WHO recommendations: induction of labour at or beyond term

WHO recommendations: Induction of labour at or beyond term WHO recommendations: Induction of labour at or beyond term WHO recommendations: induction of labour at or beyond term ISBN 978-92-4-155041-3 © World Health Organization 2018 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 appropri- ately cited, as indicated below. In any use of this work, there should be no suggestion that WHO endorses any specific organization, products or services. The use of the WHO logo is not permitted. If you adapt the work, then you must license your work under the same or equivalent Creative Commons licence. 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The mention of specific companies or of certain manufacturers’ products does not imply that they are endorsed or recommended by WHO in pref- erence 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. TABLE OF CONTENTS Acknowledgements 2 Abbreviations 3 Executive summary 4 1. Background 6 Induction of labour 6 Rationale and objectives 7 Target audience 7 Scope of the recommendations 7 Persons affected by the recommendations 7 2. Methods 8 Contributors to the guideline 8 Identification of critical outcomes 9 Evidence identification and retrieval 9 Certainty assessment and grading of the evidence 10 Formulation of recommendations 10 Declaration of interests by external contributors 11 Decision-making during the Guideline Development Group meeting 11 Document preparation 11 Peer review 12 3. Recommendations and supporting evidence 12 4. Dissemination and implementation of the recommendations 13 Recommendation dissemination and evaluation 13 Implementation considerations 13 5. Research implications 14 6. Applicability issues 14 Monitoring and evaluating guideline implementation 14 7. Updating the recommendations 15 References 16 Annex 1. External experts and WHO staff involved in the preparation of the guidelines 18 Annex 2. Priority outcomes for decision-making 22 Annex 3. Summary and management of declared interests from GDG members 23 Annex 4. Evidence to decision framework 24 Annex 5. GRADE Tables 35 ACKNOWLEDGEMENTS The Department of Reproductive Health and Research of the World Health Organization gratefully acknowledges the contributions of many individuals and organizations to the updating of these recommendations. Work on this update was coordinated by Olufemi Ola- dapo, Joshua Vogel and A. Metin Gülmezoglu of the WHO Department of Reproductive Health and Research. WHO extends its sincere thanks to Edgardo Abalos, Ebun Adejuyigbe, Shabina Ariff, Jemi- ma Dennis-Antwi, Luz Maria De-Regil, Christine East, Lynn Freedman, Pisake Lumbiganon, Anita Maepioh, James Neilson, Hiromi Obara, Rachel Plachcinski, Zahida Qureshi, Kathleen Rasmussen, Niveen Abu Rmeileh and Eleni Tsigas who served as members of the Guide- line Development Group (GDG), and to Zahida Qureshi (Chair) and Jim Neilson (Vice-Chair) for leading the meeting. We also thank José Guilherme Cecatti, Sylvia Deganus, M Jeeva Sankar, Hayfaa Wahabi, Jack Moodley, Jane Sandall, Ola Shaker and Nguyen Xuan Hoi who were members of the External Review Group. WHO also gratefully acknowledges the contri- bution of the members of the Executive Guide- line Steering Group. Anna Cuthbert, Leanne Jones, Frances Kellie and Myfanwy Williams reviewed the scientific evidence, prepared the Grading of Recom- mendations, Assessment, Development, and Evaluation (GRADE) tables and drafted the narrative summary of evidence. Joshua Vogel and Olufemi Oladapo revised the narrative summaries and double-checked the cor- responding GRADE tables and prepared the Evidence-to-Decision frameworks. Joshua Vogel, Olufemi Oladapo, A. Metin Gülmezoglu, Ana Pilar Betrán, Özge Tunçalp and Mercedes Bonet commented on the draft document before it was reviewed by participants at the WHO Guideline Development Group meeting. The External Review Group peer reviewed the final document. We acknowledge the various organizations that were represented by observers, including Deborah Armbruster and Mary-Ellen Stanton (United States Agency for International Develop- ment), Kathleen Hill (Maternal and Child Survival Program/Jhpiego), Jerker Liljestrand (Bill & Melinda Gates Foundation), Lesley Page (Inter- national Confederation of Midwives), Gerard Visser (International Federation of Gynaecology and Obstetrics) and Charlotte Warren (Ending Eclampsia Project, Population Council). We also appreciate the contributions of WHO Regional Office staff – Nino Berdzuli, Bremen De Mucio, Chandani Anoma Jayathilaka, Ramez Khairi Mahaini, Léopold Ouedraogo and Howard Sobel. The United States Agency for International Development and the Department of Reproduc- tive Health and Research provided financial support for this work. The views of the funding bodies have not influenced the content of these recommendations. 2 WHO recommendations: induction of labour at or beyond term 3WHO recommendations: induction of labour at or beyond term BMGF Bill & Melinda Gates Foundation CI Confidence interval CS Caesarean section DOI Declaration of Interest FIGO International Federation of Gynaecology and Obstetrics FWC Family, Women’s and Children’s Health (a WHO cluster) GDG Guideline Development Group GRC Guideline Review Committee GRADE Grading of Recommendations, Assessment, Development, and Evaluation GREAT Guideline development, Research priorities, Evidence synthesis, Applicability of evidence, Transfer of knowledge (a WHO project) GSG Executive Guideline Steering Group HIC High-income country ICM International Confederation of Midwives IOL Induction of labour LMIC Low and middle-income country MCA [WHO Department of] Maternal, Newborn, Child and Adolescent Health MCSP Maternal and Child Survival Programme MPA Maternal and Perinatal Health and Preventing Unsafe Abortion (a team in WHO’s Department of Reproductive Health and Research) MPH Maternal and perinatal health NNT Number needed to treat PICO Population (P), intervention (I), comparison (C), outcome (O) RHR [WHO Department of] Reproductive Health and Research RR Relative risk SDG Sustainable Development Goals UN United Nations UNFPA United Nations Population Fund USAID United States Agency for International Development WHO World Health Organization ABBREVIATIONS EXECUTIVE SUMMARY Introduction Induction of labour is defined as the process of artificially stimulating the uterus to start labour. It is usually performed by administering oxytocin or prostaglandins to the pregnant woman or by manually rupturing the amniotic membranes. Induction of labour is not risk- free, and many women find it uncomfortable. Over the past several decades, the incidence of inducing labour for shortening the duration of pregnancy has continued to rise. In high- income countries, the proportion of infants delivered at term following induction of labour can be as high as one in four births. In low- and middle-income countries the rates are generally lower, but in some settings, they can be as high as those observed in high-income countries. Improving care for women around the time of childbirth is a necessary step towards the achievement of the health targets of the Sustainable Development Goals (SDGs). Efforts to prevent and reduce morbidity and mortality during pregnancy and childbirth could help address the profound inequities in maternal and perinatal health globally. To achieve these aims, healthcare providers, health managers, policy makers and other stakeholders need up-to- date and evidence-based recommendations to inform clinical policies and practices. In 2017, the Executive Guideline Steering Group (GSG) on the World Health Organization’s (WHO) maternal and perinatal health recommendations prioritized the updating of the existing WHO recommendations on the induction of labour at or beyond term in response to important new evidence on this intervention. These recommendations are a revalidation of the previous recommendations issued in 2011 in the WHO recommendations on induction of labour. Target audience The primary audience of these recommendations includes health professionals who are responsible for developing national and local health protocols (particularly those related to induction of labour) and those directly providing care to pregnant women and their newborns, including: midwives, nurses, general medical practitioners, obstetricians, managers of maternal and child health programmes, and relevant staff in ministries of health, in all settings. Guideline development methods The updating of these recommendations was guided by standardized operating procedures in accordance with the process described in the WHO handbook for guideline development. The recommendations were initially developed using this process, namely: (i) identification of the priority question and critical outcomes; (ii) retrieval of evidence; (iii) assessment and synthesis of evidence; (iv) formulation of the recommendation; and (v) planning for the dissemination, implementation, impact evaluation and updating of the recommendations. The scientific evidence supporting the recom- mendations was synthesized using the Grading of Recommendations, Assessment, Develop- ment, and Evaluation (GRADE) approach. This systematic review was used to prepare evi- dence profiles for the prioritized question. WHO convened an online meeting on 2 May 2018 where an international group of experts – the Guideline Development Group (GDG) – reviewed and approved the recommendations. 4 WHO recommendations: induction of labour at or beyond term 5WHO recommendations: induction of labour at or beyond term The recommendations The GDG reviewed the balance between the desirable and undesirable effects and the over- all certainty of supporting evidence, values and preferences of stakeholders, resource require- ments and cost- effectiveness, acceptability, feasibility and equity. The GDG revalidated the WHO recommendations published in 2011 with minor revisions to the remarks and implementa- tion considerations. To ensure that the recommendations are cor- rectly understood and applied in practice, guideline users should refer to the remarks, as well as to the evidence summary if there is any doubt as to the basis for the recommendations and how best to implement them. Table 1: WHO recommendations on the induction of labour at or beyond term 1. Induction of labour is recommended for women who are known with certainty to have reached 41 weeks (>40 weeks + 7 days) of gestation. (conditional recommendation, low-certainty evidence) Remarks • This recommendation does not apply to settings where the gestational age cannot be reli- ably estimated. • The potential need for induction of labour for women with a post-term pregnancy should be discussed with women in advance, so that they have an opportunity to ask questions and understand the benefits and possible risks. 2. Induction of labour is not recommended for women with an uncomplicated pregnancy at gestational age less than 41 weeks. (conditional recommendation, low-certainty evidence) Remarks • There is insufficient evidence to recommend induction of labour for women with uncompli- cated pregnancies before 41 weeks of pregnancy. 6 WHO recommendations: induction of labour at or beyond term 1. BACKGROUND An estimated 303 000 women and adoles- cent girls died as a result of pregnancy and childbirth-related complications in 2015, around 99% of which occurred in low-resource settings (1). Haemorrhage, hypertensive disorders and sepsis are responsible for more than half of all maternal deaths worldwide. Thus, improving the quality of maternal healthcare for women is a necessary step towards achievement of the health targets of the Sustainable Development Goals (SDGs). International human rights law includes fundamental commitments by states to enable women and adolescent girls to survive pregnancy and childbirth as part of their enjoy- ment of sexual and reproductive health and rights and living a life of dignity (2). The World Health Organization (WHO) envisions a world where “every pregnant woman and newborn receives quality care throughout the pregnancy, childbirth and the postnatal period” (3). There is evidence that effective interventions exist at reasonable cost for the prevention or treatment of virtually all life-threatening mater- nal complications (4). Almost two-thirds of the global maternal and neonatal disease burden could be alleviated through optimal adapta- tion and uptake of existing research findings (5). To provide good quality care, healthcare providers at all levels of maternal healthcare services (particularly in low- and middle-income countries) need to have access to appropriate medications and training in relevant proce- dures. Healthcare providers, health managers, policymakers and other stakeholders also need up-to-date, evidence-based recommendations to inform clinical policies and practices, in order to optimize quality of care, and enable improved healthcare outcomes. Efforts to prevent and reduce morbidity and mortality in pregnancy and childbirth could reduce the profound ineq- uities in maternal and perinatal health globally. Induction of labour Induction of labour is the process of artificially stimulating the uterus to start labour (6). It is usually performed by administering oxytocin or prostaglandins to the pregnant woman, or by artificially rupturing the amniotic membranes. Induction of labour is not risk-free, and many women find it uncomfortable. Over the past several decades, the incidence of labour induction for shortening the dura- tion of pregnancy has continued to rise. In high-income countries (HICs), the proportion of infants delivered at term following induction of labour can be as high as one in four births (7-9). In low- and middle- income countries (LMICs), the rates are generally lower, but in some set- tings, they can be as high as those observed in HICs (10, 11). In 2011, the World Health Organization (WHO) published 17 recommendations on induction of labour, including two recommendations on the induction of labour at or beyond term (12). These recommendations were developed according to the WHO guideline development standards, including synthesis of available research evidence, use of the GRADE method- ology and formulation of recommendations by a guideline panel of international experts. The 2011 recommendations also included several general principles related to the practice of induction of labour, which are reiterated here: • Induction of labour should be performed only when there is a clear medical indication for it and the expected benefits outweigh its potential harms; • In applying the recommendations on induc- tion of labour, consideration must be given to the actual condition, wishes and preferences of each woman, with emphasis being placed on cervical status, the specific method of 7WHO recommendations: induction of labour at or beyond term induction of labour and associated conditions such as parity and rupture of membranes; • Induction of labour should be performed with caution since the procedure carries the risk of uterine hyperstimulation and rupture, and fetal distress; • 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; • Failed induction of labour does not necessarily indicate caesarean section; and • Wherever possible, induction of labour should be carried out in facilities where caesarean sections can be performed. Rationale and objectives In 2017, WHO established a new process for prioritizing and updating maternal and perinatal health recommendations whereby an Executive Guideline Steering Group (GSG) oversaw a sys- tematic prioritization of maternal and perinatal health recommendations in most urgent need of updating (13). Recommendations were prior- itized on the basis of changes or important, new uncertainties in the underlying evidence base on benefits, harms, values placed on outcomes, acceptability, feasibility, equity, resource use, cost-effectiveness or factors affecting imple- mentation. The Executive GSG prioritized the updating of the existing WHO recommenda- tions on induction of labour at or beyond term in response to new, potentially important evidence on this question. The primary goal of these recommendations is to improve the quality of care and outcomes for pregnant women, particularly related to the use of induction of labour. These recommendations provide a foundation for the sustainable imple- mentation of the intervention globally. Target audience The primary audience includes health profes- sionals who are responsible for developing national and local health guidelines and pro- tocols (particularly those related to induction of labour) and those directly providing care to women during labour and childbirth, including midwives, nurses, general medical practition- ers, obstetricians, managers of maternal and child health programmes and relevant staff in ministries of health, in all settings. These recommendations will also be of interest to professional societies involved in the care of pregnant women, nongovernmental organiza- tions concerned with promoting people-centred maternal care, and implementers of maternal and child health programmes. Scope of the recommendations Framed using the population (P), intervention (I), comparison (C), outcome (O) (PICO) format, the question for these recommendations was: • In pregnant women at or beyond term (P), does induction of labour (I), compared to expectant management (C), improve mater- nal and perinatal outcomes (O)? Persons affected by the recommendations The population affected by these recommenda- tions includes pregnant women in low, middle or high-income settings, particularly those who experience a post-term pregnancy. 8 WHO recommendations: induction of labour at or beyond term 2. METHODS The recommendations were first developed using standardized operating procedures in accordance with the process described in the WHO handbook for guideline development (14). In summary, the process included: (i) identification of the priority question and criti- cal outcomes; (ii) retrieval of the 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. WHO recommendations on induction of labour at or beyond term were identified by the Executive GSG as a high priority for updating in response to new, potentially important evidence on this question. Six main groups were involved in this process, with their specific roles described in the following sections. Contributors to the guideline Executive Guideline Steering Group (Executive GSG) The Executive GSG is an independent panel of 14 external experts and relevant stakehold- ers from the six WHO regions: African Region, Region of the Americas, South-East Asia Region, European Region, Eastern Mediterra- nean Region, and Western Pacific Region. The Executive GSG advises WHO on the prioritiza- tion of new and existing questions in maternal and perinatal health for recommendation devel- opment or updating (15). WHO Steering Group The WHO Steering Group, comprising WHO staff members from the Departments of Repro- ductive Health and Research (RHR), Maternal, Newborn, Child and Adolescent Health (MCA) and Nutrition for Health and Development (NHD) managed the updating process. The Group drafted the key recommendation ques- tions in PICO format, identified the systematic review team and guideline methodologist, as well as the guideline development and external review groups. In addition, the WHO Steering Group supervised the syntheses and retrieval of evidence, organized the Guideline Develop- ment Group meeting, drafted and finalized the guideline document, and managed the guide- line dissemination, implementation and impact assessment. The members of the WHO Steer- ing Group are listed in Annex 1. Guideline Development Group The WHO Steering Group identified a pool of approximately 50 experts and relevant stakeholders from the six WHO regions to constitute the WHO Maternal and Perinatal Health Guideline Development Group (MPH- GDG). This pool is a diverse group of experts who are skilled in the critical appraisal of research evidence, implementation of evidence-based recommendations, guideline development methods, and clinical practice, policy and programmes relating to maternal and perinatal health. Members of the MPH-GDG are identified in a way that ensures geographic representation and gender balance, and there were no significant conflicts of interest. 