WHO recommendations on mechanical methods for induction of labour: web annex: evidence-to-decision framework

WHO recommendations on mechanical methods for induction of labour Web Annex. Evidence-to-decision framework ii WHO recommendations on mechanical methods for induction of labour. Web Annex. Evidence-to- decision framework ISBN 978-92-4-005580-3 (electronic version) © World Health Organization 2022 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. 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The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. This publication forms part of the WHO guideline entitled WHO recommendations on mechanical methods for induction of labour. It is being made publicly available for transparency purposes and information, in accordance with the WHO handbook for guideline development, 2nd edition (2014). iii Contents 1. BACKGROUND ......................................................................................................................................... 1 2. QUESTION ............................................................................................................................................... 1 3. ASSESSMENT ........................................................................................................................................... 2 3.1 EFFECTS (DESIRABLE AND UNDESIRABLE) ......................................................................................................... 2 3.2 VALUES .................................................................................................................................................. 23 3.3 EFFECTS AND VALUES ................................................................................................................................ 24 3.4 RESOURCES ............................................................................................................................................. 24 3.5 EQUITY .................................................................................................................................................. 27 3.6 ACCEPTABILITY ........................................................................................................................................ 27 3.7 FEASIBILITY ............................................................................................................................................. 29 4. GRADE SUMMARY OF JUDGEMENTS TABLE .......................................................................................... 31 5. GRADE SUMMARY OF FINDINGS TABLES ............................................................................................... 32 6. REFERENCES .......................................................................................................................................... 86 The main guideline document, WHO recommendations on mechanical methods for induction of labour, is available at: https://apps.who.int/iris/bitstream/handle/10665/363140/9789240055780-eng.pdf 1 1. Background Induction of labour may be initiated by pharmacologic or mechanical methods. Mechanical methods of labour induction are used to dilate the cervix, and include a range of procedures and devices: introducing a balloon catheter into the extra-amniotic space, laminaria tents into the cervix or the injection of fluid (saline or a solution containing prostaglandins) via a catheter into the extra- amniotic space (known as extra-amniotic saline infusion, or EASI). While standard urinary catheters (Foley) have been used for many years, double balloon (“Atad”) catheters have been developed for obstetric use (1). Mechanical methods have been used for induction of labour for decades, although more recently these have been replaced or supplemented by pharmacological methods (1). Despite this, mechanical methods have continued to be used in many obstetric settings as they are relatively low- cost, and are not generally associated with some of the serious side-effects that may occur with the use of pharmacological methods. 2. Question For women at or beyond term (P), should mechanical methods (alone or in combination with pharmacological methods) (I), compared with other types of induction methods or no intervention (C), be used to improve maternal and perinatal outcomes (O)? Problem: Perinatal risks associated with post-term pregnancy Perspective: Clinical practice recommendation – population perspective Population (P): Pregnant women at or beyond term Intervention (I): Labour induction with mechanical methods (alone or in combination with pharmacological methods) Comparison (C): Other types of induction methods or no intervention Priority outcomes (O): Critical outcomes:1 Maternal • Vaginal delivery not achieved within 24 hours • Caesarean section • Uterine hyperstimulation with fetal heart rate changes • Postpartum haemorrhage • Uterine rupture • Severe maternal morbidity or death Fetal/neonatal • Apgar score less than 7 at 5 minutes • Admission to a neonatal intensive care unit • Neonatal encephalopathy • Severe neonatal morbidity • Disability in childhood • Perinatal death. 1 These outcomes reflect the outcomes used in the 2011 WHO recommendations for induction of labour (available at: https://apps.who.int/iris/handle/10665/44531). An outcome ranked as 7 or more was considered “critical”, and an outcome ranked 4–6 was considered “important” (on a scale of 1 to 9, from not important to critical). The outcomes “maternal well-being” and “maternal satisfaction” have been added as part of this update. 2 Important outcomes: Maternal • Cervix unfavourable or unchanged after 24 hours • Oxytocin augmentation • Epidural rate • Uterine hyperstimulation without fetal heart rate changes • Instrumental vaginal birth • Meconium-stained amniotic fluid • Maternal side-effects (all) • Nausea • Vomiting • Diarrhoea • Maternal well-being • Women not satisfied with the care related to induction of labour (maternal satisfaction) • Caregiver not satisfied with the care related to induction of labour. 3. Assessment 3.1 Effects (desirable and undesirable) Evidence on effectiveness and safety Evidence on the effectiveness and safety of mechanical methods for the induction of labour is from a Cochrane systematic review updated in 2019 (1). The updated review includes 113 trials, with data on relevant outcomes from 105 studies (with a total of 22 373 women), as compared with the previous review published in 2012, which included data from 71 studies (with 9722 women) (2). Data were presented across 17 different comparisons, with different mechanical methods comparing only those interventions that were listed above it in a hierarchy of interventions as outlined in a generic protocol (3). The updated review includes a total of 22 different comparisons, 18 of which are of relevance to this guideline recommendation. The update excludes studies comparing mechanical methods with placebo or no treatment, and comparisons with misoprostol are limited to only low-dose misoprostol (1). The trials were carried out in hospital settings across the world (including in low- and middle-income countries), including: Australia (2 trials), Brazil (two trials), Canada (3 trials), Czechia (4 trials), Denmark (3 trials), Egypt (3 trials), Finland (1 trial), France (2 trials), India (13 trials), Islamic Republic of Iran (4 trials), Israel (6 trials), Italy (2 trials), Jordan (2 trials), Netherlands (4 trials), Nigeria (4 trials), Norway (1 trial), Pakistan (4 trials), the Russian Federation (1 trial), Rwanda (1 trial), Singapore (1 trial), Sri Lanka (3 trials), South Africa (3 trials), Sweden (2 trials), Tunisia (1 trial), Türkiye (1 trial), the United Kingdom of Great Britain and Northern Ireland (5 trials), and the United States of America (25 trials). The earliest trial was published in 1981, although the majority were published after 2000. Nine of the studies included only nulliparous women and two only multiparous women; the rest included both. Four studies recruited only women with a history of caesarean section, but in most studies such women were excluded. The majority of studies only recruited women at term (gestational age 37 weeks or more). The review examined four broad types of interventions: • balloon catheter versus other interventions (other mechanical or pharmacologic, or mixed); • laminaria tent versus other interventions; • extra-amniotic infusion versus other interventions; and 3 • any mechanical method combined with other (non-mechanical) intervention versus other interventions. Of the 22 comparisons made, only 18 of them were relevant to the PICO for this guideline recommendation and presented to the GDG. Effects of interventions: Comparison 1 – Balloon catheter (Foley or Atad) versus vaginal prostaglandin E2 (PGE2) This comparison included 28 trials with data for 6619 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference in outcome for vaginal delivery not achieved within 24 hours between balloon catheter compared with vaginal PGE2 (very-low-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: Balloon catheter probably reduces the risk of uterine hyperstimulation with fetal heart rate changes compared with vaginal PGE2 (6 trials, 1966 women; relative risk [RR] 0.35, 95% confidence interval [CI] 0.18 to 0.67; moderate-certainty evidence). Postpartum haemorrhage (PPH): Balloon catheter makes little or no difference to PPH compared with vaginal PGE2 (8 trials, 2215 women; RR 0.82, 95% CI 0.63 to 1.06; low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between balloon catheter compared with vaginal PGE2 for uterine rupture or severe maternal morbidity or death (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between balloon catheter compared with vaginal PGE2 for severe maternal morbidity or death (very-low- certainty evidence). Important: Oxytocin augmentation: It is uncertain whether there is any difference between balloon catheter compared with vaginal PGE2 for oxytocin augmentation (very-low-certainty evidence). Epidural rate: Balloon catheter may increase epidural rate compared with vaginal PGE2 (8 trials, 2828 women; RR 1.14, 95% CI 1.00 to 1.29; low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Balloon catheter probably reduces uterine hyperstimulation without fetal heart rate changes compared with vaginal PGE2 (15 trials, 2444 women; RR 0.27, 95% CI 0.11 to 0.66; moderate-certainty evidence). Instrumental vaginal birth: Balloon catheter probably has little or no effect on instrumental vaginal birth compared with vaginal PGE2 (16 trials, 4514 women; RR 0.93, 95% CI 0.79 to 1.09; moderate- certainty evidence). Meconium-stained liquor: Balloon catheter may make little or no difference to meconium-stained liquor compared with vaginal PGE2 (4 trials, 964 women; RR 0.89, 95% CI 0.67 to 1.19; low-certainty evidence). 4 Maternal fever during labour: Balloon catheter may make little or no difference to maternal fever during labour compared with vaginal PGE2 (7 trials, 2362 women; RR 0.87, 95% CI 0.65 to 1.17; low- certainty evidence). Women not satisfied with care: Balloon catheter may make little or no difference to maternal satisfaction compared with vaginal PGE2 (1 trial, 93 women; RR 0.61, 95% CI 0.39 to 0.97; low- certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: Balloon catheter may make little or no difference to Apgar less than 7 at 5 minutes compared with vaginal PGE2 (14 trials, 4271 infants; RR 0.74, 95% CI 0.49 to 1.14; low-certainty evidence). Admission to a neonatal intensive care unit: Balloon catheter may make little or no difference to admission to a neonatal intensive care unit compared with vaginal PGE2 (12 trials, 3647 infants; RR 0.82, 95% CI 0.65 to 1.04; low-certainty evidence). Severe neonatal morbidity or perinatal death: Balloon catheter probably reduces severe neonatal morbidity or perinatal death compared with vaginal PGE2 (8 trials, 2757 infants; RR 0.48, 95% CI 0.25 to 0.93; moderate-certainty evidence). Perinatal death: Balloon catheter may make little or no difference to perinatal death compared with vaginal PGE2 (5 trials, 1036 infants; RR 0.21; 95% CI 0.01 to 4.27; low-certainty evidence). Effects of interventions: Comparison 2 – Balloon catheter (Foley or Atad) versus intracervical PGE2 This comparison included 10 trials with data for 1428 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). Caesarean section: Balloon catheter probably makes little or no difference to caesarean section compared with intracervical PGE2 (9 trials, 1309 women; RR 0.97, 95% CI 0.81 to 1.15; moderate- certainty evidence). Uterine hyperstimulation with fetal heart rate changes/PPH: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for uterine hyperstimulation with fetal heart rate changes or PPH (both very-low-certainty evidence). Important: Cervix unfavourable or unchanged after 24 hours: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for cervix unfavourable or unchanged after 24 hours (very-low-certainty evidence). 5 Oxytocin augmentation: Balloon catheter may make little or no difference to oxytocin augmentation compared with intracervical PGE2 (1 trial, 400 women; RR 1.08, 95% CI 0.93 to 1.26; low-certainty evidence). Epidural rate: Balloon catheter may make little or no difference to epidural rate compared with intracervical PGE2 (1 trial, 149 women; RR 0.91, 95% CI 0.81 to 1.02; low-certainty evidence). Instrumental vaginal birth: Balloon catheter may make little or no difference to instrumental vaginal birth compared with intracervical PGE2 (3 trials, 337 women; RR 1.18, 95% CI 0.68 to 2.05; low- certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for meconium-stained liquor (very-low-certainty evidence). Maternal side-effects: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for maternal side-effects (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than seven at 5 minutes: Balloon catheter may make little or no difference to Apgar score less than 7 at 5 minutes compared with intracervical PGE2 (2 trials, 475 infants; RR 0.79; 95% CI 0.41 to 1.53; low-certainty evidence). Admission to a neonatal intensive care unit: Balloon catheter may make little or no difference to admission to a neonatal intensive care unit compared with intracervical PGE2 (1 trial, 400 infants; RR 0.88, 95% CI 0.60 to 1.31; low-certainty evidence). Severe neonatal morbidity: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for severe neonatal morbidity (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 3 – Balloon catheter (Foley or Atad) versus low-dose vaginal misoprostol This comparison included 13 trials with data for 1818 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). 6 Serious maternal morbidity or death: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for serious maternal morbidity or death (very-low-certainty evidence). Caesarean section: Balloon catheter probably increases caesarean section compared with low-dose vaginal misoprostol (12 trials, 1756 women; RR 1.28, 95% CI 1.02 to 1.60; moderate-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: Balloon catheter may reduce uterine hyperstimulation with fetal heart rate changes compared with low-dose vaginal misoprostol (8 trials, 1322 women; RR 0.39, 95% CI 0.18 to 0.85; low-certainty evidence). Important: Cervix unfavourable or unchanged after 12 hours: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for cervical dilatation after 12 hours (very-low-certainty evidence). Oxytocin augmentation: Balloon catheter may increase oxytocin augmentation compared with low- dose vaginal misoprostol (9 trials, 911 women; RR 1.62, 95% CI 1.38 to 1.90; low-certainty evidence). Epidural rate: Balloon catheter probably increases epidural rate compared with low-dose vaginal misoprostol (2 trials, 517 women; RR 1.22, 95% CI 1.06 to 1.41; moderate-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Balloon catheter probably reduces uterine hyperstimulation without fetal heart rate changes compared with low-dose vaginal misoprostol (9 trials, 1139 women; RR 0.25, 95% CI 0.14 to 0.44; moderate-certainty evidence). Instrumental vaginal birth: Balloon catheter may make little or no difference to instrumental vaginal birth compared with low-dose vaginal misoprostol (4 trials, 721 women; RR 0.72, 95% CI 0.50 to 1.05; low-certainty evidence). Meconium-stained liquor: Balloon catheter probably reduces meconium-stained liquor compared with low-dose vaginal misoprostol (7 trials, 1268 women; RR 0.64, 95% CI 0.48 to 0.87; moderate- certainty evidence). Maternal vomiting or maternal fever during labour: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for maternal vomiting or maternal fever during labour (both very-low-certainty evidence). Fetal/neonatal outcomes Critical: Severe neonatal morbidity: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for severe neonatal morbidity (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for perinatal death (very-low-certainty evidence). Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for Apgar score < 7 at 5 minutes (very- low-certainty evidence). 7 Admission to a neonatal intensive care unit: Balloon catheter may make little or no difference to admission to a neonatal intensive care unit compared with low-dose vaginal misoprostol (9 trials, 1302 infants; RR 1.00, 95% CI 0.61 to 1.63; low-certainty evidence). Effects of interventions: Comparison 4 – Balloon (Foley or Atad) versus low-dose oral misoprostol This comparison included seven trials with data for 3178 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: Balloon catheter probably increases vaginal delivery not achieved within 24 hours compared with low-dose oral misoprostol (2 trials, 782 women; RR 1.28, 95% CI 1.13 to 1.46; moderate-certainty evidence). Caesarean section: Balloon catheter probably increases caesarean section compared with low-dose oral misoprostol (7 trials, 3178 women; RR 1.17, 95% CI 1.04 to 1.32; moderate-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: Balloon catheter may make little or no difference to uterine hyperstimulation with fetal heart rate changes compared with low-dose oral misoprostol (2 trials, 2033 women; RR 0.81, 95% CI 0.48 to 1.38; low-certainty evidence). Postpartum haemorrhage (PPH): Balloon catheter may make little or no difference to PPH compared with low-dose oral misoprostol (5 trials, 2966 women; RR 1.03, 95% CI 0.79 to 1.34; low- certainty evidence). Uterine rupture: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for uterine rupture (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for severe maternal morbidity or death ( very-low-certainty evidence). Maternal death: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for maternal death (very-low-certainty evidence). Important: Cervix unfavourable after 24 hours: Balloon catheter may make little or no difference to cervix unfavourable after 24 hours compared with low-dose oral misoprostol (4 trials, 994 women; RR 0.98, 95% CI 0.61 to 1.56; low-certainty evidence). Oxytocin augmentation: Balloon catheter may increase oxytocin augmentation compared with low- dose oral misoprostol (5 trials, 2847 women; RR 1.28, 95% CI 1.09 to 1.49; low-certainty evidence). Epidural rate: Balloon catheter probably makes little or no difference to epidural rate compared with low-dose oral misoprostol (3 trials, 2365 women; RR 1.08, 95% CI 0.96 to 1.22; moderate- certainty evidence). 8 Uterine hyperstimulation without fetal heart rate changes: Balloon catheter may make little or no difference to uterine hyperstimulation without fetal heart rate changes compared with low-dose oral misoprostol (5 trials, 2838 women; RR 0.50, 95% CI 0.12 to 2.07; low-certainty evidence). Instrumental vaginal birth: Balloon catheter probably reduces instrumental vaginal birth compared with low-dose oral misoprostol (3 trials, 2627 women; RR 0.71, 95% CI 0.55 to 0.92; moderate- certainty evidence). Meconium-stained liquor: Balloon catheter may make little or no difference to meconium-stained liquor compared with low-dose oral misoprostol (3 trials, 2627 women; RR 0.77, 95% CI 0.44 to 1.35; low-certainty evidence). Maternal side-effects (all): Balloon catheter may make little or no difference to maternal side- effects (all) compared with low-dose oral misoprostol (2 trials, 662 women; RR 0.61, 95% CI 0.33 to 1.13; low-certainty evidence). Maternal vomiting: Balloon catheter may make little or no difference to maternal vomiting compared with low-dose oral misoprostol (2 trials, 662 women; RR 0.73, 95% CI 0.37 to 1.46; low- certainty evidence). Maternal diarrhoea: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for maternal diarrhoea (very-low-certainty evidence). Maternal fever during labour: Balloon catheter probably makes little or no difference to maternal fever during labour compared with low-dose oral misoprostol (2 trials, 2033 women; RR 0.98, 95% CI 0.78 to 1.24; moderate-certainty evidence). Maternal satisfaction: Balloon catheter probably increases maternal satisfaction compared with low-dose oral misoprostol (1 trial, 602 women; RR 1.70, 95% CI 1.15 to 2.50; moderate-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: Balloon catheter may make little or no difference to Apgar score less than 7 at 5 minutes compared with low-dose oral misoprostol (4 trials, 2693 infants; RR 0.71; 95% CI 0.38 to 1.32; low-certainty evidence). Admission to a neonatal intensive care unit: Balloon catheter may make little or no difference to admission to a neonatal intensive care unit compared with low-dose oral misoprostol (5 trials, 2873 infants; RR 0.82, 95% CI 0.58 to 1.17; low-certainty evidence). Neonatal encephalopathy: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for neonatal encephalopathy (very-low-certainty evidence). Severe neonatal morbidity or perinatal death: Balloon catheter may make little or no difference to severe neonatal morbidity or perinatal death compared with low-dose oral misoprostol (3 trials, 2627 infants; RR 1.11, 95% CI 0.60 to 2.06; low-certainty evidence). 9 Effects of interventions: Comparison 5 – Balloon (Foley or Atad) versus oxytocin This comparison included eight trials with data for 781 women. Maternal outcomes Critical: Caesarean section: Balloon catheter probably reduces caesarean section compared with oxytocin (8 trials, 781 women; RR 0.68, 95% CI 0.56 to 0.83; moderate-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Postpartum haemorrhage (PPH): It is uncertain whether there is any difference between balloon catheter compared with oxytocin for PPH (very-low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for uterine rupture (very-low-certainty evidence). Serious maternal morbidity or death: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for serious maternal morbidity or death (very-low- certainty evidence). Important: Cervix unfavourable after 24 hours: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for cervix unfavourable after 24 hours (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for meconium-stained liquor (very-low-certainty evidence). Maternal fever during labour: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for maternal fever during labour (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for Apgar score less than 7 at 5 minutes (very-low- certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for admission to a neonatal intensive care unit (very-low- certainty evidence). 10 Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 6 – Laminaria tent versus vaginal PGE2 This comparison included five trials with data for 263 women. Maternal outcomes Critical: Caesarean section: Laminaria tent may make little or no difference to caesarean section compared with vaginal PGE2 (5 trials, 263 women; RR 0.91, 95% CI 0.56 to 1.48; low-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: Laminaria tent may reduce uterine hyperstimulation with fetal heart rate changes compared with vaginal PGE2 (3 trials, 188 women; RR 0.11, 95% CI 0.02 to 0.60; low-certainty evidence). Severe maternal morbidity: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for severe maternal morbidity (very-low-certainty evidence). Important: Epidural rate: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for epidural rate (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Laminaria tent may reduce uterine hyperstimulation without fetal heart rate changes compared with vaginal PGE2 (3 trials, 180 women; RR 0.22, 95% CI 0.09 to 0.49; low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for meconium-stained liquor (very-low-certainty evidence). Maternal side-effects (nausea): It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for maternal side-effects (nausea) (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for severe neonatal morbidity or perinatal death (very-low-certainty evidence). 11 Perinatal death: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 7 – Laminaria tent versus intracervical PGE2 This comparison included five trials with data for 920 women. Maternal outcomes Critical: Caesarean section: Laminaria tent may make little or no difference to caesarean section compared with intracervical PGE2 (5 trials, 920 women; RR 1.16, 95% CI 0.93 to 1.45; low-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for severe maternal morbidity or death (very-low- certainty evidence). Important: Oxytocin augmentation: Laminaria tent may increase oxytocin augmentation compared with intracervical PGE2 (1 trial, 185 women; RR 1.41, 95% CI 1.21 to 1.64; low-certainty evidence). Instrumental vaginal birth: Laminaria tent may make little or no difference to instrumental vaginal birth compared with intracervical PGE2 (3 trials, 424 women; RR 1.05, 95% CI 0.65 to 1.69; low- certainty evidence). Cervix unfavourable or unchanged after 24 hours: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for cervix unfavourable or unchanged after 24 hours (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Maternal side-effects: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for maternal side-effects (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for Apgar score less than 7 at 5 minutes (very-low- certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for admission to a neonatal intensive care unit (very-low-certainty evidence). 12 Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 8 – Laminaria tent versus oxytocin There were data from two trials with 73 women for only one relevant outcome. Maternal outcome Critical: Caesarean section: It is uncertain whether there is any difference between laminaria tent compared with oxytocin for caesarean section (very-low-certainty evidence). Effects of interventions: Comparison 9 – Extra-amniotic saline infusion (EASI) versus vaginal PGE2 This comparison included two trials with data for 221 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: EASI may increase vaginal delivery not achieved within 24 hours compared with vaginal PGE2 (1 trial, 109 women; RR 1.74, 95% CI 1.21 to 2.49; low- certainty evidence). Caesarean section or uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for caesarean section or uterine hyperstimulation with fetal heart rate changes (both very-low-certainty evidence). Important: Oxytocin augmentation: EASI may increase oxytocin augmentation compared with vaginal PGE2 (1 trial, 109 women; RR 12.71, 95% CI 3.20 to 50.57; low-certainty evidence). Epidural rate: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for epidural rate (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for meconium-stained liquor (very-low-certainty evidence). Maternal satisfaction: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for maternal satisfaction (very-low-certainty evidence). 13 Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for admission to a neonatal intensive care unit (very-low-certainty evidence). Effects of interventions: Comparison 10 – EASI versus intracervical PGE2 This comparison included two trials with data for 155 women. Maternal outcomes Critical: Caesarean section: It is uncertain whether there is any difference between EASI compared with intracervical PGE2 for caesarean section (very-low-certainty evidence). Important: Cervix unfavourable or unchanged after 24 hours: EASI may reduce cervix unfavourable or unchanged after 12–24 hours compared with intracervical PGE2 (1 trial, 85 women; RR 0.06, 95% CI 0.00 to 0.97; low-certainty evidence). Oxytocin augmentation or: It is uncertain whether there is any difference between EASI compared with intracervical PGE2 for oxytocin augmentation (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between EASI compared with intracervical PGE2 for instrumental vaginal birth (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between EASI compared with intracervical PGE2 for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Effects of interventions: Comparison 11 – Any mechanical method plus PGE2 versus PGE2 alone This comparison included eight trials with data for 639 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). Caesarean section: Any mechanical method plus PGE2 may make little or no difference to caesarean section compared with PGE2 alone (7 trials, 517 women; RR 0.96, 95% CI 0.66 to 1.40; low-certainty evidence). 14 Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Postpartum haemorrhage (PPH): It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for PPH (very-low-certainty evidence). Important: Cervix unfavourable after 24 hours: Any mechanical method plus PGE2 may reduce cervix unfavourable after 24 hours compared with PGE2 alone (1 trial, 122 women; RR 0.52, 95% CI 0.31 to 0.85; low-certainty evidence). Oxytocin augmentation: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for oxytocin augmentation (very-low-certainty evidence). Epidural rate: Any mechanical method plus PGE2 may make little or no difference to epidural rate compared with PGE2 alone (1 trial, 39 women; RR 0.98, 95% CI 0.77 to 1.24; low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for meconium-stained liquor (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for admission to neonatal intensive care (very-low-certainty evidence). Effects of interventions: Comparison 12 – Any mechanical method plus PGE2 versus low- dose misoprostol alone This comparison included only one trial with data for 127 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: Any mechanical method plus PGE2 may reduce vaginal delivery not achieved within 24 hours compared with low-dose misoprostol alone (1 trial, 127 women; RR 0.32, 95% CI 0.12 to 0.82; low-certainty evidence). 15 Caesarean section: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for caesarean section (very-low-certainty evidence). Important: Cervix unfavourable after 24 hours: Any mechanical method plus PGE2 may reduce cervix unfavourable after 24 hours compared with low-dose misoprostol alone (1 trial, 127 women; RR 0.41, 95% CI 0.25 to 0.67; low-certainty evidence). Oxytocin augmentation: Any mechanical method plus PGE2 may increase oxytocin augmentation compared with low-dose misoprostol alone (1 trial, 127 women; RR 1.21, 95% CI 1.01 to 1.46; low- certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Any mechanical method plus PGE2 may increase uterine hyperstimulation without fetal heart rate changes compared with low-dose misoprostol alone (1 trial, 127 women; RR 4.05, 95% CI 1.44 to 11.38; low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for instrumental vaginal birth (very- low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for meconium-stained liquor (very- low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for admission to neonatal intensive care (very-low-certainty evidence). Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for serious neonatal morbidity/perinatal death (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 13 – Any mechanical method plus PGE2 versus oxytocin alone This comparison included only one trial with data for 44 women and reported only two relevant outcomes. 16 Maternal outcomes Critical: Caesarean section: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with oxytocin alone for caesarean section (very-low-certainty evidence). Important: Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with oxytocin alone for instrumental vaginal birth (very-low-certainty evidence). Effects of interventions: Comparison 14 – Any mechanical method and low-dose misoprostol versus PGE2 alone This comparison included only one trial with data for 350 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: Any mechanical method plus low-dose misoprostol may make little or no difference to vaginal delivery not achieved within 24 hours compared with PGE2 alone (1 trial, 350 women; RR 1.14, 95% CI 0.89 to 1.46; low-certainty evidence). Caesarean section: Any mechanical method plus low-dose misoprostol may make little or no difference to caesarean section compared with PGE2 alone (1 trial, 350 women; RR 0.85, 95% CI 0.57 to 1.25; low-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Postpartum haemorrhage (PPH): Any mechanical method plus low-dose misoprostol may make little or no difference to PPH compared with PGE2 alone (1 trial, 350 women; RR 0.98, 95% CI 0.67 to 1.41; low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for uterine rupture (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for severe maternal morbidity or death (very-low-certainty evidence). Important: Oxytocin augmentation: Any mechanical method plus low-dose misoprostol probably reduces oxytocin augmentation compared with PGE2 alone (1 trial, 350 women; RR 0.54, 95% CI 0.34 to 0.86; moderate-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). 17 Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for instrumental vaginal birth (very- low-certainty evidence). Meconium-stained liquor: Any mechanical method plus low-dose misoprostol may make little or no difference to meconium-stained liquor compared with PGE2 alone (1 trial, 350 women; RR 1.15, 95% CI 0.60 to 2.23; low-certainty evidence). Maternal side-effects (all): Any mechanical method plus low-dose misoprostol may make little or no difference to maternal side-effects compared with PGE2 alone (1 trial, 350 women; RR 1.16, 95% CI 0.95 to 1.43; low-certainty evidence) or to maternal nausea (one trial, 350 women; RR 1.65, 95% CI 0.98 to 2.79; low-certainty evidence). Any mechanical method plus low-dose misoprostol may increase maternal diarrhoea compared with PGE2 alone (1 trial, 350 women; RR 3.27, 95% CI 1.53 to 9.00; low-certainty evidence). It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for maternal fever in labour (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for admission to a neonatal intensive care unit (very-low-certainty evidence). Severe neonatal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for severe neonatal morbidity or death (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 15 – Any mechanical method and low-dose misoprostol versus low-dose misoprostol This comparison included seven trials with data for 1422 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). Caesarean section: Any mechanical method plus low-dose misoprostol may make little or no difference to caesarean section compared with low-dose misoprostol (7 trials, 1422 women; RR 0.87, 95% CI 0.66 to 1.15; low-certainty evidence). 18 Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Postpartum haemorrhage (PPH): Any mechanical method plus low-dose misoprostol may make little or no difference to PPH compared with low-dose misoprostol 2 trials, 466 women; RR 0.93, 95% CI 0.65 to 1.33; low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for uterine rupture (very-low- certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for severe maternal morbidity or death (very-low-certainty evidence). Important: Cervix unfavourable or unchanged after 12 hours: Any mechanical method plus low-dose misoprostol may reduce cervix unfavourable or unchanged after 12 hours compared with low-dose misoprostol (1 trial, 140 women; RR 0.27, 95% CI 0.08 to 0.94; low-certainty evidence). Oxytocin augmentation: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for oxytocin augmentation (very-low-certainty evidence). Epidural rate: Any mechanical method plus low-dose misoprostol may make little or no difference to epidural rate compared with low-dose misoprostol (3 trials, 443 women; RR 1.00, 95% CI 0.91 to 1.10; moderate-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Any mechanical method plus low-dose misoprostol probably reduces uterine hyperstimulation without fetal heart rate changes compared with low-dose misoprostol (4 trials, 982 women; RR 0.53, 95% CI 0.32 to 0.90; moderate-certainty evidence). Instrumental vaginal birth: Any mechanical method plus low-dose misoprostol may make little or no difference to instrumental vaginal birth compared with low-dose misoprostol (3 trials, 676 women; RR 0.93, 95% CI 0.58 to 1.51; low-certainty evidence). Meconium-stained liquor: Any mechanical method plus low-dose misoprostol may make little or no difference to meconium-stained liquor compared with low-dose misoprostol (6 trials, 1243 women; RR 0.61, 95% CI 0.35 to 1.05; low-certainty evidence). Maternal side-effects (all): Any mechanical method plus low-dose misoprostol may make little or no difference to maternal side-effects (1 trial, 300 women; RR 1.06, 95% CI 0.87 to 1.30; low-certainty evidence). Maternal nausea: Any mechanical method plus low-dose misoprostol may make little or no difference to maternal nausea compared with low-dose misoprostol (1 trial, 300 women; RR 1.37, 95% CI 0.84 to 2.23; low-certainty evidence). 19 Maternal diarrhoea: Any mechanical method plus low-dose misoprostol may make little or no difference to maternal diarrhoea compared with low-dose misoprostol (1 trial, 298 women; RR 3.38, 95% CI 1.40 to 8.17; low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: Any mechanical method plus low-dose misoprostol may make little or no difference to Apgar score less than 7 at 5 minutes compared with low-dose misoprostol (3 trials, 802 infants; RR 0.71; 95% CI 0.37 to 1.36; low-certainty evidence). Admission to a neonatal intensive care unit: Any mechanical method plus low-dose misoprostol probably reduces admission to a neonatal intensive care unit compared with low-dose misoprostol (6 trials, 1246 infants; RR 0.57, 95% CI 0.36 to 0.91; moderate-certainty evidence). Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for perinatal death (very-low- certainty evidence). Effects of interventions: Comparison 16 – Any mechanical method and oxytocin versus PGE2 alone This comparison included four trials with data for 713 women. Maternal outcomes Critical: Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Caesarean section: Any mechanical method plus oxytocin may make little or no difference to caesarean section compared with PGE2 alone (4 trials, 713 women; RR 0.93, 95% CI 0.72 to 1.20; low-certainty evidence). Postpartum haemorrhage (PPH): It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for PPH (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with prostaglandin PGE2 alone for severe maternal morbidity or death (very-low-certainty evidence). Important: Uterine hyperstimulation without fetal heart rate changes: Any mechanical method plus oxytocin may increase uterine hyperstimulation without fetal heart rate changes compared with PGE2 alone (1 trial, 151 women; RR 2.19, 95% CI 1.39 to 3.46; low-certainty evidence). 20 Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for meconium-stained liquor (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for admission to a neonatal intensive care unit (very-low-certainty evidence). Effects of interventions: Comparison 17 – Any mechanical method and oxytocin versus misoprostol alone This comparison included six trials with data for 1779 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: Any mechanical method plus oxytocin probably reduces vaginal delivery not achieved within 24 hours compared with misoprostol alone (2 trials, 362 women; RR 0.48, 95% CI 0.37 to 0.63; moderate-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Caesarean section: Any mechanical method plus oxytocin probably makes little or no difference to caesarean section compared with misoprostol (5 trials, 1779 women; RR 0.95, 95% CI 0.80 to 1.12; moderate-certainty evidence). Important: Oxytocin augmentation: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for oxytocin augmentation (very-low- certainty evidence). Epidural rate: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for epidural rate (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Any mechanical method plus oxytocin probably reduces uterine hyperstimulation without fetal heart rate changes compared with misoprostol alone (3 trials, 498 women; RR 0.52, 95% CI 0.30 to 0.92; moderate-certainty evidence). 21 Meconium-stained liquor: Any mechanical method plus oxytocin may make little or no difference to meconium-stained liquor compared with misoprostol alone (2 trials, 362 women; RR 0.72, 95% CI 0.43 to 1.19; low-certainty evidence). Maternal fever during labour: Any mechanical method plus oxytocin may reduce maternal fever during labour compared with misoprostol alone (2 trials, 298 women; RR 0.13, 95% CI 0.04 to 0.50; low-certainty evidence). Women not satisfied: Any mechanical method plus oxytocin probably increases dissatisfaction compared with misoprostol alone (1 trial, 866 women; RR 1.68, 95% CI 1.47 to 1.93; moderate- certainty evidence). Fetal/neonatal outcomes Critical: Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: Any mechanical method plus oxytocin probably reduces admission to a neonatal intensive care unit compared with misoprostol alone (four trials, 1599 infants; RR 0.66, 95% CI 0.49 to 0.90; moderate-certainty evidence). Perinatal death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 18 – Any mechanical method and oxytocin versus oxytocin alone This comparison included six trials with data for 718 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). Caesarean section: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for caesarean section (very-low-certainty evidence). Postpartum haemorrhage (PPH): It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for PPH (very-low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for uterine rupture (very-low-certainty evidence). 22 Severe maternal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for severe maternal morbidity or death (very-low-certainty evidence). Important: Epidural rate: Any mechanical method plus oxytocin may make little or no difference to epidural rate compared with oxytocin alone (1 trial, 127 women; RR 1.03, 95% CI 0.98 to 1.09; low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for instrumental vaginal birth (very-low- certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for meconium-stained liquor (very-low- certainty evidence). Fetal/newborn outcomes Critical: Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Admission to a neonatal intensive care unit: Any mechanical method plus oxytocin may make little or no difference to admission to a neonatal intensive care unit (3 trials, 400 infants; RR 0.98, 95% CI 0.61 to 1.58; low-certainty evidence). Additional considerations The GDG noted that the evidence describes various combinations of different mechanical methods of induction, in comparison to each other, and with or without the addition of (concurrent or sequential) pharmacologic methods. The GDG discussed the use of mechanical methods in the context of considering them as potential methods for induction of labour, rather than determining whether a particular induction method (or combination of methods) is “superior” to another. Given the comparatively sparse evidence on the use of laminaria tents and EASI, the GDG focused their recommendations on the use of balloon catheters. Judgement on desirable effects How substantial are the desirable anticipated effects of mechanical methods for induction of labour? Judgement Don’t know Varies Trivial Small Moderate Large 23 Judgement on undesirable effects How substantial are the undesirable anticipated effects of mechanical methods for induction of labour? Judgement Don’t know Varies Large Moderate Small Trivial Certainty of the evidence For most comparisons and outcomes the evidence was low or very-low certainty with little or no difference between groups. The majority of the evidence on effectiveness compared the use of balloon catheters with other methods. Low‐ to moderate‐certainty evidence shows mechanical induction with a balloon catheter is probably as effective as induction of labour with vaginal PGE2 and may have fewer adverse effects. Moderate‐quality evidence shows a balloon catheter may be slightly less effective as an induction method compared to oral misoprostol, but it remains unclear if there is a difference in safety outcomes for the neonate. When compared to low‐dose vaginal misoprostol, low‐quality evidence shows a balloon catheter may be less effective, but probably has a better safety profile. Moderate-quality evidence indicates that use of a balloon catheter probably reduces the risk of a caesarean section when compared to oxytocin, and this may also be the case in women with a previous caesarean section undergoing induction of labour. What is the overall certainty of the evidence on mechanical methods for induction of labour? Judgement No included studies Very low Low Moderate High 3.2 Values Evidence on values No direct evidence was identified to address this question. Additional considerations A 2019 QES of women’s experiences of labour induction (Coates et al., 2019) (4) was selected for inclusion in the EtD on the basis of quality (high) and inclusion of the greatest breadth of qualitative primary studies compared with two other eligible QES (5, 6) and one scoping review (7). Primary studies not included in Coates et al. (2019) were screened for additional relevant findings and/or income-settings and/or clinician views. Five additional studies were identified and relevant findings extracted (8-12). 24 The QES and primary studies identified that the key outcomes of interest for women in relation to labour induction were: • the well-being of their baby • the duration of the process between induction and birth • the likelihood and severity of pain • the likelihood of caesarean delivery. Women placed great value on knowing about the potential benefits and harms of labour induction. Judgement on values Is there any important uncertainty or variability about values relating to the use of mechanical methods for induction of labour? Judgement Important uncertainty or variability Possibly important uncertainty or variability Probably no important uncertainty or variability No important uncertainty or variability 3.3 Effects and values Balance of effects and values Does the balance between desirable and undesirable effects favour the intervention (labour induction with mechanical methods alone or in combination with pharmacological methods) or the comparison (other types of induction methods or no intervention)? Judgement on the balance of effects and values Judgement Don’t know Varies Favours use of other methods Probably favours use of other methods Does not favour either Probably favours use of mechanical methods Favours use of mechanical methods 3.4 Resources Evidence on resources Economic evidence is very limited, derived from a small number of trial-based primary studies conducted in high-income settings. Any conclusions drawn from these studies should be viewed as extremely tentative. Economic analyses were eligible if the majority of the population was either at or beyond term and otherwise low risk. Included studies Two trial-based economic studies evaluating costs and cost-effectiveness were identified. 25 Ten Eikelder et al. (2018) undertook a cost-effectiveness analysis from a hospital perspective in the period from admission to antenatal care (ANC) ward to discharge (13). Effectiveness data were derived from the ten Eikelder et al. (2016) (PROBAAT-2) study, a randomized controlled trial (RCT) in 29 hospitals in the Netherlands comparing oral misoprostol with Foley catheter for labour induction in 1845 women at term with an unfavourable cervix and without previous caesarean section (14). Van Baaren et al. (2013) undertook a cost-effectiveness analysis from a hospital perspective in the period from admission to ANC ward to six weeks postpartum. Cost data were estimated using different methods and sources and expressed in 2009 Euros (15). Effectiveness data were derived from Jozwiak et al. (2011) (the PROBAAT study), an RCT in 12 hospitals in the Netherlands comparing Foley catheter with vaginal PGE2 gel for labour induction in 819 women at term with an unfavourable cervix and without previous caesarean section (16). Both studies by ten Eikelder et al. (2018) and van Baaren et al. (2013) are included in the 2019 Cochrane review of mechanical methods for induction of labour (1). Cost It is uncertain if Foley catheter is cost-saving for labour induction compared with oral misoprostol (mean difference [MD] 312 in favour of Foley catheter; 95% confidence interval [CI] 508 to 1063), even with varying resource use and unit price estimates. ten Eikelder et al. reported that oral misoprostol induction in multiparous women resulted in lower costs, mainly due to shorter time from induction to delivery (13). It is uncertain if Foley catheter is cost-saving for labour induction compared with vaginal PGE2 gel (MD 222 in favour of vaginal PGE2 gel; 95% CI –157 to 633). Van Baaren et al. (2013) reported that vaginal PGE2 gel induction in multiparous women resulted in lower costs, mainly due to shorter time from induction to delivery (15). Overall budget impact Overall budget impacts of a policy of mechanical methods for labour induction were not analysed in the studies. Value-for-money analyses ten Eikelder et al. reported that the incremental cost-effectiveness ratio (ICER) for the composite outcome of asphyxia and postpartum haemorrhage (PPH) was non-informative due to comparable efficacy between the interventions. They noted that, at a willingness-to-pay threshold of at least 30 000 (2013 Euros) per woman, oral misoprostol may be cost-effective for the outcome of caesarean section (15). Van Baaren et al. did not find the ICER for caesarean section to be informative due to comparable efficacy between the interventions. Using a Foley catheter, the ICER to prevent one neonatal admission was 2708 (2009 Euros), and 5257 to prevent one composite outcome of asphyxia and PPH (15). Additional considerations None. 26 Main resource requirements Resource Description Staff • Staff for placement/insertion of induction agent • Staff for monitoring and assessment until delivery Training • Training in performance and monitoring of labour induction Supplies • Induction agents (Foley or Cook’s catheter) • Ultrasound gel Equipment and infrastructure • Tools to accurately estimate gestational age (e.g. previous early antenatal ultrasound, gestational age wheel) • Clinical protocol for safe labour induction • Electronic fetal heart rate monitors, oxytocin infusion pumps • Equipment for vaginal birth • Availability of appropriate space, beds or both for women undergoing induction • Capacity to perform caesarean section (if required) Time • Time to deliver information on process, risks and benefits of labour induction (preferably during late-pregnancy ANC visit) • 20 minutes for initial assessment • Time for placement/insertion of agent for cervical ripening agent Supervision and monitoring • 60 minutes of additional monitoring after insertion of catheter • Intermittent monitoring and assessment until childbirth Judgement on costs What is the impact on costs of mechanical methods for induction of labour? Judgement Don’t know Varies Large costs Moderate costs Negligible costs or savings Moderate savings Large savings Certainty of the evidence What is the certainty of the evidence on costs? Judgement No included studies Very low Low Moderate High Judgement on cost-effectiveness Is the intervention cost-effective? 27 Judgement Don’t know Varies Favours use of other methods Probably favours use of other methods Does not favour either Probably favours mechanical methods Favours mechanical methods 3.5 Equity Evidence on equity No direct evidence was identified to address this question. Additional considerations The 2015 WHO report on inequality in reproductive, maternal, newborn and child health states that “the poorest, the least educated and those residing in rural areas have lower health intervention coverage and worse health outcomes than the more advantaged” (17, p. xii). The report also found that preventing and reducing morbidity and mortality in childbirth can play a key role in reducing overall health inequities. Safe, effective and equitable implementation of labour induction for improved maternal and neonatal health outcomes could contribute to reducing inequities in maternal and perinatal health. It is likely that women from low- and middle-income settings, or disadvantaged groups within a high-income setting, may also experience greater barriers to participation in health-care decision-making about labour induction than indicated in the QES findings (18). In order to ensure that implementation of labour induction does not reinforce existing inequities, the system should support all women to have access to full, timely, accessible information; to use their own social networks to assist them to understand the information if needed; and to ensure a woman’s health-care provider is aware of her needs, values and preferences (19). Judgement on equity What is the impact on equity of mechanical methods of induction of labour? Judgement Don’t know Varies Reduced Probably reduced Probably no impact Probably increased Increased 3.6 Acceptability Evidence on acceptability No direct evidence was identified to address this question. Acceptability to women The QES (4) and additional primary studies (8-11) indicate that: • Women have varying (and sometimes contradictory) views on the acceptability of labour induction. 28 • Labour induction is widely acceptable to women when there is a recognized need to avert harm to the baby. • Acceptability varies according to women’s trust in their health-care provider, their perception of birth as a natural process, their need for certainty, and the duration of waiting. Many women in the Westfall and Benoit (2004) study preferred interventions they could employ themselves to medical induction of labour. This included use of interventions such as castor oil, essential oil suppositories, homeopathic preparations or having intercourse (11). Women in the Wessberg et al. (2017) study reported that the perceived acceptability of labour induction changed as their pregnancy progressed, particularly as their concern for the well-being of their baby increased (10). Acceptability to implementers There is limited evidence available on the acceptability of labour induction to clinicians, and more research would be useful to inform recommendations. A study of obstetrician and midwife opinions on labour induction found that obstetricians felt there was a lack of clear evidence on the risks and benefits of labour induction to guide their decision- making. They were particularly concerned about neonatal safety and the potential for medical litigation, and were uncertain about the optimal timing for induction and the risks of caesarean birth following induction (12). Human rights and health To exercise their rights to make competent and well informed decisions about induction of labour, the women included in the QES and additional primary studies wanted more complete and balanced information about the risks and benefits, and process, of labour induction. They wanted to receive this information at a time and in a context that allowed them to process the information before a decision was required. Women suggested that receiving this information and discussing labour induction with their health-care provider during a third-trimester ANC visit would be beneficial. In terms of other experiences of care that uphold and protect health rights (20), women also valued continuity of care and confidence that their situation was being consistently monitored and communicated within the care team. Women also valued the ability to move freely and to have privacy and a sense of security. This allowed them to feel more in control and maintain their dignity. Feeling secure was enhanced by having a support person present, systems which enabled this support to continue from induction to delivery, and by having rapid access to the clinical expertise and equipment that might be needed. Additional considerations None. Judgement on acceptability Are mechanical methods of induction of labour acceptable? Judgement Don’t know Varies No Probably No Probably Yes Yes 29 3.7 Feasibility Evidence on feasibility No direct evidence was identified to address this question. Additional considerations Need for, usage of and impact on infrastructure Labour induction is widely implemented in high-, middle- and low-income settings. In high- income settings, 2013 rates ranged from 14% to 36% of all births (21). Secondary analyses of WHO Global Survey on Maternal and Neonatal Health data reported 2004–2005 hospital induction rates in Latin America ranging from 5% to 20% (22), and in African countries from 1% to 7% (23), with significant unmet need for non-elective inductions on the African continent (24). In Asian countries, 2007–2008 labour induction rates ranged from 3% to 36% (23). Oxytocin alone remains the most frequently used labour induction method in all income settings. Performing induction of labour safely requires availability of appropriate medicines or mechanical devices, monitoring equipment and access to facilities for safe caesarean section. Inconsistent supply or lack of medicines and medical equipment and availability of appropriate facilities may be an issue in some settings. Need for, usage of and impact on health workforce and human resources Antenatal care (ANC) ANC visits are an important opportunity to provide (25): • one scan before 24 weeks’ gestation for accurate estimation of gestational age • post-term pregnancy risk assessment • information to women about the process, risks and benefits of labour induction. Time constraints can be a barrier to information provision in ANC clinics (12). In lower- and middle-income country settings, trained health worker shortages may also reduce the feasibility of performing ANC ultrasound scans and other risk assessment (17). Performing labour induction WHO general principles for performing labour induction state (26, p. 7): • Wherever induction of labour is carried out, facilities should be available for assessing maternal and fetal well-being. • Wherever possible, induction of labour should be carried out in facilities where caesarean sections can be performed. Health worker shortages in low- and middle-income country settings may require staff to attend to much higher numbers of women on the labour ward than in other settings. Providing the required level of support, assessment and monitoring in these settings may be challenging and impact on responsiveness (24). Availability of surgical obstetric and operating theatre staff (and staff to transfer women to facilities with these capabilities) for women who require caesarean delivery if labour induction is not successful may also have an impact on feasibility. A higher number of induction deliveries are attended by medical doctors than non-induction deliveries (23). This has implications for the distribution and productivity of medical doctors, particularly in under-resourced settings. 30 Judgement on feasibility Are mechanical methods for induction of labour feasible? Judgement Don’t know Varies No Probably No Probably Yes Yes 31 4. GRADE Summary of Judgements table Summary of Judgements Table B.1: Induction of labour with mechanical methods: balloon catheter Desirable effects Don’t know ✓ Varies Trivial Small Moderate Large Undesirable effects Don’t know Varies Large Moderate Small ✓ Trivial Certainty of the evidence No included studies Very low ✓ Low Moderate High Values Important uncertainty or variability Possibly important uncertainty or variability ✓ Probably no important uncertainty or variability No important uncertainty or variability Balance of effects Don’t know Varies Favours induction with other Probably favours induction with other methods ✓ Does not favour either Probably favours induction with mechanical methods Favours induction with mechanical methods Resources required Don’t know Varies Large costs ✓ Moderate costs Negligible costs or savings Moderate savings Large savings Certainty of the evidence on required resources No included studies ✓ Very low Low Moderate High Cost- effectiveness ✓ Don’t know Varies Favours induction with other Probably favours induction with other Does not favour either Probably favours induction with mechanical methods Favours induction with mechanical methods Equity Don’t know ✓ Varies Reduced Probably reduced Probably no impact Probably increased Increased Acceptability Don’t know ✓ Varies No Probably No Probably Yes Yes Feasibility Don’t know ✓ Varies No Probably No Probably Yes Yes 32 5. GRADE Summary of Findings tables Summary of Findings Table B.1: Balloon catheter versus vaginal prostaglandin E2 Question: Should balloon catheter (Foley or Atad) versus vaginal prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved in 24 hours 7 randomized trials seriousa seriousb not serious seriousc none 507/961 (52.8%) 382/724 (52.8%) RR 1.01 (0.82 to 1.26) 5 more per 1000 (from 95 fewer to 137 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 6 randomized trials seriousa not serious not serious not serious none 10/1040 (1.0%) 29/926 (3.1%) RR 0.35 (0.18 to 0.67) 20 fewer per 1000 (from 26 fewer to 10 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Caesarean section 28 randomized trials seriousa not serious not serious not serious none 840/3423 (24.5%) 762/3196 (23.8%) RR 1.00 (0.92 to 1.09) 0 fewer per 1000 (from 19 fewer to 21 more) ⨁⨁⨁◯ MODERATE CRITICAL Serious maternal morbidity or death 4 randomized trials seriousa not serious not serious very seriousd none 0/733 (0.0%) 2/748 (0.3%) RR 0.20 (0.01 to 4.12) 2 fewer per 1000 (from 3 fewer to 8 more) ⨁◯◯◯ VERY LOW CRITICAL 33 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Oxytocin augmentation 16 randomized trials seriousa seriousb not serious not serious publication bias strongly suspected e 1986/2469 (80.4%) 1304/2359 (55.3%) RR 1.54 (1.35 to 1.76) 298 more per 1000 (from 193 more to 420 more) ⨁◯◯◯ VERY LOW IMPORTANT Epidural analgesia 8 randomized trials seriousa seriousb not serious not serious none 947/1519 (62.3%) 687/1309 (52.5%) RR 1.14 (1.00 to 1.29) 73 more per 1000 (from 0 fewer to 152 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 15 randomized trials seriousa not serious not serious not serious none 13/1263 (1.0%) 70/1181 (5.9%) RR 0.27 (0.11 to 0.66) 43 fewer per 1000 (from 53 fewer to 20 fewer) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine rupture 2 randomized trials seriousa not serious not serious very seriousd none 0/518 (0.0%) 2/527 (0.4%) RR 0.20 (0.01 to 4.12) 3 fewer per 1000 (from 4 fewer to 12 more) ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 16 randomized trials seriousa not serious not serious not serious none 261/2375 (11.0%) 251/2139 (11.7%) RR 0.93 (0.79 to 1.09) 8 fewer per 1000 (from 25 fewer to 11 more) ⨁⨁⨁◯ MODERATE IMPORTANT 34 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Meconium-stained liquor 4 randomized trials seriousa not serious not serious seriousf none 73/481 (15.2%) 82/483 (17.0%) RR 0.89 (0.67 to 1.19) 19 fewer per 1000 (from 56 fewer to 32 more) ⨁⨁◯◯ LOW CRITICAL Maternal fever during labour 7 randomized trials seriousa not serious not serious seriousf none 86/1224 (7.0%) 80/1138 (7.0%) RR 0.87 (0.65 to 1.17) 9 fewer per 1000 (from 25 fewer to 12 more) ⨁⨁◯◯ LOW IMPORTANT Postpartum haemorrhage 8 randomized trials seriousa not serious not serious seriousg none 96/1160 (8.3%) 109/1055 (10.3%) RR 0.82 (0.63 to 1.06) 19 fewer per 1000 (from 38 fewer to 6 more) ⨁⨁◯◯ LOW CRITICAL Women not satisfied 1 randomized trials seriousa not serious not serious serioush none 17/48 (35.4%) 26/45 (57.8%) RR 0.61 (0.39 to 0.97) 225 fewer per 1000 (from 352 fewer to 17 fewer) ⨁⨁◯◯ LOW CRITICAL Serious neonatal morbidity/perinatal death 8 randomized trials seriousa not serious not serious not serious none 12/1483 (0.8%) 25/1274 (2.0%) RR 0.48 (0.25 to 0.93) 10 fewer per 1000 (from 15 fewer to 1 fewer) ⨁⨁⨁◯ MODERATE CRITICAL 35 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Perinatal death 5 randomized trials seriousa not serious not serious seriousd none 0/575 (0.0%) 2/461 (0.4%) RR 0.21 (0.01 to 4.27) 3 fewer per 1000 (from 4 fewer to 14 more) ⨁⨁◯◯ LOW CRITICAL Apgar score < 7 at 5 minutes 14 randomized trials seriousa not serious not serious seriousf none 34/2239 (1.5%) 44/2032 (2.2%) RR 0.74 (0.49 to 1.14) 6 fewer per 1000 (from 11 fewer to 3 more) ⨁⨁◯◯ LOW CRITICAL Neonatal intensive care unit admission 12 randomized trials seriousa not serious not serious seriousg none 111/1882 (5.9%) 130/1765 (7.4%) RR 0.82 (0.65 to 1.04) 13 fewer per 1000 (from 26 fewer to 3 more) ⨁⨁◯◯ LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Inconsistency – substantial statistical heterogeneity (I2 > 60%) (–1). c. Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). d. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). e. Evidence of asymmetry in funnel plot (–1). f. Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). g. Wide CIs crossing the line of no effect, ranging from appreciable benefit to negligible harm (–1). h. Small single study (–1). 36 Summary of Findings Table B.2: Balloon catheter versus intracervical prostaglandin E2 Question: Should balloon catheter (Foley or Atad) versus intracervical prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa seriousb not serious seriousc none 48/100 (48.0%) 44/100 (44.0%) RR 1.01 (0.35 to 2.91) 4 more per 1000 (from 286 fewer to 840 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 4 randomized trials seriousa not serious not serious very seriousd none 0/222 (0.0%) 1/225 (0.4%) RR 0.37 (0.02 to 8.90) 3 fewer per 1000 (from 4 fewer to 35 more) ⨁◯◯◯ VERY LOW CRITICAL Caesarean section 9 randomized trials seriousa not serious not serious not serious none 164/656 (25.0%) 168/653 (25.7%) RR 0.97 (0.81 to 1.15) 8 fewer per 1000 (from 49 fewer to 39 more) ⨁⨁⨁◯ MODERATE CRITICAL Cervix unfavourable/unchanged after 24 hours 2 randomized trials seriousa not serious not serious very seriousc none 41/110 (37.3%) 42/109 (38.5%) RR 0.96 (0.70 to 1.34) 15 fewer per 1000 (from 116 fewer to 131 more) ⨁◯◯◯ VERY LOW IMPORTANT 37 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Oxytocin augmentation 1 randomized trials seriousa not serious not serious seriouse none 132/200 (66.0%) 122/200 (61.0%) RR 1.08 (0.93 to 1.26) 49 more per 1000 (from 43 fewer to 159 more) ⨁⨁◯◯ LOW IMPORTANT Epidural analgesia 1 randomized trials seriousa not serious not serious seriousf none 65/77 (84.4%) 67/72 (93.1%) RR 0.91 (0.81 to 1.02) 84 fewer per 1000 (from 177 fewer to 19 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 5 randomized trials seriousa seriousb not serious very seriousd none 11/329 (3.3%) 11/325 (3.4%) RR 0.99 (0.09 to 10.38) 0 fewer per 1000 (from 31 fewer to 317 more) ⨁◯◯◯ VERY LOW IMPORTANT Instrumental vaginal birth 3 randomized trials seriousa not serious not serious seriousj none 23/170 (13.5%) 18/167 (10.8%) RR 1.18 (0.68 to 2.05) 19 more per 1000 (from 34 fewer to 113 more) ⨁⨁◯◯ LOW IMPORTANT 38 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Meconium-stained liquor 1 randomized trials seriousa not serious not serious very seriousg none 7/59 (11.9%) 6/59 (10.2%) RR 1.17 (0.42 to 3.26) 17 more per 1000 (from 59 fewer to 230 more) ⨁◯◯◯ VERY LOW CRITICAL Maternal side-effects 2 randomized trials seriousa not serious not serious very serioush none 0/111 (0.0%) 5/100 (5.0%) RR 0.15 (0.02 to 1.24) 43 fewer per 1000 (from 49 fewer to 12 more) ⨁◯◯◯ VERY LOW IMPORTANT Postpartum haemorrhage 1 randomized trials seriousa not serious not serious very seriousi none 0/50 (0.0%) 2/50 (4.0%) RR 0.20 (0.01 to 4.06) 32 fewer per 1000 (from 40 fewer to 122 more) ⨁◯◯◯ VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 2 randomized trials seriousa not serious not serious very seriousd none 7/250 (2.8%) 9/250 (3.6%) RR 0.78 (0.29 to 2.05) 8 fewer per 1000 (from 26 fewer to 38 more) ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 2 randomized trials seriousa not serious not serious very seriousd none 7/250 (2.8%) 9/250 (3.6%) RR 0.78 (0.29 to 2.05) 8 fewer per 1000 (from 26 fewer to 38 more) ⨁◯◯◯ VERY LOW CRITICAL 39 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Apgar score < 7 at 5 minutes 2 randomized trials seriousa not serious not serious seriousj none 14/236 (5.9%) 18/239 (7.5%) RR 0.79 (0.41 to 1.53) 16 fewer per 1000 (from 44 fewer to 40 more) ⨁⨁◯◯ LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa not serious not serious seriousj none 38/200 (19.0%) 43/200 (21.5%) RR 0.88 (0.60 to 1.31) 26 fewer per 1000 (from 86 fewer to 67 more) ⨁⨁◯◯ LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Substantial statistical heterogeneity (I2 > 60%) (–1). c. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, with small samples (–2). d. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). e. Wide CIs crossing the line of no effect, ranging from negligible benefit to appreciable harm (–1). f. Single study with small sample size (–1). g. Single small study with few events, wide CIs crossing the line of no effect (–2). h. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm, and few events (–2). i. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). j. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). 40 Summary of Findings Table B.3: Balloon catheter versus low-dose vaginal misoprostol Question: Should balloon catheter (Foley or Atad) versus low-dose vaginal misoprostol be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low -dose vaginal misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa not serious not serious seriousb none 78/175 (44.6%) 68/165 (41.2%) RR 1.09 (0.85 to 1.39) 37 more per 1000 (from 62 fewer to 161 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 8 randomized trials seriousa not serious not serious seriousc none 7/654 (1.1%) 22/668 (3.3%) RR 0.39 (0.18 to 0.85) 20 fewer per 1000 (from 27 fewer to 5 fewer) ⨁⨁◯◯ LOW CRITICAL Caesarean section 12 randomized trials seriousa not serious not serious not serious none 259/874 (29.6%) 214/882 (24.3%) RR 1.28 (1.02 to 1.60) 68 more per 1000 (from 5 more to 146 more) ⨁⨁⨁◯ MODERATE CRITICAL Serious maternal morbidity or death 4 randomized trials seriousa not serious not serious very seriousd none 0/224 (0.0%) 0/240 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL Cervix unfavourable/unchanged after 12 hours 2 randomized trials seriousa not serious not serious very seriouse none 25/100 (25.0%) 11/100 (11.0%) RR 2.66 (0.60 to 11.89) 183 more per 1000 (from 44 fewer to 1000 more) ⨁◯◯◯ VERY LOW IMPORTANT 41 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low -dose vaginal misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Oxytocin augmentation 9 randomized trials seriousa seriousf not serious not serious none 372/446 (83.4%) 235/465 (50.5%) RR 1.62 (1.38 to 1.90) 313 more per 1000 (from 192 more to 455 more) ⨁⨁◯◯ LOW IMPORTANT Epidural analgesia 2 randomized trials seriousa not serious not serious not serious none 164/254 (64.6%) 137/263 (52.1%) RR 1.22 (1.06 to 1.41) 115 more per 1000 (from 31 more to 214 more) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 9 randomized trials seriousa not serious not serious not serious none 12/566 (2.1%) 54/573 (9.4%) RR 0.25 (0.14 to 0.44) 71 fewer per 1000 (from 81 fewer to 53 fewer) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine rupture 3 randomized trials seriousa not serious not serious very seriousd none 0/170 (0.0%) 0/194 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 4 randomized trials seriousa not serious not serious seriousg none 41/354 (11.6%) 59/367 (16.1%) RR 0.72 (0.50 to 1.05) 45 fewer per 1000 (from 80 fewer to 8 more) ⨁⨁◯◯ LOW IMPORTANT Meconium-stained liquor 7 randomized trials seriousa not serious not serious not serious none 59/640 (9.2%) 91/628 (14.5%) RR 0.64 (0.48 to 0.87) 52 fewer per 1000 (from 75 fewer to 19 fewer) ⨁⨁⨁◯ MODERATE CRITICAL 42 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low -dose vaginal misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Maternal vomiting 1 randomized trials seriousa not serious not serious very serioush none 0/30 (0.0%) 0/30 (0.0%) not estimable ⨁◯◯◯ VERY LOW IMPORTANT Maternal fever during labour 3 randomized trials seriousa seriousf not serious seriousi none 19/308 (6.2%) 18/309 (5.8%) RR 1.84 (0.22 to 15.62) 49 more per 1000 (from 45 fewer to 852 more) ⨁◯◯◯ VERY LOW IMPORTANT Postpartum haemorrhage 1 randomized trials seriousa not serious not serious very seriousj none 3/56 (5.4%) 3/64 (4.7%) RR 1.14 (0.24 to 5.44) 7 more per 1000 (from 36 fewer to 208 more) ⨁◯◯◯ VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 3 randomized trials seriousa not serious not serious very seriousj none 2/187 (1.1%) 4/194 (2.1%) RR 0.58 (0.12 to 2.66) 9 fewer per 1000 (from 18 fewer to 34 more) ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa not serious not serious very serioush none 0/61 (0.0%) 0/60 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 7 randomized trials seriousa not serious not serious very seriousk none 14/472 (3.0%) 14/469 (3.0%) RR 1.00 (0.50 to 1.97) 0 fewer per 1000 (from 15 fewer to 29 more) ⨁◯◯◯ VERY LOW CRITICAL 43 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low -dose vaginal misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Neonatal intensive care unit admission 9 randomized trials seriousa not serious not serious seriousi none 29/643 (4.5%) 31/659 (4.7%) RR 1.00 (0.61 to 1.63) 0 fewer per 1000 (from 18 fewer to 30 more) ⨁⨁◯◯ LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). c. Few events (–1). d. No events (–2). e. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–2). f. Substantial statistical heterogeneity (I2 > 60%) (–1). g. Wide CIs crossing the line of no effect, ranging from appreciable benefit to negligible harm (–1). h. Single small study with no events (–2). i. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). j. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). k. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 44 Summary of Findings Table B.4: Balloon catheter versus low-dose oral misoprostol Question: Should balloon catheter (Foley or Atad) versus low-dose oral misoprostol be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved within 24 hours 2 randomized trials seriousa not serious not serious not serious none 237/389 (60.9%) 187/393 (47.6%) RR 1.28 (1.13 to 1.46) 133 more per 1000 (from 62 more to 219 more) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine hyperstimulation with fetal heart rate changes 2 randomized trials seriousa not serious not serious seriousb none 24/1010 (2.4%) 30/1023 (2.9%) RR 0.81 (0.48 to 1.38) 6 fewer per 1000 (from 15 fewer to 11 more) ⨁⨁◯◯ LOW CRITICAL Caesarean section 7 randomized trials seriousa not serious not serious not serious none 411/1585 (25.9%) 353/1593 (22.2%) RR 1.17 (1.04 to 1.32) 38 more per 1000 (from 9 more to 71 more) ⨁⨁⨁◯ MODERATE CRITICAL Serious maternal morbidity or death 3 randomized trials seriousa not serious not serious very seriousc none 1/1310 (0.1%) 2/1317 (0.2%) RR 0.50 (0.05 to 5.52) 1 fewer per 1000 (from 1 fewer to 7 more) ⨁◯◯◯ VERY LOW CRITICAL 45 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Cervix unfavourable after 24 hours 4 randomized trials seriousa not serious not serious seriousb none 46/497 (9.3%) 46/497 (9.3%) RR 0.98 (0.61 to 1.56) 2 fewer per 1000 (from 36 fewer to 52 more) ⨁⨁◯◯ LOW IMPORTANT Oxytocin augmentation 5 randomized trials seriousa seriousd not serious not serious none 1154/1418 (81.4%) 939/1429 (65.7%) RR 1.28 (1.09 to 1.49) 184 more per 1000 (from 59 more to 322 more) ⨁⨁◯◯ LOW IMPORTANT Epidural 3 randomized trials seriousa not serious not serious not serious none 645/1310 (49.2%) 594/1325 (44.8%) RR 1.08 (0.96 to 1.22) 36 more per 1000 (from 18 fewer to 99 more) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 5 randomized trials seriousa not serious not serious seriousb none 17/1418 (1.2%) 19/1420 (1.3%) RR 0.50 (0.12 to 2.07) 7 fewer per 1000 (from 12 fewer to 14 more) ⨁⨁◯◯ LOW IMPORTANT Uterine rupture 3 randomized trials seriousa not serious not serious very seriouse none 0/1310 (0.0%) 0/1317 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL 46 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Instrumental vaginal birth 3 randomized trials seriousa not serious not serious not serious none 91/1310 (6.9%) 128/1317 (9.7%) RR 0.71 (0.55 to 0.92) 28 fewer per 1000 (from 44 fewer to 8 fewer) ⨁⨁⨁◯ MODERATE IMPORTANT Meconium-stained liquor 3 randomized trials seriousa not serious not serious seriousb none 116/1310 (8.9%) 127/1317 (9.6%) RR 0.77 (0.44 to 1.35) 22 fewer per 1000 (from 54 fewer to 34 more) ⨁⨁◯◯ LOW CRITICAL Maternal side-effects (all) 2 randomized trials seriousa not serious not serious seriousf none 15/330 (4.5%) 25/332 (7.5%) RR 0.61 (0.33 to 1.13) 29 fewer per 1000 (from 50 fewer to 10 more) ⨁⨁◯◯ LOW IMPORTANT Maternal vomiting 2 randomized trials seriousa not serious not serious seriousb none 13/330 (3.9%) 18/332 (5.4%) RR 0.73 (0.37 to 1.46) 15 fewer per 1000 (from 34 fewer to 25 more) ⨁⨁◯◯ LOW IMPORTANT Maternal diarrhoea 1 randomized trials seriousa not serious not serious very seriousg none 2/300 (0.7%) 7/302 (2.3%) RR 0.29 (0.06 to 1.37) 16 fewer per 1000 (from 22 fewer to 9 more) ⨁◯◯◯ VERY LOW IMPORTANT 47 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Maternal fever during labour 2 randomized trials seriousa not serious not serious not serious none 120/1010 (11.9%) 123/1023 (12.0%) RR 0.98 (0.78 to 1.24) 2 fewer per 1000 (from 26 fewer to 29 more) ⨁⨁⨁◯ MODERATE IMPORTANT Postpartum haemorrhage 5 randomized trials seriousa not serious not serious serioush none 98/1477 (6.6%) 97/1489 (6.5%) RR 1.03 (0.79 to 1.34) 2 more per 1000 (from 14 fewer to 22 more) ⨁⨁◯◯ LOW CRITICAL Women not satisfied 1 randomized trials seriousa not serious not serious not serious none 59/300 (19.7%) 35/302 (11.6%) RR 1.70 (1.15 to 2.50) 81 more per 1000 (from 17 more to 174 more) ⨁⨁⨁◯ MODERATE CRITICAL Serious perinatal morbidity/perinatal death 3 randomized trials seriousa not serious not serious seriousb none 21/1310 (1.6%) 19/1317 (1.4%) RR 1.11 (0.60 to 2.06) 2 more per 1000 (from 6 fewer to 15 more) ⨁⨁◯◯ LOW CRITICAL Perinatal death 3 randomized trials seriousa not serious not serious very seriousc none 9/1310 (0.7%) 7/1317 (0.5%) RR 1.28 (0.49 to 3.30) 1 more per 1000 (from 3 fewer to 12 more) ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 after 5 minutes 48 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) 4 randomized trials seriousa not serious not serious seriousb none 17/1338 (1.3%) 24/1355 (1.8%) RR 0.71 (0.38 to 1.32) 5 fewer per 1000 (from 11 fewer to 6 more) ⨁⨁◯◯ LOW CRITICAL Neonatal intensive care unit admission 5 randomized trials seriousa not serious not serious seriousi none 53/1427 (3.7%) 66/1446 (4.6%) RR 0.82 (0.58 to 1.17) 8 fewer per 1000 (from 19 fewer to 8 more) ⨁⨁◯◯ LOW CRITICAL Neonatal encephalopathy 1 randomized trials seriousa not serious not serious very seriousg none 8/298 (2.7%) 10/302 (3.3%) RR 0.81 (0.32 to 2.03) 6 fewer per 1000 (from 23 fewer to 34 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). c. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). d. Substantial statistical heterogeneity (I2 > 60%) (–1). e. No events (–2). f. Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). g. Single study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). h. Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). i. Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). 49 Summary of Findings Table B.5: Balloon catheter versus oxytocin Question: Should balloon catheter (Foley or Atad) versus oxytocin be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Oxytocin: all women Relative risk (95% CI) Absolute (95% CI) Uterine hyperstimulation with fetal heart rate changes 1 randomized trials seriousa not serious not serious very seriousb none 0/100 (0.0%) 2/100 (2.0%) RR 0.20 (0.01 to 4.11) 16 fewer per 1000 (from 20 fewer to 62 more) ⨁◯◯◯ VERY LOW CRITICAL Caesarean section 8 randomized trials seriousa not serious not serious not serious none 104/392 (26.5%) 152/389 (39.1%) RR 0.68 (0.56 to 0.83) 125 fewer per 1000 (from 172 fewer to 66 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Serious maternal morbidity or death 2 randomized trials seriousa not serious not serious very seriousc none 0/80 (0.0%) 0/80 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL Cervix unfavourable after 24 hours 1 randomized trials seriousa not serious not serious very seriousb none 5/50 (10.0%) 9/50 (18.0%) RR 0.56 (0.20 to 1.54) 79 fewer per 1000 (from 144 fewer to 97 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 50 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Oxytocin: all women Relative risk (95% CI) Absolute (95% CI) 3 randomized trials seriousa not serious not serious very seriousd none 3/96 (3.1%) 3/96 (3.1%) RR 1.00 (0.23 to 4.29) 0 fewer per 1000 (from 24 fewer to 103 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine rupture 1 randomized trials seriousa not serious not serious very seriouse none 0/50 (0.0%) 0/50 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa not serious not serious very seriousd none 12/110 (10.9%) 10/110 (9.1%) RR 1.19 (0.55 to 2.57) 17 more per 1000 (from 41 fewer to 143 more) ⨁◯◯◯ VERY LOW IMPORTANT Meconium-stained liquor 2 randomized trials seriousa not serious not serious very seriousf none 8/136 (5.9%) 15/136 (11.0%) RR 0.53 (0.23 to 1.21) 52 fewer per 1000 (from 85 fewer to 23 more) ⨁◯◯◯ VERY LOW CRITICAL Maternal fever during labour 1 randomized trials seriousa not serious not serious very seriousd none 0/30 (0.0%) 2/30 (6.7%) RR 0.20 (0.01 to 4.00) 53 fewer per 1000 (from 66 fewer to 200 more) ⨁◯◯◯ VERY LOW IMPORTANT Postpartum haemorrhage 51 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Oxytocin: all women Relative risk (95% CI) Absolute (95% CI) 4 randomized trials seriousa not serious not serious very seriousg none 9/197 (4.6%) 7/199 (3.5%) RR 1.26 (0.51 to 3.11) 9 more per 1000 (from 17 fewer to 74 more) ⨁◯◯◯ VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 1 randomized trials seriousa not serious not serious very seriouse none 0/50 (0.0%) 0/50 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa not serious not serious very seriouse none 0/50 (0.0%) 0/50 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 2 randomized trials seriousa not serious not serious very seriousd none 2/150 (1.3%) 3/150 (2.0%) RR 0.71 (0.14 to 3.53) 6 fewer per 1000 (from 17 fewer to 51 more) ⨁◯◯◯ VERY LOW CRITICAL Neonatal intensive care unit admission 3 randomized trials seriousa not serious not serious very seriousg none 8/186 (4.3%) 10/186 (5.4%) RR 0.80 (0.32 to 1.98) 11 fewer per 1000 (from 37 fewer to 53 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). c. Small sample size with no events (–2). d. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). e. Single small study with no events (–2). f. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm, and few events (–2). g. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 52 Summary of Findings Table B.6: Balloon catheter versus amniotomy Question: Should balloon catheter (Foley or Atad) versus amniotomy be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (foley or Atad) Amniotomy: all women Relative risk (95% CI) Absolute (95% CI) Caesarean section 1 randomized trials very seriousa not serious not serious very seriousb none 1/10 (10.0%) 4/10 (40.0%) RR 0.25 (0.03 to 1.86) 300 fewer per 1000 (from 388 fewer to 344 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. Majority of data provided by study/studies with serious design limitations (–2). b. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 53 Summary of Findings Table B.7: Single balloon catheter versus double balloon catheter Question: Should single balloon catheter (Foley) versus double balloon (Atad/Cook) be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Single balloon (Foley) Double balloon (Atad/Cook): all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved in 24 hours 3 randomized trials seriousa seriousb not serious not serious none 137/303 (45.2%) 147/305 (48.2%) RR 0.97 (0.75 to 1.25) 14 fewer per 1000 (from 120 fewer to 120 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 1 randomized trials seriousa not serious not serious very seriousc none 0/110 (0.0%) 0/107 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Caesarean section 5 randomized trials seriousa not serious not serious seriousd none 105/430 (24.4%) 113/432 (26.2%) RR 0.97 (0.71 to 1.33) 8 fewer per 1000 (from 76 fewer to 86 more) ⨁⨁◯◯ LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa not serious not serious very seriousc none 0/110 (0.0%) 0/107 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Oxytocin augmentation 2 randomized trials seriousa not serious not serious seriouse none 96/138 (69.6%) 104/140 (74.3%) RR 0.94 (0.82 to 1.08) 45 fewer per 1000 (from 134 fewer to 59 more) ⨁⨁◯◯ LOW IMPORTANT 54 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Single balloon (Foley) Double balloon (Atad/Cook): all women Relative risk (95% CI) Absolute (95% CI) Epidural analgesia 3 randomized trials seriousa not serious not serious not serious none 194/303 (64.0%) 210/305 (68.9%) RR 0.93 (0.83 to 1.03) 48 fewer per 1000 (from 117 fewer to 21 more) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 1 randomized trials seriousa not serious not serious very seriousc none 0/110 (0.0%) 0/107 (0.0%) not estimable ⨁◯◯◯ VERY LOW IMPORTANT Uterine rupture 1 randomized trials seriousa not serious not serious very seriousc none 0/110 (0.0%) 0/107 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa not serious not serious seriousf none 51/345 (14.8%) 59/345 (17.1%) RR 0.86 (0.61 to 1.20) 24 fewer per 1000 (from 67 fewer to 34 more) ⨁⨁◯◯ LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa not serious not serious very seriousg none 5/48 (10.4%) 13/50 (26.0%) RR 0.40 (0.15 to 1.04) 156 fewer per 1000 (from 221 fewer to 10 more) ⨁◯◯◯ VERY LOW CRITICAL Maternal side-effects: pain after insertion 1 randomized trials seriousa not serious not serious very seriousg none 4/37 (10.8%) 6/37 (16.2%) RR 0.67 (0.20 to 2.17) 54 fewer per 1000 (from 130 fewer to 190 more) ⨁◯◯◯ VERY LOW IMPORTANT 55 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Single balloon (Foley) Double balloon (Atad/Cook): all women Relative risk (95% CI) Absolute (95% CI) Maternal fever during labour 3 randomized trials seriousa seriousb not serious seriousd none 21/292 (7.2%) 26/292 (8.9%) RR 0.61 (0.16 to 2.34) 35 fewer per 1000 (from 75 fewer to 119 more) ⨁◯◯◯ VERY LOW IMPORTANT Postpartum haemorrhage 2 randomized trials seriousa not serious not serious very serioush none 5/147 (3.4%) 6/144 (4.2%) RR 0.83 (0.27 to 2.52) 7 fewer per 1000 (from 30 fewer to 63 more) ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 3 randomized trials seriousa not serious not serious very seriousi none 4/303 (1.3%) 5/305 (1.6%) RR 0.84 (0.25 to 2.79) 3 fewer per 1000 (from 12 fewer to 29 more) ⨁◯◯◯ VERY LOW CRITICAL Neonatal intensive care unit admission 2 randomized trials seriousa not serious not serious very seriousi none 13/193 (6.7%) 8/198 (4.0%) RR 1.67 (0.71 to 3.93) 27 more per 1000 (from 12 fewer to 118 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Substantial statistical heterogeneity (I2 > 60%) (–1). c. Single small study with no events (–2). d. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). e. Small sample size (–1). f. Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). g. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to negligible harm, and few events (–2). h. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). i. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 56 Summary of Findings Table B.8: Laminaria tent versus vaginal prostaglandin E2 Question: Should laminaria tent compared with vaginal PGE2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Uterine hyperstimulation with fetal heart rate changes 3 randomized trials seriousa not serious not serious seriousb none 0/95 (0.0%) 11/93 (11.8%) RR 0.11 (0.02 to 0.60) 105 fewer per 1000 (from 116 fewer to 47 fewer) ⨁⨁◯◯ LOW CRITICAL Caesarean section 5 randomized trials seriousa not serious not serious seriousc none 25/133 (18.8%) 27/130 (20.8%) RR 0.91 (0.56 to 1.48) 19 fewer per 1000 (from 91 fewer to 100 more) ⨁⨁◯◯ LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa not serious not serious very seriousd none 0/15 (0.0%) 0/13 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Epidural analgesia 1 randomized trials seriousa not serious not serious very seriouse none 31/40 (77.5%) 34/40 (85.0%) RR 0.91 (0.74 to 1.13) 76 fewer per 1000 (from 221 fewer to 110 more) ⨁◯◯◯ VERY LOW IMPORTANT 57 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Uterine hyperstimulation without fetal heart rate changes 3 randomized trials seriousa not serious not serious seriousf none 5/90 (5.6%) 25/90 (27.8%) RR 0.22 (0.09 to 0.49) 217 fewer per 1000 (from 253 fewer to 142 fewer) ⨁⨁◯◯ LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa not serious not serious very seriousg none 15/40 (37.5%) 21/40 (52.5%) RR 0.71 (0.43 to 1.17) 152 fewer per 1000 (from 299 fewer to 89 more) ⨁◯◯◯ VERY LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa not serious not serious very serioush none 0/40 (0.0%) 3/40 (7.5%) RR 0.14 (0.01 to 2.68) 65 fewer per 1000 (from 74 fewer to 126 more) ⨁◯◯◯ VERY LOW CRITICAL Maternal side-effects: all 1 randomized trials seriousa not serious not serious very serioush none 0/15 (0.0%) 1/13 (7.7%) RR 0.29 (0.01 to 6.60) 55 fewer per 1000 (from 76 fewer to 431 more) ⨁◯◯◯ VERY LOW IMPORTANT 58 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Maternal nausea 1 randomized trials seriousa not serious not serious very serioush none 0/15 (0.0%) 1/13 (7.7%) RR 0.29 (0.01 to 6.60) 55 fewer per 1000 (from 76 fewer to 431 more) ⨁◯◯◯ VERY LOW IMPORTANT Serious perinatal morbidity/perinatal death 1 randomized trials seriousa not serious not serious very seriousd none 0/40 (0.0%) 0/40 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa not serious not serious very seriousd none 0/40 (0.0%) 0/40 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 2 randomized trials seriousa not serious not serious very seriousi none 0/80 (0.0%) 0/80 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Small sample size with few events (–1). c. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). d. Single small study with no events (–2). e. Single small study with few events, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–2). f. Small sample size (–1). g. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–2). h. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). i. Small sample size with no events (–2). 59 Summary of Findings Table B.9: Laminaria tent versus intracervical prostaglandin E2 Question: Should laminaria tent versus intracervical prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Uterine hyperstimulation with fetal heart rate changes 2 randomized trials seriousa not serious not serious very seriousb none 0/172 (0.0%) 5/178 (2.8%) RR 0.17 (0.02 to 1.42) 23 fewer per 1000 (from 28 fewer to 12 more) ⨁◯◯◯ VERY LOW CRITICAL Caesarean section 5 randomized trials seriousa not serious not serious seriousc none 124/459 (27.0%) 107/461 (23.2%) RR 1.16 (0.93 to 1.45) 37 more per 1000 (from 16 fewer to 104 more) ⨁⨁◯◯ LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa not serious not serious very seriousd none 0/90 (0.0%) 1/95 (1.1%) RR 0.35 (0.01 to 8.52) 7 fewer per 1000 (from 10 fewer to 79 more) ⨁◯◯◯ VERY LOW CRITICAL Cervix unfavourable/unchanged after 12–24 hours 2 randomized trials very seriouse not serious not serious very seriousf none 10/109 (9.2%) 18/109 (16.5%) RR 0.46 (0.11 to 1.96) 89 fewer per 1000 (from 147 fewer to 159 more) ⨁◯◯◯ VERY LOW IMPORTANT 60 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Oxytocin augmentation 1 randomized trials seriousa not serious not serious seriousg none 84/90 (93.3%) 63/95 (66.3%) RR 1.41 (1.21 to 1.64) 272 more per 1000 (from 139 more to 424 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 2 randomized trials seriousa not serious not serious very seriousb none 0/304 (0.0%) 5/297 (1.7%) RR 0.17 (0.02 to 1.36) 14 fewer per 1000 (from 16 fewer to 6 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine rupture 1 randomized trials seriousa not serious not serious very seriousd none 0/90 (0.0%) 1/95 (1.1%) RR 0.35 (0.01 to 8.52) 7 fewer per 1000 (from 10 fewer to 79 more) ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa not serious not serious serioush none 28/208 (13.5%) 28/216 (13.0%) RR 1.05 (0.65 to 1.69) 6 more per 1000 (from 45 fewer to 89 more) ⨁⨁◯◯ LOW IMPORTANT Maternal side-effects 1 randomized trials very seriouse not serious not serious very seriousd none 0/82 (0.0%) 2/83 (2.4%) RR 0.20 (0.01 to 4.15) 19 fewer per 1000 (from 24 fewer to 76 more) ⨁◯◯◯ VERY LOW IMPORTANT 61 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Postpartum haemorrhage 2 randomized trials very seriouse not serious not serious very seriousf none 9/118 (7.6%) 8/121 (6.6%) RR 1.14 (0.46 to 2.81) 9 more per 1000 (from 36 fewer to 120 more) ⨁◯◯◯ VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 1 randomized trials seriousa not serious not serious very seriousd none 1/90 (1.1%) 0/95 (0.0%) RR 3.16 (0.13 to 76.70) 0 fewer per 1000 (from 0 fewer to 0 fewer) ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa not serious not serious very seriousd none 1/90 (1.1%) 0/95 (0.0%) RR 3.16 (0.13 to 76.70) 0 fewer per 1000 (from 0 fewer to 0 fewer) ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa not serious not serious very seriousd none 5/90 (5.6%) 1/95 (1.1%) RR 5.28 (0.63 to 44.30) 45 more per 1000 (from 4 fewer to 456 more) ⨁◯◯◯ VERY LOW CRITICAL Neonatal intensive care unit admission 2 randomized trials seriousa not serious not serious very seriousf none 9/126 (7.1%) 6/133 (4.5%) RR 1.58 (0.58 to 4.33) 26 more per 1000 (from 19 fewer to 150 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. 62 a. All data provided by study/studies with design limitations (–1). b. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). c. Wide CIs crossing the line of no effect, ranging from negligible benefit to appreciable harm (–1). d. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). e. Majority of data provided by study/studies with serious design limitations (–2). f. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). g. Single small study (–1). h. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). 63 Summary of Findings Table B.10: Balloon laminaria tent versus oxytocin Question: Should laminaria tent versus oxytocin be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Oxytocin: all women Relative risk (95% CI) Absolute (95% CI) Caesarean section 2 randomized trials seriousa not serious not serious very seriousb none 8/38 (21.1%) 9/35 (25.7%) RR 0.83 (0.36 to 1.89) 44 fewer per 1000 (from 165 fewer to 229 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 64 Summary of Findings Table B.11: Laminaria tent versus amniotomy Question: Should laminaria tent versus amniotomy be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Amniotomy: all women Relative risk (95% CI) Absolute (95% CI) Caesarean section 1 randomized trials very seriousa not serious not serious very seriousb none 3/10 (30.0%) 4/10 (40.0%) RR 0.75 (0.22 to 2.52) 100 fewer per 1000 (from 312 fewer to 608 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. Majority of data provided by study/studies with serious design limitations (–2). b. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 65 Summary of Findings Table B.12: Laminaria tent versus other hygroscopic dilator Question: Should laminaria tent versus other hygroscopic dilator be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Other hygroscopic dilator: all women Relative risk (95% CI) Absolute (95% CI) Caesarean section 1 randomized trials seriousa not serious not serious very seriousb none 4/18 (22.2%) 3/23 (13.0%) RR 1.70 (0.44 to 6.66) 91 more per 1000 (from 73 fewer to 738 more) ⨁◯◯◯ VERY LOW CRITCAL CI: confidence interval; RR: relative risk. a. Majority of data provided by study/studies with design limitations (–1). b. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 66 Summary of Findings Table B.13: Extra-amniotic saline infusion (EASI) versus vaginal prostaglandin E2 Question: Should EASI versus vaginal prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations EASI versus vaginal PGE2 Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness Seriousb none 43/59 (72.9%) 21/50 (42%) RR 1.74 (1.21 to 2.49) 311 more per 1000 (from 88 more to 626 more)  LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 0/115 (0%) 3/106 (2.8%) RR 0.23 (0.03 to 2.07) 22 fewer per 1000 (from 27 fewer to 30 more)  VERY LOW CRITICAL Caesarean section 2 randomized trials seriousa seriousd no serious indirectness very seriouse none 44/115 (38.3%) 31/106 (29.2%) RR 1.35 (0.94 to 1.96) 102 more per 1000 (from 18 fewer to 281 more)  VERY LOW CRITICAL Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousb none 30/59 (50.8%) 2/50 (4%) RR 12.71 (3.2 to 50.57) 468 more per 1000 (from 88 more to 1000 more)  LOW IMPORTANT Epidural analgesia 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousf none 56/56 (100%) 56/56 (100%) RR 1 (0.97 to 1.04) 0 fewer per 1000 (from 30 fewer to 40 more)  VERY LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 0/115 (0%) 3/106 (2.8%) RR 0.23 (0.03 to 2.07) 22 fewer per 1000 (from 27 fewer to 30 more)  VERY LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousg none 11/59 (18.6%) 16/50 (32%) RR 0.58 (0.3 to 1.14) 134 fewer per 1000 (from 224 fewer to 45 more)  VERY LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 1/56 (1.8%) 0/56 (0%) RR 3 (0.12 to 72.1)  VERY LOW CRITICAL 67 Certainty assessment No. of patients Effect Certainty Importance No of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations EASI versus vaginal PGE2 Control Relative risk (95% CI) Absolute Woman not satisfied 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/59 (3.4%) 3/50 (6%) RR 0.56 (0.1 to 3.25) 26 fewer per 1000 (from 54 fewer to 135 more)  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/59 (3.4%) 0/50 (0%) RR 4.25 (0.21 to 86.51)  VERY LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 6/56 (10.7%) 4/56 (7.1%) RR 1.5 (0.45 to 5.03) 36 more per 1000 (from 39 fewer to 288 more)  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a Majority of data provided by study/studies with design limitations (–1). b Single study with small sample size (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, small sample and few events (–2). d Substantial statistical heterogeneity (I2 > 60%) (–1). e Small sample size, wide CIs crossing the line of no effect, ranging from negligible benefit to appreciable harm (–2). f Single study with small sample size (all women had an epidural in this study) (–2). g Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm, and few events (–2). 68 Summary of Findings Table B.14: Extra-amniotic saline infusion (EASI) versus intracervical prostaglandin E2 Question: Should EASI versus intracervical prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations EASI versus intracervical PGE2 Control Relative risk (95% CI) Absolute Caesarean section 2 randomized trials seriousa seriousb no serious indirectness very seriousc none 13/78 (16.7%) 14/77 (18.2%) RR 0.73 (0.1 to 5.12) 49 fewer per 1000 (from 164 fewer to 749 more)  VERY LOW CRITICAL Cervix unfavourable/unchanged after 12–24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 0/43 (0%) 8/42 (19%) RR 0.06 (0 to 0.97) 179 fewer per 1000 (from 6 fewer to 190 fewer)  LOW IMPORTANT Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 11/35 (31.4%) 10/35 (28.6%) RR 1.1 (0.54 to 2.25) 29 more per 1000 (from 131 fewer to 357 more)  VERY LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 1/43 (2.3%) 3/42 (7.1%) RR 0.33 (0.04 to 3.01) 48 fewer per 1000 (from 69 fewer to 144 more)  VERY LOW IMPORTANT Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/43 (0%) 0/42 (0%) not pooled not pooled  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Substantial statistical heterogeneity (I2 >60%) (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and small sample with few events (–2). d Single study with small sample size and few events (–1). e Small sample size with no events (–2). 69 Summary of Findings Table B.15: Any mechanical method plus prostaglandin E2 versus prostaglandin E2 alone Question: Should any mechanical method and prostaglandin E2 versus prostaglandin E2 alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus PGE2 alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 13/22 (59.1%) 12/17 (70.6%) RR 0.84 (0.53 to 1.33) 113 fewer per 1000 (from 332 fewer to 233 more)  VERY LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 0/56 (0%) 2/66 (3%) RR 0.26 (0.01 to 5.12) 22 fewer per 1000 (from 30 fewer to 125 more)  VERY LOW CRITICAL Caesarean section 7 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 82/264 (31.1%) 85/253 (33.6%) RR 0.96 (0.66 to 1.4) 13 fewer per 1000 (from 114 fewer to 134 more)  LOW CRITICAL Cervix unfavourable/unchanged after 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 16/63 (25.4%) 29/59 (49.2%) RR 0.52 (0.31 to 0.85) 236 fewer per 1000 (from 74 fewer to 339 fewer)  LOW IMPORTANT Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 13/19 (68.4%) 18/25 (72%) RR 0.95 (0.64 to 1.41) 36 fewer per 1000 (from 259 fewer to 295 more)  VERY LOW IMPORTANT Epidural analgesia 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 19/22 (86.4%) 15/17 (88.2%) RR 0.98 (0.77 to 1.24) 18 fewer per 1000 (from 203 fewer to 212 more)  LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 3 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/122 (0%) 0/117 (0%) not pooled not pooled  VERY LOW IMPORTANT Instrumental vaginal birth 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousf none 6/42 (14.3%) 9/36 (25%) RR 0.56 (0.22 to 1.45) 110 fewer per 1000 (from 195 fewer to 113 more)  VERY LOW IMPORTANT 70 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus PGE2 alone Control Relative risk (95% CI) Absolute Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 6/61 (9.8%) 6/59 (10.2%) RR 0.97 (0.33 to 2.83) 3 fewer per 1000 (from 68 fewer to 186 more)  VERY LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 0/19 (0%) 2/25 (8%) RR 0.26 (0.01 to 5.12) 59 fewer per 1000 (from 79 fewer to 330 more)  VERY LOW CRITICAL Postpartum haemorrhage 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/22 (0%) 0/17 (0%) not pooled not pooled  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). d Single study with small sample size (–1). e Small sample size with no events (–2). f Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 71 Summary of Findings Table B.16: Any mechanical method plus prostaglandin E2 versus low-dose misoprostol alone Question: Should any mechanical method and prostaglandin E2 versus low-dose misoprostol alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousb none 5/65 (7.7%) 15/62 (24.2%) RR 0.32 (0.12 to 0.82) 165 fewer per 1000 (from 44 fewer to 213 fewer)  LOW IMPORTANT Caesarean section 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 16/65 (24.6%) 14/62 (22.6%) RR 1.09 (0.58 to 2.04) 20 more per 1000 (from 95 fewer to 235 more)  VERY LOW CRITICAL Cervix unfavourable/unchanged after 12–24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 15/65 (23.1%) 35/62 (56.5%) RR 0.41 (0.25 to 0.67) 333 fewer per 1000 (from 186 fewer to 423 fewer)  LOW IMPORTANT Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 56/65 (86.2%) 44/62 (71%) RR 1.21 (1.01 to 1.46) 149 more per 1000 (from 7 more to 326 more)  LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousb none 17/65 (26.2%) 4/62 (6.5%) RR 4.05 (1.44 to 11.38) 197 more per 1000 (from 28 more to 670 more)  LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 25/65 (38.5%) 19/62 (30.6%) RR 1.26 (0.77 to 2.04) 80 more per 1000 (from 70 fewer to 319 more)  VERY LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 7/65 (10.8%) 12/62 (19.4%) RR 0.56 (0.23 to 1.32) 85 fewer per 1000 (from 149 fewer to 62 more)  VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 0/65 (0%) 2/62 (3.2%) RR 0.19 (0.01 to 3.9) 26 fewer per 1000 (from 32 fewer to 94 more)  VERY LOW CRITICAL 72 Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 0/65 (0%) 2/62 (3.2%) RR 0.19 (0.01 to 3.9) 26 fewer per 1000 (from 32 fewer to 94 more)  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/65 (3.1%) 1/62 (1.6%) RR 1.91 (0.18 to 20.51) 15 more per 1000 (from 13 fewer to 315 more)  VERY LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 10/65 (15.4%) 15/62 (24.2%) RR 0.64 (0.31 to 1.31) 87 fewer per 1000 (from 167 fewer to 75 more)  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Small sample size with few events (–1). c Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–2). d Small sample size (–1). 73 Summary of Findings Table B.17: Any mechanical method plus prostaglandin E2 versus oxytocin alone Question: Should any mechanical method and prostaglandin E2 versus oxytocin alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus oxytocin alone Control Relative risk (95% CI) Absolute Caesarean section 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 1/20 (5%) 4/24 (16.7%) RR 0.3 (0.04 to 2.47) 117 fewer per 1000 (from 160 fewer to 245 more)  VERY LOW CRITICAL Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 2/20 (10%) 4/24 (16.7%) RR 0.6 (0.12 to 2.94) 67 fewer per 1000 (from 147 fewer to 323 more)  VERY LOW IMPORTANT CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 74 Summary of Findings Table B.18: Any mechanical method plus low-dose misoprostol versus prostaglandin E2 alone Question: Should any mechanical method and low-dose misoprostol versus prostaglandin E2 alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus PGE2 alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousb none 79/174 (45.4%) 70/176 (39.8%) RR 1.14 (0.89 to 1.46) 56 more per 1000 (from 44 fewer to 183 more)  LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 6/163 (3.7%) 8/164 (4.9%) RR 0.75 (0.27 to 2.13) 12 fewer per 1000 (from 36 fewer to 55 more)  VERY LOW CRITICAL Caesarean section 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 36/174 (20.7%) 43/176 (24.4%) RR 0.85 (0.57 to 1.25) 37 fewer per 1000 (from 105 fewer to 61 more)  LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/174 (0%) 0/176 (0%) not pooled not pooled  VERY LOW CRITICAL Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 23/174 (13.2%) 43/176 (24.4%) RR 0.54 (0.34 to 0.86) 112 fewer per 1000 (from 34 fewer to 161 fewer)  MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 7/163 (4.3%) 13/164 (7.9%) RR 0.54 (0.22 to 1.32) 36 fewer per 1000 (from 62 fewer to 25 more)  VERY LOW CRITICAL Uterine rupture 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/174 (0%) 0/176 (0%) not pooled not pooled  VERY LOW CRITICAL Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 4/174 (2.3%) 4/176 (2.3%) RR 1.01 (0.26 to 3.98) 0 more per 1000 (from 17 fewer to 68 more)  VERY LOW IMPORTANT 75 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus PGE2 alone Control Relative risk (95% CI) Absolute Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 17/168 (10.1%) 15/171 (8.8%) RR 1.15 (0.6 to 2.23) 13 more per 1000 (from 35 fewer to 108 more)  LOW CRITICAL Maternal side-effects 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousg none 86/149 (57.7%) 82/165 (49.7%) RR 1.16 (0.95 to 1.43) 80 more per 1000 (from 25 fewer to 214 more)  LOW IMPORTANT Maternal nausea 1 randomized trials seriousa no serious inconsistency no serious indirectness serioush none 31/149 (20.8%) 19/151 (12.6%) RR 1.65 (0.98 to 2.79) 82 more per 1000 (from 3 fewer to 225 more)  LOW IMPORTANT Maternal diarrhoea 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousi none 20/148 (13.5%) 6/165 (3.6%) RR 3.72 (1.53 to 9) 99 more per 1000 (from 19 more to 291 more)  LOW IMPORTANT Maternal fever during labour 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 3/172 (1.7%) 2/175 (1.1%) RR 1.53 (0.26 to 9.02) 6 more per 1000 (from 8 fewer to 92 more)  VERY LOW IMPORTANT Postpartum haemorrhage 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 42/174 (24.1%) 43/174 (24.7%) RR 0.98 (0.67 to 1.41) 5 fewer per 1000 (from 82 fewer to 101 more)  LOW CRITICAL Serious neonatal morbidity/perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/171 (1.2%) 1/174 (0.57%) RR 2.04 (0.19 to 22.24) 6 more per 1000 (from 5 fewer to 122 more)  VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 1/171 (0.58%) 1/174 (0.57%) RR 1.02 (0.06 to 16.14) 0 more per 1000 (from 5 fewer to 87 more)  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 6/171 (3.5%) 9/175 (5.1%) RR 0.68 (0.25 to 1.88) 16 fewer per 1000 (from 39 fewer to 45 more)  VERY LOW CRITICAL 76 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus PGE2 alone Control Relative risk (95% CI) Absolute Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/171 (1.2%) 3/175 (1.7%) RR 0.68 (0.12 to 4.03) 5 fewer per 1000 (from 15 fewer to 52 more)  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). d Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). e Single study with no events (–2). f Single study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). g Single study, wide CIs crossing the line of no effect, ranging from negligible benefit to appreciable harm (–1). h Wide CIs ranging from negligible benefit to appreciable harm (–1). i Single study with few events (–1). 77 Summary of Findings Table B.19: Any mechanical method plus low-dose misoprostol versus low-dose misoprostol alone Question: Should any mechanical method and low-dose misoprostol versus low-dose misoprostol alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa seriousb no serious indirectness seriousc none 98/335 (29.3%) 115/333 (34.5%) RR 0.7 (0.25 to 1.95) 104 fewer per 1000 (from 259 fewer to 328 more)  VERY LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 4 randomized trials seriousa seriousb no serious indirectness seriousc none 21/352 (6%) 44/355 (12.4%) RR 0.54 (0.2 to 1.45) 57 fewer per 1000 (from 99 fewer to 56 more)  VERY LOW CRITICAL Caesarean section 7 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 161/708 (22.7%) 187/714 (26.2%) RR 0.87 (0.66 to 1.15) 34 fewer per 1000 (from 89 fewer to 39 more)  LOW CRITICAL Serious maternal morbidity or death 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/244 (0%) 0/246 (0%) not pooled not pooled  VERY LOW CRITICAL Serious maternal complications 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/174 (0%) 0/176 (0%) not pooled not pooled  VERY LOW CRITICAL Cervix unfavourable/unchanged after 12 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 3/70 (4.3%) 11/70 (15.7%) RR 0.27 (0.08 to 0.94) 115 fewer per 1000 (from 9 fewer to 145 fewer)  LOW IMPORTANT Oxytocin augmentation 5 randomized trials seriousa seriousb no serious indirectness seriousc none 188/524 (35.9%) 208/527 (39.5%) RR 0.94 (0.7 to 1.25) 24 fewer per 1000 (from 118 fewer to 99 more)  VERY LOW IMPORTANT 78 Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Epidural analgesia 3 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 192/219 (87.7%) 195/224 (87.1%) RR 1 (0.91 to 1.1) 0 fewer per 1000 (from 78 fewer to 87 more)  MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 4 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 20/494 (4%) 37/488 (7.6%) RR 0.53 (0.32 to 0.9) 36 fewer per 1000 (from 8 fewer to 52 fewer)  MODERATE IMPORTANT Uterine rupture 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/244 (0%) 0/246 (0%) not pooled not pooled  VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 28/337 (8.3%) 30/339 (8.8%) RR 0.93 (0.58 to 1.51) 6 fewer per 1000 (from 37 fewer to 45 more)  LOW IMPORTANT Meconium-stained liquor 6 randomized trials seriousa no serious inconsistency no serious indirectness seriousg none 56/618 (9.1%) 88/625 (14.1%) RR 0.61 (0.35 to 1.04) 55 fewer per 1000 (from 92 fewer to 6 more)  LOW CRITICAL Maternal nausea 1 randomized trials seriousa no serious inconsistency no serious indirectness serioush none 31/149 (20.8%) 23/151 (15.2%) RR 1.37 (0.84 to 2.23) 56 more per 1000 (from 24 fewer to 187 more)  LOW IMPORTANT Maternal side-effects 1 randomized trials seriousa no serious inconsistency no serious indirectness serioush none 86/149 (57.7%) 82/151 (54.3%) RR 1.06 (0.87 to 1.3) 33 more per 1000 (from 71 fewer to 163 more)  LOW IMPORTANT Maternal diarrhoea 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 20/148 (13.5%) 6/150 (4%) RR 3.38 (1.4 to 8.17) 95 more per 1000 (from 16 more to 287 more)  LOW IMPORTANT Postpartum haemorrhage 2 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 44/230 (19.1%) 48/236 (20.3%) RR 0.93 (0.65 to 1.33) 14 fewer per 1000 (from 71 fewer to 67 more)  LOW CRITICAL 79 Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Serious neonatal morbidity/perinatal death 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousi none 5/244 (2%) 4/243 (1.6%) RR 1.25 (0.34 to 4.55) 4 more per 1000 (from 11 fewer to 58 more)  VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousi none 1/171 (0.58%) 0/176 (0%) RR 3.09 (0.13 to 75.26) -  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 3 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 23/402 (5.7%) 35/400 (8.8%) RR 0.71 (0.37 to 1.36) 25 fewer per 1000 (from 55 fewer to 32 more)  LOW CRITICAL Neonatal intensive care unit admission 6 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 25/621 (4%) 44/625 (7%) RR 0.57 (0.36 to 0.91) 30 fewer per 1000 (from 6 fewer to 45 fewer)  MODERATE CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Substantial statistical heterogeneity (I2 > 60%) (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). d Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). e No events (–2). f Small sample size and few events (–1). g Wide CIs crossing the line of no effect, ranging from appreciable benefit to negligible harm (–1). h Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). i Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 80 Summary of Findings Table B.20: Any mechanical method plus oxytocin versus prostaglandin E2 alone Question: Should any mechanical method and oxytocin versus PGE2 alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus PGE2 alone Control Relative risk (95% CI) Absolute Uterine hyperstimulation with fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 9/76 (11.8%) 6/75 (8%) RR 1.48 (0.55 to 3.95) 38 more per 1000 (from 36 fewer to 236 more)  VERY LOW CRITICAL Caesarean section 4 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 103/409 (25.2%) 76/304 (25%) RR 0.93 (0.72 to 1.2) 17 fewer per 1000 (from 70 fewer to 50 more)  LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousd none 0/100 (0%) 0/100 (0%) not pooled not pooled  VERY LOW CRITICAL Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness seriouse none 100/100 (100%) 40/100 (40%) RR 2.48 (1.95 to 3.15) 592 more per 1000 (from 380 more to 860 more)  LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness seriouse none 40/76 (52.6%) 18/75 (24%) RR 2.19 (1.39 to 3.46) 286 more per 1000 (from 94 more to 590 more)  LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 2/22 (9.1%) 5/19 (26.3%) RR 0.35 (0.08 to 1.58) 171 fewer per 1000 (from 242 fewer to 153 more)  VERY LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 8/76 (10.5%) 7/75 (9.3%) RR 1.13 (0.43 to 2.95) 12 more per 1000 (from 53 fewer to 182 more)  VERY LOW CRITICAL Postpartum haemorrhage 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 0/76 (0%) 3/75 (4%) RR 0.14 (0.01 to 2.68) 34 fewer per 1000 (from 40 fewer to 67 more)  VERY LOW CRITICAL 81 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus PGE2 alone Control Relative risk (95% CI) Absolute Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 1/76 (1.3%) 0/75 (0%) RR 2.96 (0.12 to 71.55) -  VERY LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 6/76 (7.9%) 7/75 (9.3%) RR 0.85 (0.3 to 2.4) 14 fewer per 1000 (from 65 fewer to 131 more)  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). d No events (–2). e Single study with small sample size (–1). 82 Summary of Findings Table B.21: Any mechanical method plus oxytocin versus low-dose misoprostol alone Question: Should any mechanical method and oxytocin versus low-dose misoprostol alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;10(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus low- dose misoprostol alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 49/183 (26.8%) 99/179 (55.3%) RR 0.48 (0.37 to 0.63) 288 fewer per 1000 (from 205 fewer to 348 fewer)  MODERATE IMPORTANT Uterine hyperstimulation with fetal heart rate changes 3 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 6/709 (0.85%) 14/754 (1.9%) RR 0.43 (0.17 to 1.11) 11 fewer per 1000 (from 15 fewer to 2 more)  VERY LOW CRITICAL Caesarean section 5 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 196/868 (22.6%) 214/911 (23.5%) RR 0.95 (0.8 to 1.12) 12 fewer per 1000 (from 47 fewer to 28 more)  MODERATE CRITICAL Oxytocin augmentation 2 randomized trials seriousa seriousc no serious indirectness seriousd none 148/166 (89.2%) 58/170 (34.1%) RR 3.89 (0.7 to 21.72) 986 more per 1000 (from 102 fewer to 1000 more)  VERY LOW IMPORTANT Epidural analgesia 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 65/83 (78.3%) 58/79 (73.4%) RR 1.07 (0.9 to 1.27) 51 more per 1000 (from 73 fewer to 198 more)  VERY LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 3 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 16/249 (6.4%) 30/249 (12%) RR 0.52 (0.3 to 0.92) 58 fewer per 1000 (from 10 fewer to 84 fewer)  MODERATE IMPORTANT Meconium-stained liquor 2 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 22/183 (12%) 30/179 (16.8%) RR 0.72 (0.43 to 1.19) 47 fewer per 1000 (from 96 fewer to 32 more)  LOW CRITICAL 83 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus low- dose misoprostol alone Control Relative risk (95% CI) Absolute Maternal fever 2 randomized trials seriousa no serious inconsistency no serious indirectness seriousg none 2/149 (1.3%) 18/149 (12.1%) RR 0.13 (0.04 to 0.5) 105 fewer per 1000 (from 60 fewer to 116 fewer)  LOW IMPORTANT Women not satisfied 1 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 256/400 (64%) 177/466 (38%) RR 1.68 (1.47 to 1.93) 258 more per 1000 (from 179 more to 353 more)  MODERATE CRITICAL Serious neonatal morbidity/perinatal death 2 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 3/609 (0.49%) 4/654 (0.61%) RR 0.82 (0.18 to 3.65) 1 fewer per 1000 (from 5 fewer to 16 more)  VERY LOW CRITICAL Perinatal death 2 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 3/609 (0.49%) 4/654 (0.61%) RR 0.82 (0.18 to 3.65) 1 fewer per 1000 (from 5 fewer to 16 more)  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 3/83 (3.6%) 3/79 (3.8%) RR 0.95 (0.2 to 4.58) 2 fewer per 1000 (from 30 fewer to 136 more)  VERY LOW CRITICAL Neonatal intensive care unit admission 4 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 59/775 (7.6%) 93/824 (11.3%) RR 0.66 (0.49 to 0.9) 38 fewer per 1000 (from 11 fewer to 58 fewer)  MODERATE CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm, and few events (–2). c Substantial statistical heterogeneity (I2 > 60%) (–1). d Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). e Single study with small sample size, wide CIs ranging from modest benefit to appreciable harm (–2). f Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). g Small sample size and few events (–1). h Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 84 Summary of Findings Table B.22: Any mechanical method plus oxytocin versus oxytocin alone Question: Should any mechanical method and oxytocin versus oxytocin alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus oxytocin alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa seriousb no serious indirectness seriousc none 53/153 (34.6%) 82/168 (48.8%) RR 0.71 (0.21 to 2.4) 142 fewer per 1000 (from 386 fewer to 683 more)  VERY LOW IMPORTANT Caesarean section 6 randomized trials seriousa seriousb no serious indirectness seriousd none 69/351 (19.7%) 95/367 (25.9%) RR 0.68 (0.39 to 1.2) 83 fewer per 1000 (from 158 fewer to 52 more)  VERY LOW CRITICAL Serious maternal morbidity or death 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/153 (0%) 0/168 (0%) not pooled not pooled  VERY LOW CRITICAL Serious maternal complications 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/93 (0%) 0/108 (0%) not pooled not pooled  VERY LOW CRITICAL Epidural analgesia 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 61/61 (100%) 64/66 (97%) RR 1.03 (0.98 to 1.09) 29 more per 1000 (from 19 fewer to 87 more)  LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousg none 7/97 (7.2%) 9/102 (8.8%) RR 0.85 (0.34 to 2.09) 13 fewer per 1000 (from 58 fewer to 96 more)  VERY LOW IMPORTANT Uterine rupture 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/60 (0%) 0/60 (0%) not pooled not pooled  VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa no serious inconsistency no serious indirectness very seriousg none 13/143 (9.1%) 14/150 (9.3%) RR 0.99 (0.48 to 2.02) 1 fewer per 1000 (from 49 fewer to 95 more)  VERY LOW IMPORTANT 85 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus oxytocin alone Control Relative risk (95% CI) Absolute Meconium-stained liquor 3 randomized trials seriousa no serious inconsistency no serious indirectness very seriousg none 9/157 (5.7%) 13/162 (8%) RR 0.72 (0.32 to 1.63) 22 fewer per 1000 (from 55 fewer to 51 more)  VERY LOW CRITICAL Postpartum haemorrhage 3 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 8/157 (5.1%) 7/162 (4.3%) RR 1.18 (0.44 to 3.18) 8 more per 1000 (from 24 fewer to 94 more)  VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 2 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 2/153 (1.3%) 3/168 (1.8%) RR 0.71 (0.12 to 4.13) 5 fewer per 1000 (from 16 fewer to 56 more)  VERY LOW CRITICAL Neonatal intensive care unit admission 3 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 26/190 (13.7%) 30/210 (14.3%) RR 0.98 (0.61 to 1.58) 3 fewer per 1000 (from 56 fewer to 83 more)  LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Substantial statistical heterogeneity (I2 > 60%) (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). d Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). e No events (–2). f Small sample size (–1). g Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). h Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 86 6. References 1. de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies-Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. 2. Jozwiak M, Bloemenkamp KWM, Kelly AJ, Mol BWJ, Irion O, Boulvain M. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2012;(3):CD001233. 3. Hofmeyr GJ, Alfirevic Z, Kelly AJ, Kavanagh J, Thomas J, Brocklehurst P, et al. Methods for cervical ripening and labour induction in late pregnancy: generic protocol. Cochrane Database Syst Rev. 2009;(3):CD002074. 4. Coates R, Cupples G, Scamell A, McCourt C. Women’s experiences of induction of labour: qualitative systematic review and thematic synthesis. Midwifery. 2019;69:17-28. doi:10.1016/j.midw.2018.10.013. 5. Akuamoah-Boateng J, Spencer R. Woman-centered care: Women’s experiences and perceptions of induction of labor for uncomplicated post-term pregnancy: a systematic review of qualitative evidence. Midwifery. 2018;67:46-56. doi:10.1016/j.midw.2018.08.018. 6. Lou S, Hvidman L, Uldbjerg N, Neumann L, Jensen TF, Haben JG, et al. Women's experiences of postterm induction of labor: a systematic review of qualitative studies. Birth. 2019;46(3):400-10. doi:10.1111/birt.12412. 7. Coates D, Goodfellow A, Sinclair L. Induction of labour: Experiences of care and decision-making of women and clinicians. Women Birth. 2020;33(1):e1-e14. doi:10.1016/j.wombi.2019.06.002. 8. Ezeanochie M, Olagbuji B, Ande A. Women’s concerns and satisfaction with induced labour at term in a Nigerian population. Niger Postgrad Med. 2013;20(1):1-4. 9. Henderson J, Redshaw M. Women’s experience of induction of labor: a mixed methods study. Acta Obstet Gynecol Scand. 2013;92(10):1159-67. doi:10.1111/aogs.12211. 10. Wessberg A, Lundgren I, Elden H. Being in limbo: women’s lived experiences of pregnancy at 41 weeks of gestation and beyond – a phenomenological study. BMC Pregnancy Childbirth. 2017;17(1):1-12. doi:10.1186/s12884-017-1342-4. 11. Westfall RE, Benoit C. The rhetoric of “natural” in natural childbirth: childbearing women's perspectives on prolonged pregnancy and induction of labour. Soc Sci Med. 2004;59(7):1397-408. doi:10.1016/j.socscimed.2004.01.017. 12. Nippita TA, Porter M, Seeho SK, Morris JM, Roberts CL. Variation in clinical decision-making for induction of labour: a qualitative study. BMC Pregnancy Childbirth. 2017;17(1):317. doi:10.1186/s12884-017-1518-y. 13. ten Eikelder M, van Baaren GJ, Oude Rengerink K, Jozwiak M, de Leeuw JW, Kleiverda G, et al. Comparing induction of labour with oral misoprostol or Foley catheter at term: cost-effectiveness analysis of a randomised controlled multi-centre non-inferiority trial. BJOG. 2018;125(3):375-83. doi:10.1111/1471-0528.14706. 14. ten Eikelder ML, Rengerink KO, Jozwiak M, De Leeuw JW, De Graaf IM, Van Pampus MG, et al. Induction of labour at term with oral misoprostol versus a Foley catheter (PROBAAT-II): a multicentre randomised controlled non-inferiority trial. Lancet. 2016;387(10028):1619-28. doi:10.1016/S0140-6736(16)00084-2. 15. van Baaren GJ, Jozwiak M, Opmeer BC, Oude Rengerink K, Benthem M, Dijksterhuis MGK, et al. Cost- effectiveness of induction of labour at term with a Foley catheter compared to vaginal prostaglandin E2 gel (PROBAAT trial). BJOG. 2013;120(8):987-95. doi:10.1111/1471-0528.12221. 16. Jozwiak M, Rengerink KO, Benthem M, van Beek E, Dijksterhuis MG, De Graaf IM, 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;378(9809):2095-103. doi:10.1016/S0140-6736(11)61484-0. 17. State of inequality: reproductive, maternal, newborn and child health. Geneva: World Health Organization; 2015 (https://apps.who.int/iris/handle/10665/164590). 18. Primary health care on the road to universal health coverage: 2019 global monitoring report. Geneva: World Health Organization; 2021 (https://apps.who.int/iris/handle/10665/344057). 19. Protheroe J, Brooks H, Chew-Graham C, Gardner C, Rogers A. “Permission to participate?” A qualitative study of participation in patients from differing socio-economic backgrounds. J Health Psychol. 2013;18(8):1046-55. doi:10.1177/1359105312459876. 20. Tunçalp Ӧ, Were W, MacLennan C, Oladapo O, Gülmezoglu A, Bahl R, et al. Quality of care for pregnant women and newborns – the WHO vision. BJOG. 2015;122(8):1045-9. doi:10.1111/1471-0528.13451. 87 21. Seijmonsbergen-Schermers AE, van den Akker T, Rydahl E, Beeckman K, Bogaerts A, Binfa L, et al. Variations in use of childbirth interventions in 13 high-income countries: a multinational cross-sectional study. PLoS Med. 2020;17(5):e1003103. doi:10.1371/journal.pmed.1003103. 22. Guerra GV, Cecatti JG, Souza JP, Faundes A, Morais SS, Gulmezoglu AM, et al. Factors and outcomes associated with the induction of labour in Latin America. BJOG. 2009;116(13):1762-72. doi:10.1111/j.1471-0528.2009.02348.x. 23. Vogel JP, Souza JP, Gülmezoglu AM. Patterns and outcomes of induction of labour in Africa and Asia: a secondary analysis of the WHO Global Survey on Maternal and Neonatal Health. PLoS One. 2013;8(6):e65612. doi:10.1371/journal.pone.0065612. 24. Vogel JP, Gülmezoglu AMM, Hofmeyr GJ, Temmerman M. Global perspectives on elective induction of labor. Clin Obstet Gynecol. 2014;57(2):331-42. doi:10.1097/GRF.0000000000000031. 25. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/handle/10665/250796). 26. WHO recommendations: induction of labour at or beyond term. Geneva: World Health Organization; 2018 (https://apps.who.int/iris/handle/10665/277233). b WHO recommendations on the use of mechanical methods for induction of labour For more information, please contact: World Health Organization Avenue Appia 20, CH-1211 Geneva 27, Switzerland Maternal and Perinatal Health Unit Department of Sexual and Reproductive Health and Research E-mail: srhmph@who.int https://www.who.int/teams/sexual-and-reproductive-health- and-research-(srh)/areas-of-work/maternal-and-perinatal-health Department of Maternal, Newborn, Child and Adolescent Health and Ageing Email: mncah@who.int Website: www.who.int/teams/maternal-newborn-child- adolescent-health-and-ageing/ ISBN 978 92 4 005580 3

