WHO recommendations: Induction of labour at or beyond term
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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. If you create a translation of this work, you should add the following disclaimer along with the suggested citation: “This trans- lation 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. Suggested citation. WHO recommendations: induction of labour at or beyond term. Geneva: World Health Organization; 2018. 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 http://www.who.int/about/licensing. 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 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
2 WHO recommendations: induction of labour at or beyond term
ACKNOWLEDGEMENTS
The Department of Reproductive Health and and Olufemi Oladapo revised the narrative
Research of the World Health Organization summaries and double-checked the cor-
gratefully acknowledges the contributions responding GRADE tables and prepared the
of many individuals and organizations to the Evidence-to-Decision frameworks. Joshua
updating of these recommendations. Work on Vogel, Olufemi Oladapo, A. Metin Gülmezoglu,
this update was coordinated by Olufemi Ola- Ana Pilar Betrán, Özge Tunçalp and Mercedes
dapo, Joshua Vogel and A. Metin Gülmezoglu Bonet commented on the draft document
of the WHO Department of Reproductive Health before it was reviewed by participants at the
and Research. WHO Guideline Development Group meeting.
The External Review Group peer reviewed the
WHO extends its sincere thanks to Edgardo
final document.
Abalos, Ebun Adejuyigbe, Shabina Ariff, Jemi-
ma Dennis-Antwi, Luz Maria De-Regil, Christine We acknowledge the various organizations
East, Lynn Freedman, Pisake Lumbiganon, that were represented by observers, including
Anita Maepioh, James Neilson, Hiromi Obara, Deborah Armbruster and Mary-Ellen Stanton
Rachel Plachcinski, Zahida Qureshi, Kathleen (United States Agency for International Develop-
Rasmussen, Niveen Abu Rmeileh and Eleni ment), Kathleen Hill (Maternal and Child Survival
Tsigas who served as members of the Guide- Program/Jhpiego), Jerker Liljestrand (Bill &
line Development Group (GDG), and to Zahida Melinda Gates Foundation), Lesley Page (Inter-
Qureshi (Chair) and Jim Neilson (Vice-Chair) national Confederation of Midwives), Gerard
for leading the meeting. We also thank José Visser (International Federation of Gynaecology
Guilherme Cecatti, Sylvia Deganus, M Jeeva and Obstetrics) and Charlotte Warren (Ending
Sankar, Hayfaa Wahabi, Jack Moodley, Jane Eclampsia Project, Population Council). We also
Sandall, Ola Shaker and Nguyen Xuan Hoi who appreciate the contributions of WHO Regional
were members of the External Review Group. Office staff – Nino Berdzuli, Bremen De Mucio,
WHO also gratefully acknowledges the contri- Chandani Anoma Jayathilaka, Ramez Khairi
bution of the members of the Executive Guide- Mahaini, Léopold Ouedraogo and Howard
line Steering Group. Sobel.
Anna Cuthbert, Leanne Jones, Frances Kellie The United States Agency for International
and Myfanwy Williams reviewed the scientific Development and the Department of Reproduc-
evidence, prepared the Grading of Recom- tive Health and Research provided financial
mendations, Assessment, Development, and support for this work. The views of the funding
Evaluation (GRADE) tables and drafted the bodies have not influenced the content of these
narrative summary of evidence. Joshua Vogel recommendations.WHO recommendations: induction of labour at or beyond term 3 ABBREVIATIONS 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
4 WHO recommendations: induction of labour at or beyond term
EXECUTIVE SUMMARY
Introduction Target audience
Induction of labour is defined as the process The primary audience of these recommendations
of artificially stimulating the uterus to start includes health professionals who are
labour. It is usually performed by administering responsible for developing national and local
oxytocin or prostaglandins to the pregnant health protocols (particularly those related to
woman or by manually rupturing the amniotic induction of labour) and those directly providing
membranes. Induction of labour is not risk- care to pregnant women and their newborns,
free, and many women find it uncomfortable. including: midwives, nurses, general medical
Over the past several decades, the incidence practitioners, obstetricians, managers of maternal
of inducing labour for shortening the duration and child health programmes, and relevant staff
of pregnancy has continued to rise. In high- in ministries of health, in all settings.
income countries, the proportion of infants
delivered at term following induction of labour
Guideline development methods
can be as high as one in four births. In low- and
middle-income countries the rates are generally The updating of these recommendations was
lower, but in some settings, they can be as high guided by standardized operating procedures in
as those observed in high-income countries. accordance with the process described in the
WHO handbook for guideline development. The
Improving care for women around the time
recommendations were initially developed using
of childbirth is a necessary step towards
this process, namely:
the achievement of the health targets of the
Sustainable Development Goals (SDGs). Efforts (i) identification of the priority question and
to prevent and reduce morbidity and mortality critical outcomes;
during pregnancy and childbirth could help
(ii) retrieval of evidence;
address the profound inequities in maternal and
perinatal health globally. To achieve these aims, (iii) assessment and synthesis of evidence;
healthcare providers, health managers, policy (iv) formulation of the recommendation; and
makers and other stakeholders need up-to-
(v) planning for the dissemination,
date and evidence-based recommendations to
implementation, impact evaluation and
inform clinical policies and practices.
updating of the recommendations.
In 2017, the Executive Guideline Steering Group
(GSG) on the World Health Organization’s The scientific evidence supporting the recom-
(WHO) maternal and perinatal health mendations was synthesized using the Grading
recommendations prioritized the updating of Recommendations, Assessment, Develop-
of the existing WHO recommendations on ment, and Evaluation (GRADE) approach. This
the induction of labour at or beyond term in systematic review was used to prepare evi-
response to important new evidence on this dence profiles for the prioritized question. WHO
intervention. These recommendations are a convened an online meeting on 2 May 2018
revalidation of the previous recommendations where an international group of experts – the
issued in 2011 in the WHO recommendations Guideline Development Group (GDG) – reviewed
on induction of labour. and approved the recommendations.WHO recommendations: induction of labour at or beyond term 5
The recommendations minor revisions to the remarks and implementa-
tion considerations.
The GDG reviewed the balance between the
desirable and undesirable effects and the over- To ensure that the recommendations are cor-
all certainty of supporting evidence, values and rectly understood and applied in practice,
preferences of stakeholders, resource require- guideline users should refer to the remarks, as
ments and cost- effectiveness, acceptability, well as to the evidence summary if there is any
feasibility and equity. The GDG revalidated the doubt as to the basis for the recommendations
WHO recommendations published in 2011 with 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- Induction of labour
cent girls died as a result of pregnancy and
Induction of labour is the process of artificially
childbirth-related complications in 2015, around
stimulating the uterus to start labour (6). It is
99% of which occurred in low-resource settings
usually performed by administering oxytocin or
(1). Haemorrhage, hypertensive disorders and
prostaglandins to the pregnant woman, or by
sepsis are responsible for more than half of all
artificially rupturing the amniotic membranes.
maternal deaths worldwide. Thus, improving
Induction of labour is not risk-free, and many
the quality of maternal healthcare for women is
women find it uncomfortable.
a necessary step towards achievement of the
health targets of the Sustainable Development Over the past several decades, the incidence
Goals (SDGs). International human rights law of labour induction for shortening the dura-
includes fundamental commitments by states to tion of pregnancy has continued to rise. In
enable women and adolescent girls to survive high-income countries (HICs), the proportion of
pregnancy and childbirth as part of their enjoy- infants delivered at term following induction of
ment of sexual and reproductive health and labour can be as high as one in four births (7-9).
rights and living a life of dignity (2). The World In low- and middle- income countries (LMICs),
Health Organization (WHO) envisions a world the rates are generally lower, but in some set-
where “every pregnant woman and newborn tings, they can be as high as those observed in
receives quality care throughout the pregnancy, HICs (10, 11).
childbirth and the postnatal period” (3).
In 2011, the World Health Organization (WHO)
There is evidence that effective interventions published 17 recommendations on induction
exist at reasonable cost for the prevention or of labour, including two recommendations
treatment of virtually all life-threatening mater- on the induction of labour at or beyond term
nal complications (4). Almost two-thirds of the (12). These recommendations were developed
global maternal and neonatal disease burden according to the WHO guideline development
could be alleviated through optimal adapta- standards, including synthesis of available
tion and uptake of existing research findings research evidence, use of the GRADE method-
(5). To provide good quality care, healthcare ology and formulation of recommendations by
providers at all levels of maternal healthcare a guideline panel of international experts. The
services (particularly in low- and middle-income 2011 recommendations also included several
countries) need to have access to appropriate general principles related to the practice of
medications and training in relevant proce- induction of labour, which are reiterated here:
dures. Healthcare providers, health managers, • Induction of labour should be performed
policymakers and other stakeholders also need only when there is a clear medical indication
up-to-date, evidence-based recommendations for it and the expected benefits outweigh its
to inform clinical policies and practices, in order potential harms;
to optimize quality of care, and enable improved • In applying the recommendations on induc-
healthcare outcomes. Efforts to prevent and tion of labour, consideration must be given to
reduce morbidity and mortality in pregnancy the actual condition, wishes and preferences
and childbirth could reduce the profound ineq- of each woman, with emphasis being placed
uities in maternal and perinatal health globally. on cervical status, the specific method ofWHO recommendations: induction of labour at or beyond term 7
induction of labour and associated conditions of induction of labour. These recommendations
such as parity and rupture of membranes; provide a foundation for the sustainable imple-
• Induction of labour should be performed with mentation of the intervention globally.
caution since the procedure carries the risk
of uterine hyperstimulation and rupture, and
Target audience
fetal distress;
• Wherever induction of labour is carried out, The primary audience includes health profes-
facilities should be available for assessing sionals who are responsible for developing
maternal and fetal well-being; national and local health guidelines and pro-
• Women receiving oxytocin, misoprostol or tocols (particularly those related to induction
other prostaglandins should never be left of labour) and those directly providing care to
unattended; women during labour and childbirth, including
• Failed induction of labour does not midwives, nurses, general medical practition-
necessarily indicate caesarean section; and ers, obstetricians, managers of maternal and
• Wherever possible, induction of labour child health programmes and relevant staff in
should be carried out in facilities where ministries of health, in all settings.
caesarean sections can be performed. These recommendations will also be of interest
to professional societies involved in the care of
Rationale and objectives pregnant women, nongovernmental organiza-
tions concerned with promoting people-centred
In 2017, WHO established a new process for
maternal care, and implementers of maternal
prioritizing and updating maternal and perinatal
and child health programmes.
health recommendations whereby an Executive
Guideline Steering Group (GSG) oversaw a sys-
tematic prioritization of maternal and perinatal Scope of the recommendations
health recommendations in most urgent need of Framed using the population (P), intervention (I),
updating (13). Recommendations were prior- comparison (C), outcome (O) (PICO) format, the
itized on the basis of changes or important, new question for these recommendations was:
uncertainties in the underlying evidence base • In pregnant women at or beyond term (P),
on benefits, harms, values placed on outcomes, does induction of labour (I), compared to
acceptability, feasibility, equity, resource use, expectant management (C), improve mater-
cost-effectiveness or factors affecting imple- nal and perinatal outcomes (O)?
mentation. The Executive GSG prioritized the
updating of the existing WHO recommenda-
Persons affected by the recommendations
tions on induction of labour at or beyond term in
response to new, potentially important evidence The population affected by these recommenda-
on this question. tions includes pregnant women in low, middle
or high-income settings, particularly those who
The primary goal of these recommendations is
experience a post-term pregnancy.
to improve the quality of care and outcomes for
pregnant women, particularly related to the use8 WHO recommendations: induction of labour at or beyond term
2. METHODS
The recommendations were first developed Group drafted the key recommendation ques-
using standardized operating procedures in tions in PICO format, identified the systematic
accordance with the process described in the review team and guideline methodologist, as
WHO handbook for guideline development (14). well as the guideline development and external
In summary, the process included: review groups. In addition, the WHO Steering
Group supervised the syntheses and retrieval
(i) identification of the priority question and criti-
of evidence, organized the Guideline Develop-
cal outcomes;
ment Group meeting, drafted and finalized the
(ii) retrieval of the evidence; guideline document, and managed the guide-
line dissemination, implementation and impact
(iii) assessment and synthesis of evidence;
assessment. The members of the WHO Steer-
(iv) formulation of the recommendations; and ing Group are listed in Annex 1.
(v) planning for the dissemination,
implementation, impact evaluation and Guideline Development Group
updating of the recommendations. The WHO Steering Group identified a pool
of approximately 50 experts and relevant
WHO recommendations on induction of labour
stakeholders from the six WHO regions to
at or beyond term were identified by the
constitute the WHO Maternal and Perinatal
Executive GSG as a high priority for updating in
Health Guideline Development Group (MPH-
response to new, potentially important evidence
GDG). This pool is a diverse group of experts
on this question. Six main groups were
who are skilled in the critical appraisal
involved in this process, with their specific roles
of research evidence, implementation of
described in the following sections.
evidence-based recommendations, guideline
development methods, and clinical practice,
Contributors to the guideline policy and programmes relating to maternal and
perinatal health. Members of the MPH-GDG
Executive Guideline Steering Group are identified in a way that ensures geographic
(Executive GSG) representation and gender balance, and
The Executive GSG is an independent panel there were no significant conflicts of interest.
of 14 external experts and relevant stakehold- Members’ expertise cuts across thematic areas
ers from the six WHO regions: African Region, within maternal and perinatal health.
Region of the Americas, South-East Asia From the MPH-GDG pool, 16 external experts
Region, European Region, Eastern Mediterra- and relevant stakeholders were invited to
nean Region, and Western Pacific Region. The constitute the Guideline Development Group
Executive GSG advises WHO on the prioritiza- (GDG) for updating these recommendations.
tion of new and existing questions in maternal Those selected were a diverse group with
and perinatal health for recommendation devel- expertise in research, guideline development
opment or updating (15). methods, and clinical policy and programmes
relating to maternal and perinatal health.
WHO Steering Group
The 16 GDG members invited for the update
The WHO Steering Group, comprising WHO of these two recommendations were also
staff members from the Departments of Repro- selected in a way that ensured geographic
ductive Health and Research (RHR), Maternal, representation and gender balance and there
Newborn, Child and Adolescent Health (MCA) were no important conflicts of interest. The
and Nutrition for Health and Development Group appraised the evidence that was used
(NHD) managed the updating process. The to inform the recommendations, advised onWHO recommendations: induction of labour at or beyond term 9
the interpretation of thi evidence, formulated Jhpiego, the Bill & Melinda Gates Foundation
the final recommendations based on the draft (BMGF), the International Confederation of
prepared by the Steering Group, and reviewed Midwives (ICM), the International Federation
and approved the final document. The members of Gynaecology and Obstetrics (FIGO) and
of this Group are listed in Annex 1. Population Council participated in the GDG
meeting as observers. These organizations,
External Review Group with a long history of collaboration with the
RHR Department in guideline dissemination
This Group included eight technical experts
and implementation, are implementers of the
with interest and expertise in the provision of
recommendations. The list of observers who
evidence- based obstetric care. None of its
participated in the GDG meeting is included in
members declared a conflict of interest. The
Annex 1.
Group reviewed the final document to identify
any errors of fact and commented on clar-
ity of the language, contextual issues and Identification of critical outcomes
implications for implementation. The Group The critical and important outcomes were
ensured that the decision-making processes aligned with the prioritized outcomes of the
had considered and incorporated contextual 2011 WHO recommendations on induction of
values and preferences of potential users of the labour (12). These outcomes were initially identi-
recommendations, healthcare professionals and fied through a search of key sources of relevant,
policy makers. They did not change the recom- published, systematic reviews and a prioritization
mendations that were formulated by the GDG. of outcomes by the 2011 GDG panel. All the out-
The members of the External Review Group are comes were included in the scope of this docu-
listed in Annex 1. ment for evidence searching, retrieval, grading
and formulation of the recommendations. The list
Systematic review team and guideline of outcomes is provided in Annex 2.
methodologists
A Cochrane systematic review on this ques- Evidence identification and retrieval
tion was updated, supported by the Cochrane
Pregnancy and Childbirth Group (15). The WHO A Cochrane systematic review was updated
Steering Group reviewed and provided input and was the primary source of evidence for
into the protocol and worked closely with the these recommendations (15).
Cochrane Pregnancy and Childbirth Group to Randomized controlled trials (RCTs) relevant to
appraise the evidence using the Grading of the key question were screened by the review
Recommendations Assessment, Development authors and data on relevant outcomes and
and Evaluation (GRADE) methodology. Rep- comparisons were entered into Review Man-
resentatives of the Cochrane Pregnancy and ager (RevMan) software. The RevMan file was
Childbirth Group attended the GDG meeting to retrieved from the Cochrane Pregnancy and
provide an overview of the available evidence Childbirth Group and customized to reflect the
and GRADE tables, and to respond to technical key comparisons and outcomes (those that
queries from the GDG. were not relevant to the recommendations were
excluded). Then the RevMan file was exported
External partners and observers to GRADE profiler software (GRADEpro) and
GRADE criteria were used to critically appraise
Representatives of the United States Agency for
the retrieved scientific evidence.
International Development (USAID), the Mater-
nal and Child Survival Programme (MCSP)/10 WHO recommendations: induction of labour at or beyond term
Finally, evidence profiles (in the form of GRADE ber of events, studies with relatively few par-
tables) were prepared for comparisons of inter- ticipants or events, and thus wide confidence
est, including the assessment and judgements intervals around effect estimates, were down-
for each outcome and the estimated risks. graded for imprecision.
Publication bias: The certainty rating could also
Certainty assessment and grading of the be affected by perceived or statistical evidence
evidence of bias to underestimate or overestimate the
effect of an intervention as a result of selective
The certainty assessment of the body of evi-
publication based on study results. Downgrad-
dence for each outcome was performed using
ing evidence by one level was considered where
the GRADE approach (16). The certainty of
there was strong suspicion of publication bias.
evidence for each outcome was rated as ‘high’,
‘moderate’, ‘low’ or ‘very low’ based on a set Certainty of evidence assessments are
of established criteria. The final rating of cer- defined according to the GRADE approach:
tainty of evidence was dependent on the factors
briefly described below. • High certainty: We are very confident that
the true effect lies close to that of the esti-
Study design limitations: The risk of bias was mate of the effect;
first examined at the level of individual study • Moderate certainty: We are moderately
and then across studies contributing to the out- confident in the effect estimate. The true
come. For randomized trials, certainty was first effect is likely to be close to the estimate of
rated as ‘high’ and then downgraded by one the effect, but there is a possibility that it is
(‘moderate’) or two (‘low’) levels, depending on substantially different;
the minimum criteria met by the majority of the • Low certainty: Our confidence in the effect
studies contributing to the outcome. estimate is limited. The true effect may be
Inconsistency of the results: The similarity in substantially different from the estimate of
the results for a given outcome was assessed the effect; and
by exploring the magnitude of differences in the • Very low certainty: We have very little con-
direction and size of effects observed in differ- fidence in the effect estimate. The true effect
ent studies. The certainty of evidence was not is likely to be substantially different from the
downgraded when the directions of the findings estimate of effect.
were similar and confidence limits overlapped,
whereas it was downgraded when the results Formulation of recommendations
were in different directions and confidence lim-
its showed minimal or no overlap. The WHO Steering Group used the evidence
profiles to summarise evidence on effects on the
Indirectness: The certainty of evidence was pre-specified outcomes. The evidence sum-
downgraded when there were serious or very mary and corresponding GRADE tables, other
serious concerns regarding the directness of related documents for assessment of values
the evidence, that is, whether there were impor- and preferences, resource requirements and
tant differences between the research reported cost-effectiveness, acceptability, feasibility and
and the context for which the recommendations equity were provided in advance to meeting par-
were being prepared. Such differences were ticipants, who were invited to submit their com-
related, for instance, to populations, interven- ments electronically in advance of the meeting.
tions, comparisons or outcomes of interest.
The GDG members and other participants
Imprecision: This assessed the degree of were then invited to attend an online GDG
uncertainty around the estimate of effect. As meeting (see Annex 1 for the list of partici-
this is often a function of sample size and num- pants) organized by the Steering Group onWHO recommendations: induction of labour at or beyond term 11
2 May 2018. During the meeting, the GDG Decision-making during the Guideline
members reviewed and discussed the balance Development Group meeting
between the desirable and undesirable effects
of the intervention and the overall certainty of During the meeting, the GDG reviewed and dis-
supporting evidence, values and preferences cussed the evidence summary and sought clari-
of stakeholders, resource requirements and fication. In addition to evaluating the balance
cost-effectiveness, acceptability, feasibility and between the desirable and undesirable effects
equity, before finalizing the recommendations of the intervention and the overall certainty
and remarks. of the evidence, the GDG applied additional
criteria based on the GRADE evidence-to-
decision framework to determine the direction
Declaration of interests by external and strength of the recommendations. These
contributors criteria included stakeholders’ values, resource
According to WHO regulations, all experts implications, acceptability, feasibility and equity.
must declare their relevant interests prior to Considerations were based on the experience
participation in WHO guideline development and opinions of members of the GDG and
processes and meetings. All GDG members supported by evidence from a literature search
were therefore required to complete a standard where available. Evidence- to-decision tables
WHO Declaration of Interest (DOI) form before were used to describe and synthesize these
engaging in the guideline development process considerations.
and before participating in the guideline-related Decisions were made based on consensus
meeting. The WHO Steering Group reviewed defined as the agreement by three quar-
each declaration before finalizing the experts’ ters or more of the participants. None of the
invitations to participate. Where any conflict GDG members expressed opposition to the
of interest was declared, the Steering Group recommendations.