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 constitute the Guideline Development Group (GDG) for updating these recommendations. Those selected were a diverse group with expertise in research, guideline development methods, and clinical policy and programmes relating to maternal and perinatal health. The 16 GDG members invited for the update of these two recommendations were also selected in a way that ensured geographic representation and gender balance and there were no important conflicts of interest. The Group appraised the evidence that was used to inform the recommendations, advised on 9WHO recommendations: induction of labour at or beyond term the interpretation of thi evidence, formulated the final recommendations based on the draft prepared by the Steering Group, and reviewed and approved the final document. The members of this Group are listed in Annex 1. External Review Group This Group included eight technical experts with interest and expertise in the provision of evidence- based obstetric care. None of its members declared a conflict of interest. The Group reviewed the final document to identify any errors of fact and commented on clar- ity of the language, contextual issues and implications for implementation. The Group ensured that the decision-making processes had considered and incorporated contextual values and preferences of potential users of the recommendations, healthcare professionals and policy makers. They did not change the recom- mendations that were formulated by the GDG. The members of the External Review Group are listed in Annex 1. Systematic review team and guideline methodologists A Cochrane systematic review on this ques- tion was updated, supported by the Cochrane Pregnancy and Childbirth Group (15). The WHO Steering Group reviewed and provided input into the protocol and worked closely with the Cochrane Pregnancy and Childbirth Group to appraise the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. Rep- resentatives of the Cochrane Pregnancy and Childbirth Group attended the GDG meeting to provide an overview of the available evidence and GRADE tables, and to respond to technical queries from the GDG. External partners and observers Representatives of the United States Agency for International Development (USAID), the Mater- nal and Child Survival Programme (MCSP)/ Jhpiego, the Bill & Melinda Gates Foundation (BMGF), the International Confederation of Midwives (ICM), the International Federation of Gynaecology and Obstetrics (FIGO) and Population Council participated in the GDG meeting as observers. These organizations, with a long history of collaboration with the RHR Department in guideline dissemination and implementation, are implementers of the recommendations. The list of observers who participated in the GDG meeting is included in Annex 1. Identification of critical outcomes The critical and important outcomes were aligned with the prioritized outcomes of the 2011 WHO recommendations on induction of labour (12). These outcomes were initially identi- fied through a search of key sources of relevant, published, systematic reviews and a prioritization of outcomes by the 2011 GDG panel. All the out- comes were included in the scope of this docu- ment for evidence searching, retrieval, grading and formulation of the recommendations. The list of outcomes is provided in Annex 2. Evidence identification and retrieval A Cochrane systematic review was updated and was the primary source of evidence for these recommendations (15). Randomized controlled trials (RCTs) relevant to the key question were screened by the review authors and data on relevant outcomes and comparisons were entered into Review Man- ager (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 recommendations were excluded). Then the RevMan file was exported to GRADE profiler software (GRADEpro) and GRADE criteria were used to critically appraise the retrieved scientific evidence. 10 WHO recommendations: induction of labour at or beyond term Finally, evidence profiles (in the form of GRADE tables) were prepared for comparisons of inter- est, including the assessment and judgements for each outcome and the estimated risks. Certainty assessment and grading of the evidence The certainty assessment of the body of evi- dence for each outcome was performed using the GRADE approach (16). The certainty of evidence for each outcome was rated as ‘high’, ‘moderate’, ‘low’ or ‘very low’ based on a set of established criteria. The final rating of cer- tainty of evidence was dependent on the factors briefly described below. Study design limitations: The risk of bias was first examined at the level of individual study and then across studies contributing to the out- come. For randomized trials, 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 the outcome. Inconsistency of the results: The similarity in the results for a given outcome was assessed by exploring the magnitude of differences in the direction and size of effects observed in differ- ent 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 lim- its 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 impor- tant differences between the research reported and the context for which the recommendations were being prepared. Such differences were related, for instance, to populations, interven- tions, comparisons or outcomes of interest. Imprecision: This assessed the degree of uncertainty around the estimate of effect. As this is often a function of sample size and num- ber of events, studies with relatively few par- ticipants or events, and thus wide confidence intervals around effect estimates, were down- graded 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. Downgrad- ing evidence by one level was considered where there was strong suspicion of publication bias. 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 esti- mate 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; and • Very low certainty: We have very little con- fidence in the effect estimate. The true effect is likely to be substantially different from the estimate of effect. Formulation of recommendations The WHO Steering Group used the evidence profiles to summarise evidence on effects on the pre-specified outcomes. The evidence sum- mary and corresponding GRADE tables, other related documents for assessment of values and preferences, resource requirements and cost-effectiveness, acceptability, feasibility and equity were provided in advance to meeting par- ticipants, who were invited to submit their com- ments electronically in advance of the meeting. The GDG members and other participants were then invited to attend an online GDG meeting (see Annex 1 for the list of partici- pants) organized by the Steering Group on 11WHO recommendations: induction of labour at or beyond term 2 May 2018. During the meeting, the GDG members reviewed and discussed the balance between the desirable and undesirable effects of the intervention and the overall certainty of supporting evidence, values and preferences of stakeholders, resource requirements and cost-effectiveness, acceptability, feasibility and equity, before finalizing the recommendations and remarks. Declaration of interests by external contributors According to WHO regulations, all experts must declare their relevant interests prior to participation in WHO guideline development processes and meetings. All GDG members were therefore required to complete a standard WHO Declaration of Interest (DOI) form before engaging in the guideline development process and before participating in the guideline-related meeting. The WHO Steering Group reviewed each declaration before finalizing the experts’ invitations to participate. Where any conflict of interest was declared, the Steering Group determined whether such conflicts were seri- ous enough to affect the expert’s objective judgement on the guideline and recommenda- tion development process. To ensure consist- ency, the Steering Group applied the criteria for assessing the severity of conflict of interests in the WHO Handbook for Guideline Development to all participating experts. All findings from the DOI statements received were managed in accordance with the WHO DOI guidelines on a case-by-case basis and communicated to the experts. Where a conflict of interest was not considered significant enough to pose any risk to the guideline development process or reduce its credibility, the experts were only required to openly declare such conflicts of interest at the beginning of the GDG meeting and no further actions were taken. Annex 3 shows a summary of the DOI state- ments, and how the conflicts of interest declared were managed by the Steering Group. Decision-making during the Guideline Development Group meeting During the meeting, the GDG reviewed and dis- cussed the evidence summary and sought clari- fication. 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 evidence-to- decision framework to determine the direction and strength of the recommendations. These criteria included stakeholders’ values, resource implications, acceptability, feasibility and equity. Considerations were based on the experience and opinions of members of the GDG and supported by evidence from a literature search where available. Evidence- to-decision tables were used to describe and synthesize these considerations. Decisions were made based on consensus defined as the agreement by three quar- ters or more of the participants. None of the GDG members expressed opposition to the recommendations. Document preparation Prior to the online meeting, the WHO Steering Group prepared a draft version of the GRADE evidence profiles, evidence summary and other documents relevant to the deliberation of the GDG. The draft documents were made available to the participants of the meeting two weeks before the meeting for their comments. Dur- ing the meeting, these documents were modi- fied in line with the participants’ deliberations and remarks. Following the meeting, members of the WHO Steering Group drafted a recom- mendation document to accurately reflect the deliberations and decisions of the participants. The draft document was sent electronically to GDG members and the External Review Group for final review and approval. 12 WHO recommendations: induction of labour at or beyond term 3. RECOMMENDATIONS AND SUPPORTING EVIDENCE The following section outlines the recommen- dations and the corresponding narrative sum- mary of evidence for the prioritized question. The evidence-to- decision table, summarizing the balance between the desirable and unde- sirable effects and the overall certainty of the supporting evidence, values and preferences of stakeholders, resource requirements, cost- effectiveness, acceptability, feasibility and equity that were considered in determining the strength and direction of the recommendations, is included in the evidence-to- decision frame- work (Annex 4). The following recommendations were adopted by the GDG. Evidence on the effectiveness of the intervention was derived from one systematic review and was summarized in GRADE tables (Annex 5). The certainty of the supporting evidence was rated as ‘low’ for most critical outcomes. To ensure that the recommendations are correctly understood and appropriately implemented in practice, additional ‘remarks’ reflecting the summary of the discussion by GDG are included under each recommendation. Peer review Following review and approval by GDG mem- bers and the External Review Group, the final document was sent to eight external inde- pendent experts who were not involved in the guideline panel for peer review. The WHO Steering Group evaluated the inputs of the peer reviewers for inclusion in this document. After the meeting and external peer review, the modifications made by the WHO Steering Group to the document consisted only of cor- recting factual errors and improving language to address any lack of clarity. 1. Induction of labour is recommended for women who are known with certainty to have reached 41 weeks (>40 weeks + 7 days) of gestation. (conditional recommendation, low- certainty evidence) Remarks • This recommendation does not apply to settings where the gestational age cannot be reli- ably estimated. • The potential need for induction of labour for women with a post-term pregnancy should be discussed with women in advance, so that they have an opportunity to ask questions and understand the benefits and possible risks. 2. Induction of labour is not recommended for women with an uncomplicated pregnancy at gestational age less than 41 weeks. (conditional recommendation, low-certainty evidence) Remarks • There is insufficient evidence to recommend induction of labour for women with uncompli- cated pregnancies before 41 weeks of pregnancy. WHO recommendations on the induction of labour at or beyond term 13WHO recommendations: induction of labour at or beyond term The dissemination and implementation of these recommendations is to be considered by all stakeholders and organizations involved in the provision of care for pregnant women at the international, national and local levels. There is a vital need to increase access and strengthen the capacity of health centres to provide high quality services to all women giving birth. It is therefore crucial that these recommendations are translated into antenatal and intrapartum care packages and programmes at country and health facility levels (where appropriate). Recommendation dissemination and evaluation A shorter document containing the recommen- dations, remarks, implementation considera- tions and research priorities will be formulated for public dissemination. This document will have annexes (also made publicly available) containing all the information in this document, including methods, evidence-to-decision frame- works and GRADE tables. The recommendations will be disseminated through WHO regional and country offices, ministries of health, professional organiza- tions, WHO collaborating centres, other United Nations agencies and nongovernmental organi- zations, among others. These recommenda- tions will be also available on the WHO website and in the WHO Reproductive Health Library. Updated recommendations are also routinely disseminated during meetings or scientific con- ferences attended by WHO MPH staff. The recommendation document will be translat- ed into the six UN languages and disseminated through the WHO regional offices. Technical assistance will be provided to any WHO region- al office willing to translate the full recommen- dations into any of these languages. Implementation considerations • The successful introduction of recommenda- tions into national programmes and health- care services depends on well-planned and participatory consensus-driven processes of adaptation and implementation. The adap- tation and implementation processes may include the development or revision of exist- ing national guidelines or protocols based on these recommendations; • The recommendations should be adapted into a locally appropriate document that can meet the specific needs of each country and health service. Any changes should be made in an explicit and transparent manner; • A set of interventions should be established to ensure that an enabling environment is created for the use of the recommenda- tions (including, for example, the availability of induction agents and monitoring capac- ity), and that the behaviour of the healthcare practitioner changes towards the use of this evidence-based practice; • In this process, the role of local professional societies is important and an all-inclusive and participatory process should be encouraged; • Providers and implementers should consider discussing with women the potential need for induction of labour at ≥41 weeks during ante- natal care contacts. This would provide women with the opportunity to ask questions, under- stand the benefits and possible risks of avail- able options and allow them to make informed decisions should post-term pregnancy occur; • In 2016, WHO recommended the routine use of one ultrasound scan before 24 weeks of gestation (30). Implementation of these recom- mendations can assist in improving the accu- racy of gestational age estimation, to ensure that the recommendations on induction of labour at ≥41 weeks are used appropriately; • Other WHO resources (such as the clinical handbook Managing Complications of Preg- nancy and Childbirth) provide further guid- ance on applying these recommendations in clinical settings (17). 4. DISSEMINATION AND IMPLEMENTATION OF THE RECOMMENDATIONS 14 WHO recommendations: induction of labour at or beyond term 5. RESEARCH IMPLICATIONS The GDG identified important knowledge gaps that need to be addressed through primary research, which may have an impact on these recommendations. The following questions were identified as those that demand urgent priority: • What risks (for both the mother and the fetus) are associated with induction of labour and, in terms of those risks, how does induction of labour compare with elective caesarean section? • What is the role of caesarean section in the management of women in whom induction of labour has failed? • In settings where reliable gestational age determination is problematic, what should be the policy for labour induction at term and post-term? • Is further research required on the experi- ence of women undergoing labour induction, and how much women value the main out- comes associated with labour induction? 6. APPLICABILITY ISSUES Anticipated impact on the organization of care and resources Implementing these evidence-based recom- mendations will require resources to ensure it is done safely, including staff time for monitor- ing of women undergoing induction of labour. The GDG noted that updating training curricula and providing training would increase impact and facilitate implementation. Standardization of care by including recommendations into existing maternity care packages and protocols can encourage healthcare provider behaviour change. Monitoring and evaluating guideline implementation Implementation should be monitored at the health-service level as part of broader efforts to monitor and improve the quality of maternal and newborn care. For example, interrupted time series, clinical audits or criterion-based clini- cal audits can be used to obtain data related to the induction of labour. Clearly defined review criteria and indicators are needed and these could be associated with locally agreed targets and aligned with the standards and indicators described in the WHO document Standards for improving quality of maternal and newborn care in health facilities (31). 15WHO recommendations: induction of labour at or beyond term The Executive GSG convenes annually to review WHO’s current portfolio of maternal and perinatal health recommendations and to advise WHO on prioritization of new and existing questions for recommendation development and updating. Accordingly, these recommendations will be reviewed and prioritized by the Executive GSG. In the event that new evidence that could potentially impact the current evidence base is identified, the recommendations may be updated. If no new reports or information is identified, the recommendations may be revalidated. Following publication and dissemination of the updated recommendations, any concern about the validity of the recommendations will be promptly communicated to the guideline imple- menters, in addition to any plans to update the recommendations. WHO welcomes suggestions regarding addi- tional questions for inclusion in the updated recommendations. Please email your sugges- tions to mpa-info@who.int. 7. UPDATING THE RECOMMENDATIONS 16 WHO recommendations: induction of labour at or beyond term 1. Trends in maternal mortality: 1990 to 2015. Estimates by WHO, UNICEF, UNFPA, World Bank Group and the United Nations Population Division. Geneva: World Health Organization; 2015. 2. Office of the United Nations High Commissioner for Human Rights. Technical guidance on the application of a human rights- based approach to the implementation of policies and programmes to reduce prevent- able maternal morbidity and mortality. Human Rights Council, twentieth session. New York: United Nations General Assembly; 2012 3. 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. 4. Campbell OM, Graham WJ, Lancet Maternal Survival Series steering group. Strategies for reducing maternal mortality: getting on with what works. Lancet. 2006; 368(9543): 1284-99. PubMed PMID: 17027735. eng. 5. Fisk NM, McKee M, Atun R. Relative and absolute addressability of global disease bur- den in maternal and perinatal health by invest- ment in R&D. Trop Med Int Health. 2011; 16(6): 662-8. 6. Managing complications in pregnancy and childbirth: a guide for midwives and doctors: World Health Organization; 2003. 7. Caughey AB, Sundaram V, Kaimal AJ, Cheng YW, Gienger A, Little SE, et al. Maternal and neonatal outcomes of elective induction of labour. Evidence report/technology assess- ment. 2009 (176):1. 8. Declercq ER, Sakala C, Corry MP, Applebaum S. Listening to mothers II: report of the second national US survey of women’s childbearing experiences: conducted January–February 2006 for childbirth connection by Harris Interactive® in partnership with Lamaze International. The Journal of perinatal educa- tion. 2007; 16(4): 9. 9. Martin JA, Hamilton BE, Sutton PD, Ventura SJ, Menacker F, Kirmeyer S, et al. Births: final data for 2005. National vital statistics reports. 2007; 56(6): 1-103. 10. 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. 11. Guerra GV, Cecatti JG, Souza JP, Faúndes A, Morais SS, Gülmezoglu AM, et al. Elective induction versus spontaneous labour in Latin America. Bull World Health Organ. 2011 Sep; 89(9): 657- 65. 12. WHO recommendations on induction of labour. Geneva: World Health Organization; 2011. 13. World Health Organization. Executive Guideline Steering Group for Updating WHO Maternal and Perinatal Health Recommendations (2017- 2019). Geneva: World Health Organization; 2017 (http://www.who.int/reproductivehealth/ publications/updating-mnh-recommendations/ en/2017,accessed 7 December 2018). 