostol administrés par voie orale toutes les quatre heures si nécessaire avec 4 prises maximum. Les critères de jugement principaux était la voie d’accouchement et la tolérance néonatale.
Durant les deux périodes d’étude, 1199 femmes ont eu un déclenchement artificiel du travail par misoprostol vaginal et 1199 femmes ont eu un déclenchement artificiel du travail par misoprostol oral. Le taux de césarienne était de 21,8 % sur la première période (groupe misoprostol vaginal) et de 21,3 % sur la seconde (groupe misoprostol oral) (p = 0,83). Un score d’Apgar < 7 à 5 minutes a été observé parmi 23 (1,9 %) et 14 (1,2 %) nouveau-nés des groupes misoprostol vaginal et misoprostol oral (p = 0,14), respectivement. Un pH artériel au cordon < 7,00 a été observé parmi 6 (0,5 %) et 7 (0,6 %) nouveau-nés, respectivement (p = 0,99).
Le misoprotol administré par voie orale à la dose de 50 μg toutes les 4 heures (avec au maximum 4 prises) présente une efficacité et une tolérance similaire à celle du misoprotol administré par voie vaginale pour le déclenchement artificiel des femmes ayant un col défavorable.
The rate of induction of labor represented 22 % of deliveries in 2016 in France. Oral misoprostol (Angusta®) was marketed in France in the last quarter of 2018. The objective of our study was to compare the efficacy and safety of induction of labor with oral misoprostol compared to vaginal misoprostol in women with an unripe cervix.
We carried out a retrospective study before and after the implementation of oral misoprostol including all women with an unripe cervix who benefited from an induction of labor with a viable infant in vertex presentation, without uterine scar. During the first two-year period, women received 50 μg of misoprostol in the posterior fornix, repeated 6 hours later if needed. If labor had not started after 24 hours, women received another dose of 50 μg, which was repeated every 4 hours until labor was established, up to a total dose of 150 μg. During the second two-year period, women received two tablets of oral misoprostol 25 μg every four hours if necessary, up to a total dose of 200 μg. The primary endpoints were mode of delivery and neonatal safety.
During the two study periods, 1199 women received vaginal misoprostol and 1199 women received oral misoprostol including. The cesarean delivery rate was 21.8% during the first period and 21,3% during the second period (P = 0.83). A 5-minutes Apgar score < 7 was observed in 23 (1.9%) and 14 (1.2%) newborns in the vaginal misoprostol and oral misoprostol groups (P = 0.14), respectively. An arterial cord pH < 7.00 was observed in 6 (0.5%) and 7 (0.6%) newborns (P = 0.99), respectively.
Oral misoprostol administered at the dose of 50 μg every 4 hours (up to a total dose of 200 μg) is as effective and safe as the vaginal misoprostol to induce labor in women with an unripe cervix.

View all citing articles on Scopus

View full text

ArticlesInduction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial

Summary

Background

Methods

Findings

Interpretation

Funding

Section snippets

Background

Study design and participants

Results

Discussion

Am J Obstet Gynecol

Obstet Gynecol

Lancet

Lancet

Elective induction for pregnancies at or beyond 41 weeks of gestation and its impact on stillbirths: a systematic review with meta-analysis

BMC Public Health

Elective delivery in diabetic pregnant women

Cochrane Database Syst Rev

ACOG Practice Bulletin No 107: induction of labor

Obstet Gynecol

Cervical ripening in the Netherlands: a survey

Obstet Gynecol Int

Oral misoprostol for induction of labour

Cochrane Database Syst Rev

Vaginal misoprostol for cervical ripening and induction of labour

Cochrane Database Syst Rev

WHO recommendations for induction of labour

Articles
Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial