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RCOG Evidence-based Clinical Guidelines Induction of labour

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RCOG Evidence-based Clinical Guidelines Induction of labour

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An evidence-based guideline produced by the RCOG with funding from the NHS Executive and the National Institute for Clinical Excellence (NICE).
Content may be subject to copyright.
RCOG Evidence-based Clinical Guidelines
This is the eighth in a series of evidence-based guidelines that are being produced by the RCOG
with funding from the NHS Executive and the National Institute for Clinical Excellence (NICE).
The other titles already published in this series are:
The Initial Management of Menorrhagia
The Initial Investigation and Management of the Infertile Couple
The Management of Infertility in Secondary Care
Male and Female Sterilisation
The Management of Menorrhagia in Secondary Care
The Management of Infertility in Tertiary Care
The Care of Women Requesting Induced Abortion
The Use of Electronic Fetal Monitoring
Guidelines still in production include:
Antenatal Care for Healthy Women
Caesarean Section
Enquiries regarding the above guidelines can be addressed to:
Clinical Effectiveness Support Unit
RCOG
27 Sussex Place
Regent’s Park
London
NW1 4RG
Email: clinicalguidelines@rcog.org.uk
9 781900 364508
ISBN 1-900364-50-6
Royal College of Obstetricians and Gynaecologists
Setting Standards to Improve Women’s Health
Induction of labour
Evidence-based Clinical Guideline Number 9
RCOG Clinical Effectiveness Support Unit June 2001
GUIDELINE
Induction of labour
9
1465 RCOG Cover 5/6/01 4:05 pm Page 1
Induction
of Labour
Evidence-based Clinical Guideline Number 9
Induction
of Labour
Evidence-based Clinical Guideline Number 9
Clinical Effectiveness Support Unit
iii
Royal College of Obstetricians and Gynaecologists
Setting standards to Improve Women’s Health
First published June 2001
© Royal College of Obstetricians and Gynaecologists 2001
ISBN 1-900364-50-6
The RCOG consents to the copying of this Guideline for the purpose of producing local
protocols/guidelines in the United Kingdom. The RCOG would appreciate being cited as
the source.
The use of registered names, trademarks, etc. in this publication does not imply, even in
the absence of a specific statement, that such names are exempt from the relevant laws
and regulation and therefore free for general use.
Product liability: the RCOG can give no guarantee for information about drug dosage and
application thereof contained in this Guideline. In every individual case the respective
user must check its accuracy by consulting other pharmaceutical literature.
Published by the RCOG Press at the
Royal College of Obstetricians and Gynaecologists
27 Sussex Place
Regent’s Park
London
NW1 4RG
Registered Charity No. 213280
Typesetting and printing: FiSH, London
All correspondence with regard to the content of this Guideline should be addressed to:
Clinical Effectiveness Support Unit
Tel: +44 (0)20 7772 6342
Email: iol@rcog.org.uk
Copies of the Guideline can be obtained from:
RCOG Bookshop
Tel: +44 (0)20 7772 6275
Fax: +44 (0)20 7724 5991
Email: bookshop@rcog.org.uk
Website: www.rcog.org.uk
www.nice.org.uk
CONTENTS
List of Tables and Figures iv
Abbreviations and glossary of terms v
Guideline Development Group membership vii
Acknowledgements viii
1. Introduction 1
2. Summary of recommendations and practice algorithm 7
3. Definitions, abbreviations and outcome measures 14
4. Care during induction of labour 18
5. Indications for induction of labour 24
6. Methods of induction of labour in specific clinical situations 33
7. Vaginal or oral misoprostol (PGE1): research to date 49
References 52
Appendix 1: Cervical scoring systems 58
Appendix 2: Methodology of collaboration between CESU
and Cochrane Pregnancy and Childbirth Group 59
Appendix 3: Conflated oxytocin versus prostaglandin E2data 64
Appendix 4: Comparison of differing dosages for induction of labour
with oxytocin and/or amniotomy 75
v
List of tables
and figures
Table Content Page
1.1 Levels of evidence 5
1.2 Grading of recommendations 5
2.1 Oxytocin infusion 11
3.1 Definition and description of terms relating to induction of labour 15
6.1 Oxytocin infusion 47
Figure Content Page
1 Induction of labour clinical practice algorithm 12
2 Trends in induction of labour in England, Wales and Scotland
for the period 1980–97 14
vi
Abbreviations and
glossary of terms
Abbreviations
The following abbreviations are used within the Guideline.
AFI Amniotic fluid index
BP Blood pressure
CTG Cardiotocograph(y)
EFM Electronic fetal monitoring
FHR Fetal heart rate
IUGR Intrauterine growth restriction
LR Likelihood ratio
NNT Number needed to treat
IOL Induction of labour
OR Odds ratio
PG Prostaglandin (E2or E1)
PNMR Perinatal mortality rate
RCT Randomised controlled trial
RR Risk ratio/Relative risk
VE Vaginal examination
Glossary of terms
Case–control study The study reviews exposures or risk factors, comparing
the exposure in people who have the outcome of
interest, for example the disease or condition (i.e. the
cases) with patients from the same population who do
not have the outcome (i.e. controls).
Cohort study The study involves identification of two groups (cohorts)
of patients, one of which has received the exposure of
interest and one of which has not. These groups are
followed forward to see if they develop the outcome (i.e.
the disease or condition) of interest.
Likelihood ratio The likelihood that a given test result would be expected
in a patient with a disease compared with the likelihood
that the same result would be expected in a patient
without that disease.
Meta-analysis An overview of a group of studies that uses quantitative
methods to produce a summary of the results.
Nested case–control study This term is used to identify those studies where cases
and controls have been selected from among subjects in
a cohort study. (i.e. a case–control study nested within a
cohort).
vii
Number needed to treat The number of patients who need to be treated to
prevent one outcome.
Odds ratio Describes the odds that a case (a person with the
condition) has been exposed to a risk factor relative to
the odds that a control (a person without the condition)
has been exposed to the risk.
Positive predictive value The percentage of people who have a positive test who
really have the condition. The predictive value is
dependent upon the prevalence of the disease in the
population being tested, i.e. if the disease is rare, the
predictive value is low, due to the greater influence of
false positive tests.
Randomised controlled trial A group of patients is randomised into an experimental
group and a control group. These groups are followed
up for the variables and outcomes of interest. This study
is similar to a cohort study but the exposure is randomly
assigned. Randomisation should ensure that both groups
are equivalent in all aspects except for the exposure of
interest.
Risk Ratio Risk is a proportion or percentage. The risk ratio is the
ratio of risk of developing the outcome of interest in an
exposed group compared with the risk of developing the
same outcome in the control group. It is used in
randomised controlled trials and cohort studies.
Risk difference The difference in risk of developing the outcome of
interest between the exposed and control groups.
Sensitivity The ability of the test to detect those who have the
disease, i.e. the proportion (%) of people with the
condition who are detected as having it by the test.
Specificity The ability of the test to identify those without the
disease, i.e. the proportion of people without the
condition who are correctly reassured by a negative test.
For further definitions readers are referred to the following link:
http://cebm.jr2.ox.ac.uk/docs/glossary.html
For the purposes of this Guideline, data are presented as risk ratios (RR) where relevant
(i.e. in RCTs and cohort studies). Where these data are statistically significant they are
converted into numbers needed to treat.
The Use of Electronic Fetal Monitoring
viii
Guideline Development
Group membership and
acknowledgements
Professor AA Calder (Chairman)
Mrs B Beech Lawrence (Association for Improvements in the Maternity Services)
Mr R Cookson (Health economist from the University of East Anglia)
Dr P Crowley (Royal College of Obstetricians and Gynaecologists)
Dr P Danielian (British Maternal Fetal Medicine Society)
Dr A Farebrother (Faculty of Public Health Medicine)
Mr A Foulkes (Royal College of General Practitioners)
Mr P Harris (Help for Health Trust)
Dr G Lewis (Department of Health observer)
Professor J Neilson (Royal College of Obstetricians and Gynaecologists)
Miss J Rogers (Royal college of Midwives)
Ms J Thomas (Director CESU)
Mr A Kelly (Research Fellow CESU)
Ms J Kavanagh (Research Fellow CESU)
Peer reviewers who responded
The document was sent out to 61 peer reviewers (21 obstetricians, 16 midwives, 5
pharmaceutical industry representatives, 1 paediatrician, 1 public heath consultant, 7
consumer representatives, 2 methodologists, 2 anaesthetists, 2 psychologists, 1 emergency
services representative, 1 nurse, 1 general practitioner and 1 health economist). Responses
were received from 33 peer reviewers (15 obstetricians, 8 midwives, 1 public health
consultant, 1 consumer representative, 1 anaesthetist, 3 pharmaceutical industry
representatives, 2 methodologists, 1 health economist and 1 general practitioner).
Peter Brocklehurst, Griselda Cooper, Sara Paterson-Brown, Sally Price, Zarko Alfirevic,
Jean Chapple, Sarah Vause, John Barber, Tina Lavender, Gill Barber, Verena Wallace,
Michel Boulvain, Suzanne Cunningham, Ian MacKenzie, Fiona MacLeod, Bernie Ruszala,
Katie Yiannouzis, Richard Tiner, Peter Thompson, David Taylor, Mike Sutton, Edward G
Hughes, Jon Martin, Helen Spiby, Christina Oppenheimer, Steve Thornton, Pat Cartlidge,
Stavros Petrou , Jill Demilew, Justus Hofmeyr, Khalid Khan, Richard Goss and Rona
McCandlish.
Comments on the draft Guideline posted on the NICE website were received from
Margaret Lynch, Jayne Cox, Louise Doyle, Kathryn Hadfield, Anne Haggerty, Vivienne
Harold, Wendy Knight, Sharon Lynch, Michelle Manion, Julie Morley, Olwen Ogden,
Patricia Ormrod, Vivien Owens, Dolores Taggart, Rachel Thompson, Amanda
Woodward, John Williams, Valerie Simmons, Belinda Ackerman, Stephen Huntridge
(Ferring Pharmaceuticals Ltd), John Barber (Alliance Pharmaceuticals), Richard Tiner
(Association of the British Pharmaceutical Industry), Brian Muller (Pharmacia Ltd).
ix
Acknowledgements
The Guideline Development Group would like to thank Beverley Marks, Clinical
Guidelines Secretary CESU, who provided both administrative and research assistance;
Patricia Want, Librarian of the RCOG Markland Library, whose professional help and
comprehensive journals collection were invaluable; also library staff Ffionamarie Rae and
Lisa Xue for their assistance; staff of the British Library Science Two South Reading Room,
who provided essential inter-library loan support; Caroline Clark and Deborah Gray for
administrative support; Miranda Mugford (University of East Anglia) and Stavros Petrou
(Perinatal Epidemiology Unit, Oxford), who provided expert advice in the economics of
maternity services.
The production of this Guideline was greatly assisted by collaboration with the Cochrane
Pregnancy and Childbirth Group (CPCG). Many thanks for the support of Sonja
Henderson, Lynn Hampson, Claire Winterbottom, Justus Hofmeyr, Peter Brocklehurst,
Zarko Alfirevic, Michel Boulvain, Brenda Tan, Leanne Bricker, Murray Luckas, Linda
French, Caroline Smith, Danie Botha, Eileen Hutton, Ellen Mozurkewich and James
Neilson.
The Use of Electronic Fetal Monitoring
x
1. Introduction
For the purposes of this Guideline, induction of labour is defined as an
intervention designed to artificially initiate uterine contractions leading to
progressive dilatation and effacement of the cervix and birth of the baby.
This includes both women with intact membranes and women with
spontaneous rupture of the membranes but who are not in labour. As with
any other intervention, induction of labour may have unwanted effects.
Induction of labour is indicated only when it is agreed that the mother or
fetus will benefit from a higher probability of a healthy outcome than if birth
is delayed. The process of induction of labour should only be considered
when vaginal delivery is felt to be the appropriate route of delivery.
Induction of labour is a common procedure: about 20% of pregnant women
will have labour induced for a variety of reasons. Induction does not usually
involve just a single intervention but is a complex set of interventions and,
as such, presents challenges for both clinicians and mothers.
1.1 Aim of the Guideline
Clinical guidelines have been defined as: ‘systematically developed
statements that assist clinicians and patients in making decisions about
appropriate treatment for specific conditions’.1
The parameters of practice included in this document were arrived at after
careful consideration of the available evidence and should be considered as
guidelines only. Clinicians involved in intrapartum care must use their
professional knowledge and judgement when applying the
recommendations to the management of individual women.
The Guideline Development Group has developed this Guideline with the
following aims:
to evaluate the role of induction of labour with a live fetus within a
variety of clinical situations
to evaluate and compare the various methods of induction of labour of
women in relation to maternal and fetal outcome measures
to consider the resource implications of the use of induction of labour.
1.2 Who has developed the Guideline?
The Guideline was developed by a multiprofessional and lay working group
(Guideline Development Group) convened by the Royal College of
Obstetricians and Gynaecologists and supported by funding awarded by the
Department of Health and the National Institute for Clinical Excellence.
Members included representatives from:
Royal College of Obstetricians and Gynaecologists
Royal College of Midwives
Royal College of General Practitioners
British Maternal Fetal Medicine Society
British Association of Perinatal Medicine
Faculty of Public Health
1
Centre for Health Information Quality
Health economists from the University of East Anglia
Consumer groups, including the Association for Improvements in the
Maternity Services and Maternity Alliance
Plus
Staff from the RCOG Clinical Effectiveness Unit
Staff from the RCOG Clinical Effectiveness Unit provided support and
guidance with the Guideline development process, undertook the
systematic searches, retrieval appraisal of the evidence and composed
successive drafts of the document.
The Guideline Development Group was convened by the RCOG prior to the
adoption of this Guideline by NICE. Following adoption of the Guideline,
the membership of the group was modified to include additional consumer
input as well as input from a health economist.
All members of the Group made formal declarations of interest at the outset,
which were recorded. This record is kept on file at the RCOG.
1.3 For whom is the Guideline intended?
The Guideline has been developed under the auspices of the RCOG Clinical
Effectiveness Support Unit, funded by the Department of Health and the
National Institute for Clinical Excellence for practitioners in the UK. The
Guideline is of relevance to:
pregnant women and their families
professional groups who share in caring for women in labour, such as
obstetricians, midwives and general practitioners
those with responsibilities for planning intrapartum services, such as
directors of public health and NHS trust managers.
1.4 Local protocol development
It is anticipated that this national Guideline will be used as the basis for the
development of local protocols or guidelines, taking into account local
service provision and the needs of the local population. Ideally, local
development should take place in a multidisciplinary group setting that
includes commissioners of health care, general practitioners, specialists and
service users.
1.5 Methods used in the development of the Guideline
1.5.1 Topic areas
The Guideline Development Group constructed specific clinical questions
relating to the risks and benefits of induction of labour in relation to specific
maternal and neonatal outcomes. The systematic reviews that underpin
many of the practice recommendations within the Guideline are based on
trials that included women undergoing induction of labour with a live fetus
after 36 weeks.
1.5.2 The remit of the Guideline
Indications for induction of labour for healthy women with an
uncomplicated pregnancy are considered, e.g. prolonged pregnancy and
Induction of Labour
2
prelabour rupture of membranes at term. Variations in this policy for specific
conditions are also included, e.g. diabetes and multifetal pregnancy.
Conditions that may affect the safety and efficacy of induction of labour are
included, e.g. previous caesarean section.
The risks and benefits of induction of labour as an intervention for specific
clinical conditions arising in pregnancy are not included, e.g. pre-eclampsia.
1.5.3 Literature search strategy
The aim of the literature review was to identify and synthesise relevant
evidence within the published literature, in order to answer specific clinical
questions. Thus, clinical practice recommendations are based on evidence
where possible and gaps in the evidence for which future research is needed
are identified. Searches were carried out for each topic of interest.
The Cochrane Library, up to Issue 3 of 2000, was searched to identify
systematic reviews (with or without meta-analyses) of randomised
controlled clinical trials and randomised controlled trials.
The Cochrane Pregnancy and Childbirth Group (CPCG) specialist
register of completed and continuing controlled trials was searched by
the CPCG Trials Search Co-ordinator.2
The electronic database, MEDLINE (CD Ovid version), was searched for
the period January 1966 to November 2000, including foreign-language
publications.
The electronic database EMBASE was searched between 1988 to
November 2000 to identify publications, usually European, not indexed
on MEDLINE.
The Midwives Information and Resource Service (MIDIRS), CINAHL
(Cumulative Index to Nursing and Allied Health Literature) and the
British Nursing Index were searched to ensure that relevant nursing and
midwifery literature were included.
Guidelines by other development groups were searched for on the
National Guidelines Clearinghouse database, as were the TRIP database
and OMNI service on the Internet.
The reference lists in these guidelines were checked against the
Guideline Development Group’s searches, in order to identify any
missing evidence.
The Database of Abstracts and Reviews of Effectiveness (DARE) was
searched.
Reference lists of non-systematic review articles and studies obtained
from the initial search were reviewed and journals in the RCOG library
were hand-searched to identify articles not yet indexed.
There was no systematic attempt to search the ‘grey literature’
(conferences, abstracts, theses and unpublished trials).
The economic evaluation included a search of the NHS Economic
Evaluation Database (The Cochrane Library, Issue 1, 2001), MEDLINE
January 1966 to November 2000 and EMBASE 1988 to November
2000. Relevant experts in the field were contacted for further
information.
Searches were performed using generic and specially developed filters,
relevant MeSH (medical subject headings) terms and free text terms.
Details of literature searches are available on application to CESU, RCOG.
1.5.4 Sifting and reviewing the literature
A preliminary scrutiny of titles and abstracts was undertaken and full papers
were obtained if the research addressed the Guideline Development
Group’s question on the topic. Following a critical review of the full version
Introduction
3
of the study, articles not relevant to the subject in question were excluded.
Studies that did not report on relevant outcomes were also excluded.
For all the subject areas, evidence from the study designs least subject to
sources of bias were included. Where possible, the highest levels of
evidence were used, but all papers were reviewed using established guides
(see below). Published systematic reviews or meta-analyses have been used
if available.
For subject areas where neither was available, other appropriate
experimental or observational studies were sought.
1.5.5 Synthesising the evidence
Identified articles were assessed methodologically and the best available
evidence was used to form and support the recommendations. The highest
level of evidence was selected for each clinical question. Using the
evidence-level structure highlighted in Table 1.1, the retrieved evidence was
graded accordingly.
The definitions of the types of evidence used in this Guideline originate from
the US Agency for Health Care Policy and Research (Table 1.1).3The clinical
question dictates the highest level of evidence that should be sought. For
issues of therapy or treatment, the highest level of evidence is meta-analyses
of randomised controlled trials or randomised controlled trials. This would
equate to a Grade A recommendation using the system outlined in Section
1.5.6.
For issues of prognosis, a cohort study is the best level of evidence available.
The best possible level of evidence would equate to a grade B
recommendation using the system outlined in Section 1.5.6. Thus, it should
not be interpreted as an inferior grade of recommendation, as it represents
the highest level of evidence attainable for that type of clinical question.
All retrieved articles have been appraised methodologically using
established guides.4Where appropriate, if a systematic review, meta-
analysis or randomised controlled trial existed in relation to a topic, studies
of a weaker design were ignored.
The evidence was synthesised using qualitative methods. These involved
summarising the content of identified papers in the form of evidence tables
and agreeing brief statements that accurately reflect the relevant evidence.
Following a preliminary review of the available evidence, it became
apparent that there were in excess of 700 randomised controlled trials
concerning induction of labour, which would need to be examined in the
development of the Guideline. A collaboration between the Cochrane
Pregnancy and Childbirth Group and the Clinical Effectiveness Support Unit
of the Royal College of Obstetricians and Gynaecologists was formed in
order to develop an integrated series of systematic reviews examining the
various methods available for induction of labour. The methods used in the
development of these systematic reviews are outlined in Appendix 1. These
reviews included unpublished data in accordance with standard Cochrane
methodology.
When making judgements about resource use implications, the Group tried
as far as possible to rely on published economic evidence. On one occasion,
however, the Guideline Development Group requested a simple costing
exercise: the comparison of vaginal tablets versus vaginal gel for induction
of labour. In this case, good evidence was available about clinical
effectiveness and there were no major cost uncertainties that would
preclude drawing conclusions from a simple costing exercise.
Induction of Labour
4
Table 1.1 Levels of evidence
Level Evidence
Ia Evidence obtained from systematic review of meta-analysis of randomised controlled trials
Ib Evidence obtained from at least one randomised controlled trial
IIa Evidence obtained from at least one well-designed controlled study without randomisation
IIb Evidence obtained from at least one other type of well-designed quasi-experimental study
III Evidence obtained from well-designed non-experimental descriptive studies, such as
comparative studies, correlation studies and case studies
IV Evidence obtained from expert committee reports or opinions and/or clinical experience of
respected authorities
1.5.6 Forming and grading the recommendations
The Guideline Development Group was presented with the available
research evidence in order to answer its questions. From this,
recommendations for clinical practice were derived using consensus
methods. Where there were areas without available research evidence,
consensus was again used.
Recommendations were based on, and explicitly linked to, the evidence that
supports them. Consensus was reached using the nominal group technique.5
This consensus method involves the grading of draft recommendations by
the members of the Guideline Development Group prior to the meeting.
These recommendations and the gradings given to them were then
considered during the meeting and a group opinion was reached. The
recommendations were then graded according to the level of evidence upon
which they were based. The grading scheme used was based on a scheme
formulated by the Clinical Outcomes Group of the NHS Executive.1The
strength of the evidence on which each recommendation is based is shown
in Table 1.2.
Table 1.2 Grading of recommendations
Grade Requirements
A Requires at least one randomised controlled trial as part of a body of literature of overall
good quality and consistency addressing the specific recommendation (evidence levels
Ia, Ib)
B Requires the availability of well-conducted clinical studies but no randomised clinical
trials on the topic of the recommendation (evidence levels IIa, IIb, III)
C Requires evidence obtained from expert committee reports or opinions and/or clinical
experience of respected authorities. Indicates an absence of directly applicable clinical
studies of good quality (evidence level IV)
Good practice points
Recommended good practice based on the clinical experience of the Guideline
Development Group
It is accepted that, in this grading system, the evidence itself is not graded
according to individual methodological quality of the studies, although it is
discussed in the text supporting each recommendation. Limited results or
data are presented in the text and these data are available in full in the
relevant evidence tables.
Grade C recommendations and good practice points are not based on
directly applicable research evidence. However, the views of the Guideline
Introduction
5
Development Group, combined with comments from the extensive peer
review as detailed below, suggest that the recommendations with these
gradings are acceptable to a wide body of expert opinion.
1.5.7 Peer review: scope and methods of peer review process
Successive drafts of the Guideline were written and discussed by the
Guideline Development Group. At the fourth draft stage, a formal peer
review process was undertaken.
Reviewers included representatives from stakeholder organisations
registered with NICE and individuals or organisations from the area of
practice represented in the Guideline Development Group. The draft
Guideline was submitted to these individuals or organisations with a request
for appraisal and comment.
The comments made by the peer reviewers were collated and presented
anonymously for consideration by the Guideline Development Group. All
peer review comments were considered systematically by the Group and the
resulting actions and responses were recorded. Seventy percent of the
comments resulted in amendments to the Guideline. Further information is
available on request.