14. WHO Handbook for Guideline Development (second edition). Geneva: World Health Organization; 2014. 15. Middleton P, Shepherd E, Crowther CA. Induction of labour for improving birth outcomes for women at or beyond term. Cochrane Database Syst Rev. 2018; 5:CD004945. 16. Balshem H, Helfand M, Schünemann HJ, Oxman AD, Kunz R, Brozek J, et al. GRADE guidelines: 3. Rating the quality of evidence. J Clin Epidemiol. 2011; 64(4): 401-6. 17. Downe S, Finlayson K, Tunçalp Ö, Metin Gülmezoglu A. What matters to women: a systematic scoping review to identify the pro- cesses and outcomes of antenatal care provi- sion that are important to healthy pregnant women. BJOG. 2016; 123(4): 529-39. 18. Downe S, Finlayson K, Oladapo O, Bonet M, Gulmezoglu A. What matters to women during childbirth: A systematic qualitative review. Plos One; 2018; 13(4):e0194906. 19. Mazzoni A, Althabe F, Liu NH, Bonotti AM, Gibbons L, Sánchez AJ, et al. Women’s pref- erence for caesarean section: a systematic review and meta-analysis of observational studies. BJOG. 2011; 118(4): 391-9. REFERENCES 17WHO recommendations: induction of labour at or beyond term 20. Kaimal AJ, Little SE, Odibo AO, Stamilio DM, Grobman WA, Long EF, et al. Cost- effectiveness of elective induction of labour at 41 weeks in nulliparous women. Am J Obstet Gynecol. 2011; 204(2): 137.e1-9. 21. Hannah ME, Hannah WJ, Hellmann J, Hewson S, Milner R, Willan A. Induction of labour as compared with serial antenatal monitoring in post-term pregnancy. A randomized controlled trial. The Canadian Multicenter Post-term Pregnancy Trial Group. N Engl J Med. 1992 ; 326(24): 1587-1592. 22. Goeree R, Hannah M, Hewson S. Cost- effectiveness of induction of labour versus serial antenatal monitoring in the Canadian Multicentre Postterm Pregnancy Trial. CMAJ. 1995; 152(9):1445-50. 23. Alfirevic Z, Keeney E, Dowswell T, Welton NJ, Medley N, Dias S, et al. Which method is best for the induction of labour? A system- atic review, network meta-analysis and cost- effectiveness analysis. Health Technol Assess. 2016; 20(65): 1-584. 24. State of inequality: Reproductive, maternal, newborn and child health. Geneva: World Health Organization; 2015. 25. Heimstad R, Romundstad PR, Hyett J, Mattsson LA, Salvesen KA. Women’s experi- ences and attitudes towards expectant man- agement and induction of labour for post-term pregnancy. Acta Obstet Gynecol Scand. 2007; 86(8): 950-6. 26. Martin D, Thompson W, Pinkerton J, Watson J. A randomized controlled trial of selective planned delivery. British Journal of Obstetrics and Gynaecology; 1978. 27. Roberts LJ, Young KR. The management of prolonged pregnancy - an analysis of women’s attitudes before and after term. Br J Obstet Gynaecol. 1991; 98(11): 1102-6. 28. Gatward H, Simpson M, Woodhart L, Stainton MC. Women’s experiences of being induced for post-date pregnancy. Women Birth. 2010; 23(1): 3-9. 29. Vogel JP, Gülmezoglu AM, Hofmeyr GJ, Temmerman M. Global perspectives on elec- tive induction of labor. Clin Obstet Gynecol. 2014; 57(2):331-42. 30. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016. 31. Standards for improving quality of maternal and newborn care in health facilities. Geneva: World Health Organization; 2016. 18 WHO recommendations: induction of labour at or beyond term Guideline development group Edgardo Abalos Vice Director Centro Rosarino de Estudios Perinatales (CREP) Rosario, Argentina Ebun Adejuyigbe Consultant Neonatologist Department of Paediatrics and Child Health Obafemi Awolowo University Ife, Nigeria Shabina Ariff* Consultant Paediatrician and Neonatologist Department of Paediatrics and Child Health Aga Khan University Karachi, Pakistan Jemima Dennis-Antwi* International Consultant in Midwifery West Legon Accra, Ghana Luz Maria de-Regil Vice President, Global Technical Services and Chief Technical Advisor Micronutrient Initiative Ottawa, Canada Christine East Professor of Midwifery Monash Women’s Maternity Services and Monash University Monash Medical Centre Melbourne, Australia Lynn Freedman* Director Averting Maternal Death and Disability Program Mailman School of Public Health Columbia University New York, USA Pisake Lumbiganon Professor of Obstetrics and Gynaecology Con- venor, Cochrane Thailand Department of Obstetrics and Gynaecology Faculty of Medicine Khon Kaen University Khon Kaen, Thailand ANNEX 1. EXTERNAL EXPERTS AND WHO STAFF INVOLVED IN THE PREPARATION OF THE GUIDELINES A. PARTICIPANTS AT THE WHO GUIDELINE DEVELOPMENT GROUP MEETING (2 MAY 2018) Anita Maepioh Nurse Educator Department of Obstetrics and Gynaecology National Referral Hospital Honiara, Solomon Islands James Neilson (GDG Vice-chair) Department of Women’s and Children’s Health The University of Liverpool Women’s NHS Foundation Trust Liverpool, United Kingdom of Great Britain and Northern Ireland Hiromi Obara Health Policy Advisor Japan International Cooperation Agency (JICA) Vientiane, Lao People’s Democratic Republic Zahida Qureshi (GDG Chair) Associate Professor Department of Obstetrics and Gynaecology School of Medicine University of Nairobi Nairobi, Kenya Kathleen Rasmussen Professor of Maternal and Child Nutrition Divi- sion of Nutritional Sciences Cornell University New York, United States of America Niveen Abu Rmeileh Director Institute of Community and Public Health Birzeit University West Bank and Gaza Strip Eleni Tsigas Chief Executive Officer Preeclampsia Foundation Melbourne, USA 19WHO recommendations: induction of labour at or beyond term Observers Deborah Armbruster Senior Maternal and Newborn Health Advisor United States Agency for International Develop- ment (USAID) Bureau for Global Health Washington (DC), United States of America Kathleen Hill Maternal Health Team Lead MCSP/Jhpiego USAID Grantee Washington DC, United States of America Jerker Liljestrand* Senior Program Officer (Maternal, Neonatal and Child Health) Bill & Melinda Gates Foundation Seattle, United States of America Lesley Page Representative International Confederation of Midwives (ICM) Sydney University Sydney, Australia Mary-Ellen Stanton* Senior Reproductive Health Advisor United States Agency for International Develop- ment (USAID) Bureau for Global Health Washington DC, United States of America Gerard H.A. Visser Chair, FIGO Committee on Safe Motherhood and Newborn Health Department of Obstetrics University Medical Center Utrecht, The Netherlands Charlotte Warren Director – Ending Eclampsia Project Senior Associate, Maternal and Newborn Health Population Council Washington DC, United States of America Systematic review team Anna Cuthbert Research Associate Cochrane Pregnancy and Childbirth Group Editorial Office University of Liverpool Liverpool, United Kingdom of Great Britain and Northern Ireland Leanne Jones Research Associate Cochrane Pregnancy and Childbirth Group Editorial Office University of Liverpool Liverpool, United Kingdom of Great Britain and Northern Ireland Frances Kellie Managing Editor Cochrane Pregnancy and Childbirth Group Editorial Office University of Liverpool Liverpool, United Kingdom of Great Britain and Northern Ireland Myfanwy Williams Research Associate Cochrane Pregnancy and Childbirth Group Editorial Office University of Liverpool Liverpool, United Kingdom of Great Britain and Northern Ireland WHO country and regional officers Nino Berdzuli* Sexual and Reproductive Health Noncommuni- cable diseases and life-course WHO Regional Office for Europe Copenhagen, Denmark 20WHO recommendations: induction of labour at or beyond term Bremen De Mucio Sexual and Reproductive Health WHO Regional Office of the Americas Montevideo, Uruguay Chandani Anoma Jayathilaka* Family Health, Gender and Life Course WHO Regional Office for South-East Asia New Delhi, India Ramez Khairi Mahaini* Reproductive and Maternal Health WHO Regional Office for the Eastern Mediter- ranean Cairo, Egypt Léopold Ouedraogo* Reproductive Health Health Promotion Cluster (HPR) WHO Regional Office for Africa Brazzaville, Republic of Congo Howard Sobel* Reproductive, Maternal, Newborn, Child and Adolescent Health Division of NCD and Health through Life-Course WHO Regional Office for the Western Pacific Manila, Philippines WHO steering group Department of Reproductive Health and Research A. Metin Gülmezoglu Coordinator, RHR/MPA Maternal and Perinatal Health and Preventing Unsafe Abortion Ana Pilar Betrán Medical Officer, RHR/MPA Maternal and Perinatal Health and Preventing Unsafe Abortion Mercedes Bonet Medical Officer, RHR/MPA Maternal and Perinatal Health and Preventing Unsafe Abortion Olufemi T. Oladapo Medical Officer, RHR/MPA Maternal and Perinatal Health and Preventing Unsafe Abortion David Stenson Volunteer, RHR/MPA Maternal and Perinatal Health and Preventing Unsafe Abortion Özge Tunçalp Scientist, RHR/MPA Maternal and Perinatal Health and Preventing Unsafe Abortion Joshua P. Vogel Technical Officer, RHR/MPA Maternal and Perinatal Health and Preventing Unsafe Abortion Department of Maternal, Newborn, Child and Adolescent Health Maurice Bucagu Medical Officer, MCA/PPP Policy, Planning and Programmes Fran McConville Technical Officer, MCA/PPP Policy, Planning and Programmes Anayda Portela Technical Officer, MCA/MRD Research and Development *unable to attend online GDG meeting 21WHO recommendations: induction of labour at or beyond term B. EXTERNAL REVIEW GROUP José Guilherme Cecatti Professor Department of Obstetrics and Gynaecology University of Campinas Campinas, Brazil Sylvia Deganus Head Department of Obstetrics and Gynaecology Tema General Hospital Tema, Ghana Nguyen Xuan Hoi Adjunct Associate Professor Hanoi Medical University National Hospital of Obstetrics and Gynaecol- ogy Hanoi, Vietnam Jack Moodley Professor and Head Department of Obstetrics and Gynaecology Nelson R Mandela School of Medicine Univer- sity of KwaZulu-Natal Durban, South Africa Jane Sandall Professor of Midwifery Women’s Health Clinical Academic Group Kings College London, United Kingdom of Great Britain and Northern Ireland M Jeeva Sankar Assistant Professor WHO Collaborating Centre for Training & Research in Newborn Care Department of Paediatrics All India Institute of Medical Sciences New Delhi, India Hayfaa Wahabi Professor and Chair Evidence-based Healthcare and Knowledge Translation College of Medicine, King Saud University Riyadh, Saudi Arabia Ola Shaker Hussien Salama Nursing Supervisor Gynaecological and Maternity Hospital El-Abaseya, Egypt 22WHO recommendations: induction of labour at or beyond term ANNEX 2. PRIORITY OUTCOMES FOR DECISION-MAKING X Woman: • Vaginal delivery not achieved within 24 hours • Uterine hyperstimulation with fetal heart rate changes • Caesarean section • Severe maternal morbidity or death • Cervix unfavourable/unchanged after 24 hours • Oxytocin augmentation • Epidural rate • Uterine hyperstimulation without fetal heart rate changes • Uterine rupture • Instrumental delivery • Meconium stained amniotic fluid • Maternal side-effects (all) • Nausea • Vomiting • Diarrhoea • Postpartum haemorrhage • Women not satisfied the care related to induction of labour • Caregiver not satisfied the care related to induction of labour X Infant/Child: • Serious neonatal morbidity • Perinatal death • Apgar score less than seven at 5 minutes • Admission to a neonatal intensive care unit • Neonatal encephalopathy • Disability in childhood 23WHO recommendations: induction of labour at or beyond term ANNEX 3. SUMMARY AND MANAGEMENT OF DECLARED INTERESTS FROM GDG MEMBERS Name Expertise contributed to guideline development Declared interest Management of conflict of interest Edgardo ABALOS Content expert and end-user None declared Not applicable Ebun ADEJUYIGBE Content expert and end-user None declared Not applicable Shabina ARIFF Content expert and end-user None declared Not applicable Jemima DENNIS- ANTWI Content expert and end-user None declared Not applicable Luz Maria DE-REGIL Content expert and end-user Global Affairs Canada awarded a grant to Dr De- Regil’s institution to implement nutrition interventions in low and middle-income countries. Some of the funded work included support for implementation research on calcium supplementation in pregnancy in Kenya and Ethiopia. The work was sub-granted to Cornell University, and Dr De-Regil was not part of the research team. As a former WHO staff member, she supported the development of a guideline on calcium supplementa- tion in pregnancy (led by NHD). The conflict was not considered serious enough to affect GDG membership or partici- pation in the Technical Consultation Chris- tine EAST Content expert and end-user None declared Not applicable Lynn FREEDMAN Content expert and end-user None declared Not applicable Pisake LUMBIGA- NON Content expert and end-user None declared Not applicable Anita MAEPIOH Content expert and end-user None declared Not applicable James NEILSON Content expert and end-user None declared Not applicable Hiromi OBARA Content expert and implementer None declared Not applicable Rachel PLACHCINSKI Consumer representative None declared Not applicable Zahida QURESHI Content expert and end-user None declared Not applicable Kathleen RASMUSSEN Content expert and end-user None declared Not applicable Niveen Abu RMEILEH Content expert and implementer None declared Not applicable Eleni TSIGAS Consumer representative Ms Tsigas represents patient experiences around preeclampsia and other hypertensive disorders of pregnancy to organizations, committees, and other multidisciplinary bodies. She is also a voting member on the Council for Patient Safety in Women's Healthcare (USA). The conflict was not considered serious enough to affect GDG membership or partici- pation in the Technical Consultation 24 WHO recommendations: induction of labour at or beyond term ANNEX 4. EVIDENCE TO DECISION FRAMEWORK A) QUESTION In pregnant women at or beyond term (P), does induction of labour (I), compared to expectant management (C), improve maternal and perinatal outcomes (O)? Problem: Perinatal risks associated with post-term pregnancy Perspective: Clinical practice recommendation – population perspective Population: Pregnant women at or beyond term Intervention: labour induction Comparison: expectant management Critical Outcomes: 1 X 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 X Fetal/Neonatal • Apgar score less than seven at 5 minutes • Admission to a neonatal intensive care unit • Neonatal encephalopathy • Serious neonatal morbidity • Disability in childhood • Perinatal death Important outcomes: 1 X 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 • Women not satisfied with the care related to induction of labour • Caregiver not satisfied with the care related to induction of labour 1 These outcomes reflect the outcomes used in the WHO recommendations for induction of labour (2011). An outcome ranked as 7 or more was considered “critical”, and an outcome ranked as 4 to 6 was considered “ important” 25WHO recommendations: induction of labour at or beyond term B) ASSESSMENT 1. EFFECTS OF INTERVENTIONS Research evidence Summary of the evidence Evidence relating to induction of labour at term and beyond term was extracted from one updated Cochrane systematic review of 30 randomized controlled trials involving 12 479 women (15). One trial involving 248 women did not contribute data to the meta-analysis. Most of the trials were judged by the Cochrane review authors to have a moderate risk of bias, largely due to unclear methods of random sequence generation and allocation concealment. The review evaluated the effect of inducing labour at 37–42 weeks, <41 weeks, and ≥41 weeks. The intervention was compared with expectant management with fetal monitoring at varying intervals. Trials were conducted in either hospitals or large medical centres in Austria (1), Canada (1), China (3), Finland (1), France (1), India (2), the Netherlands (1), Norway (3), Spain (1), Sweden (2), Thailand (2), Tunisia (1), Turkey (1), United Kingdom (4), and United States (6). The trials used a combination of methods of induction: most trials used oxytocin infusion in some or all of the women in the intervention group, with or without artificial rupture of membranes, and with or without additional methods. Some trials used prostaglandin E2 in gel or pessary form and one used laminaria tents. Some trials used only prostaglandin E2, without oxytocin infusion. One trial had three treatment arms (vaginal misoprostol, oxytocin, and Foley catheter). Two trials did not report the method used. For the majority of trials, expectant management protocols included various combina- tions of fetal heart rate monitoring, ultrasound for amniotic fluid measurements and, in earlier stud- ies, biochemical tests. X Labour induction compared to expectant management for improving birth outcomes for women at or beyond term (all trials) Effects of interventions Maternal outcomes Caesarean section: Moderate-certainty evidence suggests that induction between 37-42 weeks of gestation probably slightly reduces the caesarean section rate compared with expectant manage- ment (27 trials, 11 738 women; 980/6004 vs 1056/5734; RR 0.92, 95% CI 0.85 to 0.99). Instrumental vaginal birth: Moderate-certainty evidence suggests that induction probably makes little or no difference to the number of women with an operative vaginal birth (forceps or ventouse) (18 trials, 9281 women; 984/4775 vs 869/4506; RR 1.07, 95% CI 0.99 to 1.16). Postpartum haemorrhage: Low-certainty evidence suggests that induction may make little or no difference to the number of women with postpartum haemorrhage (five trials, 3315 women; 218/1649 vs 203/1666; RR 1.09, 95% CI 0.92 to 1.30). Maternal satisfaction with the care related to induction of labour: Two outcomes were indica- tors of maternal satisfaction. In one trial, moderate-certainty evidence suggests that women who 26WHO recommendations: induction of labour at or beyond term had an induction are probably more likely to want to be randomized to the same trial arm in future trials (one trial, 496 women; 184/250 vs 94/246; RR 1.93, 95% CI 1.62 to 2.30). In another trial, it is uncertain whether women in the induction or expectant management group preferred their allocation because the certainty of evidence is very low. Infant outcomes Serious neonatal morbidity: Low-certainty evidence suggests induction may make little or no dif- ference to neonatal trauma (three trials, 4255 neonates; 26/2128 vs 22/2127; RR 1.18, 95% CI0.68 to 2.05) or neonatal convulsions (three trials, 4365 neonates; 3/2178 vs 6/2187; RR 0.54, 95% CI 0.15 to 1.97). Moderate-certainty evidence suggests induction probably slightly reduces the number of neonates with meconium aspiration syndrome (11 trials, 7781 neonates; 133/3887 vs 173/3894; RR 0.77, 95% CI 0.62 to 0.96). Perinatal death: Moderate-certainty evidence suggests that induction between 37-42 weeks of ges- tation probably slightly reduces the number of perinatal deaths (20 trials, 9960 neonates; 2/4988 vs 16/4972; RR 0.33, 95% CI 0.14 to 0.78) and stillbirths (20 trials, 9960 neonates; 1/4988 vs 10/4972; RR 0.33, 95% CI 0.11 to 0.96). Low-certainty evidence suggests little or no difference in the number of neonatal deaths (19 trials, 9776 neonates; 1/4896 vs 6/4880; RR 0.37, 95% CI 0.10 to 1.38). Apgar score less than 7 at 5 minutes: Moderate-certainty evidence suggests that induction prob- ably slightly reduces the number of neonates with Apgar scores of less than 7 at 5 minutes (16 trials, 9047 neonates; 52/4523 vs 76/4524; RR 0.70, 95% CI 0.50 to 0.98). Admission to neonatal intensive care unit: Moderate-certainty evidence suggests that induction probably makes little or no difference to the number of neonates admitted to intensive care (13 trials, 8531 neonates; 320/4271 vs 363/4260; RR 0.88, 95% CI 0.77 to 1.01). X Labour induction compared to expectant management for improving birth outcomes for women at or beyond term (gestational age at induction < 41 weeks and ≥ 41 weeks) Effects of interventions Maternal outcomes Caesarean section < 41 weeks: Moderate-certainty evidence suggests that induction before 41 weeks probably makes little or no difference to the caesarean section rate (nine trials, 2806 women; 191/1532 vs 175/1274; RR 1.04, 95% CI 0.87 to 1.24). Caesarean section ≥ 41 weeks: Moderate-certainty evidence suggests that induction after and including 41 weeks probably slightly reduces the caesarean section rates (17 trials, 8803 women; 774/4407 vs 857/4396; RR 0.90, 95% CI 0.83 to 0.98). Instrumental vaginal birth < 41 weeks: Moderate-certainty evidence suggests that induction before 41 weeks probably increases operative vaginal birth (forceps or ventouse) (seven trials, 2401 women; 304/1327 vs 198/1074; RR 1.27, 95% CI 1.08 to 1.48). Instrumental vaginal birth ≥ 41 weeks: Moderate-certainty evidence suggests that induction after and including 41 weeks probably makes little or no difference to operative vaginal birth (forceps or ventouse) (10 trials, 6751 women; 668/3383 vs 665/3368; RR 1.00, 95% CI 0.91 to 1.10). 