WHO recommendations on mechanical methods for induction of labour Web Annex. Evidence-to-decision framework ii WHO recommendations on mechanical methods for induction of labour. Web Annex. Evidence-to- decision framework ISBN 978-92-4-005580-3 (electronic version) © World Health Organization 2022 Some rights reserved. This work is available under the Creative Commons Attribution- NonCommercial-ShareAlike 3.0 IGO licence (CC BY-NC-SA 3.0 IGO; https://creativecommons.org/licenses/by-nc-sa/3.0/igo). Under the terms of this licence, you may copy, redistribute and adapt the work for non-commercial purposes, provided the work is appropriately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. 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The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in preference to others of a similar nature that are not mentioned. Errors and omissions excepted, the names of proprietary products are distinguished by initial capital letters. All reasonable precautions have been taken by WHO to verify the information contained in this publication. However, the published material is being distributed without warranty of any kind, either expressed or implied. The responsibility for the interpretation and use of the material lies with the reader. In no event shall WHO be liable for damages arising from its use. This publication forms part of the WHO guideline entitled WHO recommendations on mechanical methods for induction of labour. It is being made publicly available for transparency purposes and information, in accordance with the WHO handbook for guideline development, 2nd edition (2014). iii Contents 1. BACKGROUND ......................................................................................................................................... 1 2. QUESTION ............................................................................................................................................... 1 3. ASSESSMENT ........................................................................................................................................... 2 3.1 EFFECTS (DESIRABLE AND UNDESIRABLE) ......................................................................................................... 2 3.2 VALUES .................................................................................................................................................. 23 3.3 EFFECTS AND VALUES ................................................................................................................................ 24 3.4 RESOURCES ............................................................................................................................................. 24 3.5 EQUITY .................................................................................................................................................. 27 3.6 ACCEPTABILITY ........................................................................................................................................ 27 3.7 FEASIBILITY ............................................................................................................................................. 29 4. GRADE SUMMARY OF JUDGEMENTS TABLE .......................................................................................... 31 5. GRADE SUMMARY OF FINDINGS TABLES ............................................................................................... 32 6. REFERENCES .......................................................................................................................................... 86 The main guideline document, WHO recommendations on mechanical methods for induction of labour, is available at: https://apps.who.int/iris/bitstream/handle/10665/363140/9789240055780-eng.pdf 1 1. Background Induction of labour may be initiated by pharmacologic or mechanical methods. Mechanical methods of labour induction are used to dilate the cervix, and include a range of procedures and devices: introducing a balloon catheter into the extra-amniotic space, laminaria tents into the cervix or the injection of fluid (saline or a solution containing prostaglandins) via a catheter into the extra- amniotic space (known as extra-amniotic saline infusion, or EASI). While standard urinary catheters (Foley) have been used for many years, double balloon (“Atad”) catheters have been developed for obstetric use (1). Mechanical methods have been used for induction of labour for decades, although more recently these have been replaced or supplemented by pharmacological methods (1). Despite this, mechanical methods have continued to be used in many obstetric settings as they are relatively low- cost, and are not generally associated with some of the serious side-effects that may occur with the use of pharmacological methods. 2. Question For women at or beyond term (P), should mechanical methods (alone or in combination with pharmacological methods) (I), compared with other types of induction methods or no intervention (C), be used to improve maternal and perinatal outcomes (O)? Problem: Perinatal risks associated with post-term pregnancy Perspective: Clinical practice recommendation – population perspective Population (P): Pregnant women at or beyond term Intervention (I): Labour induction with mechanical methods (alone or in combination with pharmacological methods) Comparison (C): Other types of induction methods or no intervention Priority outcomes (O): Critical outcomes:1 Maternal • Vaginal delivery not achieved within 24 hours • Caesarean section • Uterine hyperstimulation with fetal heart rate changes • Postpartum haemorrhage • Uterine rupture • Severe maternal morbidity or death Fetal/neonatal • Apgar score less than 7 at 5 minutes • Admission to a neonatal intensive care unit • Neonatal encephalopathy • Severe neonatal morbidity • Disability in childhood • Perinatal death. 1 These outcomes reflect the outcomes used in the 2011 WHO recommendations for induction of labour (available at: https://apps.who.int/iris/handle/10665/44531). An outcome ranked as 7 or more was considered “critical”, and an outcome ranked 4–6 was considered “important” (on a scale of 1 to 9, from not important to critical). The outcomes “maternal well-being” and “maternal satisfaction” have been added as part of this update. 2 Important outcomes: Maternal • Cervix unfavourable or unchanged after 24 hours • Oxytocin augmentation • Epidural rate • Uterine hyperstimulation without fetal heart rate changes • Instrumental vaginal birth • Meconium-stained amniotic fluid • Maternal side-effects (all) • Nausea • Vomiting • Diarrhoea • Maternal well-being • Women not satisfied with the care related to induction of labour (maternal satisfaction) • Caregiver not satisfied with the care related to induction of labour. 3. Assessment 3.1 Effects (desirable and undesirable) Evidence on effectiveness and safety Evidence on the effectiveness and safety of mechanical methods for the induction of labour is from a Cochrane systematic review updated in 2019 (1). The updated review includes 113 trials, with data on relevant outcomes from 105 studies (with a total of 22 373 women), as compared with the previous review published in 2012, which included data from 71 studies (with 9722 women) (2). Data were presented across 17 different comparisons, with different mechanical methods comparing only those interventions that were listed above it in a hierarchy of interventions as outlined in a generic protocol (3). The updated review includes a total of 22 different comparisons, 18 of which are of relevance to this guideline recommendation. The update excludes studies comparing mechanical methods with placebo or no treatment, and comparisons with misoprostol are limited to only low-dose misoprostol (1). The trials were carried out in hospital settings across the world (including in low- and middle-income countries), including: Australia (2 trials), Brazil (two trials), Canada (3 trials), Czechia (4 trials), Denmark (3 trials), Egypt (3 trials), Finland (1 trial), France (2 trials), India (13 trials), Islamic Republic of Iran (4 trials), Israel (6 trials), Italy (2 trials), Jordan (2 trials), Netherlands (4 trials), Nigeria (4 trials), Norway (1 trial), Pakistan (4 trials), the Russian Federation (1 trial), Rwanda (1 trial), Singapore (1 trial), Sri Lanka (3 trials), South Africa (3 trials), Sweden (2 trials), Tunisia (1 trial), Türkiye (1 trial), the United Kingdom of Great Britain and Northern Ireland (5 trials), and the United States of America (25 trials). The earliest trial was published in 1981, although the majority were published after 2000. Nine of the studies included only nulliparous women and two only multiparous women; the rest included both. Four studies recruited only women with a history of caesarean section, but in most studies such women were excluded. The majority of studies only recruited women at term (gestational age 37 weeks or more). The review examined four broad types of interventions: • balloon catheter versus other interventions (other mechanical or pharmacologic, or mixed); • laminaria tent versus other interventions; • extra-amniotic infusion versus other interventions; and 3 • any mechanical method combined with other (non-mechanical) intervention versus other interventions. Of the 22 comparisons made, only 18 of them were relevant to the PICO for this guideline recommendation and presented to the GDG. Effects of interventions: Comparison 1 – Balloon catheter (Foley or Atad) versus vaginal prostaglandin E2 (PGE2) This comparison included 28 trials with data for 6619 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference in outcome for vaginal delivery not achieved within 24 hours between balloon catheter compared with vaginal PGE2 (very-low-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: Balloon catheter probably reduces the risk of uterine hyperstimulation with fetal heart rate changes compared with vaginal PGE2 (6 trials, 1966 women; relative risk [RR] 0.35, 95% confidence interval [CI] 0.18 to 0.67; moderate-certainty evidence). Postpartum haemorrhage (PPH): Balloon catheter makes little or no difference to PPH compared with vaginal PGE2 (8 trials, 2215 women; RR 0.82, 95% CI 0.63 to 1.06; low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between balloon catheter compared with vaginal PGE2 for uterine rupture or severe maternal morbidity or death (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between balloon catheter compared with vaginal PGE2 for severe maternal morbidity or death (very-low- certainty evidence). Important: Oxytocin augmentation: It is uncertain whether there is any difference between balloon catheter compared with vaginal PGE2 for oxytocin augmentation (very-low-certainty evidence). Epidural rate: Balloon catheter may increase epidural rate compared with vaginal PGE2 (8 trials, 2828 women; RR 1.14, 95% CI 1.00 to 1.29; low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Balloon catheter probably reduces uterine hyperstimulation without fetal heart rate changes compared with vaginal PGE2 (15 trials, 2444 women; RR 0.27, 95% CI 0.11 to 0.66; moderate-certainty evidence). Instrumental vaginal birth: Balloon catheter probably has little or no effect on instrumental vaginal birth compared with vaginal PGE2 (16 trials, 4514 women; RR 0.93, 95% CI 0.79 to 1.09; moderate- certainty evidence). Meconium-stained liquor: Balloon catheter may make little or no difference to meconium-stained liquor compared with vaginal PGE2 (4 trials, 964 women; RR 0.89, 95% CI 0.67 to 1.19; low-certainty evidence). 4 Maternal fever during labour: Balloon catheter may make little or no difference to maternal fever during labour compared with vaginal PGE2 (7 trials, 2362 women; RR 0.87, 95% CI 0.65 to 1.17; low- certainty evidence). Women not satisfied with care: Balloon catheter may make little or no difference to maternal satisfaction compared with vaginal PGE2 (1 trial, 93 women; RR 0.61, 95% CI 0.39 to 0.97; low- certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: Balloon catheter may make little or no difference to Apgar less than 7 at 5 minutes compared with vaginal PGE2 (14 trials, 4271 infants; RR 0.74, 95% CI 0.49 to 1.14; low-certainty evidence). Admission to a neonatal intensive care unit: Balloon catheter may make little or no difference to admission to a neonatal intensive care unit compared with vaginal PGE2 (12 trials, 3647 infants; RR 0.82, 95% CI 0.65 to 1.04; low-certainty evidence). Severe neonatal morbidity or perinatal death: Balloon catheter probably reduces severe neonatal morbidity or perinatal death compared with vaginal PGE2 (8 trials, 2757 infants; RR 0.48, 95% CI 0.25 to 0.93; moderate-certainty evidence). Perinatal death: Balloon catheter may make little or no difference to perinatal death compared with vaginal PGE2 (5 trials, 1036 infants; RR 0.21; 95% CI 0.01 to 4.27; low-certainty evidence). Effects of interventions: Comparison 2 – Balloon catheter (Foley or Atad) versus intracervical PGE2 This comparison included 10 trials with data for 1428 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). Caesarean section: Balloon catheter probably makes little or no difference to caesarean section compared with intracervical PGE2 (9 trials, 1309 women; RR 0.97, 95% CI 0.81 to 1.15; moderate- certainty evidence). Uterine hyperstimulation with fetal heart rate changes/PPH: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for uterine hyperstimulation with fetal heart rate changes or PPH (both very-low-certainty evidence). Important: Cervix unfavourable or unchanged after 24 hours: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for cervix unfavourable or unchanged after 24 hours (very-low-certainty evidence). 5 Oxytocin augmentation: Balloon catheter may make little or no difference to oxytocin augmentation compared with intracervical PGE2 (1 trial, 400 women; RR 1.08, 95% CI 0.93 to 1.26; low-certainty evidence). Epidural rate: Balloon catheter may make little or no difference to epidural rate compared with intracervical PGE2 (1 trial, 149 women; RR 0.91, 95% CI 0.81 to 1.02; low-certainty evidence). Instrumental vaginal birth: Balloon catheter may make little or no difference to instrumental vaginal birth compared with intracervical PGE2 (3 trials, 337 women; RR 1.18, 95% CI 0.68 to 2.05; low- certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for meconium-stained liquor (very-low-certainty evidence). Maternal side-effects: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for maternal side-effects (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than seven at 5 minutes: Balloon catheter may make little or no difference to Apgar score less than 7 at 5 minutes compared with intracervical PGE2 (2 trials, 475 infants; RR 0.79; 95% CI 0.41 to 1.53; low-certainty evidence). Admission to a neonatal intensive care unit: Balloon catheter may make little or no difference to admission to a neonatal intensive care unit compared with intracervical PGE2 (1 trial, 400 infants; RR 0.88, 95% CI 0.60 to 1.31; low-certainty evidence). Severe neonatal morbidity: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for severe neonatal morbidity (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between balloon catheter compared with intracervical PGE2 for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 3 – Balloon catheter (Foley or Atad) versus low-dose vaginal misoprostol This comparison included 13 trials with data for 1818 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). 6 Serious maternal morbidity or death: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for serious maternal morbidity or death (very-low-certainty evidence). Caesarean section: Balloon catheter probably increases caesarean section compared with low-dose vaginal misoprostol (12 trials, 1756 women; RR 1.28, 95% CI 1.02 to 1.60; moderate-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: Balloon catheter may reduce uterine hyperstimulation with fetal heart rate changes compared with low-dose vaginal misoprostol (8 trials, 1322 women; RR 0.39, 95% CI 0.18 to 0.85; low-certainty evidence). Important: Cervix unfavourable or unchanged after 12 hours: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for cervical dilatation after 12 hours (very-low-certainty evidence). Oxytocin augmentation: Balloon catheter may increase oxytocin augmentation compared with low- dose vaginal misoprostol (9 trials, 911 women; RR 1.62, 95% CI 1.38 to 1.90; low-certainty evidence). Epidural rate: Balloon catheter probably increases epidural rate compared with low-dose vaginal misoprostol (2 trials, 517 women; RR 1.22, 95% CI 1.06 to 1.41; moderate-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Balloon catheter probably reduces uterine hyperstimulation without fetal heart rate changes compared with low-dose vaginal misoprostol (9 trials, 1139 women; RR 0.25, 95% CI 0.14 to 0.44; moderate-certainty evidence). Instrumental vaginal birth: Balloon catheter may make little or no difference to instrumental vaginal birth compared with low-dose vaginal misoprostol (4 trials, 721 women; RR 0.72, 95% CI 0.50 to 1.05; low-certainty evidence). Meconium-stained liquor: Balloon catheter probably reduces meconium-stained liquor compared with low-dose vaginal misoprostol (7 trials, 1268 women; RR 0.64, 95% CI 0.48 to 0.87; moderate- certainty evidence). Maternal vomiting or maternal fever during labour: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for maternal vomiting or maternal fever during labour (both very-low-certainty evidence). Fetal/neonatal outcomes Critical: Severe neonatal morbidity: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for severe neonatal morbidity (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for perinatal death (very-low-certainty evidence). Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between balloon catheter compared with low-dose vaginal misoprostol for Apgar score < 7 at 5 minutes (very- low-certainty evidence). 7 Admission to a neonatal intensive care unit: Balloon catheter may make little or no difference to admission to a neonatal intensive care unit compared with low-dose vaginal misoprostol (9 trials, 1302 infants; RR 1.00, 95% CI 0.61 to 1.63; low-certainty evidence). Effects of interventions: Comparison 4 – Balloon (Foley or Atad) versus low-dose oral misoprostol This comparison included seven trials with data for 3178 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: Balloon catheter probably increases vaginal delivery not achieved within 24 hours compared with low-dose oral misoprostol (2 trials, 782 women; RR 1.28, 95% CI 1.13 to 1.46; moderate-certainty evidence). Caesarean section: Balloon catheter probably increases caesarean section compared with low-dose oral misoprostol (7 trials, 3178 women; RR 1.17, 95% CI 1.04 to 1.32; moderate-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: Balloon catheter may make little or no difference to uterine hyperstimulation with fetal heart rate changes compared with low-dose oral misoprostol (2 trials, 2033 women; RR 0.81, 95% CI 0.48 to 1.38; low-certainty evidence). Postpartum haemorrhage (PPH): Balloon catheter may make little or no difference to PPH compared with low-dose oral misoprostol (5 trials, 2966 women; RR 1.03, 95% CI 0.79 to 1.34; low- certainty evidence). Uterine rupture: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for uterine rupture (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for severe maternal morbidity or death ( very-low-certainty evidence). Maternal death: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for maternal death (very-low-certainty evidence). Important: Cervix unfavourable after 24 hours: Balloon catheter may make little or no difference to cervix unfavourable after 24 hours compared with low-dose oral misoprostol (4 trials, 994 women; RR 0.98, 95% CI 0.61 to 1.56; low-certainty evidence). Oxytocin augmentation: Balloon catheter may increase oxytocin augmentation compared with low- dose oral misoprostol (5 trials, 2847 women; RR 1.28, 95% CI 1.09 to 1.49; low-certainty evidence). Epidural rate: Balloon catheter probably makes little or no difference to epidural rate compared with low-dose oral misoprostol (3 trials, 2365 women; RR 1.08, 95% CI 0.96 to 1.22; moderate- certainty evidence). 8 Uterine hyperstimulation without fetal heart rate changes: Balloon catheter may make little or no difference to uterine hyperstimulation without fetal heart rate changes compared with low-dose oral misoprostol (5 trials, 2838 women; RR 0.50, 95% CI 0.12 to 2.07; low-certainty evidence). Instrumental vaginal birth: Balloon catheter probably reduces instrumental vaginal birth compared with low-dose oral misoprostol (3 trials, 2627 women; RR 0.71, 95% CI 0.55 to 0.92; moderate- certainty evidence). Meconium-stained liquor: Balloon catheter may make little or no difference to meconium-stained liquor compared with low-dose oral misoprostol (3 trials, 2627 women; RR 0.77, 95% CI 0.44 to 1.35; low-certainty evidence). Maternal side-effects (all): Balloon catheter may make little or no difference to maternal side- effects (all) compared with low-dose oral misoprostol (2 trials, 662 women; RR 0.61, 95% CI 0.33 to 1.13; low-certainty evidence). Maternal vomiting: Balloon catheter may make little or no difference to maternal vomiting compared with low-dose oral misoprostol (2 trials, 662 women; RR 0.73, 95% CI 0.37 to 1.46; low- certainty evidence). Maternal diarrhoea: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for maternal diarrhoea (very-low-certainty evidence). Maternal fever during labour: Balloon catheter probably makes little or no difference to maternal fever during labour compared with low-dose oral misoprostol (2 trials, 2033 women; RR 0.98, 95% CI 0.78 to 1.24; moderate-certainty evidence). Maternal satisfaction: Balloon catheter probably increases maternal satisfaction compared with low-dose oral misoprostol (1 trial, 602 women; RR 1.70, 95% CI 1.15 to 2.50; moderate-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: Balloon catheter may make little or no difference to Apgar score less than 7 at 5 minutes compared with low-dose oral misoprostol (4 trials, 2693 infants; RR 0.71; 95% CI 0.38 to 1.32; low-certainty evidence). Admission to a neonatal intensive care unit: Balloon catheter may make little or no difference to admission to a neonatal intensive care unit compared with low-dose oral misoprostol (5 trials, 2873 infants; RR 0.82, 95% CI 0.58 to 1.17; low-certainty evidence). Neonatal encephalopathy: It is uncertain whether there is any difference between balloon catheter compared with low-dose oral misoprostol for neonatal encephalopathy (very-low-certainty evidence). Severe neonatal morbidity or perinatal death: Balloon catheter may make little or no difference to severe neonatal morbidity or perinatal death compared with low-dose oral misoprostol (3 trials, 2627 infants; RR 1.11, 95% CI 0.60 to 2.06; low-certainty evidence). 9 Effects of interventions: Comparison 5 – Balloon (Foley or Atad) versus oxytocin This comparison included eight trials with data for 781 women. Maternal outcomes Critical: Caesarean section: Balloon catheter probably reduces caesarean section compared with oxytocin (8 trials, 781 women; RR 0.68, 95% CI 0.56 to 0.83; moderate-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Postpartum haemorrhage (PPH): It is uncertain whether there is any difference between balloon catheter compared with oxytocin for PPH (very-low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for uterine rupture (very-low-certainty evidence). Serious maternal morbidity or death: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for serious maternal morbidity or death (very-low- certainty evidence). Important: Cervix unfavourable after 24 hours: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for cervix unfavourable after 24 hours (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for meconium-stained liquor (very-low-certainty evidence). Maternal fever during labour: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for maternal fever during labour (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for Apgar score less than 7 at 5 minutes (very-low- certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for admission to a neonatal intensive care unit (very-low- certainty evidence). 10 Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between balloon catheter compared with oxytocin for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 6 – Laminaria tent versus vaginal PGE2 This comparison included five trials with data for 263 women. Maternal outcomes Critical: Caesarean section: Laminaria tent may make little or no difference to caesarean section compared with vaginal PGE2 (5 trials, 263 women; RR 0.91, 95% CI 0.56 to 1.48; low-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: Laminaria tent may reduce uterine hyperstimulation with fetal heart rate changes compared with vaginal PGE2 (3 trials, 188 women; RR 0.11, 95% CI 0.02 to 0.60; low-certainty evidence). Severe maternal morbidity: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for severe maternal morbidity (very-low-certainty evidence). Important: Epidural rate: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for epidural rate (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Laminaria tent may reduce uterine hyperstimulation without fetal heart rate changes compared with vaginal PGE2 (3 trials, 180 women; RR 0.22, 95% CI 0.09 to 0.49; low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for meconium-stained liquor (very-low-certainty evidence). Maternal side-effects (nausea): It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for maternal side-effects (nausea) (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for severe neonatal morbidity or perinatal death (very-low-certainty evidence). 11 Perinatal death: It is uncertain whether there is any difference between laminaria compared with vaginal PGE2 for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 7 – Laminaria tent versus intracervical PGE2 This comparison included five trials with data for 920 women. Maternal outcomes Critical: Caesarean section: Laminaria tent may make little or no difference to caesarean section compared with intracervical PGE2 (5 trials, 920 women; RR 1.16, 95% CI 0.93 to 1.45; low-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for severe maternal morbidity or death (very-low- certainty evidence). Important: Oxytocin augmentation: Laminaria tent may increase oxytocin augmentation compared with intracervical PGE2 (1 trial, 185 women; RR 1.41, 95% CI 1.21 to 1.64; low-certainty evidence). Instrumental vaginal birth: Laminaria tent may make little or no difference to instrumental vaginal birth compared with intracervical PGE2 (3 trials, 424 women; RR 1.05, 95% CI 0.65 to 1.69; low- certainty evidence). Cervix unfavourable or unchanged after 24 hours: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for cervix unfavourable or unchanged after 24 hours (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Maternal side-effects: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for maternal side-effects (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for Apgar score less than 7 at 5 minutes (very-low- certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for admission to a neonatal intensive care unit (very-low-certainty evidence). 12 Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between laminaria tent compared with intracervical PGE2 for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 8 – Laminaria tent versus oxytocin There were data from two trials with 73 women for only one relevant outcome. Maternal outcome Critical: Caesarean section: It is uncertain whether there is any difference between laminaria tent compared with oxytocin for caesarean section (very-low-certainty evidence). Effects of interventions: Comparison 9 – Extra-amniotic saline infusion (EASI) versus vaginal PGE2 This comparison included two trials with data for 221 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: EASI may increase vaginal delivery not achieved within 24 hours compared with vaginal PGE2 (1 trial, 109 women; RR 1.74, 95% CI 1.21 to 2.49; low- certainty evidence). Caesarean section or uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for caesarean section or uterine hyperstimulation with fetal heart rate changes (both very-low-certainty evidence). Important: Oxytocin augmentation: EASI may increase oxytocin augmentation compared with vaginal PGE2 (1 trial, 109 women; RR 12.71, 95% CI 3.20 to 50.57; low-certainty evidence). Epidural rate: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for epidural rate (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for meconium-stained liquor (very-low-certainty evidence). Maternal satisfaction: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for maternal satisfaction (very-low-certainty evidence). 13 Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between EASI compared with vaginal PGE2 for admission to a neonatal intensive care unit (very-low-certainty evidence). Effects of interventions: Comparison 10 – EASI versus intracervical PGE2 This comparison included two trials with data for 155 women. Maternal outcomes Critical: Caesarean section: It is uncertain whether there is any difference between EASI compared with intracervical PGE2 for caesarean section (very-low-certainty evidence). Important: Cervix unfavourable or unchanged after 24 hours: EASI may reduce cervix unfavourable or unchanged after 12–24 hours compared with intracervical PGE2 (1 trial, 85 women; RR 0.06, 95% CI 0.00 to 0.97; low-certainty evidence). Oxytocin augmentation or: It is uncertain whether there is any difference between EASI compared with intracervical PGE2 for oxytocin augmentation (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between EASI compared with intracervical PGE2 for instrumental vaginal birth (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between EASI compared with intracervical PGE2 for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Effects of interventions: Comparison 11 – Any mechanical method plus PGE2 versus PGE2 alone This comparison included eight trials with data for 639 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). Caesarean section: Any mechanical method plus PGE2 may make little or no difference to caesarean section compared with PGE2 alone (7 trials, 517 women; RR 0.96, 95% CI 0.66 to 1.40; low-certainty evidence). 14 Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Postpartum haemorrhage (PPH): It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for PPH (very-low-certainty evidence). Important: Cervix unfavourable after 24 hours: Any mechanical method plus PGE2 may reduce cervix unfavourable after 24 hours compared with PGE2 alone (1 trial, 122 women; RR 0.52, 95% CI 0.31 to 0.85; low-certainty evidence). Oxytocin augmentation: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for oxytocin augmentation (very-low-certainty evidence). Epidural rate: Any mechanical method plus PGE2 may make little or no difference to epidural rate compared with PGE2 alone (1 trial, 39 women; RR 0.98, 95% CI 0.77 to 1.24; low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for meconium-stained liquor (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with PGE2 alone for admission to neonatal intensive care (very-low-certainty evidence). Effects of interventions: Comparison 12 – Any mechanical method plus PGE2 versus low- dose misoprostol alone This comparison included only one trial with data for 127 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: Any mechanical method plus PGE2 may reduce vaginal delivery not achieved within 24 hours compared with low-dose misoprostol alone (1 trial, 127 women; RR 0.32, 95% CI 0.12 to 0.82; low-certainty evidence). 