The Guideline was also reviewed by the Guidelines Advisory Committee
and Executive of NICE.
The Guideline was sent to a further group of reviewers who particularly
concentrated on the methodology used in its development under the
independent guideline appraisal system approved by the NHS Executive.
The Guideline was made available for public comment on the NICE Website
for a period of four weeks.
1.6 How will the Guideline be disseminated and
reviewed?
The Guideline has been produced in both full by the RCOG, in summary
format by NICE, and in a consumer version by the RCOG. Summaries have
been disseminated to all Fellows and Members of the RCOG and are
available on the RCOG and NICE websites. Full copies of the printed
Guideline are available to purchase from the RCOG bookshop.
Full copies of the Guideline are available on the RCOG website
(www.rcog.org.uk) as a PDF. The Summary is available through the National
Electronic Library for Health (www.nelh.nhs.uk/) and National Guideline
Clearinghouse (www.guidelines.gov).
A consumer version of the Guideline, produced in association with the
Guideline Development Group and the Centre for Health Information
Quality, is available through NHS Direct Online (www.nhsdirect.nhs.uk/).
A national launch meeting took place on 12 June 2001 to disseminate the
findings of the group to interested parties.
The Guideline will be reviewed and revised within three years by NICE.
Induction of Labour
6
2. Summary of
recommendations
and practice
algorithm
2.1 Care during induction of labour
2.1.1 Woman-centred care (see Section 4.1)
CWomen must be able to make informed choices regarding their care
or treatment via access to evidence based information. These choices
should be recognised as an integral part of the decision-making
process.
2.1.2 Place of induction (see Section 4.2)
CFor women who are healthy and have had an otherwise
uncomplicated pregnancy, induction of labour with vaginal
prostaglandin E2agents can be conducted on antenatal wards, prior
to the active phase of labour.
CWhen undertaking induction of labour in women with recognised risk
factors (including suspected fetal growth compromise, previous
caesarean section and high parity), the induction process should not
occur on an antenatal ward.
2.1.3 Fetal surveillance and induction of labour (see Section 4.3)
CWherever induction of labour occurs, facilities should be available for
continuous uterine and fetal heart rate (FHR) monitoring.
CFetal wellbeing should be established immediately prior to induction
of labour.
CFollowing induction of labour with vaginal prostaglandins (PGE2),
fetal wellbeing should be established once contractions are detected
or reported.
CFor women who are healthy and have had an otherwise
uncomplicated pregnancy, the assessment of fetal wellbeing
following the administration of vaginal prostaglandins should
comprise an initial assessment with continuous electronic fetal
monitoring and, once normality is confirmed, intermittent monitoring
can be used.
Induction of Labour
7
CWhere oxytocin is being used for induction or augmentation of
labour, continuous electronic fetal monitoring should be used.
2.1.4 Uterine hypercontractility with induction agents (see Section 4.4)
CProlonged use of maternal facial oxygen therapy may be harmful to
the fetus and should be avoided. There is no research evidence
evaluating the benefits or risks associated with the short-term use of
maternal facial oxygen therapy in cases of suspected fetal
compromise.
BIn cases of uterine hypercontractility with a suspicious or pathological
cardiotocograph (CTG) secondary to oxytocin infusions, the oxytocin
infusion should be decreased or discontinued.
AIn the presence of abnormal FHR patterns and uterine
hypercontractility (not secondary to oxytocin infusion), tocolysis
should be considered.
A suggested regimen is subcutaneous terbutaline 0.25 milligrams.
BIn cases of suspected or confirmed acute fetal compromise, delivery
should be accomplished as soon as possible, taking account of the
severity of the FHR abnormality and relevant maternal factors. The
accepted standard has been that, ideally, this should be accomplished
within 30 minutes.
2.1.5 Care of higher-risk pregnancies (see Section 4.5)
CWhen undertaking induction of labour in women with recognised risk
factors (including suspected fetal growth compromise, previous
caesarean section and high parity), the clinical discussion regarding
the timing and method of induction of labour should be undertaken
at consultant level. The induction process should not occur on an
antenatal ward.
2.2 Indications for induction of labour
2.2.1 Prolonged pregnancy (see Section 5.2)
AAn ultrasound to confirm gestation should be offered before 20 weeks
of gestation, as this reduces the need for induction for perceived post-
term pregnancy.
AWomen with uncomplicated pregnancies should be offered induction
of labour beyond 41 weeks.
AFrom 42 weeks, women who decline induction of labour should be
offered increased antenatal monitoring consisting of a twice weekly
CTG and ultrasound estimation of maximum amniotic pool depth.
2.2.2 Diabetes in pregnancy (see Section 5.3)
CWomen who have pregnancies complicated by diabetes should be
offered induction of labour prior to their estimated date for delivery.
Induction of Labour
8
Summary of recommendations and practice algorithm
9
2.2.3 Induction of labour in the presence of prelabour rupture of the
membranes (see Section 5.5)
AWomen with prelabour rupture of the membranes at term (over 37
weeks) should be offered a choice of immediate induction of labour
or expectant management.
AExpectant management of women with prelabour rupture of the
membranes at term should not exceed 96 hours following membrane
rupture.
2.2.4 Induction of labour for maternal request prior to 41 weeks
(see Section 5.7)
Where resources allow, maternal request for induction of labour
should be considered when there are compelling psychological or
social reasons and the woman has a favourable cervix.
Multifetal pregnancy, macrosomia and a history of precipitate labour were
also considered by the Guideline Development Group for inclusion within
this section, but there was insufficient evidence upon which to base any
recommendations.
2.3 Method of induction of labour in specific clinical
situations
2.3.1 Membrane sweeping (see Section 6.2)
APrior to formal induction of labour, women should be offered
sweeping of the membranes.
AWhen membrane sweeping is proposed, discussions should include
information that informs women that membrane sweeping:
is not associated with an increase in maternal or neonatal
infection
is associated with increased levels of discomfort during the
examination and bleeding.