27WHO recommendations: induction of labour at or beyond term Infant outcomes Perinatal death < 41 weeks: It is uncertain whether induction before 41 weeks reduces perinatal death because the certainty of evidence is very low. Perinatal death ≥ 41 weeks: Moderate-certainty evidence suggests that induction after and includ- ing 41 weeks probably slightly reduces perinatal mortality (15 trials, 8408 neonates; 2/4217 vs 13/4191; RR 0.33, 95% CI 0.13 to 0.87). Stillbirth < 41 weeks: It is uncertain whether induction before 41 weeks reduces stillbirth because the certainty of evidence is very low. Stillbirth ≥ 41 weeks: Low-certainty evidence suggests that induction after and including 41 weeks might make little or no difference to stillbirth (15 trials, 8408 neonates; 1/4217 vs 7/4191; RR 0.34, 95% CI 0.09 to 1.24). Admission to neonatal intensive care unit < 41 weeks: It is uncertain whether induction before 41 weeks reduces admission to neonatal intensive care units because the certainty of evidence is very low. Admission to neonatal intensive care unit ≥ 41 weeks: Moderate-certainty evidence suggests that induction after and including 41 weeks probably makes little or no difference to admissions to neonatal intensive care (nine trials, 7397 neonates; 307/3704 vs 350/3693; RR 0.88, 95% CI 0.76 X Desirable effects How substantial are the desirable anticipated effects of induction of labour at <41 weeks? Judgement Don't know Varies Trivial Small Moderate Large How substantial are the desirable anticipated effects of induction of labour at ≥41 weeks? Judgement Don't know Varies Trivial Small Moderate Large X Undesirable effects How substantial are the undesirable anticipated effects of induction of labour at <41 weeks? Judgement Don't know Varies Large Moderate Small Trivial How substantial are the undesirable anticipated effects of induction of labour at ≥41 weeks? Judgement Don't know Varies Large Moderate Small Trivial 28WHO recommendations: induction of labour at or beyond term X Certainty of the evidence What is the overall certainty of the evidence of the effects of induction of labour at <41 weeks? No included studies Very low Low Moderate High What is the overall certainty of the evidence of the effects of induction of labour at ≥41 weeks? No included studies Very low Low Moderate High Additional considerations None. X Values Is there important uncertainty about, or variability in, how much women value the main outcomes associated with induction of labour? Research evidence We did not identify any evidence that addressed this question directly. Additional considerations Evidence from a qualitative systematic review of what women want from antenatal care showed that healthy pregnant women from high-, medium- and low-resource settings valued maintenance of optimal health for mother and baby (17). Evidence from a separate qualitative systematic review found that while women place a high value on a physiological labour and birth experience, they also acknowledge that birth can be unpredictable. Even where an intervention (such as induction of labour) is needed or wanted, women usually wish to retain a sense of personal achievement and control by being involved in decision-making (18). The GDG considered it likely that women in dif- ferent settings would consider the outcomes of stillbirth and perinatal mortality very important. A 2011 systematic review assessed women’s preferences for caesarean section and included 38 studies (19 403 women) from a range of countries (19). The overall pooled preference for caesarean section was 15.6% (95% CI 12.5 – 18.9) – only a minority of women in a wide variety of countries expressed a preference for caesarean section. Judgement Important uncertainty or variability Possibly important uncer- tainty or variability Probably no important uncertainty or variability No important uncertainty or variability 29WHO recommendations: induction of labour at or beyond term X Balance of effects Does the balance between desirable and undesirable effects favour the intervention or the compari- son (for induction of labour at <41 weeks)? Judgement Don't know Varies Favours the comparison Probably favours the comparison Does not favour the intervention or the comparison Probably favours the intervention Favours the intervention Does the balance between desirable and undesirable effects favour the intervention or the compari- son (for induction of labour at ≥41 weeks)? Judgement Don't know Varies Favours the comparison Probably favours the comparison Does not favour the intervention or the comparison Probably favours the intervention Favours the intervention 2. RESOURCES How large are the resource requirements (costs) of induction of labour at ≥41 weeks? Research evidence A 2011 cost-effectiveness analysis from the USA compared induction of labour at 41 weeks vs expectant management in nulliparous women (20). The authors reported that induction of labour was cost-effective, with an incremental cost of $10 945 per quality-adjusted life year gained. A trial in Canada (included in the Cochrane review) randomly assigned 3418 women with uncompli- cated pregnancies of 41 or more weeks gestation to induction of labour or serial antenatal monitor- ing (21). While the trial did not show clear differences in perinatal mortality and neonatal morbidity, the mean cost per patient with a post-term pregnancy managed through monitoring was $3132 (95% CI $3090 to $3,174) compared to $2939 (95% CI $2898 to $2981), a difference of $193 per patient (22). Additional costs in the monitoring arm were due mainly to the costs of additional moni- toring and higher caesarean section rates. 30WHO recommendations: induction of labour at or beyond term Main resource requirements Resource Description Staff training • If ultrasound is available, trained providers who can assess gestational age accurately using obstetric ultrasound • Training in performance and monitoring of labour induction Supplies • Induction agents (e.g. misoprostol or prostaglandin E2) (12) • Ultrasound gel Equipment • Tools to accurately estimate gestational age (e.g. antenatal ultrasound, gestational age wheel) • Clinical protocol for safe labour induction • Equipment for vaginal birth Infrastructure • Capacity to perform caesarean section (if required) • Availability of appropriate space, beds or both for women undergoing induction Staff time • 20 minutes for initial assessment • After administration of misoprostol, 40 minutes additional monitoring Additional considerations A 2016 systematic review assessed the effectiveness, safety and cost-effectiveness of different labour induction methods (23). The cost-effectiveness analysis compared only 20 induction inter- ventions. Findings suggest that most interventions have similar utility but differ in cost. The authors report that titrated misoprostol solution and buccal or sublingual misoprostol have the highest likelihood of being cost-effective, though this is uncertain. X Resources required Judgement Don't know Varies Large costs Moderate costs Negligible costs or savings Moderate savings Large savings X Certainty of evidence on required resources What is the certainty of evidence on costs? Judgement No included studies Very low Low Moderate High X Cost-effectiveness Judgement Don't know Varies Favours the comparison Probably favours the comparison Does not favour either the intervention or the comparison Probably favours the intervention Favours the intervention 31WHO recommendations: induction of labour at or beyond term 3. EQUITY What would be the impact of induction of labour at >41 weeks on health equity? Research evidence No direct evidence was identified to address this question. Additional considerations In LMICs, women who are poor, least educated, and residing in rural areas have lower health inter- vention coverage and worse health outcomes than more advantaged women (24). Safe, effective, equitable implementation of this intervention to prevent perinatal mortality and morbidity could therefore reduce health inequities. Judgement Don't know Varies Reduced Probably reduced Probably no impact Probably increased Increased 4. ACCEPTABILITY Is the intervention acceptable to key stakeholders? Research evidence In one trial of 496 women (25) that was included in the Cochrane review, more women in the induc- tion group said that they would choose the same arm in a future trial, compared with women in the expectant management group (RR 1.93, 95% CI 1.62 to 2.30). In an older trial of 184 women, similar numbers of women indicated that they preferred the group they had been allocated to (RR 0.90, 95% CI 0.72 to 1.13) (26). Additional considerations A 1991 survey of 500 pregnant women in the UK showed that at 37 weeks of gestation, 45% of women preferred conservative management. Of women undelivered by 41 weeks, 31% desired conservative management (27). In a 2009 study, 23 primigravid women in Australia (18 of whom were induced) were interviewed before and after induction (28). The women described feeling that induction was being imposed externally, with hospital policy defining “when time was up”. Being booked for induction required a shift in women’s expectations on what would happen during labour and birth. Women reported a lack of meaningful information given to them and some were afraid of the increased interventions. After birth, induced women were generally positive about the outcome of a healthy baby, if not necessarily positive about the induction experience. 32WHO recommendations: induction of labour at or beyond term Judgement Don't know Varies No Probably No Probably Yes Yes 5. FEASIBILITY Is the intervention feasible to implement? Research evidence No direct evidence was identified to address this question. Additional considerations Labour induction is a common practice worldwide. Induction rates exceed 20% in some high- income countries, however it is also widely used in hospitals in lower-income countries. A WHO multi-country, facility-based survey reported hospital induction rates of 11.4% in eight Latin American countries, 4.4% in seven African countries and 12.1% in nine Asian countries. Hospitals in some low-income countries (such as Sri Lanka and Cuba) had induction rates comparable to high-income countries.