15 Caesarean section: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for caesarean section (very-low-certainty evidence). Important: Cervix unfavourable after 24 hours: Any mechanical method plus PGE2 may reduce cervix unfavourable after 24 hours compared with low-dose misoprostol alone (1 trial, 127 women; RR 0.41, 95% CI 0.25 to 0.67; low-certainty evidence). Oxytocin augmentation: Any mechanical method plus PGE2 may increase oxytocin augmentation compared with low-dose misoprostol alone (1 trial, 127 women; RR 1.21, 95% CI 1.01 to 1.46; low- certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Any mechanical method plus PGE2 may increase uterine hyperstimulation without fetal heart rate changes compared with low-dose misoprostol alone (1 trial, 127 women; RR 4.05, 95% CI 1.44 to 11.38; low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for instrumental vaginal birth (very- low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for meconium-stained liquor (very- low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for admission to neonatal intensive care (very-low-certainty evidence). Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for serious neonatal morbidity/perinatal death (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with low-dose misoprostol alone for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 13 – Any mechanical method plus PGE2 versus oxytocin alone This comparison included only one trial with data for 44 women and reported only two relevant outcomes. 16 Maternal outcomes Critical: Caesarean section: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with oxytocin alone for caesarean section (very-low-certainty evidence). Important: Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus PGE2 compared with oxytocin alone for instrumental vaginal birth (very-low-certainty evidence). Effects of interventions: Comparison 14 – Any mechanical method and low-dose misoprostol versus PGE2 alone This comparison included only one trial with data for 350 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: Any mechanical method plus low-dose misoprostol may make little or no difference to vaginal delivery not achieved within 24 hours compared with PGE2 alone (1 trial, 350 women; RR 1.14, 95% CI 0.89 to 1.46; low-certainty evidence). Caesarean section: Any mechanical method plus low-dose misoprostol may make little or no difference to caesarean section compared with PGE2 alone (1 trial, 350 women; RR 0.85, 95% CI 0.57 to 1.25; low-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Postpartum haemorrhage (PPH): Any mechanical method plus low-dose misoprostol may make little or no difference to PPH compared with PGE2 alone (1 trial, 350 women; RR 0.98, 95% CI 0.67 to 1.41; low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for uterine rupture (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for severe maternal morbidity or death (very-low-certainty evidence). Important: Oxytocin augmentation: Any mechanical method plus low-dose misoprostol probably reduces oxytocin augmentation compared with PGE2 alone (1 trial, 350 women; RR 0.54, 95% CI 0.34 to 0.86; moderate-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). 17 Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for instrumental vaginal birth (very- low-certainty evidence). Meconium-stained liquor: Any mechanical method plus low-dose misoprostol may make little or no difference to meconium-stained liquor compared with PGE2 alone (1 trial, 350 women; RR 1.15, 95% CI 0.60 to 2.23; low-certainty evidence). Maternal side-effects (all): Any mechanical method plus low-dose misoprostol may make little or no difference to maternal side-effects compared with PGE2 alone (1 trial, 350 women; RR 1.16, 95% CI 0.95 to 1.43; low-certainty evidence) or to maternal nausea (one trial, 350 women; RR 1.65, 95% CI 0.98 to 2.79; low-certainty evidence). Any mechanical method plus low-dose misoprostol may increase maternal diarrhoea compared with PGE2 alone (1 trial, 350 women; RR 3.27, 95% CI 1.53 to 9.00; low-certainty evidence). It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for maternal fever in labour (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for admission to a neonatal intensive care unit (very-low-certainty evidence). Severe neonatal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for severe neonatal morbidity or death (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with PGE2 alone for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 15 – Any mechanical method and low-dose misoprostol versus low-dose misoprostol This comparison included seven trials with data for 1422 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). Caesarean section: Any mechanical method plus low-dose misoprostol may make little or no difference to caesarean section compared with low-dose misoprostol (7 trials, 1422 women; RR 0.87, 95% CI 0.66 to 1.15; low-certainty evidence). 18 Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Postpartum haemorrhage (PPH): Any mechanical method plus low-dose misoprostol may make little or no difference to PPH compared with low-dose misoprostol 2 trials, 466 women; RR 0.93, 95% CI 0.65 to 1.33; low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for uterine rupture (very-low- certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for severe maternal morbidity or death (very-low-certainty evidence). Important: Cervix unfavourable or unchanged after 12 hours: Any mechanical method plus low-dose misoprostol may reduce cervix unfavourable or unchanged after 12 hours compared with low-dose misoprostol (1 trial, 140 women; RR 0.27, 95% CI 0.08 to 0.94; low-certainty evidence). Oxytocin augmentation: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for oxytocin augmentation (very-low-certainty evidence). Epidural rate: Any mechanical method plus low-dose misoprostol may make little or no difference to epidural rate compared with low-dose misoprostol (3 trials, 443 women; RR 1.00, 95% CI 0.91 to 1.10; moderate-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Any mechanical method plus low-dose misoprostol probably reduces uterine hyperstimulation without fetal heart rate changes compared with low-dose misoprostol (4 trials, 982 women; RR 0.53, 95% CI 0.32 to 0.90; moderate-certainty evidence). Instrumental vaginal birth: Any mechanical method plus low-dose misoprostol may make little or no difference to instrumental vaginal birth compared with low-dose misoprostol (3 trials, 676 women; RR 0.93, 95% CI 0.58 to 1.51; low-certainty evidence). Meconium-stained liquor: Any mechanical method plus low-dose misoprostol may make little or no difference to meconium-stained liquor compared with low-dose misoprostol (6 trials, 1243 women; RR 0.61, 95% CI 0.35 to 1.05; low-certainty evidence). Maternal side-effects (all): Any mechanical method plus low-dose misoprostol may make little or no difference to maternal side-effects (1 trial, 300 women; RR 1.06, 95% CI 0.87 to 1.30; low-certainty evidence). Maternal nausea: Any mechanical method plus low-dose misoprostol may make little or no difference to maternal nausea compared with low-dose misoprostol (1 trial, 300 women; RR 1.37, 95% CI 0.84 to 2.23; low-certainty evidence). 19 Maternal diarrhoea: Any mechanical method plus low-dose misoprostol may make little or no difference to maternal diarrhoea compared with low-dose misoprostol (1 trial, 298 women; RR 3.38, 95% CI 1.40 to 8.17; low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: Any mechanical method plus low-dose misoprostol may make little or no difference to Apgar score less than 7 at 5 minutes compared with low-dose misoprostol (3 trials, 802 infants; RR 0.71; 95% CI 0.37 to 1.36; low-certainty evidence). Admission to a neonatal intensive care unit: Any mechanical method plus low-dose misoprostol probably reduces admission to a neonatal intensive care unit compared with low-dose misoprostol (6 trials, 1246 infants; RR 0.57, 95% CI 0.36 to 0.91; moderate-certainty evidence). Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Perinatal death: It is uncertain whether there is any difference between any mechanical method plus low-dose misoprostol compared with low-dose misoprostol for perinatal death (very-low- certainty evidence). Effects of interventions: Comparison 16 – Any mechanical method and oxytocin versus PGE2 alone This comparison included four trials with data for 713 women. Maternal outcomes Critical: Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Caesarean section: Any mechanical method plus oxytocin may make little or no difference to caesarean section compared with PGE2 alone (4 trials, 713 women; RR 0.93, 95% CI 0.72 to 1.20; low-certainty evidence). Postpartum haemorrhage (PPH): It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for PPH (very-low-certainty evidence). Severe maternal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with prostaglandin PGE2 alone for severe maternal morbidity or death (very-low-certainty evidence). Important: Uterine hyperstimulation without fetal heart rate changes: Any mechanical method plus oxytocin may increase uterine hyperstimulation without fetal heart rate changes compared with PGE2 alone (1 trial, 151 women; RR 2.19, 95% CI 1.39 to 3.46; low-certainty evidence). 20 Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for instrumental vaginal birth (very-low-certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for meconium-stained liquor (very-low-certainty evidence). Fetal/neonatal outcomes Critical: Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with PGE2 alone for admission to a neonatal intensive care unit (very-low-certainty evidence). Effects of interventions: Comparison 17 – Any mechanical method and oxytocin versus misoprostol alone This comparison included six trials with data for 1779 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: Any mechanical method plus oxytocin probably reduces vaginal delivery not achieved within 24 hours compared with misoprostol alone (2 trials, 362 women; RR 0.48, 95% CI 0.37 to 0.63; moderate-certainty evidence). Uterine hyperstimulation with fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for uterine hyperstimulation with fetal heart rate changes (very-low-certainty evidence). Caesarean section: Any mechanical method plus oxytocin probably makes little or no difference to caesarean section compared with misoprostol (5 trials, 1779 women; RR 0.95, 95% CI 0.80 to 1.12; moderate-certainty evidence). Important: Oxytocin augmentation: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for oxytocin augmentation (very-low- certainty evidence). Epidural rate: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for epidural rate (very-low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: Any mechanical method plus oxytocin probably reduces uterine hyperstimulation without fetal heart rate changes compared with misoprostol alone (3 trials, 498 women; RR 0.52, 95% CI 0.30 to 0.92; moderate-certainty evidence). 21 Meconium-stained liquor: Any mechanical method plus oxytocin may make little or no difference to meconium-stained liquor compared with misoprostol alone (2 trials, 362 women; RR 0.72, 95% CI 0.43 to 1.19; low-certainty evidence). Maternal fever during labour: Any mechanical method plus oxytocin may reduce maternal fever during labour compared with misoprostol alone (2 trials, 298 women; RR 0.13, 95% CI 0.04 to 0.50; low-certainty evidence). Women not satisfied: Any mechanical method plus oxytocin probably increases dissatisfaction compared with misoprostol alone (1 trial, 866 women; RR 1.68, 95% CI 1.47 to 1.93; moderate- certainty evidence). Fetal/neonatal outcomes Critical: Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Apgar score less than 7 at 5 minutes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for Apgar score less than 7 at 5 minutes (very-low-certainty evidence). Admission to a neonatal intensive care unit: Any mechanical method plus oxytocin probably reduces admission to a neonatal intensive care unit compared with misoprostol alone (four trials, 1599 infants; RR 0.66, 95% CI 0.49 to 0.90; moderate-certainty evidence). Perinatal death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with misoprostol alone for perinatal death (very-low-certainty evidence). Effects of interventions: Comparison 18 – Any mechanical method and oxytocin versus oxytocin alone This comparison included six trials with data for 718 women. Maternal outcomes Critical: Vaginal delivery not achieved within 24 hours: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for vaginal delivery not achieved within 24 hours (very-low-certainty evidence). Caesarean section: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for caesarean section (very-low-certainty evidence). Postpartum haemorrhage (PPH): It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for PPH (very-low-certainty evidence). Uterine rupture: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for uterine rupture (very-low-certainty evidence). 22 Severe maternal morbidity or death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for severe maternal morbidity or death (very-low-certainty evidence). Important: Epidural rate: Any mechanical method plus oxytocin may make little or no difference to epidural rate compared with oxytocin alone (1 trial, 127 women; RR 1.03, 95% CI 0.98 to 1.09; low-certainty evidence). Uterine hyperstimulation without fetal heart rate changes: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for uterine hyperstimulation without fetal heart rate changes (very-low-certainty evidence). Instrumental vaginal birth: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for instrumental vaginal birth (very-low- certainty evidence). Meconium-stained liquor: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for meconium-stained liquor (very-low- certainty evidence). Fetal/newborn outcomes Critical: Severe neonatal morbidity or perinatal death: It is uncertain whether there is any difference between any mechanical method plus oxytocin compared with oxytocin alone for severe neonatal morbidity or perinatal death (very-low-certainty evidence). Admission to a neonatal intensive care unit: Any mechanical method plus oxytocin may make little or no difference to admission to a neonatal intensive care unit (3 trials, 400 infants; RR 0.98, 95% CI 0.61 to 1.58; low-certainty evidence). Additional considerations The GDG noted that the evidence describes various combinations of different mechanical methods of induction, in comparison to each other, and with or without the addition of (concurrent or sequential) pharmacologic methods. The GDG discussed the use of mechanical methods in the context of considering them as potential methods for induction of labour, rather than determining whether a particular induction method (or combination of methods) is “superior” to another. Given the comparatively sparse evidence on the use of laminaria tents and EASI, the GDG focused their recommendations on the use of balloon catheters. Judgement on desirable effects How substantial are the desirable anticipated effects of mechanical methods for induction of labour? Judgement Don’t know Varies Trivial Small Moderate Large 23 Judgement on undesirable effects How substantial are the undesirable anticipated effects of mechanical methods for induction of labour? Judgement Don’t know Varies Large Moderate Small Trivial Certainty of the evidence For most comparisons and outcomes the evidence was low or very-low certainty with little or no difference between groups. The majority of the evidence on effectiveness compared the use of balloon catheters with other methods. Low‐ to moderate‐certainty evidence shows mechanical induction with a balloon catheter is probably as effective as induction of labour with vaginal PGE2 and may have fewer adverse effects. Moderate‐quality evidence shows a balloon catheter may be slightly less effective as an induction method compared to oral misoprostol, but it remains unclear if there is a difference in safety outcomes for the neonate. When compared to low‐dose vaginal misoprostol, low‐quality evidence shows a balloon catheter may be less effective, but probably has a better safety profile. Moderate-quality evidence indicates that use of a balloon catheter probably reduces the risk of a caesarean section when compared to oxytocin, and this may also be the case in women with a previous caesarean section undergoing induction of labour. What is the overall certainty of the evidence on mechanical methods for induction of labour? Judgement No included studies Very low Low Moderate High 3.2 Values Evidence on values No direct evidence was identified to address this question. Additional considerations A 2019 QES of women’s experiences of labour induction (Coates et al., 2019) (4) was selected for inclusion in the EtD on the basis of quality (high) and inclusion of the greatest breadth of qualitative primary studies compared with two other eligible QES (5, 6) and one scoping review (7). Primary studies not included in Coates et al. (2019) were screened for additional relevant findings and/or income-settings and/or clinician views. Five additional studies were identified and relevant findings extracted (8-12). 24 The QES and primary studies identified that the key outcomes of interest for women in relation to labour induction were: • the well-being of their baby • the duration of the process between induction and birth • the likelihood and severity of pain • the likelihood of caesarean delivery. Women placed great value on knowing about the potential benefits and harms of labour induction. Judgement on values Is there any important uncertainty or variability about values relating to the use of mechanical methods for induction of labour? Judgement Important uncertainty or variability Possibly important uncertainty or variability Probably no important uncertainty or variability No important uncertainty or variability 3.3 Effects and values Balance of effects and values Does the balance between desirable and undesirable effects favour the intervention (labour induction with mechanical methods alone or in combination with pharmacological methods) or the comparison (other types of induction methods or no intervention)? Judgement on the balance of effects and values Judgement Don’t know Varies Favours use of other methods Probably favours use of other methods Does not favour either Probably favours use of mechanical methods Favours use of mechanical methods 3.4 Resources Evidence on resources Economic evidence is very limited, derived from a small number of trial-based primary studies conducted in high-income settings. Any conclusions drawn from these studies should be viewed as extremely tentative. Economic analyses were eligible if the majority of the population was either at or beyond term and otherwise low risk. Included studies Two trial-based economic studies evaluating costs and cost-effectiveness were identified. 25 Ten Eikelder et al. (2018) undertook a cost-effectiveness analysis from a hospital perspective in the period from admission to antenatal care (ANC) ward to discharge (13). Effectiveness data were derived from the ten Eikelder et al. (2016) (PROBAAT-2) study, a randomized controlled trial (RCT) in 29 hospitals in the Netherlands comparing oral misoprostol with Foley catheter for labour induction in 1845 women at term with an unfavourable cervix and without previous caesarean section (14). Van Baaren et al. (2013) undertook a cost-effectiveness analysis from a hospital perspective in the period from admission to ANC ward to six weeks postpartum. Cost data were estimated using different methods and sources and expressed in 2009 Euros (15). Effectiveness data were derived from Jozwiak et al. (2011) (the PROBAAT study), an RCT in 12 hospitals in the Netherlands comparing Foley catheter with vaginal PGE2 gel for labour induction in 819 women at term with an unfavourable cervix and without previous caesarean section (16). Both studies by ten Eikelder et al. (2018) and van Baaren et al. (2013) are included in the 2019 Cochrane review of mechanical methods for induction of labour (1). Cost It is uncertain if Foley catheter is cost-saving for labour induction compared with oral misoprostol (mean difference [MD] 312 in favour of Foley catheter; 95% confidence interval [CI] 508 to 1063), even with varying resource use and unit price estimates. ten Eikelder et al. reported that oral misoprostol induction in multiparous women resulted in lower costs, mainly due to shorter time from induction to delivery (13). It is uncertain if Foley catheter is cost-saving for labour induction compared with vaginal PGE2 gel (MD 222 in favour of vaginal PGE2 gel; 95% CI –157 to 633). Van Baaren et al. (2013) reported that vaginal PGE2 gel induction in multiparous women resulted in lower costs, mainly due to shorter time from induction to delivery (15). Overall budget impact Overall budget impacts of a policy of mechanical methods for labour induction were not analysed in the studies. Value-for-money analyses ten Eikelder et al. reported that the incremental cost-effectiveness ratio (ICER) for the composite outcome of asphyxia and postpartum haemorrhage (PPH) was non-informative due to comparable efficacy between the interventions. They noted that, at a willingness-to-pay threshold of at least 30 000 (2013 Euros) per woman, oral misoprostol may be cost-effective for the outcome of caesarean section (15). Van Baaren et al. did not find the ICER for caesarean section to be informative due to comparable efficacy between the interventions. Using a Foley catheter, the ICER to prevent one neonatal admission was 2708 (2009 Euros), and 5257 to prevent one composite outcome of asphyxia and PPH (15). Additional considerations None. 26 Main resource requirements Resource Description Staff • Staff for placement/insertion of induction agent • Staff for monitoring and assessment until delivery Training • Training in performance and monitoring of labour induction Supplies • Induction agents (Foley or Cook’s catheter) • Ultrasound gel Equipment and infrastructure • Tools to accurately estimate gestational age (e.g. previous early antenatal ultrasound, gestational age wheel) • Clinical protocol for safe labour induction • Electronic fetal heart rate monitors, oxytocin infusion pumps • Equipment for vaginal birth • Availability of appropriate space, beds or both for women undergoing induction • Capacity to perform caesarean section (if required) Time • Time to deliver information on process, risks and benefits of labour induction (preferably during late-pregnancy ANC visit) • 20 minutes for initial assessment • Time for placement/insertion of agent for cervical ripening agent Supervision and monitoring • 60 minutes of additional monitoring after insertion of catheter • Intermittent monitoring and assessment until childbirth Judgement on costs What is the impact on costs of mechanical methods for induction of labour? Judgement Don’t know Varies Large costs Moderate costs Negligible costs or savings Moderate savings Large savings Certainty of the evidence What is the certainty of the evidence on costs? Judgement No included studies Very low Low Moderate High Judgement on cost-effectiveness Is the intervention cost-effective? 27 Judgement Don’t know Varies Favours use of other methods Probably favours use of other methods Does not favour either Probably favours mechanical methods Favours mechanical methods 3.5 Equity Evidence on equity No direct evidence was identified to address this question. Additional considerations The 2015 WHO report on inequality in reproductive, maternal, newborn and child health states that “the poorest, the least educated and those residing in rural areas have lower health intervention coverage and worse health outcomes than the more advantaged” (17, p. xii). The report also found that preventing and reducing morbidity and mortality in childbirth can play a key role in reducing overall health inequities. Safe, effective and equitable implementation of labour induction for improved maternal and neonatal health outcomes could contribute to reducing inequities in maternal and perinatal health. It is likely that women from low- and middle-income settings, or disadvantaged groups within a high-income setting, may also experience greater barriers to participation in health-care decision-making about labour induction than indicated in the QES findings (18). In order to ensure that implementation of labour induction does not reinforce existing inequities, the system should support all women to have access to full, timely, accessible information; to use their own social networks to assist them to understand the information if needed; and to ensure a woman’s health-care provider is aware of her needs, values and preferences (19). Judgement on equity What is the impact on equity of mechanical methods of induction of labour? Judgement Don’t know Varies Reduced Probably reduced Probably no impact Probably increased Increased 3.6 Acceptability Evidence on acceptability No direct evidence was identified to address this question. Acceptability to women The QES (4) and additional primary studies (8-11) indicate that: • Women have varying (and sometimes contradictory) views on the acceptability of labour induction. 28 • Labour induction is widely acceptable to women when there is a recognized need to avert harm to the baby. • Acceptability varies according to women’s trust in their health-care provider, their perception of birth as a natural process, their need for certainty, and the duration of waiting. Many women in the Westfall and Benoit (2004) study preferred interventions they could employ themselves to medical induction of labour. This included use of interventions such as castor oil, essential oil suppositories, homeopathic preparations or having intercourse (11). Women in the Wessberg et al. (2017) study reported that the perceived acceptability of labour induction changed as their pregnancy progressed, particularly as their concern for the well-being of their baby increased (10). Acceptability to implementers There is limited evidence available on the acceptability of labour induction to clinicians, and more research would be useful to inform recommendations. A study of obstetrician and midwife opinions on labour induction found that obstetricians felt there was a lack of clear evidence on the risks and benefits of labour induction to guide their decision- making. They were particularly concerned about neonatal safety and the potential for medical litigation, and were uncertain about the optimal timing for induction and the risks of caesarean birth following induction (12). Human rights and health To exercise their rights to make competent and well informed decisions about induction of labour, the women included in the QES and additional primary studies wanted more complete and balanced information about the risks and benefits, and process, of labour induction. They wanted to receive this information at a time and in a context that allowed them to process the information before a decision was required. Women suggested that receiving this information and discussing labour induction with their health-care provider during a third-trimester ANC visit would be beneficial. In terms of other experiences of care that uphold and protect health rights (20), women also valued continuity of care and confidence that their situation was being consistently monitored and communicated within the care team. Women also valued the ability to move freely and to have privacy and a sense of security. This allowed them to feel more in control and maintain their dignity. Feeling secure was enhanced by having a support person present, systems which enabled this support to continue from induction to delivery, and by having rapid access to the clinical expertise and equipment that might be needed. Additional considerations None. Judgement on acceptability Are mechanical methods of induction of labour acceptable? Judgement Don’t know Varies No Probably No Probably Yes Yes 29 3.7 Feasibility Evidence on feasibility No direct evidence was identified to address this question. Additional considerations Need for, usage of and impact on infrastructure Labour induction is widely implemented in high-, middle- and low-income settings. In high- income settings, 2013 rates ranged from 14% to 36% of all births (21). Secondary analyses of WHO Global Survey on Maternal and Neonatal Health data reported 2004–2005 hospital induction rates in Latin America ranging from 5% to 20% (22), and in African countries from 1% to 7% (23), with significant unmet need for non-elective inductions on the African continent (24). In Asian countries, 2007–2008 labour induction rates ranged from 3% to 36% (23). Oxytocin alone remains the most frequently used labour induction method in all income settings. Performing induction of labour safely requires availability of appropriate medicines or mechanical devices, monitoring equipment and access to facilities for safe caesarean section. Inconsistent supply or lack of medicines and medical equipment and availability of appropriate facilities may be an issue in some settings. Need for, usage of and impact on health workforce and human resources Antenatal care (ANC) ANC visits are an important opportunity to provide (25): • one scan before 24 weeks’ gestation for accurate estimation of gestational age • post-term pregnancy risk assessment • information to women about the process, risks and benefits of labour induction. Time constraints can be a barrier to information provision in ANC clinics (12). In lower- and middle-income country settings, trained health worker shortages may also reduce the feasibility of performing ANC ultrasound scans and other risk assessment (17). Performing labour induction WHO general principles for performing labour induction state (26, p. 7): • Wherever induction of labour is carried out, facilities should be available for assessing maternal and fetal well-being. • Wherever possible, induction of labour should be carried out in facilities where caesarean sections can be performed. Health worker shortages in low- and middle-income country settings may require staff to attend to much higher numbers of women on the labour ward than in other settings. Providing the required level of support, assessment and monitoring in these settings may be challenging and impact on responsiveness (24). Availability of surgical obstetric and operating theatre staff (and staff to transfer women to facilities with these capabilities) for women who require caesarean delivery if labour induction is not successful may also have an impact on feasibility. A higher number of induction deliveries are attended by medical doctors than non-induction deliveries (23). This has implications for the distribution and productivity of medical doctors, particularly in under-resourced settings. 