determined whether such conflicts were seri-
ous enough to affect the expert’s objective
Document preparation
judgement on the guideline and recommenda-
tion development process. To ensure consist- Prior to the online meeting, the WHO Steering
ency, the Steering Group applied the criteria for Group prepared a draft version of the GRADE
assessing the severity of conflict of interests in evidence profiles, evidence summary and other
the WHO Handbook for Guideline Development documents relevant to the deliberation of the
to all participating experts. All findings from GDG. The draft documents were made available
the DOI statements received were managed in to the participants of the meeting two weeks
accordance with the WHO DOI guidelines on a before the meeting for their comments. Dur-
case-by-case basis and communicated to the ing the meeting, these documents were modi-
experts. Where a conflict of interest was not fied in line with the participants’ deliberations
considered significant enough to pose any risk and remarks. Following the meeting, members
to the guideline development process or reduce of the WHO Steering Group drafted a recom-
its credibility, the experts were only required to mendation document to accurately reflect the
openly declare such conflicts of interest at the deliberations and decisions of the participants.
beginning of the GDG meeting and no further The draft document was sent electronically to
actions were taken. GDG members and the External Review Group
for final review and approval.
Annex 3 shows a summary of the DOI state-
ments, and how the conflicts of interest
declared were managed by the Steering Group.12 WHO recommendations: induction of labour at or beyond term
Peer review
Following review and approval by GDG mem- peer reviewers for inclusion in this document.
bers and the External Review Group, the final After the meeting and external peer review,
document was sent to eight external inde- the modifications made by the WHO Steering
pendent experts who were not involved in Group to the document consisted only of cor-
the guideline panel for peer review. The WHO recting factual errors and improving language
Steering Group evaluated the inputs of the to address any lack of clarity.
3. RECOMMENDATIONS strength and direction of the recommendations,
is included in the evidence-to- decision frame-
AND SUPPORTING work (Annex 4).
EVIDENCE The following recommendations were adopted
by the GDG. Evidence on the effectiveness of
The following section outlines the recommen- the intervention was derived from one
dations and the corresponding narrative sum- systematic review and was summarized in
mary of evidence for the prioritized question. GRADE tables (Annex 5). The certainty of the
The evidence-to- decision table, summarizing supporting evidence was rated as ‘low’ for
the balance between the desirable and unde- most critical outcomes. To ensure that the
sirable effects and the overall certainty of the recommendations are correctly understood
supporting evidence, values and preferences and appropriately implemented in practice,
of stakeholders, resource requirements, cost- additional ‘remarks’ reflecting the summary
effectiveness, acceptability, feasibility and of the discussion by GDG are included under
equity that were considered in determining the each recommendation.
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.WHO recommendations: induction of labour at or beyond term 13
4. DISSEMINATION AND IMPLEMENTATION
OF THE RECOMMENDATIONS
The dissemination and implementation of these Implementation considerations
recommendations is to be considered by all • The successful introduction of recommenda-
stakeholders and organizations involved in the tions into national programmes and health-
provision of care for pregnant women at the care services depends on well-planned and
international, national and local levels. There is participatory consensus-driven processes of
a vital need to increase access and strengthen adaptation and implementation. The adap-
the capacity of health centres to provide high tation and implementation processes may
quality services to all women giving birth. It is include the development or revision of exist-
therefore crucial that these recommendations ing national guidelines or protocols based on
are translated into antenatal and intrapartum these recommendations;
care packages and programmes at country and • The recommendations should be adapted
health facility levels (where appropriate). into a locally appropriate document that can
meet the specific needs of each country and
Recommendation dissemination and health service. Any changes should be made
in an explicit and transparent manner;
evaluation
• A set of interventions should be established
A shorter document containing the recommen- to ensure that an enabling environment is
dations, remarks, implementation considera- created for the use of the recommenda-
tions and research priorities will be formulated tions (including, for example, the availability
for public dissemination. This document will of induction agents and monitoring capac-
have annexes (also made publicly available) ity), and that the behaviour of the healthcare
containing all the information in this document, practitioner changes towards the use of this
including methods, evidence-to-decision frame- evidence-based practice;
works and GRADE tables. • In this process, the role of local professional
The recommendations will be disseminated societies is important and an all-inclusive and
through WHO regional and country offices, participatory process should be encouraged;
ministries of health, professional organiza- • Providers and implementers should consider
tions, WHO collaborating centres, other United discussing with women the potential need for
Nations agencies and nongovernmental organi- induction of labour at ≥41 weeks during ante-
zations, among others. These recommenda- natal care contacts. This would provide women
tions will be also available on the WHO website with the opportunity to ask questions, under-
and in the WHO Reproductive Health Library. stand the benefits and possible risks of avail-
Updated recommendations are also routinely able options and allow them to make informed
disseminated during meetings or scientific con- decisions should post-term pregnancy occur;
ferences attended by WHO MPH staff. • In 2016, WHO recommended the routine use
of one ultrasound scan before 24 weeks of
The recommendation document will be translat-
gestation (30). Implementation of these recom-
ed into the six UN languages and disseminated
mendations can assist in improving the accu-
through the WHO regional offices. Technical
racy of gestational age estimation, to ensure
assistance will be provided to any WHO region-
that the recommendations on induction of
al office willing to translate the full recommen-
labour at ≥41 weeks are used appropriately;
dations into any of these languages.