(29) Judgement Don't know Varies No Probably No Probably Yes Yes 33WHO recommendations: induction of labour at or beyond term C) SUMMARY OF JUDGEMENTS – LABOUR INDUCTION < 41 WEEKS Desirable effects — Don't know — Varies Trivial — Small — Moderate — Large Undesirable effects — Don't know — Varies — Large — Moderate Small — Trivial Certainty of the evidence — No included studies Very low — Low — Moderate — High Values — Important uncertainty or variability — Possibly important uncertainty or variability Probably no important uncertainty or variability — No important uncertainty or variability Balance of effects — Don't know — Varies Favours the comparison — Probably favours the comparison — Does not favour either the interven- tion or the comparison — Probably favours the intervention — Favours the intervention Resources required Don't know — Varies — Large costs — Moderate costs — Negligible costs or savings — Moderate savings — Large savings Certainty of evidence of required resources No included studies — Very low — Low — Moderate — High Cost- effectiveness Don't know — Varies — Favours the comparison — Probably favours the comparison Does not favour either the interven- tion or the comparison — Probably favours the intervention — Favours the intervention Equity Don't know — Varies — Reduced — Probably reduced — Probably no impact — Probably increased — Increased Acceptability Don't know — Varies — No — Probably No — Probably Yes — Yes Feasibility Don't know — Varies — No — Probably No — Probably Yes — Yes 34WHO recommendations: induction of labour at or beyond term C) SUMMARY OF JUDGEMENTS – LABOUR INDUCTION ≥ 41 WEEKS Desirable effects — Don't know — Varies — Trivial — Small — Moderate Large Undesirable effects — Don't know — Varies — Large — Moderate — Small Trivial Certainty of the evidence — No included studies — Very low Low — Moderate — High Values — Important uncertainty or variability — Possibly important uncertainty or variability Probably no important uncertainty or variability — No important uncertainty or variability Balance of effects — Don't know — Varies — Favours the comparison — Probably favours the comparison — Does not favour either the interven- tion or the comparison — Probably favours the intervention Favours the intervention Resources required — Don't know — Varies — Large costs Moderate costs — Negligible costs or savings — Moderate savings — Large savings Certainty of evidence of required resources — No included studies — Very low Low — Moderate — High Cost- effectiveness — Don't know — Varies — Favours the comparison — Probably favours the comparison Does not favour either the interven- tion or the comparison Probably favours the intervention — Favours the intervention Equity — Don't know — Varies — Reduced — Probably reduced — Probably no impact Probably increased — Increased Acceptability Don't know — Varies — No — Probably No — Probably Yes — Yes Feasibility — Don't know — Varies — No — Probably No — Probably Yes Yes 35WHO recommendations: induction of labour at or beyond term ANNEX 5. GRADE TABLES Question: Labour induction compared to expectant management (all trials) for improving birth outcomes for women at or beyond term Setting: Hospital or medical centres in Austria, Canada, China, Finland, France, India, Netherlands, Norway, Spain, Sweden, Thailand, Tunisia, Turkey, UK, US Certainty assessment № of patients Effect Certainty Importance № of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Labour induction Expectant management (all trials) Relative (95% CI) Absolute (95% CI) Caesarean section 27 randomized trials serious a not serious not serious not serious none 980/6004 (16.3%) 1056/5734 (18.4%) RR 0.92 (0.85 to 0.99) 15 fewer per 1,000 (from 2 fewer to 28 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Operative vaginal birth (forceps or ventouse) 18 randomized trials serious a not serious not serious not serious none 984/4775 (20.6%) 869/4506 (19.3%) RR 1.07 (0.99 to 1.16) 91 fewer per 1,000 (from 21 fewer to 137 fewer) ⨁⨁⨁◯ MODERATE IMPORTANT Postpartum haemorrhage 5 randomized trials serious a not serious not serious serious b none 218/1649 (13.2%) 203/1666 (12.2%) RR 1.09 (0.92 to 1.30) 11 more per 1,000 (from 10 fewer to 37 more) ⨁⨁◯◯ LOW CRITICAL Maternal satisfaction (Hoping to be randomized to the same trial arm as they had been in this study) 1 randomized trials serious c not serious not serious not serious none 184/250 (73.6%) 94/246 (38.2%) RR 1.93 (1.62 to 2.30) 355 more per 1,000 (from 237 more to 497 more) ⨁⨁⨁◯ MODERATE IMPORTANT Maternal satisfaction (Preferred their allocation) 1 randomized trials serious c not serious not serious very serious d none 55/92 (59.8%) 61/92 (66.3%) RR 0.90 (0.72 to 1.13) 66 fewer per 1,000 (from 86 more to 186 fewer) ⨁◯◯◯ VERY LOW IMPORTANT 36 WHO recommendations: induction of labour at or beyond term Certainty assessment № of patients Effect Certainty Importance № of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Labour induction Expectant management (all trials) Relative (95% CI) Absolute (95% CI) Neonatal trauma 3 randomized trials serious a not serious not serious serious b none 26/2128 (1.2%) 22/2127 (1.0%) RR 1.18 (0.68 to 2.05) 2 more per 1,000 (from 3 fewer to 11 more) ⨁⨁◯◯ LOW CRITICAL Neonatal convulsions 3 randomized trials serious a not serious not serious serious b none 3/2178 (0.1%) 6/2187 (0.3%) RR 0.54 (0.15 to 1.97) 1 fewer per 1,000 (from 2 fewer to 3 more) ⨁⨁◯◯ LOW CRITICAL Meconium aspiration syndrome 11 randomized trials serious a not serious not serious not serious none 133/3887 (3.4%) 173/3894 (4.4%) RR 0.77 (0.62 to 0.96) 10 fewer per 1,000 (from 2 fewer to 17 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Perinatal death 20 randomized trials serious a not serious not serious not serious none 2/4988 (0.0%) 16/4972 (0.3%) RR 0.33 (0.14 to 0.78) 2 fewer per 1,000 (from 1 fewer to 3 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Stillbirth 20 randomized trials serious a not serious not serious not serious none 1/4988 (0.0%) 10/4972 (0.2%) RR 0.33 (0.11 to 0.96) 1 fewer per 1,000 (from 0 fewer to 2 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Neonatal death 19 randomized trials serious a not serious not serious serious b none 1/4896 (0.0%) 6/4880 (0.1%) RR 0.37 (0.10 to 1.38) 1 fewer per 1,000 (from 0 fewer to 1 fewer) ⨁⨁◯◯ LOW CRITICAL 37WHO recommendations: induction of labour at or beyond term Certainty assessment № of patients Effect Certainty Importance № of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Labour induction Expectant management (all trials) Relative (95% CI) Absolute (95% CI) Apgar score less than 7 at 5 minutes 16 randomized trials serious a not serious not serious not serious none 52/4523 (1.1%) 76/4524 (1.7%) RR 0.70 (0.50 to 0.98) 5 fewer per 1,000 (from 0 fewer to 8 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Admission to neonatal intensive care unit 13 randomized trials serious a not serious not serious not serious none 320/4271 (7.5%) 363/4260 (8.5%) RR 0.88 (0.77 to 1.01) 10 fewer per 1,000 (from 1 more to 20 fewer) ⨁⨁⨁◯ MODERATE CRITICAL CI: Confidence interval; RR: Risk ratio Explanations a. All studies have design limitations (-1) b. Wide 95% CI crossing the line of no effect (-1) c. Single study with design limitations (-1) d. Wide 95% CI crossing the line of no effect, and small sample size (-2) 38 WHO recommendations: induction of labour at or beyond term Question: Labour induction compared to expectant management (gestational age at induction) for improving birth outcomes for women at or beyond term Setting: Hospital or medical centres in Austria, Canada, China, Finland, France, India, Netherlands, Norway, Spain, Sweden, Thailand, Tunisia, Turkey, UK, US Certainty assessment № of patients Effect Certainty Importance № of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Labour induction Expectant management (gestational age at induction) Relative (95% CI) Absolute (95% CI) Caesarean section < 41 weeks 9 randomized trials serious c not serious not serious not serious none 191/1532 (12.5%) 175/1274 (13.7%) RR 1.04 (0.87 to 1.24) 5 more per 1,000 (from 18 fewer to 33 more) ⨁⨁⨁◯ MODERATE CRITICAL Caesarean section ≥ 41 weeks 17 randomized trials serious c not serious not serious not serious none 774/4407 (17.6%) 857/4396 (19.5%) RR 0.90 (0.83 to 0.98) 19 fewer per 1,000 (from 4 fewer to 33 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Operative vaginal birth (forceps or ventouse) < 41 weeks 7 randomized trials serious c not serious not serious not serious none 304/1327 (22.9%) 198/1074 (18.4%) RR 1.27 (1.08 to 1.48) 50 more per 1,000 (from 15 more to 88 more) ⨁⨁⨁◯ MODERATE IMPORTANT Operative vaginal birth (forceps or ventouse) ≥ 41 weeks 10 randomized trials serious c not serious not serious not serious none 668/3383 (19.7%) 665/3368 (19.7%) RR 1.00 (0.91 to 1.10) 0 fewer per 1,000 (from 18 fewer to 20 more) ⨁⨁⨁◯ MODERATE IMPORTANT Perinatal death < 41 weeks 5 randomized trials serious c not serious not serious very serious d none 0/771 (0.0%) 3/781 (0.4%) RR 0.33 (0.05 to 2.06) 3 fewer per 1,000 (from 4 fewer to 4 more) ⨁◯◯◯ VERY LOW CRITICAL 39WHO recommendations: induction of labour at or beyond term Certainty assessment № of patients Effect Certainty Importance№ of studies Study design Risk of bias Inconsistency Indirectness Imprecision Other considerations Labour induction Expectant management (gestational age at induction) Relative (95% CI) Absolute (95% CI) Perinatal death ≥ 41 weeks 15 randomized trials serious c not serious not serious not serious none 2/4217 (0.0%) 13/4191 (0.3%) RR 0.33 (0.13 to 0.87) 2 fewer per 1,000 (from 0 fewer to 3 fewer) ⨁⨁⨁◯ MODERATE CRITICAL Stillbirth < 41 weeks 5 randomized trials serious c not serious not serious very serious d none 0/771 (0.0%) 3/781 (0.4%) RR 0.33 (0.05 to 2.06) 3 fewer per 1,000 (from 4 fewer to 4 more) ⨁◯◯◯ VERY LOW CRITICAL Stillbirth ≥ 41 weeks 15 randomized trials serious c not serious not serious serious e none 1/4217 (0.0%) 7/4191 (0.2%) RR 0.34 (0.09 to 1.24) 1 fewer per 1,000 (from 0 fewer to 2 fewer) ⨁⨁◯◯ LOW CRITICAL Admission to neonatal intensive care unit < 41 weeks 3 randomized trials serious c not serious not serious very serious d none 11/502 (2.2%) 12/503 (2.4%) RR 0.92 (0.41 to 2.05) 2 fewer per 1,000 (from 14 fewer to 25 more) ⨁◯◯◯ VERY LOW CRITICAL Admission to neonatal intensive care unit ≥ 41 weeks 9 randomized trials serious c not serious not serious not serious none 307/3704 (8.3%) 350/3693 (9.5%) RR 0.88 (0.76 to 1.01) 11 fewer per 1,000 (from 1 more to 23 fewer) ⨁⨁⨁◯ MODERATE CRITICAL CI: Confidence interval; RR: Risk ratio Explanations a. Single study with design limitations (-1) b. Wide 95% CI crossing the line of no effect, and small sample size (-2) c. All studies have design limitations (-1) d. Wide 95% CI crossing the line of no effect, and low event rate (-2) e. Wide 95% CI crossing the line of no effect (-1) 40WHO recommendations: induction of labour at or beyond term For more information, please contact the following departments: Reproductive Health and Research Fax: +41 22 791 4171 E-mail: reproductivehealth@who.int www.who.int/reproductivehealth Maternal, Newborn, Child and Adolescent Health E-mail: mncah@who.int World Health Organization Avenue Appia 20, CH-1211 Geneva 27, Switzerland ISBN 978-92-4-155041-3