30 Judgement on feasibility Are mechanical methods for induction of labour feasible? Judgement Don’t know Varies No Probably No Probably Yes Yes 31 4. GRADE Summary of Judgements table Summary of Judgements Table B.1: Induction of labour with mechanical methods: balloon catheter Desirable effects Don’t know ✓ Varies Trivial Small Moderate Large Undesirable effects Don’t know Varies Large Moderate Small ✓ Trivial Certainty of the evidence No included studies Very low ✓ Low Moderate High Values Important uncertainty or variability Possibly important uncertainty or variability ✓ Probably no important uncertainty or variability No important uncertainty or variability Balance of effects Don’t know Varies Favours induction with other Probably favours induction with other methods ✓ Does not favour either Probably favours induction with mechanical methods Favours induction with mechanical methods Resources required Don’t know Varies Large costs ✓ Moderate costs Negligible costs or savings Moderate savings Large savings Certainty of the evidence on required resources No included studies ✓ Very low Low Moderate High Cost- effectiveness ✓ Don’t know Varies Favours induction with other Probably favours induction with other Does not favour either Probably favours induction with mechanical methods Favours induction with mechanical methods Equity Don’t know ✓ Varies Reduced Probably reduced Probably no impact Probably increased Increased Acceptability Don’t know ✓ Varies No Probably No Probably Yes Yes Feasibility Don’t know ✓ Varies No Probably No Probably Yes Yes 32 5. GRADE Summary of Findings tables Summary of Findings Table B.1: Balloon catheter versus vaginal prostaglandin E2 Question: Should balloon catheter (Foley or Atad) versus vaginal prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved in 24 hours 7 randomized trials seriousa seriousb not serious seriousc none 507/961 (52.8%) 382/724 (52.8%) RR 1.01 (0.82 to 1.26) 5 more per 1000 (from 95 fewer to 137 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 6 randomized trials seriousa not serious not serious not serious none 10/1040 (1.0%) 29/926 (3.1%) RR 0.35 (0.18 to 0.67) 20 fewer per 1000 (from 26 fewer to 10 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Caesarean section 28 randomized trials seriousa not serious not serious not serious none 840/3423 (24.5%) 762/3196 (23.8%) RR 1.00 (0.92 to 1.09) 0 fewer per 1000 (from 19 fewer to 21 more) ⨁⨁⨁◯ MODERATE CRITICAL Serious maternal morbidity or death 4 randomized trials seriousa not serious not serious very seriousd none 0/733 (0.0%) 2/748 (0.3%) RR 0.20 (0.01 to 4.12) 2 fewer per 1000 (from 3 fewer to 8 more) ⨁◯◯◯ VERY LOW CRITICAL 33 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Oxytocin augmentation 16 randomized trials seriousa seriousb not serious not serious publication bias strongly suspected e 1986/2469 (80.4%) 1304/2359 (55.3%) RR 1.54 (1.35 to 1.76) 298 more per 1000 (from 193 more to 420 more) ⨁◯◯◯ VERY LOW IMPORTANT Epidural analgesia 8 randomized trials seriousa seriousb not serious not serious none 947/1519 (62.3%) 687/1309 (52.5%) RR 1.14 (1.00 to 1.29) 73 more per 1000 (from 0 fewer to 152 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 15 randomized trials seriousa not serious not serious not serious none 13/1263 (1.0%) 70/1181 (5.9%) RR 0.27 (0.11 to 0.66) 43 fewer per 1000 (from 53 fewer to 20 fewer) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine rupture 2 randomized trials seriousa not serious not serious very seriousd none 0/518 (0.0%) 2/527 (0.4%) RR 0.20 (0.01 to 4.12) 3 fewer per 1000 (from 4 fewer to 12 more) ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 16 randomized trials seriousa not serious not serious not serious none 261/2375 (11.0%) 251/2139 (11.7%) RR 0.93 (0.79 to 1.09) 8 fewer per 1000 (from 25 fewer to 11 more) ⨁⨁⨁◯ MODERATE IMPORTANT 34 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Meconium-stained liquor 4 randomized trials seriousa not serious not serious seriousf none 73/481 (15.2%) 82/483 (17.0%) RR 0.89 (0.67 to 1.19) 19 fewer per 1000 (from 56 fewer to 32 more) ⨁⨁◯◯ LOW CRITICAL Maternal fever during labour 7 randomized trials seriousa not serious not serious seriousf none 86/1224 (7.0%) 80/1138 (7.0%) RR 0.87 (0.65 to 1.17) 9 fewer per 1000 (from 25 fewer to 12 more) ⨁⨁◯◯ LOW IMPORTANT Postpartum haemorrhage 8 randomized trials seriousa not serious not serious seriousg none 96/1160 (8.3%) 109/1055 (10.3%) RR 0.82 (0.63 to 1.06) 19 fewer per 1000 (from 38 fewer to 6 more) ⨁⨁◯◯ LOW CRITICAL Women not satisfied 1 randomized trials seriousa not serious not serious serioush none 17/48 (35.4%) 26/45 (57.8%) RR 0.61 (0.39 to 0.97) 225 fewer per 1000 (from 352 fewer to 17 fewer) ⨁⨁◯◯ LOW CRITICAL Serious neonatal morbidity/perinatal death 8 randomized trials seriousa not serious not serious not serious none 12/1483 (0.8%) 25/1274 (2.0%) RR 0.48 (0.25 to 0.93) 10 fewer per 1000 (from 15 fewer to 1 fewer) ⨁⨁⨁◯ MODERATE CRITICAL 35 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Perinatal death 5 randomized trials seriousa not serious not serious seriousd none 0/575 (0.0%) 2/461 (0.4%) RR 0.21 (0.01 to 4.27) 3 fewer per 1000 (from 4 fewer to 14 more) ⨁⨁◯◯ LOW CRITICAL Apgar score < 7 at 5 minutes 14 randomized trials seriousa not serious not serious seriousf none 34/2239 (1.5%) 44/2032 (2.2%) RR 0.74 (0.49 to 1.14) 6 fewer per 1000 (from 11 fewer to 3 more) ⨁⨁◯◯ LOW CRITICAL Neonatal intensive care unit admission 12 randomized trials seriousa not serious not serious seriousg none 111/1882 (5.9%) 130/1765 (7.4%) RR 0.82 (0.65 to 1.04) 13 fewer per 1000 (from 26 fewer to 3 more) ⨁⨁◯◯ LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Inconsistency – substantial statistical heterogeneity (I2 > 60%) (–1). c. Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). d. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). e. Evidence of asymmetry in funnel plot (–1). f. Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). g. Wide CIs crossing the line of no effect, ranging from appreciable benefit to negligible harm (–1). h. Small single study (–1). 36 Summary of Findings Table B.2: Balloon catheter versus intracervical prostaglandin E2 Question: Should balloon catheter (Foley or Atad) versus intracervical prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa seriousb not serious seriousc none 48/100 (48.0%) 44/100 (44.0%) RR 1.01 (0.35 to 2.91) 4 more per 1000 (from 286 fewer to 840 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 4 randomized trials seriousa not serious not serious very seriousd none 0/222 (0.0%) 1/225 (0.4%) RR 0.37 (0.02 to 8.90) 3 fewer per 1000 (from 4 fewer to 35 more) ⨁◯◯◯ VERY LOW CRITICAL Caesarean section 9 randomized trials seriousa not serious not serious not serious none 164/656 (25.0%) 168/653 (25.7%) RR 0.97 (0.81 to 1.15) 8 fewer per 1000 (from 49 fewer to 39 more) ⨁⨁⨁◯ MODERATE CRITICAL Cervix unfavourable/unchanged after 24 hours 2 randomized trials seriousa not serious not serious very seriousc none 41/110 (37.3%) 42/109 (38.5%) RR 0.96 (0.70 to 1.34) 15 fewer per 1000 (from 116 fewer to 131 more) ⨁◯◯◯ VERY LOW IMPORTANT 37 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Oxytocin augmentation 1 randomized trials seriousa not serious not serious seriouse none 132/200 (66.0%) 122/200 (61.0%) RR 1.08 (0.93 to 1.26) 49 more per 1000 (from 43 fewer to 159 more) ⨁⨁◯◯ LOW IMPORTANT Epidural analgesia 1 randomized trials seriousa not serious not serious seriousf none 65/77 (84.4%) 67/72 (93.1%) RR 0.91 (0.81 to 1.02) 84 fewer per 1000 (from 177 fewer to 19 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 5 randomized trials seriousa seriousb not serious very seriousd none 11/329 (3.3%) 11/325 (3.4%) RR 0.99 (0.09 to 10.38) 0 fewer per 1000 (from 31 fewer to 317 more) ⨁◯◯◯ VERY LOW IMPORTANT Instrumental vaginal birth 3 randomized trials seriousa not serious not serious seriousj none 23/170 (13.5%) 18/167 (10.8%) RR 1.18 (0.68 to 2.05) 19 more per 1000 (from 34 fewer to 113 more) ⨁⨁◯◯ LOW IMPORTANT 38 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Meconium-stained liquor 1 randomized trials seriousa not serious not serious very seriousg none 7/59 (11.9%) 6/59 (10.2%) RR 1.17 (0.42 to 3.26) 17 more per 1000 (from 59 fewer to 230 more) ⨁◯◯◯ VERY LOW CRITICAL Maternal side-effects 2 randomized trials seriousa not serious not serious very serioush none 0/111 (0.0%) 5/100 (5.0%) RR 0.15 (0.02 to 1.24) 43 fewer per 1000 (from 49 fewer to 12 more) ⨁◯◯◯ VERY LOW IMPORTANT Postpartum haemorrhage 1 randomized trials seriousa not serious not serious very seriousi none 0/50 (0.0%) 2/50 (4.0%) RR 0.20 (0.01 to 4.06) 32 fewer per 1000 (from 40 fewer to 122 more) ⨁◯◯◯ VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 2 randomized trials seriousa not serious not serious very seriousd none 7/250 (2.8%) 9/250 (3.6%) RR 0.78 (0.29 to 2.05) 8 fewer per 1000 (from 26 fewer to 38 more) ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 2 randomized trials seriousa not serious not serious very seriousd none 7/250 (2.8%) 9/250 (3.6%) RR 0.78 (0.29 to 2.05) 8 fewer per 1000 (from 26 fewer to 38 more) ⨁◯◯◯ VERY LOW CRITICAL 39 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Apgar score < 7 at 5 minutes 2 randomized trials seriousa not serious not serious seriousj none 14/236 (5.9%) 18/239 (7.5%) RR 0.79 (0.41 to 1.53) 16 fewer per 1000 (from 44 fewer to 40 more) ⨁⨁◯◯ LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa not serious not serious seriousj none 38/200 (19.0%) 43/200 (21.5%) RR 0.88 (0.60 to 1.31) 26 fewer per 1000 (from 86 fewer to 67 more) ⨁⨁◯◯ LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Substantial statistical heterogeneity (I2 > 60%) (–1). c. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, with small samples (–2). d. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). e. Wide CIs crossing the line of no effect, ranging from negligible benefit to appreciable harm (–1). f. Single study with small sample size (–1). g. Single small study with few events, wide CIs crossing the line of no effect (–2). h. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm, and few events (–2). i. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). j. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). 40 Summary of Findings Table B.3: Balloon catheter versus low-dose vaginal misoprostol Question: Should balloon catheter (Foley or Atad) versus low-dose vaginal misoprostol be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low -dose vaginal misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa not serious not serious seriousb none 78/175 (44.6%) 68/165 (41.2%) RR 1.09 (0.85 to 1.39) 37 more per 1000 (from 62 fewer to 161 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 8 randomized trials seriousa not serious not serious seriousc none 7/654 (1.1%) 22/668 (3.3%) RR 0.39 (0.18 to 0.85) 20 fewer per 1000 (from 27 fewer to 5 fewer) ⨁⨁◯◯ LOW CRITICAL Caesarean section 12 randomized trials seriousa not serious not serious not serious none 259/874 (29.6%) 214/882 (24.3%) RR 1.28 (1.02 to 1.60) 68 more per 1000 (from 5 more to 146 more) ⨁⨁⨁◯ MODERATE CRITICAL Serious maternal morbidity or death 4 randomized trials seriousa not serious not serious very seriousd none 0/224 (0.0%) 0/240 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL Cervix unfavourable/unchanged after 12 hours 2 randomized trials seriousa not serious not serious very seriouse none 25/100 (25.0%) 11/100 (11.0%) RR 2.66 (0.60 to 11.89) 183 more per 1000 (from 44 fewer to 1000 more) ⨁◯◯◯ VERY LOW IMPORTANT 41 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low -dose vaginal misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Oxytocin augmentation 9 randomized trials seriousa seriousf not serious not serious none 372/446 (83.4%) 235/465 (50.5%) RR 1.62 (1.38 to 1.90) 313 more per 1000 (from 192 more to 455 more) ⨁⨁◯◯ LOW IMPORTANT Epidural analgesia 2 randomized trials seriousa not serious not serious not serious none 164/254 (64.6%) 137/263 (52.1%) RR 1.22 (1.06 to 1.41) 115 more per 1000 (from 31 more to 214 more) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 9 randomized trials seriousa not serious not serious not serious none 12/566 (2.1%) 54/573 (9.4%) RR 0.25 (0.14 to 0.44) 71 fewer per 1000 (from 81 fewer to 53 fewer) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine rupture 3 randomized trials seriousa not serious not serious very seriousd none 0/170 (0.0%) 0/194 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 4 randomized trials seriousa not serious not serious seriousg none 41/354 (11.6%) 59/367 (16.1%) RR 0.72 (0.50 to 1.05) 45 fewer per 1000 (from 80 fewer to 8 more) ⨁⨁◯◯ LOW IMPORTANT Meconium-stained liquor 7 randomized trials seriousa not serious not serious not serious none 59/640 (9.2%) 91/628 (14.5%) RR 0.64 (0.48 to 0.87) 52 fewer per 1000 (from 75 fewer to 19 fewer) ⨁⨁⨁◯ MODERATE CRITICAL 42 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low -dose vaginal misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Maternal vomiting 1 randomized trials seriousa not serious not serious very serioush none 0/30 (0.0%) 0/30 (0.0%) not estimable ⨁◯◯◯ VERY LOW IMPORTANT Maternal fever during labour 3 randomized trials seriousa seriousf not serious seriousi none 19/308 (6.2%) 18/309 (5.8%) RR 1.84 (0.22 to 15.62) 49 more per 1000 (from 45 fewer to 852 more) ⨁◯◯◯ VERY LOW IMPORTANT Postpartum haemorrhage 1 randomized trials seriousa not serious not serious very seriousj none 3/56 (5.4%) 3/64 (4.7%) RR 1.14 (0.24 to 5.44) 7 more per 1000 (from 36 fewer to 208 more) ⨁◯◯◯ VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 3 randomized trials seriousa not serious not serious very seriousj none 2/187 (1.1%) 4/194 (2.1%) RR 0.58 (0.12 to 2.66) 9 fewer per 1000 (from 18 fewer to 34 more) ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa not serious not serious very serioush none 0/61 (0.0%) 0/60 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 7 randomized trials seriousa not serious not serious very seriousk none 14/472 (3.0%) 14/469 (3.0%) RR 1.00 (0.50 to 1.97) 0 fewer per 1000 (from 15 fewer to 29 more) ⨁◯◯◯ VERY LOW CRITICAL 43 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low -dose vaginal misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Neonatal intensive care unit admission 9 randomized trials seriousa not serious not serious seriousi none 29/643 (4.5%) 31/659 (4.7%) RR 1.00 (0.61 to 1.63) 0 fewer per 1000 (from 18 fewer to 30 more) ⨁⨁◯◯ LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). c. Few events (–1). d. No events (–2). e. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–2). f. Substantial statistical heterogeneity (I2 > 60%) (–1). g. Wide CIs crossing the line of no effect, ranging from appreciable benefit to negligible harm (–1). h. Single small study with no events (–2). i. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). j. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). k. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 44 Summary of Findings Table B.4: Balloon catheter versus low-dose oral misoprostol Question: Should balloon catheter (Foley or Atad) versus low-dose oral misoprostol be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved within 24 hours 2 randomized trials seriousa not serious not serious not serious none 237/389 (60.9%) 187/393 (47.6%) RR 1.28 (1.13 to 1.46) 133 more per 1000 (from 62 more to 219 more) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine hyperstimulation with fetal heart rate changes 2 randomized trials seriousa not serious not serious seriousb none 24/1010 (2.4%) 30/1023 (2.9%) RR 0.81 (0.48 to 1.38) 6 fewer per 1000 (from 15 fewer to 11 more) ⨁⨁◯◯ LOW CRITICAL Caesarean section 7 randomized trials seriousa not serious not serious not serious none 411/1585 (25.9%) 353/1593 (22.2%) RR 1.17 (1.04 to 1.32) 38 more per 1000 (from 9 more to 71 more) ⨁⨁⨁◯ MODERATE CRITICAL Serious maternal morbidity or death 3 randomized trials seriousa not serious not serious very seriousc none 1/1310 (0.1%) 2/1317 (0.2%) RR 0.50 (0.05 to 5.52) 1 fewer per 1000 (from 1 fewer to 7 more) ⨁◯◯◯ VERY LOW CRITICAL 45 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Cervix unfavourable after 24 hours 4 randomized trials seriousa not serious not serious seriousb none 46/497 (9.3%) 46/497 (9.3%) RR 0.98 (0.61 to 1.56) 2 fewer per 1000 (from 36 fewer to 52 more) ⨁⨁◯◯ LOW IMPORTANT Oxytocin augmentation 5 randomized trials seriousa seriousd not serious not serious none 1154/1418 (81.4%) 939/1429 (65.7%) RR 1.28 (1.09 to 1.49) 184 more per 1000 (from 59 more to 322 more) ⨁⨁◯◯ LOW IMPORTANT Epidural 3 randomized trials seriousa not serious not serious not serious none 645/1310 (49.2%) 594/1325 (44.8%) RR 1.08 (0.96 to 1.22) 36 more per 1000 (from 18 fewer to 99 more) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 5 randomized trials seriousa not serious not serious seriousb none 17/1418 (1.2%) 19/1420 (1.3%) RR 0.50 (0.12 to 2.07) 7 fewer per 1000 (from 12 fewer to 14 more) ⨁⨁◯◯ LOW IMPORTANT Uterine rupture 3 randomized trials seriousa not serious not serious very seriouse none 0/1310 (0.0%) 0/1317 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL 46 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Instrumental vaginal birth 3 randomized trials seriousa not serious not serious not serious none 91/1310 (6.9%) 128/1317 (9.7%) RR 0.71 (0.55 to 0.92) 28 fewer per 1000 (from 44 fewer to 8 fewer) ⨁⨁⨁◯ MODERATE IMPORTANT Meconium-stained liquor 3 randomized trials seriousa not serious not serious seriousb none 116/1310 (8.9%) 127/1317 (9.6%) RR 0.77 (0.44 to 1.35) 22 fewer per 1000 (from 54 fewer to 34 more) ⨁⨁◯◯ LOW CRITICAL Maternal side-effects (all) 2 randomized trials seriousa not serious not serious seriousf none 15/330 (4.5%) 25/332 (7.5%) RR 0.61 (0.33 to 1.13) 29 fewer per 1000 (from 50 fewer to 10 more) ⨁⨁◯◯ LOW IMPORTANT Maternal vomiting 2 randomized trials seriousa not serious not serious seriousb none 13/330 (3.9%) 18/332 (5.4%) RR 0.73 (0.37 to 1.46) 15 fewer per 1000 (from 34 fewer to 25 more) ⨁⨁◯◯ LOW IMPORTANT Maternal diarrhoea 1 randomized trials seriousa not serious not serious very seriousg none 2/300 (0.7%) 7/302 (2.3%) RR 0.29 (0.06 to 1.37) 16 fewer per 1000 (from 22 fewer to 9 more) ⨁◯◯◯ VERY LOW IMPORTANT 47 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) Maternal fever during labour 2 randomized trials seriousa not serious not serious not serious none 120/1010 (11.9%) 123/1023 (12.0%) RR 0.98 (0.78 to 1.24) 2 fewer per 1000 (from 26 fewer to 29 more) ⨁⨁⨁◯ MODERATE IMPORTANT Postpartum haemorrhage 5 randomized trials seriousa not serious not serious serioush none 98/1477 (6.6%) 97/1489 (6.5%) RR 1.03 (0.79 to 1.34) 2 more per 1000 (from 14 fewer to 22 more) ⨁⨁◯◯ LOW CRITICAL Women not satisfied 1 randomized trials seriousa not serious not serious not serious none 59/300 (19.7%) 35/302 (11.6%) RR 1.70 (1.15 to 2.50) 81 more per 1000 (from 17 more to 174 more) ⨁⨁⨁◯ MODERATE CRITICAL Serious perinatal morbidity/perinatal death 3 randomized trials seriousa not serious not serious seriousb none 21/1310 (1.6%) 19/1317 (1.4%) RR 1.11 (0.60 to 2.06) 2 more per 1000 (from 6 fewer to 15 more) ⨁⨁◯◯ LOW CRITICAL Perinatal death 3 randomized trials seriousa not serious not serious very seriousc none 9/1310 (0.7%) 7/1317 (0.5%) RR 1.28 (0.49 to 3.30) 1 more per 1000 (from 3 fewer to 12 more) ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 after 5 minutes 48 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Low-dose oral misoprostol: all women Relative risk (95% CI) Absolute (95% CI) 4 randomized trials seriousa not serious not serious seriousb none 17/1338 (1.3%) 24/1355 (1.8%) RR 0.71 (0.38 to 1.32) 5 fewer per 1000 (from 11 fewer to 6 more) ⨁⨁◯◯ LOW CRITICAL Neonatal intensive care unit admission 5 randomized trials seriousa not serious not serious seriousi none 53/1427 (3.7%) 66/1446 (4.6%) RR 0.82 (0.58 to 1.17) 8 fewer per 1000 (from 19 fewer to 8 more) ⨁⨁◯◯ LOW CRITICAL Neonatal encephalopathy 1 randomized trials seriousa not serious not serious very seriousg none 8/298 (2.7%) 10/302 (3.3%) RR 0.81 (0.32 to 2.03) 6 fewer per 1000 (from 23 fewer to 34 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). c. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). d. Substantial statistical heterogeneity (I2 > 60%) (–1). e. No events (–2). f. Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). g. Single study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). h. Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). i. Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). 49 Summary of Findings Table B.5: Balloon catheter versus oxytocin Question: Should balloon catheter (Foley or Atad) versus oxytocin be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Oxytocin: all women Relative risk (95% CI) Absolute (95% CI) Uterine hyperstimulation with fetal heart rate changes 1 randomized trials seriousa not serious not serious very seriousb none 0/100 (0.0%) 2/100 (2.0%) RR 0.20 (0.01 to 4.11) 16 fewer per 1000 (from 20 fewer to 62 more) ⨁◯◯◯ VERY LOW CRITICAL Caesarean section 8 randomized trials seriousa not serious not serious not serious none 104/392 (26.5%) 152/389 (39.1%) RR 0.68 (0.56 to 0.83) 125 fewer per 1000 (from 172 fewer to 66 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Serious maternal morbidity or death 2 randomized trials seriousa not serious not serious very seriousc none 0/80 (0.0%) 0/80 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL Cervix unfavourable after 24 hours 1 randomized trials seriousa not serious not serious very seriousb none 5/50 (10.0%) 9/50 (18.0%) RR 0.56 (0.20 to 1.54) 79 fewer per 1000 (from 144 fewer to 97 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 50 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Oxytocin: all women Relative risk (95% CI) Absolute (95% CI) 3 randomized trials seriousa not serious not serious very seriousd none 3/96 (3.1%) 3/96 (3.1%) RR 1.00 (0.23 to 4.29) 0 fewer per 1000 (from 24 fewer to 103 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine rupture 1 randomized trials seriousa not serious not serious very seriouse none 0/50 (0.0%) 0/50 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa not serious not serious very seriousd none 12/110 (10.9%) 10/110 (9.1%) RR 1.19 (0.55 to 2.57) 17 more per 1000 (from 41 fewer to 143 more) ⨁◯◯◯ VERY LOW IMPORTANT Meconium-stained liquor 2 randomized trials seriousa not serious not serious very seriousf none 8/136 (5.9%) 15/136 (11.0%) RR 0.53 (0.23 to 1.21) 52 fewer per 1000 (from 85 fewer to 23 more) ⨁◯◯◯ VERY LOW CRITICAL Maternal fever during labour 1 randomized trials seriousa not serious not serious very seriousd none 0/30 (0.0%) 2/30 (6.7%) RR 0.20 (0.01 to 4.00) 53 fewer per 1000 (from 66 fewer to 200 more) ⨁◯◯◯ VERY LOW IMPORTANT Postpartum haemorrhage 51 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (Foley or Atad) Oxytocin: all women Relative risk (95% CI) Absolute (95% CI) 4 randomized trials seriousa not serious not serious very seriousg none 9/197 (4.6%) 7/199 (3.5%) RR 1.26 (0.51 to 3.11) 9 more per 1000 (from 17 fewer to 74 more) ⨁◯◯◯ VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 1 randomized trials seriousa not serious not serious very seriouse none 0/50 (0.0%) 0/50 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa not serious not serious very seriouse none 0/50 (0.0%) 0/50 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 2 randomized trials seriousa not serious not serious very seriousd none 2/150 (1.3%) 3/150 (2.0%) RR 0.71 (0.14 to 3.53) 6 fewer per 1000 (from 17 fewer to 51 more) ⨁◯◯◯ VERY LOW CRITICAL Neonatal intensive care unit admission 3 randomized trials seriousa not serious not serious very seriousg none 8/186 (4.3%) 10/186 (5.4%) RR 0.80 (0.32 to 1.98) 11 fewer per 1000 (from 37 fewer to 53 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). c. Small sample size with no events (–2). d. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). e. Single small study with no events (–2). f. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm, and few events (–2). g. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 52 Summary of Findings Table B.6: Balloon catheter versus amniotomy Question: Should balloon catheter (Foley or Atad) versus amniotomy be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Balloon (foley or Atad) Amniotomy: all women Relative risk (95% CI) Absolute (95% CI) Caesarean section 1 randomized trials very seriousa not serious not serious very seriousb none 1/10 (10.0%) 4/10 (40.0%) RR 0.25 (0.03 to 1.86) 300 fewer per 1000 (from 388 fewer to 344 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. Majority of data provided by study/studies with serious design limitations (–2). b. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 53 Summary of Findings Table B.7: Single balloon catheter versus double balloon catheter Question: Should single balloon catheter (Foley) versus double balloon (Atad/Cook) be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Single balloon (Foley) Double balloon (Atad/Cook): all women Relative risk (95% CI) Absolute (95% CI) Vaginal delivery not achieved in 24 hours 3 randomized trials seriousa seriousb not serious not serious none 137/303 (45.2%) 147/305 (48.2%) RR 0.97 (0.75 to 1.25) 14 fewer per 1000 (from 120 fewer to 120 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 1 randomized trials seriousa not serious not serious very seriousc none 0/110 (0.0%) 0/107 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Caesarean section 5 randomized trials seriousa not serious not serious seriousd none 105/430 (24.4%) 113/432 (26.2%) RR 0.97 (0.71 to 1.33) 8 fewer per 1000 (from 76 fewer to 86 more) ⨁⨁◯◯ LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa not serious not serious very seriousc none 0/110 (0.0%) 0/107 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Oxytocin augmentation 2 randomized trials seriousa not serious not serious seriouse none 96/138 (69.6%) 104/140 (74.3%) RR 0.94 (0.82 to 1.08) 45 fewer per 1000 (from 134 fewer to 59 more) ⨁⨁◯◯ LOW IMPORTANT 54 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Single balloon (Foley) Double balloon (Atad/Cook): all women Relative risk (95% CI) Absolute (95% CI) Epidural analgesia 3 randomized trials seriousa not serious not serious not serious none 194/303 (64.0%) 210/305 (68.9%) RR 0.93 (0.83 to 1.03) 48 fewer per 1000 (from 117 fewer to 21 more) ⨁⨁⨁◯ MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 1 randomized trials seriousa not serious not serious very seriousc none 0/110 (0.0%) 0/107 (0.0%) not estimable ⨁◯◯◯ VERY LOW IMPORTANT Uterine rupture 1 randomized trials seriousa not serious not serious very seriousc none 0/110 (0.0%) 0/107 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa not serious not serious seriousf none 51/345 (14.8%) 59/345 (17.1%) RR 0.86 (0.61 to 1.20) 24 fewer per 1000 (from 67 fewer to 34 more) ⨁⨁◯◯ LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa not serious not serious very seriousg none 5/48 (10.4%) 13/50 (26.0%) RR 0.40 (0.15 to 1.04) 156 fewer per 1000 (from 221 fewer to 10 more) ⨁◯◯◯ VERY LOW CRITICAL Maternal side-effects: pain after insertion 1 randomized trials seriousa not serious not serious very seriousg none 4/37 (10.8%) 6/37 (16.2%) RR 0.67 (0.20 to 2.17) 54 fewer per 1000 (from 130 fewer to 190 more) ⨁◯◯◯ VERY LOW IMPORTANT 55 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Single balloon (Foley) Double balloon (Atad/Cook): all women Relative risk (95% CI) Absolute (95% CI) Maternal fever during labour 3 randomized trials seriousa seriousb not serious seriousd none 21/292 (7.2%) 26/292 (8.9%) RR 0.61 (0.16 to 2.34) 35 fewer per 1000 (from 75 fewer to 119 more) ⨁◯◯◯ VERY LOW IMPORTANT Postpartum haemorrhage 2 randomized trials seriousa not serious not serious very serioush none 5/147 (3.4%) 6/144 (4.2%) RR 0.83 (0.27 to 2.52) 7 fewer per 1000 (from 30 fewer to 63 more) ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 3 randomized trials seriousa not serious not serious very seriousi none 4/303 (1.3%) 5/305 (1.6%) RR 0.84 (0.25 to 2.79) 3 fewer per 1000 (from 12 fewer to 29 more) ⨁◯◯◯ VERY LOW CRITICAL Neonatal intensive care unit admission 2 randomized trials seriousa not serious not serious very seriousi none 13/193 (6.7%) 8/198 (4.0%) RR 1.67 (0.71 to 3.93) 27 more per 1000 (from 12 fewer to 118 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Substantial statistical heterogeneity (I2 > 60%) (–1). c. Single small study with no events (–2). d. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). e. Small sample size (–1). f. Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). g. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to negligible harm, and few events (–2). h. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). i. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 56 Summary of Findings Table B.8: Laminaria tent versus vaginal prostaglandin E2 Question: Should laminaria tent compared with vaginal PGE2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Uterine hyperstimulation with fetal heart rate changes 3 randomized trials seriousa not serious not serious seriousb none 0/95 (0.0%) 11/93 (11.8%) RR 0.11 (0.02 to 0.60) 105 fewer per 1000 (from 116 fewer to 47 fewer) ⨁⨁◯◯ LOW CRITICAL Caesarean section 5 randomized trials seriousa not serious not serious seriousc none 25/133 (18.8%) 27/130 (20.8%) RR 0.91 (0.56 to 1.48) 19 fewer per 1000 (from 91 fewer to 100 more) ⨁⨁◯◯ LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa not serious not serious very seriousd none 0/15 (0.0%) 0/13 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Epidural analgesia 1 randomized trials seriousa not serious not serious very seriouse none 31/40 (77.5%) 34/40 (85.0%) RR 0.91 (0.74 to 1.13) 76 fewer per 1000 (from 221 fewer to 110 more) ⨁◯◯◯ VERY LOW IMPORTANT 57 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Uterine hyperstimulation without fetal heart rate changes 3 randomized trials seriousa not serious not serious seriousf none 5/90 (5.6%) 25/90 (27.8%) RR 0.22 (0.09 to 0.49) 217 fewer per 1000 (from 253 fewer to 142 fewer) ⨁⨁◯◯ LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa not serious not serious very seriousg none 15/40 (37.5%) 21/40 (52.5%) RR 0.71 (0.43 to 1.17) 152 fewer per 1000 (from 299 fewer to 89 more) ⨁◯◯◯ VERY LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa not serious not serious very serioush none 0/40 (0.0%) 3/40 (7.5%) RR 0.14 (0.01 to 2.68) 65 fewer per 1000 (from 74 fewer to 126 more) ⨁◯◯◯ VERY LOW CRITICAL Maternal side-effects: all 1 randomized trials seriousa not serious not serious very serioush none 0/15 (0.0%) 1/13 (7.7%) RR 0.29 (0.01 to 6.60) 55 fewer per 1000 (from 76 fewer to 431 more) ⨁◯◯◯ VERY LOW IMPORTANT 58 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Vaginal PGE2: all women Relative risk (95% CI) Absolute (95% CI) Maternal nausea 1 randomized trials seriousa not serious not serious very serioush none 0/15 (0.0%) 1/13 (7.7%) RR 0.29 (0.01 to 6.60) 55 fewer per 1000 (from 76 fewer to 431 more) ⨁◯◯◯ VERY LOW IMPORTANT Serious perinatal morbidity/perinatal death 1 randomized trials seriousa not serious not serious very seriousd none 0/40 (0.0%) 0/40 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa not serious not serious very seriousd none 0/40 (0.0%) 0/40 (0.0%) not estimable ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 2 randomized trials seriousa not serious not serious very seriousi none 0/80 (0.0%) 0/80 (0.0%) not pooled ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Small sample size with few events (–1). c. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). d. Single small study with no events (–2). e. Single small study with few events, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–2). f. Small sample size (–1). g. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–2). h. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). i. Small sample size with no events (–2). 59 Summary of Findings Table B.9: Laminaria tent versus intracervical prostaglandin E2 Question: Should laminaria tent versus intracervical prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Uterine hyperstimulation with fetal heart rate changes 2 randomized trials seriousa not serious not serious very seriousb none 0/172 (0.0%) 5/178 (2.8%) RR 0.17 (0.02 to 1.42) 23 fewer per 1000 (from 28 fewer to 12 more) ⨁◯◯◯ VERY LOW CRITICAL Caesarean section 5 randomized trials seriousa not serious not serious seriousc none 124/459 (27.0%) 107/461 (23.2%) RR 1.16 (0.93 to 1.45) 37 more per 1000 (from 16 fewer to 104 more) ⨁⨁◯◯ LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa not serious not serious very seriousd none 0/90 (0.0%) 1/95 (1.1%) RR 0.35 (0.01 to 8.52) 7 fewer per 1000 (from 10 fewer to 79 more) ⨁◯◯◯ VERY LOW CRITICAL Cervix unfavourable/unchanged after 12–24 hours 2 randomized trials very seriouse not serious not serious very seriousf none 10/109 (9.2%) 18/109 (16.5%) RR 0.46 (0.11 to 1.96) 89 fewer per 1000 (from 147 fewer to 159 more) ⨁◯◯◯ VERY LOW IMPORTANT 60 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Oxytocin augmentation 1 randomized trials seriousa not serious not serious seriousg none 84/90 (93.3%) 63/95 (66.3%) RR 1.41 (1.21 to 1.64) 272 more per 1000 (from 139 more to 424 more) ⨁⨁◯◯ LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 2 randomized trials seriousa not serious not serious very seriousb none 0/304 (0.0%) 5/297 (1.7%) RR 0.17 (0.02 to 1.36) 14 fewer per 1000 (from 16 fewer to 6 more) ⨁◯◯◯ VERY LOW IMPORTANT Uterine rupture 1 randomized trials seriousa not serious not serious very seriousd none 0/90 (0.0%) 1/95 (1.1%) RR 0.35 (0.01 to 8.52) 7 fewer per 1000 (from 10 fewer to 79 more) ⨁◯◯◯ VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa not serious not serious serioush none 28/208 (13.5%) 28/216 (13.0%) RR 1.05 (0.65 to 1.69) 6 more per 1000 (from 45 fewer to 89 more) ⨁⨁◯◯ LOW IMPORTANT Maternal side-effects 1 randomized trials very seriouse not serious not serious very seriousd none 0/82 (0.0%) 2/83 (2.4%) RR 0.20 (0.01 to 4.15) 19 fewer per 1000 (from 24 fewer to 76 more) ⨁◯◯◯ VERY LOW IMPORTANT 61 Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Intracervical PGE2: all women Relative risk (95% CI) Absolute (95% CI) Postpartum haemorrhage 2 randomized trials very seriouse not serious not serious very seriousf none 9/118 (7.6%) 8/121 (6.6%) RR 1.14 (0.46 to 2.81) 9 more per 1000 (from 36 fewer to 120 more) ⨁◯◯◯ VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 1 randomized trials seriousa not serious not serious very seriousd none 1/90 (1.1%) 0/95 (0.0%) RR 3.16 (0.13 to 76.70) 0 fewer per 1000 (from 0 fewer to 0 fewer) ⨁◯◯◯ VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa not serious not serious very seriousd none 1/90 (1.1%) 0/95 (0.0%) RR 3.16 (0.13 to 76.70) 0 fewer per 1000 (from 0 fewer to 0 fewer) ⨁◯◯◯ VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa not serious not serious very seriousd none 5/90 (5.6%) 1/95 (1.1%) RR 5.28 (0.63 to 44.30) 45 more per 1000 (from 4 fewer to 456 more) ⨁◯◯◯ VERY LOW CRITICAL Neonatal intensive care unit admission 2 randomized trials seriousa not serious not serious very seriousf none 9/126 (7.1%) 6/133 (4.5%) RR 1.58 (0.58 to 4.33) 26 more per 1000 (from 19 fewer to 150 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. 