• 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).14 WHO recommendations: induction of labour at or beyond term
5. RESEARCH 6. APPLICABILITY
IMPLICATIONS ISSUES
The GDG identified important knowledge gaps Anticipated impact on the organization of
that need to be addressed through primary care and resources
research, which may have an impact on these
recommendations. The following questions Implementing these evidence-based recom-
were identified as those that demand urgent mendations will require resources to ensure it
priority: is done safely, including staff time for monitor-
• What risks (for both the mother and the fetus) ing of women undergoing induction of labour.
are associated with induction of labour and, The GDG noted that updating training curricula
in terms of those risks, how does induction and providing training would increase impact
of labour compare with elective caesarean and facilitate implementation. Standardization
section? of care by including recommendations into
• What is the role of caesarean section in the existing maternity care packages and protocols
management of women in whom induction of can encourage healthcare provider behaviour
labour has failed? change.
• In settings where reliable gestational age
determination is problematic, what should be Monitoring and evaluating guideline
the policy for labour induction at term and implementation
post-term?
Implementation should be monitored at the
• Is further research required on the experi-
health-service level as part of broader efforts to
ence of women undergoing labour induction,
monitor and improve the quality of maternal and
and how much women value the main out-
newborn care. For example, interrupted time
comes associated with labour induction?
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).WHO recommendations: induction of labour at or beyond term 15
7. UPDATING THE
RECOMMENDATIONS
The Executive GSG convenes annually to review Following publication and dissemination of the
WHO’s current portfolio of maternal and perinatal updated recommendations, any concern about
health recommendations and to advise WHO on the validity of the recommendations will be
prioritization of new and existing questions for promptly communicated to the guideline imple-
recommendation development and updating. menters, in addition to any plans to update the
Accordingly, these recommendations will be recommendations.
reviewed and prioritized by the Executive GSG. In
WHO welcomes suggestions regarding addi-
the event that new evidence that could potentially
tional questions for inclusion in the updated
impact the current evidence base is identified,
recommendations. Please email your sugges-
the recommendations may be updated. If no new
tions to mpa-info@who.int.
reports or information is identified, the
recommendations may be revalidated.16 WHO recommendations: induction of labour at or beyond term
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86(8): 950-6.18 WHO recommendations: induction of labour at or beyond term
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)
Guideline development group Anita Maepioh
Nurse Educator
Edgardo Abalos
Department of Obstetrics and Gynaecology
Vice Director
National Referral Hospital
Centro Rosarino de Estudios Perinatales (CREP)
Honiara, Solomon Islands
Rosario, Argentina
James Neilson (GDG Vice-chair)
Ebun Adejuyigbe
Department of Women’s and Children’s Health
Consultant Neonatologist
The University of Liverpool
Department of Paediatrics and Child Health
Women’s NHS Foundation Trust
Obafemi Awolowo University
Liverpool, United Kingdom of Great Britain and
Ife, Nigeria
Northern Ireland
Shabina Ariff*
Hiromi Obara
Consultant Paediatrician and Neonatologist
Health Policy Advisor
Department of Paediatrics and Child Health
Japan International Cooperation Agency (JICA)
Aga Khan University
Vientiane, Lao People’s Democratic Republic
Karachi, Pakistan
Zahida Qureshi (GDG Chair)
Jemima Dennis-Antwi*
Associate Professor
International Consultant in Midwifery
Department of Obstetrics and Gynaecology
West Legon
School of Medicine
Accra, Ghana
University of Nairobi
Luz Maria de-Regil Nairobi, Kenya
Vice President, Global Technical Services and
Kathleen Rasmussen
Chief Technical Advisor
Professor of Maternal and Child Nutrition Divi-
Micronutrient Initiative
sion of Nutritional Sciences
Ottawa, Canada
Cornell University