2.3.2 Oxytocin compared with prostaglandins for induction of labour
(see Section 6.3)
AProstaglandins should be used in preference to oxytocin when induction
of labour is undertaken in either nulliparous or multiparous women with
intact membranes, regardless of their cervical favourability.
AEither prostaglandins or oxytocin may be used when induction of
labour is undertaken in nulliparous or multiparous women who have
ruptured membranes, regardless of cervical status, as they are equally
effective.
2.3.3 Comparison of intracervical and intravaginal prostaglandins (PGE2)
(see Section 6.4)
AWhen induction of labour is undertaken with prostaglandins,
intravaginal PGE2should be used in preference to intracervical
preparations, as they are equally effective and administration of
vaginal PGE2is less invasive.
2.3.4 Comparison of different preparations of vaginal prostaglandin (PGE2)
(see Section 6.5)
AGiven that they are clinically equivalent, when induction of labour is
undertaken with vaginal PGE2preparations, vaginal tablets should be
considered in preference to gel formulations.
CRecommended regimens for vaginal PGE2preparations include:
PGE2tablets: 3 milligrams PGE26–8 hourly.
The maximum total dose is 6 milligrams for all women.
PGE2gels: 2 milligrams PGE2in nulliparous women with an
unfavourable cervix (Bishop’s score less than 4), 1 milligram for
all other women.
In either, a second dose of 1–2 milligrams can be administered
six hours later.
The maximum dose is 4 milligrams PGE2for nulliparous women
with an unfavourable cervix and 3 milligrams for all other women.
2.3.5 Comparison of different regimens of oxytocin administration
(see Section 6.6)
COxytocin should not be started for six hours following administration
of vaginal prostaglandins.
CIn women with intact membranes, amniotomy should be performed
where feasible prior to commencement of an infusion of oxytocin.
CWhen induction of labour is undertaken with oxytocin the
recommended regimen is:
a starting dose of 1–2 milliunits per minute
increased at intervals of 30 minutes or more.
The minimum dose possible of oxytocin should be used and this
should be titrated against uterine contractions aiming for a
maximum of three to four contractions every ten minutes.
Adequate contractions may be established at 12 milliunits per
minute.
In the summary of product characteristics the licensed maximum
dose is 20 milliunits per minute.
If higher doses are used the maximum dose used should not
exceed 32 milliunits per minute.
CLocal protocols for delivery of oxytocin for induction of labour
should:
specify and use the dose of oxytocin being delivered (milliunits
per minute) in preference to the volume of fluid being infused
(millilitres per minute)
be delivered through an infusion pump or via a syringe driver with
a non-return valve.
CTo reduce error, a standard dilution should always be used.
Suggested standardised dilutions and dose regimens include:
30 iu in 500 ml of normal saline; hence 1 ml/hr = 1milliunits per
minute
10 iu in 500 ml of normal saline; hence 3 ml/hr = 1milliunits per
minute.
Induction of Labour
10
Table 2.1 Oxytocin infusion
Time after Oxytocin dose
starting (minutes) (milliunits per minute) Volume infused (ml/hour)
Dilution 30 iu Dilution 10 iu
in 500 ml in 500 ml
0113
30226
60 4 4 12
90 8 8 24
120 12 12 36
150 16 16 48
180 20 20 60
210 24 24 72
240 28 28 84
270 32 32 96
Doses highlighted are quantities above those referred to in the summary of product
characteristics of 20 milliunits per minute
2.4 Future research recommendations (See Section 6.8)
Adequately powered randomised controlled trials reporting relevant clinical
outcomes in specific clinical groups are needed in order to:
evaluate further the effectiveness of different vaginal PGE2formulations
for induction of labour
evaluate the risks and benefits of vaginal/oral misoprostol for induction
of labour using commercially produced tablets of appropriate dose
evaluate the risks and benefits of induction of labour for women whose
pregnancies are complicated by:
– diabetes (divided according to aetiology of diabetes)
– multifetal pregnancy
– suspected fetal growth compromise
– macrosomia
evaluate screening in the UK for abnormal vaginal colonisation in cases
of prelabour rupture of the membranes at term.
Further studies are needed in order to develop and standardise measures of
maternal satisfaction, attitude and response to induction of labour.
Clinical practice algorithm
The recommendations have been combined into a clinical practice
algorithm, in order to allow the findings from this Guideline to be integrated
and implemented in clinical practice. The algorithm aims to guide users
through the decision pathways for evaluation of the needs of any woman
undergoing induction of labour. The algorithm draws directly on the
evidence presented in the Guideline and, hence, is not recommended for
use without prior consultation of this evidence.
Figure 1 Clinical practice algorithm for induction of labour
Summary of recommendations and practice algorithm
11
C
Induction of Labour
12
Induction of labour
Offer booking scan at < 20 weeks by LMP
Confirm expected date of delivery prior to induction
Induction should only be considered when vaginal delivery is felt to be the most appropriate mode of delivery
Due consideration should be given to maternal preferences and priorities prior to commencement of induction
Augment discussions where possible
with written information
Cervical feature Pelvic score
01 23
Dilatation (cm) < 1 1–2 2–4 > 4
Length of cervix (cm) > 4 2–4 1–2 < 1
Station (relative to ischial spines) –3 –2 –1/0 +1/+2
Consistency Firm Average Soft
Position Posterior Mid/Anterior –
Pregnancy complications present?
No Yes
Review at 40+ weeks Consideration of individual woman’s
clinical condition
Offer
Membrane sweep
Induction after 41 weeks
Offer
Membrane sweep
Induction at appropriate gestation
Initiate serial monitoring at 42 weeks
Measurement of single deepest pool of liquor
Twice-weekly CTG
Propose induction if
monitoring abnormal
Offer of induction declined from 42 weeks
Modified Bishop’s score
CTG = Cardiotocograph
IV = Intravenous
LMP = last menstrual period
PGE2= Prostaglandin E2
Induction of Labour
13
Method of induction of labour
Although parity does not appear to effect the choice of method of induction of labour
it should influence the dosage of drugs used.