62 a. All data provided by study/studies with design limitations (–1). b. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). c. Wide CIs crossing the line of no effect, ranging from negligible benefit to appreciable harm (–1). d. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). e. Majority of data provided by study/studies with serious design limitations (–2). f. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). g. Single small study (–1). h. Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). 63 Summary of Findings Table B.10: Balloon laminaria tent versus oxytocin Question: Should laminaria tent versus oxytocin be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Oxytocin: all women Relative risk (95% CI) Absolute (95% CI) Caesarean section 2 randomized trials seriousa not serious not serious very seriousb none 8/38 (21.1%) 9/35 (25.7%) RR 0.83 (0.36 to 1.89) 44 fewer per 1000 (from 165 fewer to 229 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. All data provided by study/studies with design limitations (–1). b. Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 64 Summary of Findings Table B.11: Laminaria tent versus amniotomy Question: Should laminaria tent versus amniotomy be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Amniotomy: all women Relative risk (95% CI) Absolute (95% CI) Caesarean section 1 randomized trials very seriousa not serious not serious very seriousb none 3/10 (30.0%) 4/10 (40.0%) RR 0.75 (0.22 to 2.52) 100 fewer per 1000 (from 312 fewer to 608 more) ⨁◯◯◯ VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a. Majority of data provided by study/studies with serious design limitations (–2). b. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 65 Summary of Findings Table B.12: Laminaria tent versus other hygroscopic dilator Question: Should laminaria tent versus other hygroscopic dilator be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Laminaria tent Other hygroscopic dilator: all women Relative risk (95% CI) Absolute (95% CI) Caesarean section 1 randomized trials seriousa not serious not serious very seriousb none 4/18 (22.2%) 3/23 (13.0%) RR 1.70 (0.44 to 6.66) 91 more per 1000 (from 73 fewer to 738 more) ⨁◯◯◯ VERY LOW CRITCAL CI: confidence interval; RR: relative risk. a. Majority of data provided by study/studies with design limitations (–1). b. Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 66 Summary of Findings Table B.13: Extra-amniotic saline infusion (EASI) versus vaginal prostaglandin E2 Question: Should EASI versus vaginal prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations EASI versus vaginal PGE2 Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness Seriousb none 43/59 (72.9%) 21/50 (42%) RR 1.74 (1.21 to 2.49) 311 more per 1000 (from 88 more to 626 more)  LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 0/115 (0%) 3/106 (2.8%) RR 0.23 (0.03 to 2.07) 22 fewer per 1000 (from 27 fewer to 30 more)  VERY LOW CRITICAL Caesarean section 2 randomized trials seriousa seriousd no serious indirectness very seriouse none 44/115 (38.3%) 31/106 (29.2%) RR 1.35 (0.94 to 1.96) 102 more per 1000 (from 18 fewer to 281 more)  VERY LOW CRITICAL Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousb none 30/59 (50.8%) 2/50 (4%) RR 12.71 (3.2 to 50.57) 468 more per 1000 (from 88 more to 1000 more)  LOW IMPORTANT Epidural analgesia 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousf none 56/56 (100%) 56/56 (100%) RR 1 (0.97 to 1.04) 0 fewer per 1000 (from 30 fewer to 40 more)  VERY LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 0/115 (0%) 3/106 (2.8%) RR 0.23 (0.03 to 2.07) 22 fewer per 1000 (from 27 fewer to 30 more)  VERY LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousg none 11/59 (18.6%) 16/50 (32%) RR 0.58 (0.3 to 1.14) 134 fewer per 1000 (from 224 fewer to 45 more)  VERY LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 1/56 (1.8%) 0/56 (0%) RR 3 (0.12 to 72.1)  VERY LOW CRITICAL 67 Certainty assessment No. of patients Effect Certainty Importance No of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations EASI versus vaginal PGE2 Control Relative risk (95% CI) Absolute Woman not satisfied 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/59 (3.4%) 3/50 (6%) RR 0.56 (0.1 to 3.25) 26 fewer per 1000 (from 54 fewer to 135 more)  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/59 (3.4%) 0/50 (0%) RR 4.25 (0.21 to 86.51)  VERY LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 6/56 (10.7%) 4/56 (7.1%) RR 1.5 (0.45 to 5.03) 36 more per 1000 (from 39 fewer to 288 more)  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a Majority of data provided by study/studies with design limitations (–1). b Single study with small sample size (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, small sample and few events (–2). d Substantial statistical heterogeneity (I2 > 60%) (–1). e Small sample size, wide CIs crossing the line of no effect, ranging from negligible benefit to appreciable harm (–2). f Single study with small sample size (all women had an epidural in this study) (–2). g Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm, and few events (–2). 68 Summary of Findings Table B.14: Extra-amniotic saline infusion (EASI) versus intracervical prostaglandin E2 Question: Should EASI versus intracervical prostaglandin E2 be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations EASI versus intracervical PGE2 Control Relative risk (95% CI) Absolute Caesarean section 2 randomized trials seriousa seriousb no serious indirectness very seriousc none 13/78 (16.7%) 14/77 (18.2%) RR 0.73 (0.1 to 5.12) 49 fewer per 1000 (from 164 fewer to 749 more)  VERY LOW CRITICAL Cervix unfavourable/unchanged after 12–24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 0/43 (0%) 8/42 (19%) RR 0.06 (0 to 0.97) 179 fewer per 1000 (from 6 fewer to 190 fewer)  LOW IMPORTANT Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 11/35 (31.4%) 10/35 (28.6%) RR 1.1 (0.54 to 2.25) 29 more per 1000 (from 131 fewer to 357 more)  VERY LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 1/43 (2.3%) 3/42 (7.1%) RR 0.33 (0.04 to 3.01) 48 fewer per 1000 (from 69 fewer to 144 more)  VERY LOW IMPORTANT Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/43 (0%) 0/42 (0%) not pooled not pooled  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Substantial statistical heterogeneity (I2 >60%) (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and small sample with few events (–2). d Single study with small sample size and few events (–1). e Small sample size with no events (–2). 69 Summary of Findings Table B.15: Any mechanical method plus prostaglandin E2 versus prostaglandin E2 alone Question: Should any mechanical method and prostaglandin E2 versus prostaglandin E2 alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus PGE2 alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 13/22 (59.1%) 12/17 (70.6%) RR 0.84 (0.53 to 1.33) 113 fewer per 1000 (from 332 fewer to 233 more)  VERY LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 0/56 (0%) 2/66 (3%) RR 0.26 (0.01 to 5.12) 22 fewer per 1000 (from 30 fewer to 125 more)  VERY LOW CRITICAL Caesarean section 7 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 82/264 (31.1%) 85/253 (33.6%) RR 0.96 (0.66 to 1.4) 13 fewer per 1000 (from 114 fewer to 134 more)  LOW CRITICAL Cervix unfavourable/unchanged after 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 16/63 (25.4%) 29/59 (49.2%) RR 0.52 (0.31 to 0.85) 236 fewer per 1000 (from 74 fewer to 339 fewer)  LOW IMPORTANT Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 13/19 (68.4%) 18/25 (72%) RR 0.95 (0.64 to 1.41) 36 fewer per 1000 (from 259 fewer to 295 more)  VERY LOW IMPORTANT Epidural analgesia 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 19/22 (86.4%) 15/17 (88.2%) RR 0.98 (0.77 to 1.24) 18 fewer per 1000 (from 203 fewer to 212 more)  LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 3 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/122 (0%) 0/117 (0%) not pooled not pooled  VERY LOW IMPORTANT Instrumental vaginal birth 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousf none 6/42 (14.3%) 9/36 (25%) RR 0.56 (0.22 to 1.45) 110 fewer per 1000 (from 195 fewer to 113 more)  VERY LOW IMPORTANT 70 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus PGE2 alone Control Relative risk (95% CI) Absolute Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 6/61 (9.8%) 6/59 (10.2%) RR 0.97 (0.33 to 2.83) 3 fewer per 1000 (from 68 fewer to 186 more)  VERY LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 0/19 (0%) 2/25 (8%) RR 0.26 (0.01 to 5.12) 59 fewer per 1000 (from 79 fewer to 330 more)  VERY LOW CRITICAL Postpartum haemorrhage 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/22 (0%) 0/17 (0%) not pooled not pooled  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). d Single study with small sample size (–1). e Small sample size with no events (–2). f Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 71 Summary of Findings Table B.16: Any mechanical method plus prostaglandin E2 versus low-dose misoprostol alone Question: Should any mechanical method and prostaglandin E2 versus low-dose misoprostol alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousb none 5/65 (7.7%) 15/62 (24.2%) RR 0.32 (0.12 to 0.82) 165 fewer per 1000 (from 44 fewer to 213 fewer)  LOW IMPORTANT Caesarean section 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 16/65 (24.6%) 14/62 (22.6%) RR 1.09 (0.58 to 2.04) 20 more per 1000 (from 95 fewer to 235 more)  VERY LOW CRITICAL Cervix unfavourable/unchanged after 12–24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 15/65 (23.1%) 35/62 (56.5%) RR 0.41 (0.25 to 0.67) 333 fewer per 1000 (from 186 fewer to 423 fewer)  LOW IMPORTANT Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 56/65 (86.2%) 44/62 (71%) RR 1.21 (1.01 to 1.46) 149 more per 1000 (from 7 more to 326 more)  LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousb none 17/65 (26.2%) 4/62 (6.5%) RR 4.05 (1.44 to 11.38) 197 more per 1000 (from 28 more to 670 more)  LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 25/65 (38.5%) 19/62 (30.6%) RR 1.26 (0.77 to 2.04) 80 more per 1000 (from 70 fewer to 319 more)  VERY LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 7/65 (10.8%) 12/62 (19.4%) RR 0.56 (0.23 to 1.32) 85 fewer per 1000 (from 149 fewer to 62 more)  VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 0/65 (0%) 2/62 (3.2%) RR 0.19 (0.01 to 3.9) 26 fewer per 1000 (from 32 fewer to 94 more)  VERY LOW CRITICAL 72 Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 0/65 (0%) 2/62 (3.2%) RR 0.19 (0.01 to 3.9) 26 fewer per 1000 (from 32 fewer to 94 more)  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/65 (3.1%) 1/62 (1.6%) RR 1.91 (0.18 to 20.51) 15 more per 1000 (from 13 fewer to 315 more)  VERY LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 10/65 (15.4%) 15/62 (24.2%) RR 0.64 (0.31 to 1.31) 87 fewer per 1000 (from 167 fewer to 75 more)  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Small sample size with few events (–1). c Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–2). d Small sample size (–1). 73 Summary of Findings Table B.17: Any mechanical method plus prostaglandin E2 versus oxytocin alone Question: Should any mechanical method and prostaglandin E2 versus oxytocin alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and PGE2 versus oxytocin alone Control Relative risk (95% CI) Absolute Caesarean section 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 1/20 (5%) 4/24 (16.7%) RR 0.3 (0.04 to 2.47) 117 fewer per 1000 (from 160 fewer to 245 more)  VERY LOW CRITICAL Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 2/20 (10%) 4/24 (16.7%) RR 0.6 (0.12 to 2.94) 67 fewer per 1000 (from 147 fewer to 323 more)  VERY LOW IMPORTANT CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 74 Summary of Findings Table B.18: Any mechanical method plus low-dose misoprostol versus prostaglandin E2 alone Question: Should any mechanical method and low-dose misoprostol versus prostaglandin E2 alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus PGE2 alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousb none 79/174 (45.4%) 70/176 (39.8%) RR 1.14 (0.89 to 1.46) 56 more per 1000 (from 44 fewer to 183 more)  LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 6/163 (3.7%) 8/164 (4.9%) RR 0.75 (0.27 to 2.13) 12 fewer per 1000 (from 36 fewer to 55 more)  VERY LOW CRITICAL Caesarean section 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 36/174 (20.7%) 43/176 (24.4%) RR 0.85 (0.57 to 1.25) 37 fewer per 1000 (from 105 fewer to 61 more)  LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/174 (0%) 0/176 (0%) not pooled not pooled  VERY LOW CRITICAL Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 23/174 (13.2%) 43/176 (24.4%) RR 0.54 (0.34 to 0.86) 112 fewer per 1000 (from 34 fewer to 161 fewer)  MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 7/163 (4.3%) 13/164 (7.9%) RR 0.54 (0.22 to 1.32) 36 fewer per 1000 (from 62 fewer to 25 more)  VERY LOW CRITICAL Uterine rupture 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/174 (0%) 0/176 (0%) not pooled not pooled  VERY LOW CRITICAL Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 4/174 (2.3%) 4/176 (2.3%) RR 1.01 (0.26 to 3.98) 0 more per 1000 (from 17 fewer to 68 more)  VERY LOW IMPORTANT 75 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus PGE2 alone Control Relative risk (95% CI) Absolute Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 17/168 (10.1%) 15/171 (8.8%) RR 1.15 (0.6 to 2.23) 13 more per 1000 (from 35 fewer to 108 more)  LOW CRITICAL Maternal side-effects 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousg none 86/149 (57.7%) 82/165 (49.7%) RR 1.16 (0.95 to 1.43) 80 more per 1000 (from 25 fewer to 214 more)  LOW IMPORTANT Maternal nausea 1 randomized trials seriousa no serious inconsistency no serious indirectness serioush none 31/149 (20.8%) 19/151 (12.6%) RR 1.65 (0.98 to 2.79) 82 more per 1000 (from 3 fewer to 225 more)  LOW IMPORTANT Maternal diarrhoea 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousi none 20/148 (13.5%) 6/165 (3.6%) RR 3.72 (1.53 to 9) 99 more per 1000 (from 19 more to 291 more)  LOW IMPORTANT Maternal fever during labour 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 3/172 (1.7%) 2/175 (1.1%) RR 1.53 (0.26 to 9.02) 6 more per 1000 (from 8 fewer to 92 more)  VERY LOW IMPORTANT Postpartum haemorrhage 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 42/174 (24.1%) 43/174 (24.7%) RR 0.98 (0.67 to 1.41) 5 fewer per 1000 (from 82 fewer to 101 more)  LOW CRITICAL Serious neonatal morbidity/perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/171 (1.2%) 1/174 (0.57%) RR 2.04 (0.19 to 22.24) 6 more per 1000 (from 5 fewer to 122 more)  VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 1/171 (0.58%) 1/174 (0.57%) RR 1.02 (0.06 to 16.14) 0 more per 1000 (from 5 fewer to 87 more)  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 6/171 (3.5%) 9/175 (5.1%) RR 0.68 (0.25 to 1.88) 16 fewer per 1000 (from 39 fewer to 45 more)  VERY LOW CRITICAL 76 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus PGE2 alone Control Relative risk (95% CI) Absolute Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousc none 2/171 (1.2%) 3/175 (1.7%) RR 0.68 (0.12 to 4.03) 5 fewer per 1000 (from 15 fewer to 52 more)  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). d Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). e Single study with no events (–2). f Single study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). g Single study, wide CIs crossing the line of no effect, ranging from negligible benefit to appreciable harm (–1). h Wide CIs ranging from negligible benefit to appreciable harm (–1). i Single study with few events (–1). 77 Summary of Findings Table B.19: Any mechanical method plus low-dose misoprostol versus low-dose misoprostol alone Question: Should any mechanical method and low-dose misoprostol versus low-dose misoprostol alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa seriousb no serious indirectness seriousc none 98/335 (29.3%) 115/333 (34.5%) RR 0.7 (0.25 to 1.95) 104 fewer per 1000 (from 259 fewer to 328 more)  VERY LOW IMPORTANT Uterine hyperstimulation with fetal heart rate changes 4 randomized trials seriousa seriousb no serious indirectness seriousc none 21/352 (6%) 44/355 (12.4%) RR 0.54 (0.2 to 1.45) 57 fewer per 1000 (from 99 fewer to 56 more)  VERY LOW CRITICAL Caesarean section 7 randomized trials seriousa no serious inconsistency no serious indirectness seriousd none 161/708 (22.7%) 187/714 (26.2%) RR 0.87 (0.66 to 1.15) 34 fewer per 1000 (from 89 fewer to 39 more)  LOW CRITICAL Serious maternal morbidity or death 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/244 (0%) 0/246 (0%) not pooled not pooled  VERY LOW CRITICAL Serious maternal complications 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/174 (0%) 0/176 (0%) not pooled not pooled  VERY LOW CRITICAL Cervix unfavourable/unchanged after 12 hours 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 3/70 (4.3%) 11/70 (15.7%) RR 0.27 (0.08 to 0.94) 115 fewer per 1000 (from 9 fewer to 145 fewer)  LOW IMPORTANT Oxytocin augmentation 5 randomized trials seriousa seriousb no serious indirectness seriousc none 188/524 (35.9%) 208/527 (39.5%) RR 0.94 (0.7 to 1.25) 24 fewer per 1000 (from 118 fewer to 99 more)  VERY LOW IMPORTANT 78 Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Epidural analgesia 3 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 192/219 (87.7%) 195/224 (87.1%) RR 1 (0.91 to 1.1) 0 fewer per 1000 (from 78 fewer to 87 more)  MODERATE IMPORTANT Uterine hyperstimulation without fetal heart rate changes 4 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 20/494 (4%) 37/488 (7.6%) RR 0.53 (0.32 to 0.9) 36 fewer per 1000 (from 8 fewer to 52 fewer)  MODERATE IMPORTANT Uterine rupture 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/244 (0%) 0/246 (0%) not pooled not pooled  VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 28/337 (8.3%) 30/339 (8.8%) RR 0.93 (0.58 to 1.51) 6 fewer per 1000 (from 37 fewer to 45 more)  LOW IMPORTANT Meconium-stained liquor 6 randomized trials seriousa no serious inconsistency no serious indirectness seriousg none 56/618 (9.1%) 88/625 (14.1%) RR 0.61 (0.35 to 1.04) 55 fewer per 1000 (from 92 fewer to 6 more)  LOW CRITICAL Maternal nausea 1 randomized trials seriousa no serious inconsistency no serious indirectness serioush none 31/149 (20.8%) 23/151 (15.2%) RR 1.37 (0.84 to 2.23) 56 more per 1000 (from 24 fewer to 187 more)  LOW IMPORTANT Maternal side-effects 1 randomized trials seriousa no serious inconsistency no serious indirectness serioush none 86/149 (57.7%) 82/151 (54.3%) RR 1.06 (0.87 to 1.3) 33 more per 1000 (from 71 fewer to 163 more)  LOW IMPORTANT Maternal diarrhoea 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 20/148 (13.5%) 6/150 (4%) RR 3.38 (1.4 to 8.17) 95 more per 1000 (from 16 more to 287 more)  LOW IMPORTANT Postpartum haemorrhage 2 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 44/230 (19.1%) 48/236 (20.3%) RR 0.93 (0.65 to 1.33) 14 fewer per 1000 (from 71 fewer to 67 more)  LOW CRITICAL 79 Certainty assessment No. of patients Effect Quality Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and low-dose misoprostol versus low-dose misoprostol alone Control Relative risk (95% CI) Absolute Serious neonatal morbidity/perinatal death 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousi none 5/244 (2%) 4/243 (1.6%) RR 1.25 (0.34 to 4.55) 4 more per 1000 (from 11 fewer to 58 more)  VERY LOW CRITICAL Perinatal death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousi none 1/171 (0.58%) 0/176 (0%) RR 3.09 (0.13 to 75.26) -  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 3 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 23/402 (5.7%) 35/400 (8.8%) RR 0.71 (0.37 to 1.36) 25 fewer per 1000 (from 55 fewer to 32 more)  LOW CRITICAL Neonatal intensive care unit admission 6 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 25/621 (4%) 44/625 (7%) RR 0.57 (0.36 to 0.91) 30 fewer per 1000 (from 6 fewer to 45 fewer)  MODERATE CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Substantial statistical heterogeneity (I2 > 60%) (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). d Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). e No events (–2). f Small sample size and few events (–1). g Wide CIs crossing the line of no effect, ranging from appreciable benefit to negligible harm (–1). h Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). i Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 80 Summary of Findings Table B.20: Any mechanical method plus oxytocin versus prostaglandin E2 alone Question: Should any mechanical method and oxytocin versus PGE2 alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus PGE2 alone Control Relative risk (95% CI) Absolute Uterine hyperstimulation with fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 9/76 (11.8%) 6/75 (8%) RR 1.48 (0.55 to 3.95) 38 more per 1000 (from 36 fewer to 236 more)  VERY LOW CRITICAL Caesarean section 4 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 103/409 (25.2%) 76/304 (25%) RR 0.93 (0.72 to 1.2) 17 fewer per 1000 (from 70 fewer to 50 more)  LOW CRITICAL Serious maternal morbidity or death 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousd none 0/100 (0%) 0/100 (0%) not pooled not pooled  VERY LOW CRITICAL Oxytocin augmentation 1 randomized trials seriousa no serious inconsistency no serious indirectness seriouse none 100/100 (100%) 40/100 (40%) RR 2.48 (1.95 to 3.15) 592 more per 1000 (from 380 more to 860 more)  LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 1 randomized trials seriousa no serious inconsistency no serious indirectness seriouse none 40/76 (52.6%) 18/75 (24%) RR 2.19 (1.39 to 3.46) 286 more per 1000 (from 94 more to 590 more)  LOW IMPORTANT Instrumental vaginal birth 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 2/22 (9.1%) 5/19 (26.3%) RR 0.35 (0.08 to 1.58) 171 fewer per 1000 (from 242 fewer to 153 more)  VERY LOW IMPORTANT Meconium-stained liquor 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 8/76 (10.5%) 7/75 (9.3%) RR 1.13 (0.43 to 2.95) 12 more per 1000 (from 53 fewer to 182 more)  VERY LOW CRITICAL Postpartum haemorrhage 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 0/76 (0%) 3/75 (4%) RR 0.14 (0.01 to 2.68) 34 fewer per 1000 (from 40 fewer to 67 more)  VERY LOW CRITICAL 81 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus PGE2 alone Control Relative risk (95% CI) Absolute Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 1/76 (1.3%) 0/75 (0%) RR 2.96 (0.12 to 71.55) -  VERY LOW CRITICAL Neonatal intensive care unit admission 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 6/76 (7.9%) 7/75 (9.3%) RR 0.85 (0.3 to 2.4) 14 fewer per 1000 (from 65 fewer to 131 more)  VERY LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Single small study, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). d No events (–2). e Single study with small sample size (–1). 82 Summary of Findings Table B.21: Any mechanical method plus oxytocin versus low-dose misoprostol alone Question: Should any mechanical method and oxytocin versus low-dose misoprostol alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;10(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus low- dose misoprostol alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 49/183 (26.8%) 99/179 (55.3%) RR 0.48 (0.37 to 0.63) 288 fewer per 1000 (from 205 fewer to 348 fewer)  MODERATE IMPORTANT Uterine hyperstimulation with fetal heart rate changes 3 randomized trials seriousa no serious inconsistency no serious indirectness very seriousb none 6/709 (0.85%) 14/754 (1.9%) RR 0.43 (0.17 to 1.11) 11 fewer per 1000 (from 15 fewer to 2 more)  VERY LOW CRITICAL Caesarean section 5 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 196/868 (22.6%) 214/911 (23.5%) RR 0.95 (0.8 to 1.12) 12 fewer per 1000 (from 47 fewer to 28 more)  MODERATE CRITICAL Oxytocin augmentation 2 randomized trials seriousa seriousc no serious indirectness seriousd none 148/166 (89.2%) 58/170 (34.1%) RR 3.89 (0.7 to 21.72) 986 more per 1000 (from 102 fewer to 1000 more)  VERY LOW IMPORTANT Epidural analgesia 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 65/83 (78.3%) 58/79 (73.4%) RR 1.07 (0.9 to 1.27) 51 more per 1000 (from 73 fewer to 198 more)  VERY LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 3 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 16/249 (6.4%) 30/249 (12%) RR 0.52 (0.3 to 0.92) 58 fewer per 1000 (from 10 fewer to 84 fewer)  MODERATE IMPORTANT Meconium-stained liquor 2 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 22/183 (12%) 30/179 (16.8%) RR 0.72 (0.43 to 1.19) 47 fewer per 1000 (from 96 fewer to 32 more)  LOW CRITICAL 83 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus low- dose misoprostol alone Control Relative risk (95% CI) Absolute Maternal fever 2 randomized trials seriousa no serious inconsistency no serious indirectness seriousg none 2/149 (1.3%) 18/149 (12.1%) RR 0.13 (0.04 to 0.5) 105 fewer per 1000 (from 60 fewer to 116 fewer)  LOW IMPORTANT Women not satisfied 1 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 256/400 (64%) 177/466 (38%) RR 1.68 (1.47 to 1.93) 258 more per 1000 (from 179 more to 353 more)  MODERATE CRITICAL Serious neonatal morbidity/perinatal death 2 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 3/609 (0.49%) 4/654 (0.61%) RR 0.82 (0.18 to 3.65) 1 fewer per 1000 (from 5 fewer to 16 more)  VERY LOW CRITICAL Perinatal death 2 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 3/609 (0.49%) 4/654 (0.61%) RR 0.82 (0.18 to 3.65) 1 fewer per 1000 (from 5 fewer to 16 more)  VERY LOW CRITICAL Apgar score < 7 at 5 minutes 1 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 3/83 (3.6%) 3/79 (3.8%) RR 0.95 (0.2 to 4.58) 2 fewer per 1000 (from 30 fewer to 136 more)  VERY LOW CRITICAL Neonatal intensive care unit admission 4 randomized trials seriousa no serious inconsistency no serious indirectness no serious imprecision none 59/775 (7.6%) 93/824 (11.3%) RR 0.66 (0.49 to 0.9) 38 fewer per 1000 (from 11 fewer to 58 fewer)  MODERATE CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm, and few events (–2). c Substantial statistical heterogeneity (I2 > 60%) (–1). d Wide CIs crossing the line of no effect, ranging from modest benefit to appreciable harm (–1). e Single study with small sample size, wide CIs ranging from modest benefit to appreciable harm (–2). f Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). g Small sample size and few events (–1). h Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 84 Summary of Findings Table B.22: Any mechanical method plus oxytocin versus oxytocin alone Question: Should any mechanical method and oxytocin versus oxytocin alone be used for induction of labour? Bibliography: de Vaan MD, ten Eikelder ML, Jozwiak M, Palmer KR, Davies‐Tuck M, Bloemenkamp KW, et al. Mechanical methods for induction of labour. Cochrane Database Syst Rev. 2019;(10):CD001233. Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus oxytocin alone Control Relative risk (95% CI) Absolute Vaginal delivery not achieved in 24 hours 2 randomized trials seriousa seriousb no serious indirectness seriousc none 53/153 (34.6%) 82/168 (48.8%) RR 0.71 (0.21 to 2.4) 142 fewer per 1000 (from 386 fewer to 683 more)  VERY LOW IMPORTANT Caesarean section 6 randomized trials seriousa seriousb no serious indirectness seriousd none 69/351 (19.7%) 95/367 (25.9%) RR 0.68 (0.39 to 1.2) 83 fewer per 1000 (from 158 fewer to 52 more)  VERY LOW CRITICAL Serious maternal morbidity or death 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/153 (0%) 0/168 (0%) not pooled not pooled  VERY LOW CRITICAL Serious maternal complications 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/93 (0%) 0/108 (0%) not pooled not pooled  VERY LOW CRITICAL Epidural analgesia 1 randomized trials seriousa no serious inconsistency no serious indirectness seriousf none 61/61 (100%) 64/66 (97%) RR 1.03 (0.98 to 1.09) 29 more per 1000 (from 19 fewer to 87 more)  LOW IMPORTANT Uterine hyperstimulation without fetal heart rate changes 2 randomized trials seriousa no serious inconsistency no serious indirectness very seriousg none 7/97 (7.2%) 9/102 (8.8%) RR 0.85 (0.34 to 2.09) 13 fewer per 1000 (from 58 fewer to 96 more)  VERY LOW IMPORTANT Uterine rupture 1 randomized trials seriousa no serious inconsistency no serious indirectness very seriouse none 0/60 (0%) 0/60 (0%) not pooled not pooled  VERY LOW CRITICAL Instrumental vaginal birth 3 randomized trials seriousa no serious inconsistency no serious indirectness very seriousg none 13/143 (9.1%) 14/150 (9.3%) RR 0.99 (0.48 to 2.02) 1 fewer per 1000 (from 49 fewer to 95 more)  VERY LOW IMPORTANT 85 Certainty assessment No. of patients Effect Certainty Importance No. of studies Design Risk of bias Inconsistency Indirectness Imprecision Other considerations Any mechanical method and oxytocin versus oxytocin alone Control Relative risk (95% CI) Absolute Meconium-stained liquor 3 randomized trials seriousa no serious inconsistency no serious indirectness very seriousg none 9/157 (5.7%) 13/162 (8%) RR 0.72 (0.32 to 1.63) 22 fewer per 1000 (from 55 fewer to 51 more)  VERY LOW CRITICAL Postpartum haemorrhage 3 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 8/157 (5.1%) 7/162 (4.3%) RR 1.18 (0.44 to 3.18) 8 more per 1000 (from 24 fewer to 94 more)  VERY LOW CRITICAL Serious neonatal morbidity/perinatal death 2 randomized trials seriousa no serious inconsistency no serious indirectness very serioush none 2/153 (1.3%) 3/168 (1.8%) RR 0.71 (0.12 to 4.13) 5 fewer per 1000 (from 16 fewer to 56 more)  VERY LOW CRITICAL Neonatal intensive care unit admission 3 randomized trials seriousa no serious inconsistency no serious indirectness seriousc none 26/190 (13.7%) 30/210 (14.3%) RR 0.98 (0.61 to 1.58) 3 fewer per 1000 (from 56 fewer to 83 more)  LOW CRITICAL CI: confidence interval; RR: relative risk. a All data provided by study/studies with design limitations (–1). b Substantial statistical heterogeneity (I2 > 60%) (–1). c Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm (–1). d Wide CIs crossing the line of no effect, ranging from appreciable benefit to modest harm (–1). e No events (–2). f Small sample size (–1). g Small sample size, wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). h Wide CIs crossing the line of no effect, ranging from appreciable benefit to appreciable harm, and few events (–2). 86 6. 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Geneva: World Health Organization; 2018 (https://apps.who.int/iris/handle/10665/277233). b WHO recommendations on the use of mechanical methods for induction of labour For more information, please contact: World Health Organization Avenue Appia 20, CH-1211 Geneva 27, Switzerland Maternal and Perinatal Health Unit Department of Sexual and Reproductive Health and Research E-mail: srhmph@who.int https://www.who.int/teams/sexual-and-reproductive-health- and-research-(srh)/areas-of-work/maternal-and-perinatal-health Department of Maternal, Newborn, Child and Adolescent Health and Ageing Email: mncah@who.int Website: www.who.int/teams/maternal-newborn-child- adolescent-health-and-ageing/ ISBN 978 92 4 005580 3