Christine East New York, United States of America
Professor of Midwifery
Niveen Abu Rmeileh
Monash Women’s Maternity Services and
Director
Monash University
Institute of Community and Public Health
Monash Medical Centre
Birzeit University
Melbourne, Australia
West Bank and Gaza Strip
Lynn Freedman*
Eleni Tsigas
Director
Chief Executive Officer
Averting Maternal Death and Disability Program
Preeclampsia Foundation
Mailman School of Public Health
Melbourne, USA
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, ThailandWHO recommendations: induction of labour at or beyond term 19
Observers Systematic review team
Deborah Armbruster Anna Cuthbert
Senior Maternal and Newborn Health Advisor Research Associate
United States Agency for International Develop- Cochrane Pregnancy and Childbirth Group
ment (USAID) Editorial Office
Bureau for Global Health University of Liverpool
Washington (DC), United States of America Liverpool, United Kingdom of Great Britain and
Northern Ireland
Kathleen Hill
Maternal Health Team Lead MCSP/Jhpiego Leanne Jones
USAID Grantee Research Associate
Washington DC, United States of America Cochrane Pregnancy and Childbirth Group
Editorial Office
Jerker Liljestrand*
University of Liverpool
Senior Program Officer (Maternal, Neonatal and
Liverpool, United Kingdom of Great Britain and
Child Health)
Northern Ireland
Bill & Melinda Gates Foundation
Seattle, United States of America Frances Kellie
Managing Editor
Lesley Page
Cochrane Pregnancy and Childbirth Group
Representative
Editorial Office
International Confederation of Midwives (ICM)
University of Liverpool
Sydney University
Liverpool, United Kingdom of Great Britain and
Sydney, Australia
Northern Ireland
Mary-Ellen Stanton*
Myfanwy Williams
Senior Reproductive Health Advisor
Research Associate
United States Agency for International Develop-
Cochrane Pregnancy and Childbirth Group
ment (USAID)
Editorial Office
Bureau for Global Health
University of Liverpool
Washington DC, United States of America
Liverpool, United Kingdom of Great Britain and
Gerard H.A. Visser Northern Ireland
Chair, FIGO Committee on Safe Motherhood
and Newborn Health Department of Obstetrics
WHO country and regional officers
University Medical Center
Utrecht, The Netherlands Nino Berdzuli*
Sexual and Reproductive Health Noncommuni-
Charlotte Warren
cable diseases and life-course
Director – Ending Eclampsia Project
WHO Regional Office for Europe
Senior Associate, Maternal and Newborn Health
Copenhagen, Denmark
Population Council
Washington DC, United States of America20 WHO recommendations: induction of labour at or beyond term
Bremen De Mucio Mercedes Bonet
Sexual and Reproductive Health Medical Officer, RHR/MPA
WHO Regional Office of the Americas Maternal and Perinatal Health and Preventing
Montevideo, Uruguay Unsafe Abortion
Chandani Anoma Jayathilaka* Olufemi T. Oladapo
Family Health, Gender and Life Course Medical Officer, RHR/MPA
WHO Regional Office for South-East Asia Maternal and Perinatal Health and Preventing
New Delhi, India Unsafe Abortion
Ramez Khairi Mahaini* David Stenson
Reproductive and Maternal Health Volunteer, RHR/MPA
WHO Regional Office for the Eastern Mediter- Maternal and Perinatal Health and Preventing
ranean Unsafe Abortion
Cairo, Egypt
Özge Tunçalp
Léopold Ouedraogo* Scientist, RHR/MPA
Reproductive Health Maternal and Perinatal Health and Preventing
Health Promotion Cluster (HPR) Unsafe Abortion
WHO Regional Office for Africa
Joshua P. Vogel
Brazzaville, Republic of Congo
Technical Officer, RHR/MPA
Howard Sobel* Maternal and Perinatal Health and Preventing
Reproductive, Maternal, Newborn, Child and Unsafe Abortion
Adolescent Health Division of NCD and Health
through Life-Course Department of Maternal, Newborn, Child and
WHO Regional Office for the Western Pacific Adolescent Health
Manila, Philippines Maurice Bucagu
Medical Officer, MCA/PPP
WHO steering group Policy, Planning and Programmes
Department of Reproductive Health and Fran McConville
Research Technical Officer, MCA/PPP
Policy, Planning and Programmes
A. Metin Gülmezoglu
Coordinator, RHR/MPA Anayda Portela
Maternal and Perinatal Health and Preventing Technical Officer, MCA/MRD
Unsafe Abortion Research and Development
Ana Pilar Betrán
Medical Officer, RHR/MPA *unable to attend online GDG meeting
Maternal and Perinatal Health and Preventing
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