Induction with vaginal
PGE2agents
Consideration should be
given to PGE2tablets in
preference to gel where
possible
Oxytocin not to be started
within six hours of last PGE2
Intravaginal
PGE2tablet
3 milligram PGE2
tablet 6–8 hourly
Maximum dose
6 milligrams
Induction with oxytocin
Treatment regimes:
milliunits per minute not
millilitres per minute
30 iu in 500 ml normal saline
1 millilitres/hr =
1 milliunits/minute
Deliver via either syringe
driver or infusion pump with
non-return valve
Oxytocin performance
optimised with ruptured
membranes
Intravaginal PGE2gel
Nulliparous women with a modified
Bishops score < 4 give 2 milligrams
All other patients give 1 milligrams
Repeat dose of 1–2 milligrams six
hourly
Maximum dose 4 milligrams
Most women should have adequate
contractions at 12 milliunits per
minute
Trials have used doses up to
32 milliunits per minute
Maximum licensed dose is
20 milliunits per minute
If regular contraction not established
after TOTAL of 5 iu (five hours on
suggested regimen) then induction
should be stopped
Consider
Intravaginal PGE2tablet or gel
Consider either
Intravaginal PGE2(tablet or gel)
IV oxytocin (in the presence of ruptured
membranes, spontaneous or amniotomy
Intact membranes
Irrespective of parity or cervical status
Ruptured membranes
Irrespective of parity or cervical status
Oxytocin (in the presence of ruptured membranes)
Time after Dose
starting delivery
(minutes) (milliunits/
minute)
01
30 2
60 4
90 8
120 12
150 16
180 20
210 24
240 28
270 32
3. Definitions,
abbreviations and
outcome measures
Induction of labour is a common procedure within obstetric practice. Data
on the rates of induction in England, Wales and Scotland are presented in
Figure 2 below. These data are taken from a recently produced Department
of Health report, but only reports on induction in England and Wales up
to1995 and for Scotland up to 1997.
It has been reported that some women who receive oxytocin augmentation
may be misclassified as having had induction of labour. These data for
England and Wales are probably overestimates as a result of this
misclassification.
Overall, in England and Wales for the period 1980–1995, the induction rate
varied between 16.8% and 20.6%. In Scotland there was a marked decrease
in induction rate between 1980 and 1992, following which there was a
return to the level seen in 1987.6
Figure 2 Trends in induction of labour in England, Wales and Scotland for
the period 1980–97
3.1 Definitions
The definitions in Table 3.1 below relate to a number of terms discussed in
the Guideline. These were agreed by the Guideline Development Group
and are used as working definitions in the remainder of the document.
Induction of Labour
14
0
5
10
15
20
25
30
1980 1985 89/90 90/91 91/92 92/93 93/94 94/95 96 1997
England & Wales Scotland
Table 3.1 Definitions and descriptions of terms relating to induction of labour
Term Definition
Labour The process of uterine contractions leading to progressive
effacement and dilatation of the cervix and birth of the baby. The
term is usually restricted to pregnancies at gestations greater than the
legal definition of fetal viability (24 weeks in the UK)
Induction of labour An intervention designed to artificially initiate uterine contractions
leading to progressive dilatation and effacement of the cervix and
birth of the baby. This includes both women with intact membranes
and women with spontaneous rupture of the membranes but who
are not in labour. The term is usually restricted to pregnancies at
gestations greater than the legal definition of fetal viability (24 weeks
in the UK)
Cervical ripening A component part of induction of labour employed when the cervix
is unfavourable in order to facilitate dilatation when labour is
established
Augmentation An intervention designed to increase the rate of progress of labour
Prolonged pregnancy For the purpose of this Guideline, defined as those pregnancies
continuing past 287 days (41 weeks) from the first day of the last
menstrual period
Cervical favourability Within the systematic reviews focusing on induction of labour, the
definition of favourable vs. unfavourable cervix varied depending on
the scoring system used (see Appendix 2); however, the cut-off
between unfavourable and favourable within the trials was set
between four and eight.
For the purposes of this Guideline, a favourable cervix
is defined as one with a modified Bishops score of
greater than eight7
Uterine hypercontractility The terminology of uterine hypercontractility is problematic. For the
(with or without FHR purpose of this Guideline, uterine hypercontractility without FHR
changes) changes included uterine tachysystole (more than five contractions
per ten minutes for at least 20 minutes) and uterine
hypersystole/hypertonus (a contraction lasting at least two minutes).
Uterine hyperstimulation with FHR changes denoted uterine
hyperstimulation syndrome (tachysystole or hypersystole with FHR
changes such as persistent decelerations, tachycardia or decreased
short term variability). However, due to varied reporting of this
outcome there is the possibility of subjective bias in interpretation.
In addition, it was not always clear from trials if these outcomes
were reported in a mutually exclusive manner
3.2 Outcome measures
A series of outcome measures was agreed during the production of the new
series of Cochrane systematic reviews on induction of labour (See Appendix
1). The Guideline Development Group used these outcome measures as the
basis for evaluating the efficacy of the different methods of induction of
labour examined in Section 3.
All the outcomes listed below were examined for each clinical situation
considered in the later sections.
Definitions, abbreviations and outcome measures
15
3.3 Maternal outcomes
The main outcomes considered to be important in relation to induction of
labour for the mother include:
time to vaginal delivery or vaginal delivery rates within a specified time
operative delivery rates (caesarean section and instrumental vaginal
delivery)
length of labour/incidence of prolonged labour
measures of effectiveness (oxytocin augmentation rates, epidural usage,
cervix unfavourable/unchanged at 1224 hours)
serious maternal morbidity or death
other adverse outcomes (e.g. uterine hypercontractility, postpartum
haemorrhage, maternal adverse effects)
measures of maternal satisfaction.
