WHO recommendations on outpatient settings for induction of labour

WHO recommendations on outpatient settings for induction of labour

WHO recommendations on outpatient settings for induction of labour WHO recommendations on outpatient settings for induction of labour ISBN 978-92-4-005581-0 (electronic version) ISBN 978-92-4-005582-7 (print version) This publication includes an update of some recommendations published in 2011 under the title WHO recommendations for induction of labour. © 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. 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Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. 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. Cover design: Janet Petitpierre Layout: Green Ink Publishing Services Ltd. iii Contents Acknowledgements iv Acronyms and abbreviations v Executive summary vi 1. Introduction 1 1.1 Background 2 1.2 Rationale and objectives 2 1.3 Target audience 3 1.4 Scope of the recommendations 3 1.5 Persons affected by the recommendations 3 2. Methods 5 2.1 Contributors to the guideline 6 2.2 Identification of priority questions and outcomes 8 2.3 Evidence identification and retrieval 8 2.4 Certainty assessment and grading of the evidence 9 2.5 Formulation of the recommendations 10 2.6 Management of declarations and conflicts of interests 11 2.7 Decision-making during the GDG meetings 12 2.8 Document review and preparation 12 3. Recommendations and supporting evidence 13 3.1 Summary of the evidence 14 4. Dissemination, adaptation and implementation of the recommendation 17 4.1 Dissemination 18 4.2 Adaptation 18 4.3 Implementation considerations 18 5. Research priorities 21 6. Applicability issues 23 6.1 Anticipated impact on the organization of care and resources 24 6.2 Monitoring and evaluating guideline implementation 24 7. Updating the recommendations 25 References 27 Annex 1. Contributors to the guideline development process 32 Annex 2. Priority outcomes used in decision-making 35 Annex 3. Summary and management of declared interests from GDG members and reviewers 36 Web Annex. Evidence-to-Decision framework Available at: https://apps.who.int/iris/bitstream/handle/10665/363144/9789240055834-eng.pdf iv Acknowledgements The World Health Organization (WHO) Department of Sexual and Reproductive Health and Research, and the Department of Maternal, Newborn, Child and Adolescent Health and Ageing gratefully acknowledge the contribution of many individuals and organizations to the updating of these recommendations. The work on this update was coordinated by the Department of Sexual and Reproductive Health and Research, led by Doris Chou and Olufemi Oladapo, with Mercedes Bonet, Tina Lavin and Joshua Vogel; as well as Maurice Bucagu, Anayda Gerarda Portela and Frances Emma McConville of the Department of Maternal, Newborn, Child and Adolescent Health and Ageing. WHO extends its sincere thanks to Edgardo Abalos, Niveen Abu Rmeileh, Ebunoluwa Adejuyigbe, Melania de Amorim, Shabina Ariff, Michel Boulvain, Maria Laura Costa, Christine East, Lynn Freedman, Justus Hofmeyer, Pisake Lumbiganon, Jiji Mathews, Rose Mukisa, Hiromi Obara and Andrew Weeks, who served as members of the Guideline Development Group (GDG), and to James Neilson (Chair) for leading the GDG meeting. WHO also thanks the members of the External Review Group (ERG): Guilherme Ceccati, Caroline Homer, Jack Moodley and Jeeva Sankar. WHO also gratefully acknowledges the contribution of the members of the Executive Guideline Steering Group (GSG). Institutional affiliations for all contributors are provided in Annex 1. Anna Cuthbert, Leanne Jones, Frances Kellie and Myfanwy Williams reviewed the scientific evidence, prepared the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tables, and drafted the narrative summary of the evidence. Melissa Murano and Tari Turner prepared analyses of qualitative evidence. Doris Chou, Olufemi Oladapo and Joshua Vogel revised the narrative summaries and double-checked the corresponding GRADE tables and prepared the Evidence-to-Decision (EtD) frameworks. The ERG peer reviewed the final document prior to its receiving executive clearance by WHO and its publication. WHO acknowledges the various organizations that were represented by observers, who included Deborah Armbruster (United States Agency for International Development [USAID]), Robyn Churchill (USAID), Emma Clark (USAID), Lia Brigante (International Confederation of Midwives [ICM]), William Grobman (International Federation of Gynecology and Obstetrics [FIGO]) and Daniela Drandić (RODA – Parents in Action). WHO also appreciates the contributions of staff at the WHO regional offices, including Nancy Kidula (Regional Office for Africa); Bremen de Mucio and Adrian Pablo Duran (Pan American Health Organization); Karima Gholbzouri (Regional Office for the Eastern Mediterranean); Oleg Kuzmenko (Regional Office for Europe); Chandani Anoma Jayathilaka and Neena Raina (Regional Office for South-East Asia); Priya Mannava and Howard Sobel (Regional Office for the Western Pacific). WHO acknowledges the financial support for this work received from USAID and the UNDP-UNFPA- UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research. WHO would like to emphasize that donors do not participate in any decision-making related to the guideline development process, including the composition of research questions, membership of the guideline development groups, conducting and interpretation of systematic reviews, or formulation of the recommendations. The views of the funding bodies have not influenced the content of these recommendations. vAcronyms and abbreviations ANC antenatal care DOI declaration of interests ERG Evidence Review Group ESG Evidence Synthesis Group EtD Evidence-to-Decision FIGO International Federation of Gynecology and Obstetrics GDG Guideline Development Group GRADE Grading of Recommendations Assessment, Development and Evaluation GSG Guideline Steering Group HRP UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction ICM International Confederation of Midwives MPH maternal and perinatal health MPH-GDG WHO Maternal and Perinatal Health Guideline Development Group NGO nongovernmental organization PGE2 prostaglandin E2 PICO population (P), intervention (I), comparator (C), outcome (O) QES quality evidence synthesis RCT randomized controlled trial SDG Sustainable Development Goal UNDP United Nations Development Programme UNFPA United Nations Population Fund UNICEF United Nations Children’s Fund USAID United States Agency for International Development WHO World Health Organization vi Executive summary Introduction In 2019, the Executive Guideline Steering Group (GSG) for the World Health Organization (WHO) maternal and perinatal health recommendations prioritized updating three then-current WHO recommendations on induction of labour at term or beyond (i.e. the timing of induction of labour), the use of mechanical methods for induction of labour and the use of outpatient settings for induction of labour.1 This decision was based on new evidence on these subjects that had become available. The updated recommendation in this document on the use of outpatient settings for induction of labour supersedes the previous WHO recommendation on this topic in the 2011 publication WHO recommendations for induction of labour. Target audience The primary audience for these recommendations includes health professionals who are responsible for developing national and local health-care guidelines and protocols and health workers involved in the provision of care to women and their newborns during pregnancy, labour and childbirth; this includes midwives, nurses, general medical practitioners and obstetricians. The primary audience also includes managers of maternal and child health programmes, and relevant staff in ministries of health and educational and training institutions, in all settings. Guideline development methods Updating these recommendations was guided by standardized operating procedures in accordance with the process outlined in the WHO handbook for guideline development, second edition. The recommendations were developed and updated using the following steps: 1 The updated recommendations on induction of labour at term or beyond and mechanical methods for induction of labour are presented in separate publications, available at https://apps.who.int/iris/bitstream/handle/10665/363138/9789240052796-eng.pdf and https://apps.who. int/iris/bitstream/handle/10665/363140/9789240055780-eng.pdf, respectively. 2 The Web Annex is available at: https://apps.who.int/iris/bitstream/handle/10665/363144/9789240055834-eng.pdf (i) identification of evidence; (iv) formulation of the recommendations; and (v) planning for the priority questions and outcomes; (ii) retrieval of evidence; (iii) assessment and synthesis of dissemination, implementation, impact evaluation and future updating of the recommendations. The scientific evidence supporting the recommendations was synthesized using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Updated systematic reviews were used to prepare the evidence profiles for the priority questions for each of the three thematic areas relating to induction of labour. For the recommendation in this guideline, the priority question was: In pregnant women requiring induction of labour, does outpatient care, compared with inpatient care, improve maternal and perinatal outcomes? WHO convened a meeting on 21–22 October 2021 at which the Guideline Development Group (GDG) members reviewed, deliberated and achieved consensus on the strength and direction of the recommendation presented herein. Through a structured process, the GDG reviewed the balance between the desirable and undesirable effects and the overall certainty of the supporting evidence, values and preferences of stakeholders, resource requirements and cost-effectiveness, equity, acceptability and feasibility. Recommendations Following the review of the Evidence-to-Decision (EtD) framework, the GDG formulated the updated recommendation presented in the box below. To ensure that the recommendation is correctly understood and applied in practice, guideline users should refer to the remarks, which summarize the deliberations of the GDG and specify the conditions under which the recommendation is applicable, as well as to the summary of supporting evidence available in the EtD framework (Web Annex).2 In addition, implementation considerations are presented in the section following the recommendation in the full document. vii RECOMMENDATION 1. Routine outpatient induction of labour is not recommended for improving birth outcomes (low-certainty evidence). Remarks: • The evidence reviewed for this recommendation was derived from high-income country settings and defined the outpatient setting as the “home”, where home induction is defined as cervical ripening at home. Most commonly, after the induction agents have been administered in a hospital/health-care facility, the woman spends time at home before being admitted back to the facility once in labour. Inpatient inductions are defined as induction in health-care facilities (hospitals or birth centres, or midwife-led units), such that the woman remains there following induction while awaiting the start of labour. • The GDG noted that outpatient induction of labour might not be expected to improve birth outcomes. Low-certainty evidence in the systematic review found no difference in birth outcomes when comparing labour induction between inpatient and home settings. • The GDG noted that in some settings, women considered to be at low risk for complications during induction are offered outpatient induction of labour when they have good transportation options and live near the delivery facility. Considering the potential preference of pregnant women to return to their home setting following placement of a cervical ripening agent or initiation of induction, outpatient induction of labour may be undertaken where feasible, following shared decision-making between the provider and the woman. If outpatient induction of labour is considered, this should be in the context of a well organized programme, with adequate staff resources available to remotely monitor/assess and/or reassure women at home. Women should have suitable arrangements in place to return rapidly to the hospital/ facility if and when needed. Executive summary

1CHAPTER TITLE Introduction 2 WHO recommendations on outpatient settings for induction of labour 1.1 Background The World Health Organization (WHO) envisions a world where “every pregnant woman and newborn receives quality care throughout the pregnancy, childbirth and postnatal period” (1). High-quality maternal health care for women is a necessary step towards the achievement of the health targets agreed in the Sustainable Development Goals (SDGs) and the targets and indicators of WHO’s Thirteenth General Programme of Work, particularly those for achieving universal health coverage (2, 3). High-quality health care is essential for the prevention of morbidity and mortality in pregnancy and childbirth, and could reduce the profound inequities and inequalities in maternal and perinatal health globally (2, 4). Ensuring accessibility and acceptability of interventions to improve maternal health is consistent with international human rights laws, which include fundamental commitments of States to enable women and adolescent girls to survive pregnancy and childbirth as part of their enjoyment of sexual and reproductive health and rights, and living a life of dignity (4). To provide good-quality care and maximize maternal and perinatal outcomes, once a woman’s pregnancy has reached term gestation, health practitioners must balance the risks and benefits of continued gestation or induction of labour. Induction of labour is only recommended when there are clear indications that continuing with a pregnancy poses greater risk to the mother or baby than the risk of inducing labour (5). WHO general principles for performing labour induction state (5, 6): • Wherever induction of labour is carried out, facilities should be available for assessing maternal and fetal well-being; • Women receiving oxytocin, misoprostol or other prostaglandins should never be left unattended; and 3 Cervical ripening is also known as cervical priming or cervical preparation. • Wherever possible, induction of labour should be carried out in facilities where caesarean sections can be performed. Induction of labour usually takes place in a hospital, clinic or health-care facility setting using a range of interventions (7). In recent times, there has been increasing interest in outpatient induction of labour. Outpatient induction is defined as “induction at home, or more commonly, after the induction process has been started in a hospital/health-care facility the woman spends time at home” (8). As an outpatient setting, the home environment has been reported to offer women a more positive experience of labour induction, in terms of providing increased autonomy, compared with induction in the hospital (8). Women are either induced at home or more commonly attend the hospital, clinic or health-care facility to receive the cervical ripening/induction agent (8).3 Initial assessments of maternal and fetal well-being are conducted in the hospital, clinic or health-care facility and then the woman returns home. Once regular contractions commence, or at a given time point, the woman returns to the hospital for the birth. 1.2 Rationale and objectives WHO has established a new process for prioritizing and updating maternal and perinatal health (MPH) recommendations, whereby an international group of independent experts – the Executive Guideline Steering Group (GSG) – oversees a systematic prioritization of MPH recommendations in most urgent need of updating. Recommendations are prioritized for updating on the basis of changes or important new uncertainties in the underlying evidence base on the effects (benefits and harms), the values placed on outcomes, resource use and cost-effectiveness, equity, acceptability and feasibility, or the factors affecting implementation. In 2019, the Executive GSG for the WHO MPH recommendations prioritized updating the existing WHO recommendations on induction 3of labour at term or beyond (i.e. the timing of induction of labour), the use of mechanical methods for induction of labour, and the use of outpatient settings for induction of labour. This decision was based on new evidence on these subjects that had become available since the publication of the previous WHO recommendations in 2011 and 2018 (5, 6). These updated recommendations were developed in accordance with the standards and procedures in the WHO handbook for guideline development, including the synthesis of available research evidence; use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE),4 application of the WHO-INTEGRATE framework; and formulation of recommendations by a Guideline Development Group (GDG) composed of international experts and stakeholders (9–12). The recommendation in this document, on outpatient settings for induction of labour, thus supersedes the previous 2011 WHO recommendations on this topic as new evidence on effectiveness became available (5).5 The primary aim of these recommendations is to improve the quality of care and outcomes for women whose pregnancies have reached term or gone beyond term. This document describes the evidence reviewed and the factors taken into consideration by the GDG to inform the updated recommendation on the use of outpatient settings for induction of labour. 1.3 Target audience The primary audience includes health professionals who are responsible for developing national and local health-care guidelines and protocols and health workers involved in the provision of care to women during labour and childbirth, including midwives, nurses, general medical practitioners and obstetricians. The primary audience also includes managers of maternal and child health programmes, 4 Further information is available at: http://www.gradeworkinggroup.org/. 5 The updated recommendations on induction of labour at term or beyond and on the use of mechanical methods for induction of labour are presented in separate publications, available at https://apps.who.int/iris/bitstream/handle/10665/363138/9789240052796-eng.pdf and https://apps.who.int/iris/bitstream/handle/10665/363140/9789240055780-eng.pdf, respectively. 6 Throughout this guideline, to be concise and to facilitate readability, the term “woman” is used to refer to pregnant women and others/ gender-diverse people who can get pregnant. While a majority of persons who are or can get pregnant are cisgender women, who were born and identify as female, transgender men and other gender-diverse people may have the reproductive capacity to become pregnant. and relevant staff in ministries of health and educational and training institutions, in all settings. These recommendations will also be of interest to pregnant women, as well as members of professional societies involved in the care of pregnant women, staff of nongovernmental organizations (NGOs) concerned with promoting people-centred maternal care and implementers of maternal and perinatal health programmes. 1.4 Scope of the recommendations The recommendation was framed using the population (P), intervention (I), comparator (C), outcome (O) (PICO) format. The priority question for this recommendation in PICO format was: In pregnant women requiring induction of labour (P), does outpatient care (I), compared with inpatient care (C), improve maternal and perinatal outcomes (O)? Problem: Perinatal risks associated with the setting for induction of labour Perspective: Clinical practice recommendation – population perspective Population: Pregnant women requiring induction of labour Intervention: Outpatient care Comparator: Inpatient care Outcomes: See Annex 2 Setting: Community settings/hospital settings 1.5 Persons affected by the recommendations The population affected by the recommendation includes all pregnant women.6 Introduction 4 WHO recommendations on outpatient settings for induction of labour 5CHAPTER TITLE Methods 6 WHO recommendations on outpatient settings for induction of labour The recommendations were developed using standardized operating procedures in accordance with the process described in the WHO handbook for guideline development, second edition (13). In summary, the process included: (i) identification of the priority question and critical outcomes; (ii) retrieval of evidence; (iii) assessment and synthesis of evidence; (iv) formulation of the recommendations; and (v) planning for the dissemination, implementation, impact evaluation and updating of the recommendations. Following the “living guideline” approach adopted by the WHO Maternal Perinatal Health (MPH) Unit, the full complement of recommendations and the evidence base underlying those recommendations are reviewed at regular intervals by the WHO MPH Executive Guideline Steering Group (GSG) (14). In 2019, the GSG identified the recommendation on the use of outpatient settings for induction of labour as high priority for updating. This decision was made in response to the availability of new evidence from women undergoing induction of labour in outpatient settings. Six main groups of experts and stakeholders were involved in this process, with their specific roles as described below. 2.1 Contributors to the guideline 2.1.1 Executive Guideline Steering Group (GSG) The Executive GSG is an independent panel of 14 external experts and relevant stakeholders from the six WHO regions: the African Region, the Region of the Americas, the Eastern Mediterranean Region, the European Region, the South-East Asia Region and the Western Pacific Region. The Executive GSG advises WHO on the prioritization of new and existing PICO questions in maternal and perinatal health for development or updating of recommendations. 2.1.2 WHO Steering Group The WHO Steering Group, comprising WHO staff members from the Department of Sexual and Reproductive Health and Research and the Department of Maternal, Newborn, Child and Adolescent Health and Ageing, managed the process of updating the recommendations. The WHO Steering Group drafted the key recommendation questions in PICO format, engaged the systematic review teams and guideline methodologists (i.e. the Evidence Synthesis Group [ESG]), as well as the members of the GDG and the External Review Group (ERG) (see below). In addition, the WHO Steering Group supervised the retrieval and syntheses of evidence, organized the GDG meetings, drafted and finalized the guideline document, and will also manage the guideline dissemination, implementation and impact assessment. The members of the WHO Steering Group are listed in Annex 1. 2.1.3 Guideline Development Group (GDG) The WHO Steering Group identified a pool of approximately 50 experts and stakeholders from the six WHO regions to constitute the WHO Maternal and Perinatal Health Guideline Development Group (MPH-GDG). This pool consists of a diverse group of experts who are skilled in the critical appraisal of research evidence; implementation of evidence- informed recommendations; guideline development methods; and clinical practice, policy and programmes relating to maternal and perinatal health; it also includes consumer representatives. The members of the MPH-GDG are identified in a way that ensures geographic representation and gender balance, and that there are no perceived or real conflicts of interest. The members’ expertise cuts across thematic areas within maternal and perinatal health. From the MPH-GDG pool, 16 external experts and relevant stakeholders were invited to 7Methods participate as members of the GDG for updating the recommendations on all three thematic areas for induction of labour (timing, mechanical methods, outpatient settings). Those selected from the MPH-GDG pool of experts were a diverse group with expertise in perinatal research; guideline development methods; gender, equity and rights; clinical practice, policy and programmes; and included consumer representatives relating to all three of the thematic areas. The GDG members were also selected in a manner that ensured geographic representation and gender balance and that there were no significant conflicts of interest. The GDG appraised the evidence that was used to inform the recommendations, advised on the interpretation of this evidence, formulated the final recommendations based on the draft prepared by the WHO Steering Group, and reviewed and reached a unanimous consensus on the recommendations in the final document. The members of the GDG are listed in Annex 1. 2.1.4 Evidence Synthesis Group (ESG) WHO convened an ESG composed of guideline methodologists and systematic review teams to conduct or update systematic reviews, appraise the evidence and develop the Evidence-to- Decision (EtD) frameworks. Systematic reviews on the effects of the interventions for each of the three thematic areas (timing, mechanical methods and outpatient settings for induction of labour) were updated, supported by the Cochrane Pregnancy and Childbirth Group. A literature review for qualitative evidence on the values, preferences, costs, feasibility and impact on equity was undertaken by Cochrane Australia.7 The WHO Steering Group reviewed and provided input into the reviews and worked closely with the review authors and the guideline methodologists to appraise the evidence. Evidence on effectiveness was appraised using the GRADE methodology. Representatives of the Cochrane Pregnancy and Childbirth Group and the guideline 7 Murano M, Chou D, Costa do Nascimento ML, Turner T. Using the WHO-INTEGRATE evidence to decision framework to develop induction of labour recommendations. Health Res Policy Syst. 2022 (in press). methodologists attended the GDG meeting to provide an overview of the available evidence and GRADE tables, and to respond to technical queries from the GDG members. Evidence on the qualitative aspects of the intervention was evaluated using the criteria of the WHO- INTEGRATE framework (12). The authors of the literature review on qualitative evidence attended the GDG meeting to provide an overview of the qualitative evidence and to respond to queries from the GDG. The members of the ESG are listed in Annex 1. 2.1.5 External partners and observers External partners and observers included representatives from the United States Agency for International Development (USAID), the International Confederation of Midwives (ICM) and the International Federation of Gynecology and Obstetrics (FIGO). These organizations, with their history of collaboration with WHO in the dissemination and implementation of maternal and perinatal health guidelines, were identified as potential implementers of the recommendations. The list of observers who participated in the GDG meetings is included in Annex 1. 2.1.6 External Review Group (ERG) The ERG included four technical experts with interests and expertise in the management of labour. The group was geographically diverse and gender balanced, and the members reported no significant conflicts of interest. The experts reviewed the final documents to identify any factual errors and commented on the clarity of language, contextual issues and implications for implementation. They ensured that the decision-making processes had considered and incorporated contextual values and the preferences of persons affected by the recommendations, health professionals, health practitioners and policy-makers. It was not within the remit of this group to change the recommendations that were formulated by the GDG. Members of the ERG are listed in Annex 1. 8 WHO recommendations on outpatient settings for induction of labour 2.2 Identification of priority questions and outcomes For the thematic area addressed in this guideline – the use of outpatient settings for induction of labour – the priority outcomes were aligned with those from the 2011 WHO recommendations for induction of labour (5). These outcomes were initially identified through a search of scientific databases for relevant, published systematic reviews and a prioritization of outcomes by the GDG for the guideline. In recognition of the importance of women’s experiences of care, two additional outcomes – maternal well-being and maternal satisfaction – were included in this update to ensure that evidence synthesis and recommendation decision-making by the GDG were driven by outcomes that are important to women and to ensure that the final set of recommendations would be woman-centred. All the outcomes were included in the scope of this document for evidence searching, retrieval, synthesis, grading and formulation of the recommendation. The list of priority outcomes is provided in Annex 2. 2.3 Evidence identification and retrieval Evidence to support this update was derived from several sources by the ESG working in collaboration with the WHO Steering Group. Evidence on the effects of this intervention is from a Cochrane systematic review updated in 2020 assessing outpatient versus inpatient induction of labour for improving birth outcomes (15). The update included three new trials, providing evidence from an additional 238 women. The evidence base now includes a total of seven randomized controlled trials (RCTs), six of which provide data on 1610 women and their babies, with one trial providing no usable data. The trials were conducted between 1998 and 2015, and all were in high- or upper-middle-income countries: Australia, Canada, Portugal and the United States of America. Most women in the trials were induced at term or beyond. 8 Murano M, Chou D, Costa do Nascimento ML, Turner T. Using the WHO-INTEGRATE evidence to decision framework to develop induction of labour recommendations. Health Res Policy Syst. 2022 (in press). Two studies used vaginal prostaglandin E2 (PGE2) induction, one study used controlled- release vaginal prostaglandin, and three studies used balloon or Foley catheters for induction. The interventions examined in all of the studies involved induction and initial monitoring in hospital, with subsequent discharge home to await the start of labour or for a fixed period of time for women in the home induction group. The comparators were all with induction, labour and birth in the hospital (15). This systematic review was the primary source of evidence of effectiveness for this recommendation. RCTs relevant to the key questions were screened by the review authors and data on their outcomes and comparisons were entered into Review Manager 5 (RevMan) software. The RevMan file was retrieved from the Cochrane Pregnancy and Childbirth Group and customized to reflect the key comparisons and outcomes (those that were not relevant to the recommendation were excluded). The RevMan file was then exported to GRADE profiler software (GRADEpro) and GRADE criteria were used to critically appraise the retrieved scientific evidence (9). Finally, evidence profiles (in the form of GRADE summary of findings tables) were prepared for comparisons of interest, including the assessment and judgements of each outcome and the estimated risks (see Web Annex). 2.3.1 Evidence on values, resource use and cost-effectiveness, equity, acceptability and feasibility Evidence on values, acceptability and feasibility were obtained by combining the findings of a qualitative evidence synthesis (QES) with additional primary papers.8 The systematic review provided information on women’s and providers’ perspectives and experiences relating to pregnancy and childbirth. The evidence on resource use and cost-effectiveness was very limited. As the review was based on a small number of primary studies involving trials conducted in high-income settings, the 9Methods conclusions should be viewed as extremely tentative. No direct evidence on equity was identified; therefore, the GDG based their decisions on the general findings of the 2015 WHO report on inequality (16). 2.4 Certainty assessment and grading of the evidence The GRADE approach (9–11) was used to assess the certainty of the evidence on effects. The certainty for each outcome was rated as “high”, “moderate”, “low” or “very low” based on a set of established criteria (see Box 2.1). The final rating was dependent on the factors briefly described below. BOX 2.1. Certainty of evidence assessments are defined according to the GRADE approach High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect. Study design limitations: The risk of bias was first examined at the level of each individual study and then across the studies contributing to each outcome. For RCTs, certainty was first rated as “high” and then downgraded by one (“moderate”) or two (“low”) levels, depending on the minimum criteria met by the majority of the studies contributing to each outcome. Inconsistency of the results: The consistency across the results for a given outcome was assessed by exploring the magnitude of differences in the direction and size of effects observed in different studies. The certainty of evidence was not downgraded when the directions of the findings were similar and confidence limits overlapped, whereas it was downgraded when the results were in different directions and confidence limits showed minimal or no overlap. Indirectness: The certainty of evidence was downgraded when there were serious or very serious concerns regarding the directness of the evidence – that is, whether there were important differences between the research reported and the context for which the recommendation was being prepared. Such differences were related, for instance, to populations, interventions, comparisons or outcomes of interest. Imprecision: Imprecision refers to the degree of uncertainty around the estimate of the effect. As this is often a function of sample size and number of events, studies with relatively few participants or events – and thus wide confidence intervals around effect estimates – were downgraded for imprecision. Publication bias: The certainty rating could also be affected by perceived or statistical evidence of bias to underestimate or overestimate the effect of an intervention as a result of selective publication based on study results. Downgrading evidence by one level was considered where there was strong suspicion of publication bias. The findings of the qualitative reviews (qualitative evidence) were appraised for eligibility and quality (rather than certainty) using a two- step process, informed by the Enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) statement (17). As for certainty, quality was also rated as “high”, “moderate”, “low” or “very low”. Findings from individual cost-effectiveness studies were reported narratively for each comparison of interest (15, 18, 19). 10 WHO recommendations on outpatient settings for induction of labour 2.5 Formulation of the recommendations The WHO Steering Group supervised and finalized the preparation of GRADE Summary of Findings tables and narrative evidence summaries in collaboration with the ESG using the GRADE EtD framework (see Web Annex). EtD frameworks include explicit and systematic consideration of evidence on prioritized interventions in terms of specified domains: effects, values, resources, equity, acceptability and feasibility. For the priority questions, judgement was made on the impact of the intervention on each domain to inform and guide the decision-making process. Using the EtD framework template, the WHO Steering Group and ESG created summary documents for each priority question covering evidence on each domain, as follows. • Effects: The evidence on the priority outcomes was summarized in this domain to answer the questions: “What are the desirable and undesirable effects of the intervention?” and “What is the certainty of the evidence on effects?” Where desirable effects (benefits) clearly outweighed undesirable effects (harms) for outcomes that are highly valued by women, or vice versa, there was a greater likelihood of a clear judgement in favour of or against the intervention, respectively. Uncertainty about the net benefits or harms, or small net benefits, usually led to a judgement that did not favour the intervention or the comparator. The higher the certainty of the evidence of benefits across outcomes, the higher the likelihood of a judgement in favour of the intervention. In the absence of evidence of benefits, evidence of potential harm led to a recommendation against the intervention. Where the intervention showed evidence of potential harm and was also found to have evidence of important benefits, depending on the level of certainty and the likely impact of the harm, such evidence of potential harm was more likely to result in a context-specific recommendation, with the context explicitly stated within the recommendation. • Values: This domain relates to the relative importance assigned to the outcomes associated with the intervention by those affected, how such importance varies within and across settings, and whether this importance is surrounded by any uncertainty. The question asked was: “Is there important uncertainty or variability in how much women value the main outcomes associated with the intervention?” When the intervention resulted in benefits or outcomes that most women consistently value (regardless of setting), this was more likely to lead to a judgement in favour of the intervention. This domain, together with the “effects” domain (see above), informed the “balance of effects” judgement. • Resources: For this domain, the questions asked were: “What are the resources associated with the intervention?” and “Is the intervention cost-effective?” A judgement in favour of or against the intervention was likely where the resource implications were clearly advantageous or disadvantageous, respectively. • Equity: This domain encompasses evidence or considerations as to whether or not the intervention would reduce health inequities. Therefore, this domain addressed the question: “What is the anticipated impact of the intervention on equity?” The intervention was likely to be recommended if its proven (or anticipated) effects reduce (or could reduce) health inequities among different groups of women and their families. • Acceptability: For this domain, the questions were: “Is the intervention acceptable to women and health workers?” and “Is the intervention in accordance with universal human rights standards and principles?” The lower the acceptability, the lower the likelihood of a judgement in favour of the intervention. • Feasibility: The feasibility of implementing this intervention depends on factors such as the resources, infrastructure and training requirements, and the perceptions of health 11Methods workers responsible for administering it. The question addressed was: “Is it feasible for the relevant stakeholders to implement the intervention?” Where major barriers were identified, it was less likely that a judgement would be made in favour of the intervention. For each of the above domains, additional evidence of potential harms or unintended consequences are described in the EtD framework (see the Additional considerations subsections in the Web Annex). Such considerations were derived from studies that might not have directly addressed the priority question but provided pertinent information in the absence of direct evidence. These were extracted from single studies, systematic reviews or other relevant sources. The WHO Steering Group provided the EtD framework (including evidence summaries, GRADE Summary of Findings tables and other documents related to the recommendation) to GDG members two weeks in advance of the GDG meeting. The GDG members were asked to review and provide comments electronically on the documents before the virtual GDG meeting. During the GDG meeting on 21–22 October 2021, GDG members collectively reviewed the EtD framework and any comments received through preliminary feedback, and formulated the recommendations. The purpose of the meeting was to reach consensus on the recommendations and the specific context, based on explicit consideration of the range of evidence presented in the EtD framework and the judgement of the GDG members. The GDG members were collectively required to select one of the following categories for the recommendations. • Recommended: This category indicates that the intervention should be implemented. • Not recommended: This category indicates that the intervention should not be implemented. • Recommended only in specific contexts (“context-specific recommendation”): This category indicates that the intervention is applicable only to the condition, setting or population specified in the recommendation and should only be implemented in these contexts. • Recommended only in the context of rigorous research (“research-context recommendation”): This category indicates that there are important uncertainties about the intervention. With this category of recommendation, implementation can still be undertaken on a large scale, provided it takes the form of research that addresses unanswered questions and uncertainties related both to effectiveness of the intervention or option, and its acceptability and feasibility. 2.6 Management of declarations and conflicts of interests WHO has a robust process for management of conflicts of interests, which requires that experts serving in an advisory role disclose any circumstances that could give rise to actual or ostensible conflicts of interest (financial or non- financial). According to the WHO guidelines for declaration of interests (DOI), all experts must declare their interests prior to participation in WHO guideline development processes and meetings (20). All potential GDG members were therefore required to complete a standard WHO DOI form, which was reviewed by the WHO Steering Group before confirming the experts’ invitations to participate. Two GDG members declared interests (prior involvement in research support), and the WHO Steering Group subsequently applied the criteria as outlined in the WHO handbook for guideline development (13) and determined that these declared interests were not serious enough to affect their objective judgement in the process of developing the guideline and recommendations. These two experts were only required to openly declare such conflicts of interest at the beginning of the GDG meeting, and no further actions were taken. All findings from the DOI statements received were managed in accordance with the WHO procedures to ensure the work of WHO and the contribution of its experts is objective and independent. Annex 3 shows a summary of 12 WHO recommendations on outpatient settings for induction of labour the DOI statements and how conflicts of interest declared by invited experts were managed by the WHO Steering Group. 2.7 Decision-making during the GDG meetings During the meeting, the GDG reviewed and discussed the evidence summary and sought clarification as needed. In addition to evaluating the balance between the desirable and undesirable effects of the intervention and the overall certainty of the evidence, the GDG applied additional criteria based on the GRADE EtD framework to determine the direction and strength of the recommendation. These criteria included stakeholders’ values, resource implications, equity, acceptability and feasibility. Considerations were supported by evidence from a literature search where available, or were based on the experience and opinions of the GDG members. EtD tables were used to describe and synthesize these considerations (see Web Annex). Decisions were made based on consensus, defined as the agreement by three quarters or more of the participants. None of the GDG members expressed opposition to the recommendation. 2.8 Document review and preparation Prior to the online GDG meeting, the WHO Steering Group prepared a draft version of the GRADE evidence profiles, the evidence summary and other relevant documents, and made these available to the GDG members in advance, as described above. During the GDG meeting, these documents were modified in line with the participants’ deliberations and remarks. Following the meeting, members of the WHO Steering Group drafted a full guideline document to accurately reflect the deliberations and decisions of the participants. The draft document was sent electronically to the GDG for their final review and approval. Following review and approval by GDG members, the final document was sent for peer review to four external independent experts (comprising the ERG) who were not involved in the GDG. The ERG members were tasked with identifying any factual errors, any lack of clarity, contextual issues and implications for implementation, and were also asked to determine if the recommendations made were aligned with stakeholder interests. The WHO Steering Group evaluated the inputs of the peer reviewers and any modifications made by the WHO Steering Group to the document at that time consisted only of the correction of factual errors along with the editing process to improve language, style and address any lack of clarity. 13CHAPTER TITLE 3 Recommendations and supporting evidence 14 WHO recommendations on outpatient settings for induction of labour RECOMMENDATION 1. Routine outpatient induction of labour is not recommended for improving birth outcomes (low-certainty evidence). Remarks: • The evidence reviewed for this recommendation was derived from high-income country settings and defined the outpatient setting as the “home”, where home induction is defined as cervical ripening at home. Most commonly, after the induction agents have been administered in a hospital/health-care facility, the woman spends time at home before being admitted back to the facility once in labour. Inpatient inductions are defined as induction in health-care facilities (hospitals or birth centres, or midwife-led units), such that the woman remains there following induction while awaiting the start of labour. • The GDG noted that outpatient induction of labour might not be expected to improve birth outcomes. Low-certainty evidence in the systematic review indicated no difference in birth outcomes when comparing labour induction between inpatient and home settings. • The GDG noted that in some settings, women considered to be at low risk for complications during induction are offered outpatient induction of labour when they have good transportation options and live near the delivery facility. Considering the potential preference of pregnant women to return to their home setting following placement of a cervical ripening agent or initiation of induction, outpatient induction of labour may be undertaken where feasible, following shared decision-making between the provider and the woman. If outpatient induction of labour is considered, this should be in the context of a well organized programme, with adequate staff resources available to remotely monitor/assess and/or reassure women at home. Women should have suitable arrangements in place to return rapidly to the hospital/facility if and when needed. This section presents the updated recommendation on outpatient settings for induction of labour that was formulated by the GDG, followed by the corresponding narrative summary of the evidence. To ensure that the recommendation is correctly understood and appropriately implemented in practice, additional remarks reflecting the summary of the discussion by the GDG are included after the recommendation. 3.1 Summary of the evidence Effects (desirable and undesirable) The evidence on the effectiveness and safety of outpatient settings for induction of labour was derived from a Cochrane systematic review updated in 2020 (15). The review included three new trials, providing evidence from an additional 238 women, such that the evidence base now includes seven RCTs, six of which provide data on 1610 women and their babies, while one trial provided no usable data. The interventions examined in all of the studies involved induction and initial monitoring in hospital, with subsequent discharge home to await the start of labour or for a fixed period of time for women in the home induction group. The comparators were all with induction, labour and birth in the hospital. The evidence is summarized in GRADE tables presented as part of the EtD framework in the Web Annex. Values and preferences Considering the benefits and risks of outpatient induction of labour in a home setting, the GDG considers it unlikely that there would be important variability in how women value the outcomes of interest (see Annex 2). During induction of labour women value the ability to move about freely and to have privacy and a 15Recommendations and supporting evidence sense of security. This allows them to feel more in control and maintain their dignity. Feeling secure was enhanced by: having a support person present; systems that enabled this support to continue from induction to delivery; and having rapid access to the clinical expertise and equipment that might be needed. Resource use and costs The resources required to implement the routine induction of labour are primarily the costs of training skilled health personnel. Evidence for resource use and costs is very limited; information from one trial-based primary study and data from a study included within the systematic review on effectiveness was available. Together, they described aspects of cost, resource usage, budget impact and value for money, when considering induction of labour (15, 18, 19). Equity The equity domain was discussed at length by the GDG members as they formulated this recommendation. It is likely that women from low- and middle-income settings, or from 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.9 Acceptability The evidence for acceptability of methods for induction of labour was derived from a synthesis of a published QES and additional primary studies (21–28). When there is a recognized need to avert harm to the baby, labour induction is widely acceptable to women. 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. The QES authors found that “outpatient labour induction is not preferable for all women, and individuals 9 Murano M, Chou D, Costa do Nascimento ML, Turner T. Using the WHO-INTEGRATE evidence to decision framework to develop induction of labour recommendations. Health Res Policy Syst. 2022 (in press). will have preferences about what constitutes a comfortable and safe environment for labour” (21–28).9 There is limited evidence available on the acceptability of labour induction to clinicians. Health practitioners report 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 (29). Feasibility The feasibility of implementing these recommendations was considered by the GDG. WHO general principles for performing labour induction state (5, 6): • Wherever induction of labour is carried out, facilities should be available for assessing maternal and fetal well-being. • Women receiving oxytocin, misoprostol or other prostaglandins should never be left unattended. • Wherever possible, induction of labour should be carried out in facilities where caesarean sections can be performed. 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, medical equipment and appropriate facilities may be an issue in some settings. The GDG considered outpatient induction of labour in this context. Note: The EtD table – which summarizes the balance between the desirable and undesirable effects and the overall certainty of the supporting evidence, values and preferences of stakeholders, resource requirements, cost-effectiveness, equity, acceptability and feasibility that were considered by the GDG in determining the strength and direction of the recommendation – is presented in the EtD framework (Web Annex). 16 WHO recommendations on outpatient settings for induction of labour 17CHAPTER TITLE 4 Dissemination, adaptation and implementation of the recommendation 18 WHO recommendations on outpatient settings for induction of labour The dissemination and implementation of this recommendation are to be considered by all stakeholders involved in the provision of care for pregnant women at the international, national and local levels. There is a vital need to increase women’s access to maternal health care at the community level and to strengthen the capacity at all levels of health-care facilities to ensure they can provide high-quality services and information to all women giving birth. It is therefore crucial that this recommendation be translated into care packages and programmes at country, health-care facility and community levels, where appropriate. 4.1 Dissemination The recommendation will be disseminated through WHO regional and country offices, WHO advisory groups, ministries of health, country and regional technical advisory groups, professional organizations, WHO collaborating centres, other United Nations agencies and NGOs, among others. This recommendation will also be available on the WHO website. Updated recommendations are also routinely disseminated during meetings or scientific conferences attended by WHO staff. This document will be translated into the six United Nations languages and disseminated through the WHO regional offices. Technical assistance will be provided to any WHO regional office willing to translate the full guideline into any of these languages. 4.2 Adaptation National and subnational subgroups may be established to adapt and implement this recommendation based on an existing strategy. This process may include the development or revision of existing national guidelines or protocols based on the updated recommendation. The successful introduction of evidence- based policies (relating to the updated recommendation) depends on well planned and participatory consensus-driven processes of adaptation and implementation. These processes may include the development or revision of existing national or local guidelines and protocols, often supported by ministries of health, United Nations agencies, local professional societies and other relevant leadership groups. An enabling environment should be created for the use of this recommendation, including changes in the behaviour of health practitioners to enable the use of evidence-based practices. In the context of humanitarian emergencies, the adaptation of recommendations should consider integration and alignment with other response strategies. Additional considerations about the unique needs of women in emergency settings, including their values and preferences, should be taken into account. Context-specific tools and toolkits may be required in addition to standard tools to support the implementation of this updated recommendation by stakeholders in the context of humanitarian emergencies. 4.3 Implementation considerations The successful introduction of this recommendation into national programmes and health services depends on well planned and participatory consensus-driven processes of adaptation and implementation. The adaptation and implementation processes may include the development or revision of existing national guidelines or protocols. Recommendations should be adapted into documents and tools that are appropriate for different locations and contexts, to meet the specific needs of each country and health service. Modifications to the recommendation, where necessary, should be justified in an explicit and transparent manner. An enabling environment should be created for the implementation of this recommendation, including education to support behaviour change among skilled health personnel providing care during childbirth (30), to facilitate the use of evidence-based practices. To implement this recommendation, the following should be considered. 19Dissemination, adaptation and implementation of the recommendation • To ensure accurate assessment of gestational age prior to induction, clear policies concerning the provision of early ultrasounds are required. Health workers in antenatal care (ANC) settings require training and supportive supervision on how to perform dating ultrasounds • Health professionals will require training to counsel women on the benefits and side- effects of different methods for induction of labour. Women should be adequately counselled and engaged in shared decision- making when considering the indications for induction of labour and the methods for induction. • Health worker shortages in low- and middle- income country settings may mean that staff are required to attend to much higher numbers of women on the labour ward than in other settings. Providing the necessary level of support, assessment and monitoring in these settings may be challenging and the impact may be reduced capacity among health workers to monitor as frequently as needed or to respond quickly to emergencies (31). • A higher number of induction deliveries are attended by medical doctors than non- induction deliveries (32). This has implications for the distribution and productivity of medical doctors, particularly in under- resourced settings. • Performing induction of labour safely requires availability of appropriate medicines and/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. In order to ensure that implementation of labour induction does not reinforce existing inequities or inequalities, the system should support all women (i) to have access to full and timely information; (ii) to use their own social networks to assist them to understand the information if needed; and (iii) to ensure a woman’s health- care provider is aware of her needs, values and preferences (31). 20 WHO recommendations on outpatient settings for induction of labour 21CHAPTER TITLE 5 Research priorities 22 WHO recommendations on outpatient settings for induction of labour The GDG noted the following evidence gaps. • It is uncertain for which women, and in which high-income versus low- and middle-income countries outpatient induction of labour could be recommended. Large, randomized studies are needed to assess safety and women’s views (when comparing outpatient with inpatient induction of labour). If safety is equivalent, the best method (Foley or low- dose misoprostol) could be evaluated. • In comparing the different settings (outpatient versus inpatient), the GDG noted that the evidence reviewed reported outcomes for women who initiated the induction process in a hospital or health-care facility, and then returned home. Outpatient settings should be differentiated – that is, home (unsupervised), or maternity waiting homes/non-home environments (semi-supervised) – as should the different phases of cervical ripening and induction. The GDG acknowledges that there is planned or ongoing research relevant to some of the identified research priorities. Since there is no certainty that the planned or ongoing research will give conclusive results, the research topics below were identified as research priorities. Potential PICO questions are suggested below. Problem: Perinatal risks associated with the setting for induction of labour Perspective: Clinical practice recommendation – population perspective PICO question: In pregnant women requiring induction of labour (P), does initiating induction in a health-care setting and then returning home to await labour (unsupervised outpatient induction) (I), compared with initiating induction in a hospital or health-care facility and remaining there (C), improve maternal and perinatal outcomes (O)? (Settings: hospital/ community [home settings]; see Annex 2 for outcomes.) PICO question: In pregnant women requiring induction of labour (P), does initiating induction in a health-care setting and then continuing induction in an outpatient setting such as a maternity waiting home (semi-supervised in a non-home environment) (I), compared with initiating induction in a hospital or health- care facility and remaining there (C), improve maternal and perinatal outcomes (O)? (Settings: community [non-home environment]; see Annex 2 for outcomes.) PICO question: In pregnant women requiring induction of labour (P), does induction with a provider-inserted/placed method (I), compared with induction with a self-administered method (C), improve maternal and perinatal outcomes (O)? (Settings: hospital/community; see Annex 2 for outcomes.) 23CHAPTER TITLE 6 Applicability issues 24 WHO recommendations on outpatient settings for induction of labour 6.1 Anticipated impact on the organization of care and resources Implementing this evidence-based recommendation requires health workers to identify and provide counselling to those women with pregnancies that have reached or gone beyond term. Health worker shortages may also reduce the feasibility of performing ANC ultrasound scans and other risk assessments (16, 31). The GDG noted that updating training curricula and providing training on accurate gestational age assessment would increase the impact and facilitate implementation of the recommendation. A number of factors may hinder the effective implementation and scale-up of this recommendation. These factors may be related to the behaviours of patients (women or families) or health professionals, and to the organization of care or health-service delivery. As part of efforts to implement this recommendation, health system stakeholders should consider the need to ensure (33, 34): • one scan before 24 weeks of gestation for accurate estimation of gestational age; • post-term pregnancy risk assessment; and • schedule planning that allows for adequate time to provide information and counselling in ANC clinics. 6.2 Monitoring and evaluating guideline implementation The implementation and impact of this recommendation will be monitored at the health service, country and regional levels, as part of broader efforts to monitor and improve the quality of maternal and newborn care. The WHO document Standards for improving quality of maternal and newborn care in health facilities (35) provides a list of prioritized input, output and outcome measures that can be used to define quality-of-care criteria and indicators, and that should be aligned with locally agreed targets. In collaboration with the monitoring and evaluation teams of the WHO Department of Sexual and Reproductive Health and Research and the WHO Department of Maternal, Newborn, Child and Adolescent Health and Ageing, data on country- and regional-level implementation of the recommendation can be collected and evaluated in the short-to-medium term to assess its impact on national policies of individual WHO Member States. Information on recommended indicators can also be obtained at the local level by interrupted time series or clinical audits. In this context, the GDG suggests the following indicators be considered. • The proportion of pregnant women who have an ultrasound prior to 24 weeks of gestation. • The proportion of pregnant women who have a documented indication for undergoing induction of labour. 25CHAPTER TITLE 7 Updating the recommendations 26 WHO recommendations on outpatient settings for induction of labour The Executive GSG convenes annually to review WHO’s current portfolio of maternal and perinatal health recommendations and to help WHO prioritize new and existing questions for recommendation development and updating. Accordingly, this recommendation will be reviewed along with other recommendations for prioritization by the Executive GSG. If new evidence that could potentially impact the current evidence base is identified, the recommendation may be updated. If no new reports or information are identified, the recommendation may be revalidated. Following publication and dissemination of the updated recommendation, any concerns about the validity of the recommendation will be promptly communicated to the guideline implementers, along with information about plans to update the recommendation. WHO welcomes suggestions regarding additional questions for future inclusion in the process of updating the recommendation. Please email your suggestions to srhmph@who.int. 27 References 1. Tunçalp Ö, Were WM, MacLennan C, Oladapo OT, Gülmezoglu AM, 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. 2. The 17 Goals. In: United Nations Department of Economic and Social Affairs [website]. New York (NY): UN DESA (https://sdgs.un.org/goals, accessed 28 April 2022). 3. Thirteenth general programme of work, 2019–2023: promote health, keep the world safe, serve the vulnerable. 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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. 22. 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. 23. 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. 24. 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. 25. Lou S, Hvidman L, Uldbjerg N, Neumann L, Jensen TF, Haben JG, et al. 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Definition of skilled health personnel providing care during childbirth. The 2018 joint statement by WHO, UNFPA, UNICEF, ICM, ICN, FIGO, IPA. Geneva: World Health Organization; 2018 (https://apps. who.int/iris/handle/10665/272818). 31. 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. 32. 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. 33. WHO recommendations on antenatal care for a positive pregnancy experience. Maternal and fetal assessment update: imaging ultrasound before 24 weeks of pregnancy. Geneva: World Health Organization; 2022 (https://apps.who.int/ iris/handle/10665/352620). 34. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (https://apps.who.int/iris/ handle/10665/250796). 35. Standards for improving quality of maternal and newborn care in health facilities. Geneva: World Health Organization; 2016 (https://apps.who.int/ iris/handle/10665/249155). 30 WHO recommendations on outpatient settings for induction of labour 31CHAPTER TITLE Annexes 32 WHO recommendations on outpatient settings for induction of labour Annex 1. Contributors to the guideline development process Guideline Development Group (GDG) Edgardo Abalos Vice Director Centro Rosarino de Estudios Perinatales Santa Fe, Argentina Niveen Abu Rmeileh Professor of Epidemiology and Public Health Birzeit University Birzeit, Occupied Palestinian Territory Ebunoluwa Adejuyigbe Professor of Pediatrics Obafemi Awolowo University Osun, Nigeria Melania de Amorim Professor of Obstetrics and Gynecology Instituto de Medicina Integral Instituto Paraibano de Pesquisa Professor Joaquim Amorim Neto Figueira, Brazil Shabina Ariff Associate Professor of Paediatrics and Child Health Department of Pediatrics & Child Health Aga Khan University Karachi, Pakistan Michel Boulvain Group leader and Professor of Gynecology and Obstetrics University of Geneva Geneva, Switzerland Maria Laura Costa Associate Professor of Gynecology and Obstetrics State University of Campinas Campinas, Brazil Christine East Professor of Nursing and Midwifery College of Science Health and Engineering La Trobe University Bundoora, Australia Lynn Freedman Professor of Population and Family Health Mailman School of Public Health Columbia University Director, Averting Maternal Death and Disability Program (AMDD) New York, United States of America (USA) Justus Hofmeyr Professor of Obstetrics and Gynaecology University of Botswana Gaborone, Botswana Pisake Lumbiganon Professor of Obstetrics and Gynecology Faculty of Medicine Khon Kaen University Khon Kaen, Thailand Jiji Mathews Head of Obstetrics and Gynaecology Christian Medical College Vellore, India Rose Mukisa Executive Director White Ribbon Alliance Kampala, Uganda Jim Neilson Emeritus Professor Former Coordinating Editor Cochrane Pregnancy and Childbirth Group University of Liverpool Liverpool, United Kingdom of Great Britain and Northern Ireland Hiromi Obara Deputy Director Division of Global Health Policy and Research Department of Health Planning and Management Bureau of International Health Cooperation National Center for Global Health and Medicine Tokyo, Japan Andrew Weeks Professor of International Maternal Health Sanyu Research Unit University of Liverpool Liverpool, United Kingdom 33Annex 1 Partner organizations/observers Deborah Armbruster Senior Maternal and Newborn Health Advisor United States Agency for International Development (USAID), Bureau for Global Health Washington, DC, USA Lia Brigante (representing ICM) Consultant Midwife in Public Health Development Post Guy’s and St Thomas’ NHS Foundation Trust London, United Kingdom Daniela Drandić Reproductive Rights Program Lead Human rights advocacy specialist Human Rights in Childbirth RODA – Parents in Action Bale-Valle, Croatia Emma Clark Senior Maternal Health Advisor Maternal Child Health and Nutrition USAID Bureau for Global Health Washington, DC, USA Robyn Churchill Maternal Health Team Lead Maternal Child Health and Nutrition USAID Bureau for Global Health Washington, DC, USA Bill Grobman (representing FIGO) Vice Chair, Clinical Operations Maternal Fetal Medicine Department of Obstetrics and Gynecology Leadership Ohio State University Columbus, USA Evidence Synthesis Group (ESG) Leanne Jones Deputy Managing Editor Cochrane Pregnancy and Childbirth Department of Women’s and Children’s Health University of Liverpool Liverpool, United Kingdom Frances Kellie Managing Editor Cochrane Pregnancy and Childbirth Department of Women’s and Children’s Health University of Liverpool Liverpool Women’s NHS Foundation Trust Liverpool, United Kingdom Melissa Murano Senior Research Officer Cochrane Australia Monash University Clayton, Australia Tari Turner Associate Professor Cochrane Australia Monash University Clayton, Australia External Review Group (ERG) Guilherme Ceccati Professor of Obstetrics State University of Campinas Campinas, Brazil Caroline Homer Professor and Co-Program Director of Maternal Child and Adolescent Health Burnet Institute Melbourne, Australia Jack Moodley Emeritus Professor University of KwaZulu-Natal Women’s Health and HIV Research Unit Durban, South Africa Jeeva Sankar Assistant Professor of Pediatrics All India Institute of Medical Sciences New Delhi, India 34 WHO recommendations on outpatient settings for induction of labour WHO country and regional offices Bremen de Mucio Advisor, Sexual and Reproductive Health Latin American Center of Perinatology Women and Reproductive Health WHO Regional Office for the Americas Montevideo, Uruguay Adrian Pablo Duran Advisor, Perinatal Health Latin American Center of Perinatology Women and Reproductive Health WHO Regional Office for the Americas Montevideo, Uruguay Karima Gholbzouri Regional Adviser, Reproductive and Maternal Health WHO Regional Office for the Eastern Mediterranean Cairo, Egypt Chandani Anoma Jayathilaka Advisor, Sexual and Reproductive Health, Maternal and Reproductive Health WHO Regional Office for South-East Asia New Delhi, India Nancy Kidula Medical Officer, Reproductive, Maternal, Newborn, Child and Adolescent Health WHO Uganda Country Office Kampala, Uganda Oleg Kuzmenko Advisor, Sexual and Reproductive Health Noncommunicable Diseases and the Life-course WHO Regional Office for Europe Copenhagen, Denmark Neena Raina Coordinator, Family Health, Gender and Life Course WHO Regional Office for South-East Asia New Delhi, India Howard Sobel Coordinator, Reproductive, Maternal, Newborn, Child and Adolescent Health Division of Noncommunicable Diseases and Health through the Life-course WHO Regional Office for the Western Pacific Manila, Philippines WHO Steering Group, WHO headquarters, Geneva, Switzerland Department of Sexual and Reproductive Health and Research (SRH) Maternal and Perinatal Health Unit Olufemi Oladapo Unit Head Mercedes Bonet Semenas Medical Officer Doris Chou Medical Officer Tina Lavin Technical Officer Jen Ransom Consultant Joshua Vogel Consultant Department of Maternal, Newborn, Child and Adolescent Health and Ageing (MCA) Maurice Bucagu Medical Officer Anayda Gerarda Portela Technical Officer Frances Emma McConville Technical Officer 35 Annex 2. Priority outcomes used in decision-making 10 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. Priority outcomes (O): Critical outcomes:10 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. 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. 36 WHO recommendations on outpatient settings for induction of labour Annex 3. Summary and management of declared interests from GDG members and reviewers Name Expertise contributed to guideline development process Declared interest Management of conflict of interest Edgardo Abalos Content expert and end-user None Not applicable Niveen Abu Rmeileh Content expert and end-user None Not applicable Ebunoluwa Adejuyigbe Content expert and end-user None Not applicable Melania de Amorim Content expert and end-user None Not applicable Shabina Ariff Content expert and end-user None Not applicable Michel Boulvain Content expert and end-user None Not applicable Maria Laura Costa Content expert and end-user None Not applicable Christine East Content expert and end-user Research support, including grants, collaborations, sponsorships, and other funding The conflict was not considered serious enough to affect GDG membership or participation in the technical consultation. The conflicts were disclosed prior to discussion. Lynn Freedman Content expert and end-user None Not applicable Justus Hofmeyer Content expert and end-user None Not applicable Pisake Lumbiganon Content expert and end-user None Not applicable Jiji Mathews Content expert and end-user None Not applicable Rose Mukisa Content expert and end-user None Not applicable Jim Neilson Content expert and end-user None Not applicable Hiromi Obara Content expert and end-user None Not applicable Andrew Weeks Content expert and end-user Research support and consulting, including service as a technical or other advisor The conflict was not considered serious enough to affect GDG membership or participation in the technical consultation. The conflicts were disclosed prior to discussion. Leanne Jones Content expert and methodologist None Not applicable Frances Kellie Content expert and methodologist None Not applicable Melissa Murano Content expert and methodologist None Not applicable Tari Turner Content expert and methodologist None Not applicable Jen Ransom Content expert and methodologist None Not applicable Guilherme Ceccati External reviewer None Not applicable Caroline Homer External reviewer None Not applicable Jack Moodley External reviewer None Not applicable Jeeva Sankar External reviewer None Not applicable

38 WHO recommendations on outpatient settings 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 005581 0

WHO recommendations on outpatient settings for induction of labour

WHO recommendations on outpatient settings for induction of labour WHO recommendations on outpatient settings for induction of labour ISBN 978-92-4-005581-0 (electronic version) ISBN 978-92-4-005582-7 (print version) This publication includes an update of some recommendations published in 2011 under the title WHO recommendations for induction of labour. © 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. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This translation was not created by the World Health Organization (WHO). WHO is not responsible for the content or accuracy of this translation. The original English edition shall be the binding and authentic edition”. Any mediation relating to disputes arising under the licence shall be conducted in accordance with the mediation rules of the World Intellectual Property Organization (http://www.wipo.int/amc/en/mediation/rules/). Suggested citation. WHO recommendations on outpatient settings for induction of labour. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO. Cataloguing-in-Publication (CIP) data. CIP data are available at http://apps.who.int/iris. Sales, rights and licensing. To purchase WHO publications, see http://apps.who.int/bookorders. To submit requests for commercial use and queries on rights and licensing, see https://www.who.int/copyright. Third-party materials. If you wish to reuse material from this work that is attributed to a third party, such as tables, figures or images, it is your responsibility to determine whether permission is needed for that reuse and to obtain permission from the copyright holder. The risk of claims resulting from infringement of any third-party- owned component in the work rests solely with the user. General disclaimers. The designations employed and the presentation of the material in this publication do not imply the expression of any opinion whatsoever on the part of WHO concerning the legal status of any country, territory, city or area or of its authorities, or concerning the delimitation of its frontiers or boundaries. Dotted and dashed lines on maps represent approximate border lines for which there may not yet be full agreement. 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. Cover design: Janet Petitpierre Layout: Green Ink Publishing Services Ltd. iii Contents Acknowledgements iv Acronyms and abbreviations v Executive summary vi 1. Introduction 1 1.1 Background 2 1.2 Rationale and objectives 2 1.3 Target audience 3 1.4 Scope of the recommendations 3 1.5 Persons affected by the recommendations 3 2. Methods 5 2.1 Contributors to the guideline 6 2.2 Identification of priority questions and outcomes 8 2.3 Evidence identification and retrieval 8 2.4 Certainty assessment and grading of the evidence 9 2.5 Formulation of the recommendations 10 2.6 Management of declarations and conflicts of interests 11 2.7 Decision-making during the GDG meetings 12 2.8 Document review and preparation 12 3. Recommendations and supporting evidence 13 3.1 Summary of the evidence 14 4. Dissemination, adaptation and implementation of the recommendation 17 4.1 Dissemination 18 4.2 Adaptation 18 4.3 Implementation considerations 18 5. Research priorities 21 6. Applicability issues 23 6.1 Anticipated impact on the organization of care and resources 24 6.2 Monitoring and evaluating guideline implementation 24 7. Updating the recommendations 25 References 27 Annex 1. Contributors to the guideline development process 32 Annex 2. Priority outcomes used in decision-making 35 Annex 3. Summary and management of declared interests from GDG members and reviewers 36 Web Annex. Evidence-to-Decision framework Available at: https://apps.who.int/iris/bitstream/handle/10665/363144/9789240055834-eng.pdf iv Acknowledgements The World Health Organization (WHO) Department of Sexual and Reproductive Health and Research, and the Department of Maternal, Newborn, Child and Adolescent Health and Ageing gratefully acknowledge the contribution of many individuals and organizations to the updating of these recommendations. The work on this update was coordinated by the Department of Sexual and Reproductive Health and Research, led by Doris Chou and Olufemi Oladapo, with Mercedes Bonet, Tina Lavin and Joshua Vogel; as well as Maurice Bucagu, Anayda Gerarda Portela and Frances Emma McConville of the Department of Maternal, Newborn, Child and Adolescent Health and Ageing. WHO extends its sincere thanks to Edgardo Abalos, Niveen Abu Rmeileh, Ebunoluwa Adejuyigbe, Melania de Amorim, Shabina Ariff, Michel Boulvain, Maria Laura Costa, Christine East, Lynn Freedman, Justus Hofmeyer, Pisake Lumbiganon, Jiji Mathews, Rose Mukisa, Hiromi Obara and Andrew Weeks, who served as members of the Guideline Development Group (GDG), and to James Neilson (Chair) for leading the GDG meeting. WHO also thanks the members of the External Review Group (ERG): Guilherme Ceccati, Caroline Homer, Jack Moodley and Jeeva Sankar. WHO also gratefully acknowledges the contribution of the members of the Executive Guideline Steering Group (GSG). Institutional affiliations for all contributors are provided in Annex 1. Anna Cuthbert, Leanne Jones, Frances Kellie and Myfanwy Williams reviewed the scientific evidence, prepared the Grading of Recommendations Assessment, Development and Evaluation (GRADE) tables, and drafted the narrative summary of the evidence. Melissa Murano and Tari Turner prepared analyses of qualitative evidence. Doris Chou, Olufemi Oladapo and Joshua Vogel revised the narrative summaries and double-checked the corresponding GRADE tables and prepared the Evidence-to-Decision (EtD) frameworks. The ERG peer reviewed the final document prior to its receiving executive clearance by WHO and its publication. WHO acknowledges the various organizations that were represented by observers, who included Deborah Armbruster (United States Agency for International Development [USAID]), Robyn Churchill (USAID), Emma Clark (USAID), Lia Brigante (International Confederation of Midwives [ICM]), William Grobman (International Federation of Gynecology and Obstetrics [FIGO]) and Daniela Drandić (RODA – Parents in Action). WHO also appreciates the contributions of staff at the WHO regional offices, including Nancy Kidula (Regional Office for Africa); Bremen de Mucio and Adrian Pablo Duran (Pan American Health Organization); Karima Gholbzouri (Regional Office for the Eastern Mediterranean); Oleg Kuzmenko (Regional Office for Europe); Chandani Anoma Jayathilaka and Neena Raina (Regional Office for South-East Asia); Priya Mannava and Howard Sobel (Regional Office for the Western Pacific). WHO acknowledges the financial support for this work received from USAID and the UNDP-UNFPA- UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research. WHO would like to emphasize that donors do not participate in any decision-making related to the guideline development process, including the composition of research questions, membership of the guideline development groups, conducting and interpretation of systematic reviews, or formulation of the recommendations. The views of the funding bodies have not influenced the content of these recommendations. vAcronyms and abbreviations ANC antenatal care DOI declaration of interests ERG Evidence Review Group ESG Evidence Synthesis Group EtD Evidence-to-Decision FIGO International Federation of Gynecology and Obstetrics GDG Guideline Development Group GRADE Grading of Recommendations Assessment, Development and Evaluation GSG Guideline Steering Group HRP UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction ICM International Confederation of Midwives MPH maternal and perinatal health MPH-GDG WHO Maternal and Perinatal Health Guideline Development Group NGO nongovernmental organization PGE2 prostaglandin E2 PICO population (P), intervention (I), comparator (C), outcome (O) QES quality evidence synthesis RCT randomized controlled trial SDG Sustainable Development Goal UNDP United Nations Development Programme UNFPA United Nations Population Fund UNICEF United Nations Children’s Fund USAID United States Agency for International Development WHO World Health Organization vi Executive summary Introduction In 2019, the Executive Guideline Steering Group (GSG) for the World Health Organization (WHO) maternal and perinatal health recommendations prioritized updating three then-current WHO recommendations on induction of labour at term or beyond (i.e. the timing of induction of labour), the use of mechanical methods for induction of labour and the use of outpatient settings for induction of labour.1 This decision was based on new evidence on these subjects that had become available. The updated recommendation in this document on the use of outpatient settings for induction of labour supersedes the previous WHO recommendation on this topic in the 2011 publication WHO recommendations for induction of labour. Target audience The primary audience for these recommendations includes health professionals who are responsible for developing national and local health-care guidelines and protocols and health workers involved in the provision of care to women and their newborns during pregnancy, labour and childbirth; this includes midwives, nurses, general medical practitioners and obstetricians. The primary audience also includes managers of maternal and child health programmes, and relevant staff in ministries of health and educational and training institutions, in all settings. Guideline development methods Updating these recommendations was guided by standardized operating procedures in accordance with the process outlined in the WHO handbook for guideline development, second edition. The recommendations were developed and updated using the following steps: 1 The updated recommendations on induction of labour at term or beyond and mechanical methods for induction of labour are presented in separate publications, available at https://apps.who.int/iris/bitstream/handle/10665/363138/9789240052796-eng.pdf and https://apps.who. int/iris/bitstream/handle/10665/363140/9789240055780-eng.pdf, respectively. 2 The Web Annex is available at: https://apps.who.int/iris/bitstream/handle/10665/363144/9789240055834-eng.pdf (i) identification of evidence; (iv) formulation of the recommendations; and (v) planning for the priority questions and outcomes; (ii) retrieval of evidence; (iii) assessment and synthesis of dissemination, implementation, impact evaluation and future updating of the recommendations. The scientific evidence supporting the recommendations was synthesized using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Updated systematic reviews were used to prepare the evidence profiles for the priority questions for each of the three thematic areas relating to induction of labour. For the recommendation in this guideline, the priority question was: In pregnant women requiring induction of labour, does outpatient care, compared with inpatient care, improve maternal and perinatal outcomes? WHO convened a meeting on 21–22 October 2021 at which the Guideline Development Group (GDG) members reviewed, deliberated and achieved consensus on the strength and direction of the recommendation presented herein. Through a structured process, the GDG reviewed the balance between the desirable and undesirable effects and the overall certainty of the supporting evidence, values and preferences of stakeholders, resource requirements and cost-effectiveness, equity, acceptability and feasibility. Recommendations Following the review of the Evidence-to-Decision (EtD) framework, the GDG formulated the updated recommendation presented in the box below. To ensure that the recommendation is correctly understood and applied in practice, guideline users should refer to the remarks, which summarize the deliberations of the GDG and specify the conditions under which the recommendation is applicable, as well as to the summary of supporting evidence available in the EtD framework (Web Annex).2 In addition, implementation considerations are presented in the section following the recommendation in the full document. vii RECOMMENDATION 1. Routine outpatient induction of labour is not recommended for improving birth outcomes (low-certainty evidence). Remarks: • The evidence reviewed for this recommendation was derived from high-income country settings and defined the outpatient setting as the “home”, where home induction is defined as cervical ripening at home. Most commonly, after the induction agents have been administered in a hospital/health-care facility, the woman spends time at home before being admitted back to the facility once in labour. Inpatient inductions are defined as induction in health-care facilities (hospitals or birth centres, or midwife-led units), such that the woman remains there following induction while awaiting the start of labour. • The GDG noted that outpatient induction of labour might not be expected to improve birth outcomes. Low-certainty evidence in the systematic review found no difference in birth outcomes when comparing labour induction between inpatient and home settings. • The GDG noted that in some settings, women considered to be at low risk for complications during induction are offered outpatient induction of labour when they have good transportation options and live near the delivery facility. Considering the potential preference of pregnant women to return to their home setting following placement of a cervical ripening agent or initiation of induction, outpatient induction of labour may be undertaken where feasible, following shared decision-making between the provider and the woman. If outpatient induction of labour is considered, this should be in the context of a well organized programme, with adequate staff resources available to remotely monitor/assess and/or reassure women at home. Women should have suitable arrangements in place to return rapidly to the hospital/ facility if and when needed. Executive summary

1CHAPTER TITLE Introduction 2 WHO recommendations on outpatient settings for induction of labour 1.1 Background The World Health Organization (WHO) envisions a world where “every pregnant woman and newborn receives quality care throughout the pregnancy, childbirth and postnatal period” (1). High-quality maternal health care for women is a necessary step towards the achievement of the health targets agreed in the Sustainable Development Goals (SDGs) and the targets and indicators of WHO’s Thirteenth General Programme of Work, particularly those for achieving universal health coverage (2, 3). High-quality health care is essential for the prevention of morbidity and mortality in pregnancy and childbirth, and could reduce the profound inequities and inequalities in maternal and perinatal health globally (2, 4). Ensuring accessibility and acceptability of interventions to improve maternal health is consistent with international human rights laws, which include fundamental commitments of States to enable women and adolescent girls to survive pregnancy and childbirth as part of their enjoyment of sexual and reproductive health and rights, and living a life of dignity (4). To provide good-quality care and maximize maternal and perinatal outcomes, once a woman’s pregnancy has reached term gestation, health practitioners must balance the risks and benefits of continued gestation or induction of labour. Induction of labour is only recommended when there are clear indications that continuing with a pregnancy poses greater risk to the mother or baby than the risk of inducing labour (5). WHO general principles for performing labour induction state (5, 6): • Wherever induction of labour is carried out, facilities should be available for assessing maternal and fetal well-being; • Women receiving oxytocin, misoprostol or other prostaglandins should never be left unattended; and 3 Cervical ripening is also known as cervical priming or cervical preparation. • Wherever possible, induction of labour should be carried out in facilities where caesarean sections can be performed. Induction of labour usually takes place in a hospital, clinic or health-care facility setting using a range of interventions (7). In recent times, there has been increasing interest in outpatient induction of labour. Outpatient induction is defined as “induction at home, or more commonly, after the induction process has been started in a hospital/health-care facility the woman spends time at home” (8). As an outpatient setting, the home environment has been reported to offer women a more positive experience of labour induction, in terms of providing increased autonomy, compared with induction in the hospital (8). Women are either induced at home or more commonly attend the hospital, clinic or health-care facility to receive the cervical ripening/induction agent (8).3 Initial assessments of maternal and fetal well-being are conducted in the hospital, clinic or health-care facility and then the woman returns home. Once regular contractions commence, or at a given time point, the woman returns to the hospital for the birth. 1.2 Rationale and objectives WHO has established a new process for prioritizing and updating maternal and perinatal health (MPH) recommendations, whereby an international group of independent experts – the Executive Guideline Steering Group (GSG) – oversees a systematic prioritization of MPH recommendations in most urgent need of updating. Recommendations are prioritized for updating on the basis of changes or important new uncertainties in the underlying evidence base on the effects (benefits and harms), the values placed on outcomes, resource use and cost-effectiveness, equity, acceptability and feasibility, or the factors affecting implementation. In 2019, the Executive GSG for the WHO MPH recommendations prioritized updating the existing WHO recommendations on induction 3of labour at term or beyond (i.e. the timing of induction of labour), the use of mechanical methods for induction of labour, and the use of outpatient settings for induction of labour. This decision was based on new evidence on these subjects that had become available since the publication of the previous WHO recommendations in 2011 and 2018 (5, 6). These updated recommendations were developed in accordance with the standards and procedures in the WHO handbook for guideline development, including the synthesis of available research evidence; use of the Grading of Recommendations Assessment, Development and Evaluation (GRADE),4 application of the WHO-INTEGRATE framework; and formulation of recommendations by a Guideline Development Group (GDG) composed of international experts and stakeholders (9–12). The recommendation in this document, on outpatient settings for induction of labour, thus supersedes the previous 2011 WHO recommendations on this topic as new evidence on effectiveness became available (5).5 The primary aim of these recommendations is to improve the quality of care and outcomes for women whose pregnancies have reached term or gone beyond term. This document describes the evidence reviewed and the factors taken into consideration by the GDG to inform the updated recommendation on the use of outpatient settings for induction of labour. 1.3 Target audience The primary audience includes health professionals who are responsible for developing national and local health-care guidelines and protocols and health workers involved in the provision of care to women during labour and childbirth, including midwives, nurses, general medical practitioners and obstetricians. The primary audience also includes managers of maternal and child health programmes, 4 Further information is available at: http://www.gradeworkinggroup.org/. 5 The updated recommendations on induction of labour at term or beyond and on the use of mechanical methods for induction of labour are presented in separate publications, available at https://apps.who.int/iris/bitstream/handle/10665/363138/9789240052796-eng.pdf and https://apps.who.int/iris/bitstream/handle/10665/363140/9789240055780-eng.pdf, respectively. 6 Throughout this guideline, to be concise and to facilitate readability, the term “woman” is used to refer to pregnant women and others/ gender-diverse people who can get pregnant. While a majority of persons who are or can get pregnant are cisgender women, who were born and identify as female, transgender men and other gender-diverse people may have the reproductive capacity to become pregnant. and relevant staff in ministries of health and educational and training institutions, in all settings. These recommendations will also be of interest to pregnant women, as well as members of professional societies involved in the care of pregnant women, staff of nongovernmental organizations (NGOs) concerned with promoting people-centred maternal care and implementers of maternal and perinatal health programmes. 1.4 Scope of the recommendations The recommendation was framed using the population (P), intervention (I), comparator (C), outcome (O) (PICO) format. The priority question for this recommendation in PICO format was: In pregnant women requiring induction of labour (P), does outpatient care (I), compared with inpatient care (C), improve maternal and perinatal outcomes (O)? Problem: Perinatal risks associated with the setting for induction of labour Perspective: Clinical practice recommendation – population perspective Population: Pregnant women requiring induction of labour Intervention: Outpatient care Comparator: Inpatient care Outcomes: See Annex 2 Setting: Community settings/hospital settings 1.5 Persons affected by the recommendations The population affected by the recommendation includes all pregnant women.6 Introduction 4 WHO recommendations on outpatient settings for induction of labour 5CHAPTER TITLE Methods 6 WHO recommendations on outpatient settings for induction of labour The recommendations were developed using standardized operating procedures in accordance with the process described in the WHO handbook for guideline development, second edition (13). In summary, the process included: (i) identification of the priority question and critical outcomes; (ii) retrieval of evidence; (iii) assessment and synthesis of evidence; (iv) formulation of the recommendations; and (v) planning for the dissemination, implementation, impact evaluation and updating of the recommendations. Following the “living guideline” approach adopted by the WHO Maternal Perinatal Health (MPH) Unit, the full complement of recommendations and the evidence base underlying those recommendations are reviewed at regular intervals by the WHO MPH Executive Guideline Steering Group (GSG) (14). In 2019, the GSG identified the recommendation on the use of outpatient settings for induction of labour as high priority for updating. This decision was made in response to the availability of new evidence from women undergoing induction of labour in outpatient settings. Six main groups of experts and stakeholders were involved in this process, with their specific roles as described below. 2.1 Contributors to the guideline 2.1.1 Executive Guideline Steering Group (GSG) The Executive GSG is an independent panel of 14 external experts and relevant stakeholders from the six WHO regions: the African Region, the Region of the Americas, the Eastern Mediterranean Region, the European Region, the South-East Asia Region and the Western Pacific Region. The Executive GSG advises WHO on the prioritization of new and existing PICO questions in maternal and perinatal health for development or updating of recommendations. 2.1.2 WHO Steering Group The WHO Steering Group, comprising WHO staff members from the Department of Sexual and Reproductive Health and Research and the Department of Maternal, Newborn, Child and Adolescent Health and Ageing, managed the process of updating the recommendations. The WHO Steering Group drafted the key recommendation questions in PICO format, engaged the systematic review teams and guideline methodologists (i.e. the Evidence Synthesis Group [ESG]), as well as the members of the GDG and the External Review Group (ERG) (see below). In addition, the WHO Steering Group supervised the retrieval and syntheses of evidence, organized the GDG meetings, drafted and finalized the guideline document, and will also manage the guideline dissemination, implementation and impact assessment. The members of the WHO Steering Group are listed in Annex 1. 2.1.3 Guideline Development Group (GDG) The WHO Steering Group identified a pool of approximately 50 experts and stakeholders from the six WHO regions to constitute the WHO Maternal and Perinatal Health Guideline Development Group (MPH-GDG). This pool consists of a diverse group of experts who are skilled in the critical appraisal of research evidence; implementation of evidence- informed recommendations; guideline development methods; and clinical practice, policy and programmes relating to maternal and perinatal health; it also includes consumer representatives. The members of the MPH-GDG are identified in a way that ensures geographic representation and gender balance, and that there are no perceived or real conflicts of interest. The members’ expertise cuts across thematic areas within maternal and perinatal health. From the MPH-GDG pool, 16 external experts and relevant stakeholders were invited to 7Methods participate as members of the GDG for updating the recommendations on all three thematic areas for induction of labour (timing, mechanical methods, outpatient settings). Those selected from the MPH-GDG pool of experts were a diverse group with expertise in perinatal research; guideline development methods; gender, equity and rights; clinical practice, policy and programmes; and included consumer representatives relating to all three of the thematic areas. The GDG members were also selected in a manner that ensured geographic representation and gender balance and that there were no significant conflicts of interest. The GDG appraised the evidence that was used to inform the recommendations, advised on the interpretation of this evidence, formulated the final recommendations based on the draft prepared by the WHO Steering Group, and reviewed and reached a unanimous consensus on the recommendations in the final document. The members of the GDG are listed in Annex 1. 2.1.4 Evidence Synthesis Group (ESG) WHO convened an ESG composed of guideline methodologists and systematic review teams to conduct or update systematic reviews, appraise the evidence and develop the Evidence-to- Decision (EtD) frameworks. Systematic reviews on the effects of the interventions for each of the three thematic areas (timing, mechanical methods and outpatient settings for induction of labour) were updated, supported by the Cochrane Pregnancy and Childbirth Group. A literature review for qualitative evidence on the values, preferences, costs, feasibility and impact on equity was undertaken by Cochrane Australia.7 The WHO Steering Group reviewed and provided input into the reviews and worked closely with the review authors and the guideline methodologists to appraise the evidence. Evidence on effectiveness was appraised using the GRADE methodology. Representatives of the Cochrane Pregnancy and Childbirth Group and the guideline 7 Murano M, Chou D, Costa do Nascimento ML, Turner T. Using the WHO-INTEGRATE evidence to decision framework to develop induction of labour recommendations. Health Res Policy Syst. 2022 (in press). methodologists attended the GDG meeting to provide an overview of the available evidence and GRADE tables, and to respond to technical queries from the GDG members. Evidence on the qualitative aspects of the intervention was evaluated using the criteria of the WHO- INTEGRATE framework (12). The authors of the literature review on qualitative evidence attended the GDG meeting to provide an overview of the qualitative evidence and to respond to queries from the GDG. The members of the ESG are listed in Annex 1. 2.1.5 External partners and observers External partners and observers included representatives from the United States Agency for International Development (USAID), the International Confederation of Midwives (ICM) and the International Federation of Gynecology and Obstetrics (FIGO). These organizations, with their history of collaboration with WHO in the dissemination and implementation of maternal and perinatal health guidelines, were identified as potential implementers of the recommendations. The list of observers who participated in the GDG meetings is included in Annex 1. 2.1.6 External Review Group (ERG) The ERG included four technical experts with interests and expertise in the management of labour. The group was geographically diverse and gender balanced, and the members reported no significant conflicts of interest. The experts reviewed the final documents to identify any factual errors and commented on the clarity of language, contextual issues and implications for implementation. They ensured that the decision-making processes had considered and incorporated contextual values and the preferences of persons affected by the recommendations, health professionals, health practitioners and policy-makers. It was not within the remit of this group to change the recommendations that were formulated by the GDG. Members of the ERG are listed in Annex 1. 8 WHO recommendations on outpatient settings for induction of labour 2.2 Identification of priority questions and outcomes For the thematic area addressed in this guideline – the use of outpatient settings for induction of labour – the priority outcomes were aligned with those from the 2011 WHO recommendations for induction of labour (5). These outcomes were initially identified through a search of scientific databases for relevant, published systematic reviews and a prioritization of outcomes by the GDG for the guideline. In recognition of the importance of women’s experiences of care, two additional outcomes – maternal well-being and maternal satisfaction – were included in this update to ensure that evidence synthesis and recommendation decision-making by the GDG were driven by outcomes that are important to women and to ensure that the final set of recommendations would be woman-centred. All the outcomes were included in the scope of this document for evidence searching, retrieval, synthesis, grading and formulation of the recommendation. The list of priority outcomes is provided in Annex 2. 2.3 Evidence identification and retrieval Evidence to support this update was derived from several sources by the ESG working in collaboration with the WHO Steering Group. Evidence on the effects of this intervention is from a Cochrane systematic review updated in 2020 assessing outpatient versus inpatient induction of labour for improving birth outcomes (15). The update included three new trials, providing evidence from an additional 238 women. The evidence base now includes a total of seven randomized controlled trials (RCTs), six of which provide data on 1610 women and their babies, with one trial providing no usable data. The trials were conducted between 1998 and 2015, and all were in high- or upper-middle-income countries: Australia, Canada, Portugal and the United States of America. Most women in the trials were induced at term or beyond. 8 Murano M, Chou D, Costa do Nascimento ML, Turner T. Using the WHO-INTEGRATE evidence to decision framework to develop induction of labour recommendations. Health Res Policy Syst. 2022 (in press). Two studies used vaginal prostaglandin E2 (PGE2) induction, one study used controlled- release vaginal prostaglandin, and three studies used balloon or Foley catheters for induction. The interventions examined in all of the studies involved induction and initial monitoring in hospital, with subsequent discharge home to await the start of labour or for a fixed period of time for women in the home induction group. The comparators were all with induction, labour and birth in the hospital (15). This systematic review was the primary source of evidence of effectiveness for this recommendation. RCTs relevant to the key questions were screened by the review authors and data on their outcomes and comparisons were entered into Review Manager 5 (RevMan) software. The RevMan file was retrieved from the Cochrane Pregnancy and Childbirth Group and customized to reflect the key comparisons and outcomes (those that were not relevant to the recommendation were excluded). The RevMan file was then exported to GRADE profiler software (GRADEpro) and GRADE criteria were used to critically appraise the retrieved scientific evidence (9). Finally, evidence profiles (in the form of GRADE summary of findings tables) were prepared for comparisons of interest, including the assessment and judgements of each outcome and the estimated risks (see Web Annex). 2.3.1 Evidence on values, resource use and cost-effectiveness, equity, acceptability and feasibility Evidence on values, acceptability and feasibility were obtained by combining the findings of a qualitative evidence synthesis (QES) with additional primary papers.8 The systematic review provided information on women’s and providers’ perspectives and experiences relating to pregnancy and childbirth. The evidence on resource use and cost-effectiveness was very limited. As the review was based on a small number of primary studies involving trials conducted in high-income settings, the 9Methods conclusions should be viewed as extremely tentative. No direct evidence on equity was identified; therefore, the GDG based their decisions on the general findings of the 2015 WHO report on inequality (16). 2.4 Certainty assessment and grading of the evidence The GRADE approach (9–11) was used to assess the certainty of the evidence on effects. The certainty for each outcome was rated as “high”, “moderate”, “low” or “very low” based on a set of established criteria (see Box 2.1). The final rating was dependent on the factors briefly described below. BOX 2.1. Certainty of evidence assessments are defined according to the GRADE approach High certainty: We are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: We are moderately confident in the effect estimate. The true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: Our confidence in the effect estimate is limited. The true effect may be substantially different from the estimate of the effect. Very low certainty: We have very little confidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect. Study design limitations: The risk of bias was first examined at the level of each individual study and then across the studies contributing to each outcome. For RCTs, certainty was first rated as “high” and then downgraded by one (“moderate”) or two (“low”) levels, depending on the minimum criteria met by the majority of the studies contributing to each outcome. Inconsistency of the results: The consistency across the results for a given outcome was assessed by exploring the magnitude of differences in the direction and size of effects observed in different studies. The certainty of evidence was not downgraded when the directions of the findings were similar and confidence limits overlapped, whereas it was downgraded when the results were in different directions and confidence limits showed minimal or no overlap. Indirectness: The certainty of evidence was downgraded when there were serious or very serious concerns regarding the directness of the evidence – that is, whether there were important differences between the research reported and the context for which the recommendation was being prepared. Such differences were related, for instance, to populations, interventions, comparisons or outcomes of interest. Imprecision: Imprecision refers to the degree of uncertainty around the estimate of the effect. As this is often a function of sample size and number of events, studies with relatively few participants or events – and thus wide confidence intervals around effect estimates – were downgraded for imprecision. Publication bias: The certainty rating could also be affected by perceived or statistical evidence of bias to underestimate or overestimate the effect of an intervention as a result of selective publication based on study results. Downgrading evidence by one level was considered where there was strong suspicion of publication bias. The findings of the qualitative reviews (qualitative evidence) were appraised for eligibility and quality (rather than certainty) using a two- step process, informed by the Enhancing transparency in reporting the synthesis of qualitative research (ENTREQ) statement (17). As for certainty, quality was also rated as “high”, “moderate”, “low” or “very low”. Findings from individual cost-effectiveness studies were reported narratively for each comparison of interest (15, 18, 19). 10 WHO recommendations on outpatient settings for induction of labour 2.5 Formulation of the recommendations The WHO Steering Group supervised and finalized the preparation of GRADE Summary of Findings tables and narrative evidence summaries in collaboration with the ESG using the GRADE EtD framework (see Web Annex). EtD frameworks include explicit and systematic consideration of evidence on prioritized interventions in terms of specified domains: effects, values, resources, equity, acceptability and feasibility. For the priority questions, judgement was made on the impact of the intervention on each domain to inform and guide the decision-making process. Using the EtD framework template, the WHO Steering Group and ESG created summary documents for each priority question covering evidence on each domain, as follows. • Effects: The evidence on the priority outcomes was summarized in this domain to answer the questions: “What are the desirable and undesirable effects of the intervention?” and “What is the certainty of the evidence on effects?” Where desirable effects (benefits) clearly outweighed undesirable effects (harms) for outcomes that are highly valued by women, or vice versa, there was a greater likelihood of a clear judgement in favour of or against the intervention, respectively. Uncertainty about the net benefits or harms, or small net benefits, usually led to a judgement that did not favour the intervention or the comparator. The higher the certainty of the evidence of benefits across outcomes, the higher the likelihood of a judgement in favour of the intervention. In the absence of evidence of benefits, evidence of potential harm led to a recommendation against the intervention. Where the intervention showed evidence of potential harm and was also found to have evidence of important benefits, depending on the level of certainty and the likely impact of the harm, such evidence of potential harm was more likely to result in a context-specific recommendation, with the context explicitly stated within the recommendation. • Values: This domain relates to the relative importance assigned to the outcomes associated with the intervention by those affected, how such importance varies within and across settings, and whether this importance is surrounded by any uncertainty. The question asked was: “Is there important uncertainty or variability in how much women value the main outcomes associated with the intervention?” When the intervention resulted in benefits or outcomes that most women consistently value (regardless of setting), this was more likely to lead to a judgement in favour of the intervention. This domain, together with the “effects” domain (see above), informed the “balance of effects” judgement. • Resources: For this domain, the questions asked were: “What are the resources associated with the intervention?” and “Is the intervention cost-effective?” A judgement in favour of or against the intervention was likely where the resource implications were clearly advantageous or disadvantageous, respectively. • Equity: This domain encompasses evidence or considerations as to whether or not the intervention would reduce health inequities. Therefore, this domain addressed the question: “What is the anticipated impact of the intervention on equity?” The intervention was likely to be recommended if its proven (or anticipated) effects reduce (or could reduce) health inequities among different groups of women and their families. • Acceptability: For this domain, the questions were: “Is the intervention acceptable to women and health workers?” and “Is the intervention in accordance with universal human rights standards and principles?” The lower the acceptability, the lower the likelihood of a judgement in favour of the intervention. • Feasibility: The feasibility of implementing this intervention depends on factors such as the resources, infrastructure and training requirements, and the perceptions of health 11Methods workers responsible for administering it. The question addressed was: “Is it feasible for the relevant stakeholders to implement the intervention?” Where major barriers were identified, it was less likely that a judgement would be made in favour of the intervention. For each of the above domains, additional evidence of potential harms or unintended consequences are described in the EtD framework (see the Additional considerations subsections in the Web Annex). Such considerations were derived from studies that might not have directly addressed the priority question but provided pertinent information in the absence of direct evidence. These were extracted from single studies, systematic reviews or other relevant sources. The WHO Steering Group provided the EtD framework (including evidence summaries, GRADE Summary of Findings tables and other documents related to the recommendation) to GDG members two weeks in advance of the GDG meeting. The GDG members were asked to review and provide comments electronically on the documents before the virtual GDG meeting. During the GDG meeting on 21–22 October 2021, GDG members collectively reviewed the EtD framework and any comments received through preliminary feedback, and formulated the recommendations. The purpose of the meeting was to reach consensus on the recommendations and the specific context, based on explicit consideration of the range of evidence presented in the EtD framework and the judgement of the GDG members. The GDG members were collectively required to select one of the following categories for the recommendations. • Recommended: This category indicates that the intervention should be implemented. • Not recommended: This category indicates that the intervention should not be implemented. • Recommended only in specific contexts (“context-specific recommendation”): This category indicates that the intervention is applicable only to the condition, setting or population specified in the recommendation and should only be implemented in these contexts. • Recommended only in the context of rigorous research (“research-context recommendation”): This category indicates that there are important uncertainties about the intervention. With this category of recommendation, implementation can still be undertaken on a large scale, provided it takes the form of research that addresses unanswered questions and uncertainties related both to effectiveness of the intervention or option, and its acceptability and feasibility. 2.6 Management of declarations and conflicts of interests WHO has a robust process for management of conflicts of interests, which requires that experts serving in an advisory role disclose any circumstances that could give rise to actual or ostensible conflicts of interest (financial or non- financial). According to the WHO guidelines for declaration of interests (DOI), all experts must declare their interests prior to participation in WHO guideline development processes and meetings (20). All potential GDG members were therefore required to complete a standard WHO DOI form, which was reviewed by the WHO Steering Group before confirming the experts’ invitations to participate. Two GDG members declared interests (prior involvement in research support), and the WHO Steering Group subsequently applied the criteria as outlined in the WHO handbook for guideline development (13) and determined that these declared interests were not serious enough to affect their objective judgement in the process of developing the guideline and recommendations. These two experts were only required to openly declare such conflicts of interest at the beginning of the GDG meeting, and no further actions were taken. All findings from the DOI statements received were managed in accordance with the WHO procedures to ensure the work of WHO and the contribution of its experts is objective and independent. Annex 3 shows a summary of 12 WHO recommendations on outpatient settings for induction of labour the DOI statements and how conflicts of interest declared by invited experts were managed by the WHO Steering Group. 2.7 Decision-making during the GDG meetings During the meeting, the GDG reviewed and discussed the evidence summary and sought clarification as needed. In addition to evaluating the balance between the desirable and undesirable effects of the intervention and the overall certainty of the evidence, the GDG applied additional criteria based on the GRADE EtD framework to determine the direction and strength of the recommendation. These criteria included stakeholders’ values, resource implications, equity, acceptability and feasibility. Considerations were supported by evidence from a literature search where available, or were based on the experience and opinions of the GDG members. EtD tables were used to describe and synthesize these considerations (see Web Annex). Decisions were made based on consensus, defined as the agreement by three quarters or more of the participants. None of the GDG members expressed opposition to the recommendation. 2.8 Document review and preparation Prior to the online GDG meeting, the WHO Steering Group prepared a draft version of the GRADE evidence profiles, the evidence summary and other relevant documents, and made these available to the GDG members in advance, as described above. During the GDG meeting, these documents were modified in line with the participants’ deliberations and remarks. Following the meeting, members of the WHO Steering Group drafted a full guideline document to accurately reflect the deliberations and decisions of the participants. The draft document was sent electronically to the GDG for their final review and approval. Following review and approval by GDG members, the final document was sent for peer review to four external independent experts (comprising the ERG) who were not involved in the GDG. The ERG members were tasked with identifying any factual errors, any lack of clarity, contextual issues and implications for implementation, and were also asked to determine if the recommendations made were aligned with stakeholder interests. The WHO Steering Group evaluated the inputs of the peer reviewers and any modifications made by the WHO Steering Group to the document at that time consisted only of the correction of factual errors along with the editing process to improve language, style and address any lack of clarity. 13CHAPTER TITLE 3 Recommendations and supporting evidence 14 WHO recommendations on outpatient settings for induction of labour RECOMMENDATION 1. Routine outpatient induction of labour is not recommended for improving birth outcomes (low-certainty evidence). Remarks: • The evidence reviewed for this recommendation was derived from high-income country settings and defined the outpatient setting as the “home”, where home induction is defined as cervical ripening at home. Most commonly, after the induction agents have been administered in a hospital/health-care facility, the woman spends time at home before being admitted back to the facility once in labour. Inpatient inductions are defined as induction in health-care facilities (hospitals or birth centres, or midwife-led units), such that the woman remains there following induction while awaiting the start of labour. • The GDG noted that outpatient induction of labour might not be expected to improve birth outcomes. Low-certainty evidence in the systematic review indicated no difference in birth outcomes when comparing labour induction between inpatient and home settings. • The GDG noted that in some settings, women considered to be at low risk for complications during induction are offered outpatient induction of labour when they have good transportation options and live near the delivery facility. Considering the potential preference of pregnant women to return to their home setting following placement of a cervical ripening agent or initiation of induction, outpatient induction of labour may be undertaken where feasible, following shared decision-making between the provider and the woman. If outpatient induction of labour is considered, this should be in the context of a well organized programme, with adequate staff resources available to remotely monitor/assess and/or reassure women at home. Women should have suitable arrangements in place to return rapidly to the hospital/facility if and when needed. This section presents the updated recommendation on outpatient settings for induction of labour that was formulated by the GDG, followed by the corresponding narrative summary of the evidence. To ensure that the recommendation is correctly understood and appropriately implemented in practice, additional remarks reflecting the summary of the discussion by the GDG are included after the recommendation. 3.1 Summary of the evidence Effects (desirable and undesirable) The evidence on the effectiveness and safety of outpatient settings for induction of labour was derived from a Cochrane systematic review updated in 2020 (15). The review included three new trials, providing evidence from an additional 238 women, such that the evidence base now includes seven RCTs, six of which provide data on 1610 women and their babies, while one trial provided no usable data. The interventions examined in all of the studies involved induction and initial monitoring in hospital, with subsequent discharge home to await the start of labour or for a fixed period of time for women in the home induction group. The comparators were all with induction, labour and birth in the hospital. The evidence is summarized in GRADE tables presented as part of the EtD framework in the Web Annex. Values and preferences Considering the benefits and risks of outpatient induction of labour in a home setting, the GDG considers it unlikely that there would be important variability in how women value the outcomes of interest (see Annex 2). During induction of labour women value the ability to move about freely and to have privacy and a 15Recommendations and supporting evidence sense of security. This allows them to feel more in control and maintain their dignity. Feeling secure was enhanced by: having a support person present; systems that enabled this support to continue from induction to delivery; and having rapid access to the clinical expertise and equipment that might be needed. Resource use and costs The resources required to implement the routine induction of labour are primarily the costs of training skilled health personnel. Evidence for resource use and costs is very limited; information from one trial-based primary study and data from a study included within the systematic review on effectiveness was available. Together, they described aspects of cost, resource usage, budget impact and value for money, when considering induction of labour (15, 18, 19). Equity The equity domain was discussed at length by the GDG members as they formulated this recommendation. It is likely that women from low- and middle-income settings, or from 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.9 Acceptability The evidence for acceptability of methods for induction of labour was derived from a synthesis of a published QES and additional primary studies (21–28). When there is a recognized need to avert harm to the baby, labour induction is widely acceptable to women. 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. The QES authors found that “outpatient labour induction is not preferable for all women, and individuals 9 Murano M, Chou D, Costa do Nascimento ML, Turner T. Using the WHO-INTEGRATE evidence to decision framework to develop induction of labour recommendations. Health Res Policy Syst. 2022 (in press). will have preferences about what constitutes a comfortable and safe environment for labour” (21–28).9 There is limited evidence available on the acceptability of labour induction to clinicians. Health practitioners report 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 (29). Feasibility The feasibility of implementing these recommendations was considered by the GDG. WHO general principles for performing labour induction state (5, 6): • Wherever induction of labour is carried out, facilities should be available for assessing maternal and fetal well-being. • Women receiving oxytocin, misoprostol or other prostaglandins should never be left unattended. • Wherever possible, induction of labour should be carried out in facilities where caesarean sections can be performed. 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, medical equipment and appropriate facilities may be an issue in some settings. The GDG considered outpatient induction of labour in this context. Note: The EtD table – which summarizes the balance between the desirable and undesirable effects and the overall certainty of the supporting evidence, values and preferences of stakeholders, resource requirements, cost-effectiveness, equity, acceptability and feasibility that were considered by the GDG in determining the strength and direction of the recommendation – is presented in the EtD framework (Web Annex). 16 WHO recommendations on outpatient settings for induction of labour 17CHAPTER TITLE 4 Dissemination, adaptation and implementation of the recommendation 18 WHO recommendations on outpatient settings for induction of labour The dissemination and implementation of this recommendation are to be considered by all stakeholders involved in the provision of care for pregnant women at the international, national and local levels. There is a vital need to increase women’s access to maternal health care at the community level and to strengthen the capacity at all levels of health-care facilities to ensure they can provide high-quality services and information to all women giving birth. It is therefore crucial that this recommendation be translated into care packages and programmes at country, health-care facility and community levels, where appropriate. 4.1 Dissemination The recommendation will be disseminated through WHO regional and country offices, WHO advisory groups, ministries of health, country and regional technical advisory groups, professional organizations, WHO collaborating centres, other United Nations agencies and NGOs, among others. This recommendation will also be available on the WHO website. Updated recommendations are also routinely disseminated during meetings or scientific conferences attended by WHO staff. This document will be translated into the six United Nations languages and disseminated through the WHO regional offices. Technical assistance will be provided to any WHO regional office willing to translate the full guideline into any of these languages. 4.2 Adaptation National and subnational subgroups may be established to adapt and implement this recommendation based on an existing strategy. This process may include the development or revision of existing national guidelines or protocols based on the updated recommendation. The successful introduction of evidence- based policies (relating to the updated recommendation) depends on well planned and participatory consensus-driven processes of adaptation and implementation. These processes may include the development or revision of existing national or local guidelines and protocols, often supported by ministries of health, United Nations agencies, local professional societies and other relevant leadership groups. An enabling environment should be created for the use of this recommendation, including changes in the behaviour of health practitioners to enable the use of evidence-based practices. In the context of humanitarian emergencies, the adaptation of recommendations should consider integration and alignment with other response strategies. Additional considerations about the unique needs of women in emergency settings, including their values and preferences, should be taken into account. Context-specific tools and toolkits may be required in addition to standard tools to support the implementation of this updated recommendation by stakeholders in the context of humanitarian emergencies. 4.3 Implementation considerations The successful introduction of this recommendation into national programmes and health services depends on well planned and participatory consensus-driven processes of adaptation and implementation. The adaptation and implementation processes may include the development or revision of existing national guidelines or protocols. Recommendations should be adapted into documents and tools that are appropriate for different locations and contexts, to meet the specific needs of each country and health service. Modifications to the recommendation, where necessary, should be justified in an explicit and transparent manner. An enabling environment should be created for the implementation of this recommendation, including education to support behaviour change among skilled health personnel providing care during childbirth (30), to facilitate the use of evidence-based practices. To implement this recommendation, the following should be considered. 19Dissemination, adaptation and implementation of the recommendation • To ensure accurate assessment of gestational age prior to induction, clear policies concerning the provision of early ultrasounds are required. Health workers in antenatal care (ANC) settings require training and supportive supervision on how to perform dating ultrasounds • Health professionals will require training to counsel women on the benefits and side- effects of different methods for induction of labour. Women should be adequately counselled and engaged in shared decision- making when considering the indications for induction of labour and the methods for induction. • Health worker shortages in low- and middle- income country settings may mean that staff are required to attend to much higher numbers of women on the labour ward than in other settings. Providing the necessary level of support, assessment and monitoring in these settings may be challenging and the impact may be reduced capacity among health workers to monitor as frequently as needed or to respond quickly to emergencies (31). • A higher number of induction deliveries are attended by medical doctors than non- induction deliveries (32). This has implications for the distribution and productivity of medical doctors, particularly in under- resourced settings. • Performing induction of labour safely requires availability of appropriate medicines and/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. In order to ensure that implementation of labour induction does not reinforce existing inequities or inequalities, the system should support all women (i) to have access to full and timely information; (ii) to use their own social networks to assist them to understand the information if needed; and (iii) to ensure a woman’s health- care provider is aware of her needs, values and preferences (31). 20 WHO recommendations on outpatient settings for induction of labour 21CHAPTER TITLE 5 Research priorities 22 WHO recommendations on outpatient settings for induction of labour The GDG noted the following evidence gaps. • It is uncertain for which women, and in which high-income versus low- and middle-income countries outpatient induction of labour could be recommended. Large, randomized studies are needed to assess safety and women’s views (when comparing outpatient with inpatient induction of labour). If safety is equivalent, the best method (Foley or low- dose misoprostol) could be evaluated. • In comparing the different settings (outpatient versus inpatient), the GDG noted that the evidence reviewed reported outcomes for women who initiated the induction process in a hospital or health-care facility, and then returned home. Outpatient settings should be differentiated – that is, home (unsupervised), or maternity waiting homes/non-home environments (semi-supervised) – as should the different phases of cervical ripening and induction. The GDG acknowledges that there is planned or ongoing research relevant to some of the identified research priorities. Since there is no certainty that the planned or ongoing research will give conclusive results, the research topics below were identified as research priorities. Potential PICO questions are suggested below. Problem: Perinatal risks associated with the setting for induction of labour Perspective: Clinical practice recommendation – population perspective PICO question: In pregnant women requiring induction of labour (P), does initiating induction in a health-care setting and then returning home to await labour (unsupervised outpatient induction) (I), compared with initiating induction in a hospital or health-care facility and remaining there (C), improve maternal and perinatal outcomes (O)? (Settings: hospital/ community [home settings]; see Annex 2 for outcomes.) PICO question: In pregnant women requiring induction of labour (P), does initiating induction in a health-care setting and then continuing induction in an outpatient setting such as a maternity waiting home (semi-supervised in a non-home environment) (I), compared with initiating induction in a hospital or health- care facility and remaining there (C), improve maternal and perinatal outcomes (O)? (Settings: community [non-home environment]; see Annex 2 for outcomes.) PICO question: In pregnant women requiring induction of labour (P), does induction with a provider-inserted/placed method (I), compared with induction with a self-administered method (C), improve maternal and perinatal outcomes (O)? (Settings: hospital/community; see Annex 2 for outcomes.) 23CHAPTER TITLE 6 Applicability issues 24 WHO recommendations on outpatient settings for induction of labour 6.1 Anticipated impact on the organization of care and resources Implementing this evidence-based recommendation requires health workers to identify and provide counselling to those women with pregnancies that have reached or gone beyond term. Health worker shortages may also reduce the feasibility of performing ANC ultrasound scans and other risk assessments (16, 31). The GDG noted that updating training curricula and providing training on accurate gestational age assessment would increase the impact and facilitate implementation of the recommendation. A number of factors may hinder the effective implementation and scale-up of this recommendation. These factors may be related to the behaviours of patients (women or families) or health professionals, and to the organization of care or health-service delivery. As part of efforts to implement this recommendation, health system stakeholders should consider the need to ensure (33, 34): • one scan before 24 weeks of gestation for accurate estimation of gestational age; • post-term pregnancy risk assessment; and • schedule planning that allows for adequate time to provide information and counselling in ANC clinics. 6.2 Monitoring and evaluating guideline implementation The implementation and impact of this recommendation will be monitored at the health service, country and regional levels, as part of broader efforts to monitor and improve the quality of maternal and newborn care. The WHO document Standards for improving quality of maternal and newborn care in health facilities (35) provides a list of prioritized input, output and outcome measures that can be used to define quality-of-care criteria and indicators, and that should be aligned with locally agreed targets. In collaboration with the monitoring and evaluation teams of the WHO Department of Sexual and Reproductive Health and Research and the WHO Department of Maternal, Newborn, Child and Adolescent Health and Ageing, data on country- and regional-level implementation of the recommendation can be collected and evaluated in the short-to-medium term to assess its impact on national policies of individual WHO Member States. Information on recommended indicators can also be obtained at the local level by interrupted time series or clinical audits. In this context, the GDG suggests the following indicators be considered. • The proportion of pregnant women who have an ultrasound prior to 24 weeks of gestation. • The proportion of pregnant women who have a documented indication for undergoing induction of labour. 25CHAPTER TITLE 7 Updating the recommendations 26 WHO recommendations on outpatient settings for induction of labour The Executive GSG convenes annually to review WHO’s current portfolio of maternal and perinatal health recommendations and to help WHO prioritize new and existing questions for recommendation development and updating. Accordingly, this recommendation will be reviewed along with other recommendations for prioritization by the Executive GSG. If new evidence that could potentially impact the current evidence base is identified, the recommendation may be updated. If no new reports or information are identified, the recommendation may be revalidated. Following publication and dissemination of the updated recommendation, any concerns about the validity of the recommendation will be promptly communicated to the guideline implementers, along with information about plans to update the recommendation. WHO welcomes suggestions regarding additional questions for future inclusion in the process of updating the recommendation. Please email your suggestions to srhmph@who.int. 27 References 1. Tunçalp Ö, Were WM, MacLennan C, Oladapo OT, Gülmezoglu AM, 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. 2. The 17 Goals. In: United Nations Department of Economic and Social Affairs [website]. New York (NY): UN DESA (https://sdgs.un.org/goals, accessed 28 April 2022). 3. Thirteenth general programme of work, 2019–2023: promote health, keep the world safe, serve the vulnerable. 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Definition of skilled health personnel providing care during childbirth. The 2018 joint statement by WHO, UNFPA, UNICEF, ICM, ICN, FIGO, IPA. Geneva: World Health Organization; 2018 (https://apps. who.int/iris/handle/10665/272818). 31. 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. 32. 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. 33. WHO recommendations on antenatal care for a positive pregnancy experience. Maternal and fetal assessment update: imaging ultrasound before 24 weeks of pregnancy. Geneva: World Health Organization; 2022 (https://apps.who.int/ iris/handle/10665/352620). 34. WHO recommendations on antenatal care for a positive pregnancy experience. 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Contributors to the guideline development process Guideline Development Group (GDG) Edgardo Abalos Vice Director Centro Rosarino de Estudios Perinatales Santa Fe, Argentina Niveen Abu Rmeileh Professor of Epidemiology and Public Health Birzeit University Birzeit, Occupied Palestinian Territory Ebunoluwa Adejuyigbe Professor of Pediatrics Obafemi Awolowo University Osun, Nigeria Melania de Amorim Professor of Obstetrics and Gynecology Instituto de Medicina Integral Instituto Paraibano de Pesquisa Professor Joaquim Amorim Neto Figueira, Brazil Shabina Ariff Associate Professor of Paediatrics and Child Health Department of Pediatrics & Child Health Aga Khan University Karachi, Pakistan Michel Boulvain Group leader and Professor of Gynecology and Obstetrics University of Geneva Geneva, Switzerland Maria Laura Costa Associate Professor of Gynecology and Obstetrics State University of Campinas Campinas, Brazil Christine East Professor of Nursing and Midwifery College of Science Health and Engineering La Trobe University Bundoora, Australia Lynn Freedman Professor of Population and Family Health Mailman School of Public Health Columbia University Director, Averting Maternal Death and Disability Program (AMDD) New York, United States of America (USA) Justus Hofmeyr Professor of Obstetrics and Gynaecology University of Botswana Gaborone, Botswana Pisake Lumbiganon Professor of Obstetrics and Gynecology Faculty of Medicine Khon Kaen University Khon Kaen, Thailand Jiji Mathews Head of Obstetrics and Gynaecology Christian Medical College Vellore, India Rose Mukisa Executive Director White Ribbon Alliance Kampala, Uganda Jim Neilson Emeritus Professor Former Coordinating Editor Cochrane Pregnancy and Childbirth Group University of Liverpool Liverpool, United Kingdom of Great Britain and Northern Ireland Hiromi Obara Deputy Director Division of Global Health Policy and Research Department of Health Planning and Management Bureau of International Health Cooperation National Center for Global Health and Medicine Tokyo, Japan Andrew Weeks Professor of International Maternal Health Sanyu Research Unit University of Liverpool Liverpool, United Kingdom 33Annex 1 Partner organizations/observers Deborah Armbruster Senior Maternal and Newborn Health Advisor United States Agency for International Development (USAID), Bureau for Global Health Washington, DC, USA Lia Brigante (representing ICM) Consultant Midwife in Public Health Development Post Guy’s and St Thomas’ NHS Foundation Trust London, United Kingdom Daniela Drandić Reproductive Rights Program Lead Human rights advocacy specialist Human Rights in Childbirth RODA – Parents in Action Bale-Valle, Croatia Emma Clark Senior Maternal Health Advisor Maternal Child Health and Nutrition USAID Bureau for Global Health Washington, DC, USA Robyn Churchill Maternal Health Team Lead Maternal Child Health and Nutrition USAID Bureau for Global Health Washington, DC, USA Bill Grobman (representing FIGO) Vice Chair, Clinical Operations Maternal Fetal Medicine Department of Obstetrics and Gynecology Leadership Ohio State University Columbus, USA Evidence Synthesis Group (ESG) Leanne Jones Deputy Managing Editor Cochrane Pregnancy and Childbirth Department of Women’s and Children’s Health University of Liverpool Liverpool, United Kingdom Frances Kellie Managing Editor Cochrane Pregnancy and Childbirth Department of Women’s and Children’s Health University of Liverpool Liverpool Women’s NHS Foundation Trust Liverpool, United Kingdom Melissa Murano Senior Research Officer Cochrane Australia Monash University Clayton, Australia Tari Turner Associate Professor Cochrane Australia Monash University Clayton, Australia External Review Group (ERG) Guilherme Ceccati Professor of Obstetrics State University of Campinas Campinas, Brazil Caroline Homer Professor and Co-Program Director of Maternal Child and Adolescent Health Burnet Institute Melbourne, Australia Jack Moodley Emeritus Professor University of KwaZulu-Natal Women’s Health and HIV Research Unit Durban, South Africa Jeeva Sankar Assistant Professor of Pediatrics All India Institute of Medical Sciences New Delhi, India 34 WHO recommendations on outpatient settings for induction of labour WHO country and regional offices Bremen de Mucio Advisor, Sexual and Reproductive Health Latin American Center of Perinatology Women and Reproductive Health WHO Regional Office for the Americas Montevideo, Uruguay Adrian Pablo Duran Advisor, Perinatal Health Latin American Center of Perinatology Women and Reproductive Health WHO Regional Office for the Americas Montevideo, Uruguay Karima Gholbzouri Regional Adviser, Reproductive and Maternal Health WHO Regional Office for the Eastern Mediterranean Cairo, Egypt Chandani Anoma Jayathilaka Advisor, Sexual and Reproductive Health, Maternal and Reproductive Health WHO Regional Office for South-East Asia New Delhi, India Nancy Kidula Medical Officer, Reproductive, Maternal, Newborn, Child and Adolescent Health WHO Uganda Country Office Kampala, Uganda Oleg Kuzmenko Advisor, Sexual and Reproductive Health Noncommunicable Diseases and the Life-course WHO Regional Office for Europe Copenhagen, Denmark Neena Raina Coordinator, Family Health, Gender and Life Course WHO Regional Office for South-East Asia New Delhi, India Howard Sobel Coordinator, Reproductive, Maternal, Newborn, Child and Adolescent Health Division of Noncommunicable Diseases and Health through the Life-course WHO Regional Office for the Western Pacific Manila, Philippines WHO Steering Group, WHO headquarters, Geneva, Switzerland Department of Sexual and Reproductive Health and Research (SRH) Maternal and Perinatal Health Unit Olufemi Oladapo Unit Head Mercedes Bonet Semenas Medical Officer Doris Chou Medical Officer Tina Lavin Technical Officer Jen Ransom Consultant Joshua Vogel Consultant Department of Maternal, Newborn, Child and Adolescent Health and Ageing (MCA) Maurice Bucagu Medical Officer Anayda Gerarda Portela Technical Officer Frances Emma McConville Technical Officer 35 Annex 2. Priority outcomes used in decision-making 10 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. Priority outcomes (O): Critical outcomes:10 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. 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. 36 WHO recommendations on outpatient settings for induction of labour Annex 3. Summary and management of declared interests from GDG members and reviewers Name Expertise contributed to guideline development process Declared interest Management of conflict of interest Edgardo Abalos Content expert and end-user None Not applicable Niveen Abu Rmeileh Content expert and end-user None Not applicable Ebunoluwa Adejuyigbe Content expert and end-user None Not applicable Melania de Amorim Content expert and end-user None Not applicable Shabina Ariff Content expert and end-user None Not applicable Michel Boulvain Content expert and end-user None Not applicable Maria Laura Costa Content expert and end-user None Not applicable Christine East Content expert and end-user Research support, including grants, collaborations, sponsorships, and other funding The conflict was not considered serious enough to affect GDG membership or participation in the technical consultation. The conflicts were disclosed prior to discussion. Lynn Freedman Content expert and end-user None Not applicable Justus Hofmeyer Content expert and end-user None Not applicable Pisake Lumbiganon Content expert and end-user None Not applicable Jiji Mathews Content expert and end-user None Not applicable Rose Mukisa Content expert and end-user None Not applicable Jim Neilson Content expert and end-user None Not applicable Hiromi Obara Content expert and end-user None Not applicable Andrew Weeks Content expert and end-user Research support and consulting, including service as a technical or other advisor The conflict was not considered serious enough to affect GDG membership or participation in the technical consultation. The conflicts were disclosed prior to discussion. Leanne Jones Content expert and methodologist None Not applicable Frances Kellie Content expert and methodologist None Not applicable Melissa Murano Content expert and methodologist None Not applicable Tari Turner Content expert and methodologist None Not applicable Jen Ransom Content expert and methodologist None Not applicable Guilherme Ceccati External reviewer None Not applicable Caroline Homer External reviewer None Not applicable Jack Moodley External reviewer None Not applicable Jeeva Sankar External reviewer None Not applicable

38 WHO recommendations on outpatient settings 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 005581 0