Vaginal delivery rates per se can be assumed to be a reciprocal of operative
delivery rates (instrumental and caesarean section). Therefore, it was felt to
be more informative to include a time factor in the outcome, such as time to
delivery or delivery achieved within a specific time interval. Data in trials
are inconsistently reported, e.g. time from treatment to vaginal delivery or
time from randomisation to delivery. As only summarised statistics of these
variables are presented, for example mean number of hours, pooling of
results from the trials is not possible.
Vaginal delivery not achieved in 24 hours is a useful benchmark to measure
efficacy of a chosen induction method, as it was felt that this represented a
realistic end-point for induction of labour. However, it is recognised a
number of methods used for induction of labour (e.g. sweeping of the
membranes) are not designed to initiate labour within 24 hours and, hence,
will not report on this outcome. Delivery after this period therefore should
not be interpreted as a failure of induction of labour.
Due to inconsistent reporting between trials, there is a paucity of available
data in the Cochrane reviews relating to successful vaginal delivery within
24 hours. The data available are presented in the relevant sections.
Data relating to length of labour or incidence of prolonged labour were not
collected for the new series of Cochrane reviews, due to the difficulties
mentioned above.
Uterine hypercontractility with or without FHR changes is used as an
adverse outcome measure related to the specific method of induction of
labour. The division between episodes of hypercontractility with associated
FHR changes and those without is often not clear in trial reports. The
definitions used in this Guideline and in the systematic reviews have been
standardised (see Appendix 2).
Maternal satisfaction was included as a pre-specified outcome in the series
of systematic reviews. However, it was reported infrequently and was largely
restricted to comparing different methods of induction of labour, rather than
womens views of induction of labour generally. Evidence derived from
qualitative or observational studies is not included, due to the availability of
higher levels of evidence.
3.4 Fetal outcomes
The main outcomes examined in relation to induction of labour for the fetus
include:
serious neonatal morbidity or perinatal death
Induction of Labour
16
other adverse perinatal outcomes (meconium-stained liquor, five-minute
Apgar score of less than seven, neonatal intensive care unit admission).
Serious neonatal morbidity and perinatal death were reported as a
composite outcome in the systematic reviews and included perinatal death,
neonatal encephalopathy, disability in childhood, and seizures and birth
asphyxia as defined by the trialists.
Definitions, abbreviations and outcome measures
17
4. Care during
induction of labour
Where research evidence was unavailable, the Guideline Development
Group used other quality appraised Guidelines to support their
recommendations.8,9 The recommendations regarding fetal surveillance
during induction of labour are taken from The Use of Electronic Fetal
Monitoring: The use and interpretation of cardiotocography in intrapartum
fetal surveillance.10
4.1 Woman-centred care
One of the priorities of intrapartum care is to enable women to make
informed choices regarding their care or treatment. To do so, they require
access to evidence-based information to help them in making their choices.
Verbal advice should be supported by accurate printed information, in a
format that women can understand and which they may take away with
them and read before the procedure.
Part of the dilemma of choice in relation to induction of labour can be
summarised by the following quote: It is difficult to determine true
choice, especially for some clinical issues, but the extent to which women
feel involved in such decisions may be one indicator of the quality of the
interaction with the professional, from the womens perspective.11
Induction of labour should only follow informed consent by the woman. For
consent to be fully informed it should include the reasons for induction, the
choice of method to be used and the potential risks and consequences of
accepting or declining an offer of induction of labour.
The process of induction of labour should only be considered when vaginal
delivery is felt to be the appropriate route of delivery.9
CWomen must be able to make informed choices regarding their care
or treatment via access to evidence based information. These choices
should be recognised as an integral part of the decision-making
process.
4.2 Place of induction
In the absence of specific risk factors, induction of labour with vaginal PGE2
may be initiated on the antenatal ward. However, there should be facilities
for continuous electronic monitoring of both FHR and uterine activity.8
When oxytocin is used for induction of labour (or augmentation), the
process should occur on a delivery suite.
Women receiving oxytocin for induction of labour (or augmentation) should
receive one-to-one midwifery care.
The issue of outpatient induction of labour with prostaglandin agents has
Induction of Labour
18
III
Evidence level
III
III
III
III
III
been addressed in a number of studies.12 However, none of these studies has
been performed in the UK. In the absence of relevant evidence, the
Guideline Development Group did not feel able to make any
recommendations regarding the safety of outpatient treatment.
Readers are referred to Section 6.5.3 for further discussion regarding time of
administration of vaginal PGE2.
Continuous care of the mother in labour has been shown to reduce
caesarean section rates and the use of analgesia. One systematic review of
continuous support in labour considered a variety of outcomes. Continuous
support in the included trials was provided by healthcare workers or lay
people. Therefore, no extrapolation to the provision of one-to-one midwifery
care can be made from these data.13
The importance of one-to-one midwifery care has been highlighted in a
number of expert reports.14,15
CFor women who are healthy and have had an otherwise
uncomplicated pregnancy, induction of labour with vaginal
prostaglandin E2agents can be conducted on antenatal wards, prior
to the active phase of labour.
CWhen undertaking induction of labour in women, with recognised
risk factors (including suspected fetal growth compromise, previous
caesarean section and high parity) the induction process should not
occur on an antenatal ward.
4.3 Fetal surveillance and induction of labour
The assessment of fetal wellbeing is only one component of intrapartum
care. It is an important area where due consideration must be given to
maternal preference and priorities in light of potential risk factors to both
mother and baby. The provision of accurate information in these
circumstances is essential to allow each woman to make the right decision
for her.
As with any other intervention induction of labour has unwanted effects. In
the current series of systematic reviews of vaginal or intracervical
prostaglandin PGE2the incidence of hypercontractility with or without FHR
changes ranged from 1% to 5%. There was no difference between the
different preparations.
When oxytocin is being used for induction of labour there is a similar risk of
FHR changes and, hence, continuous electronic fetal monitoring should be
used.10
Following instillation of prostaglandin agents, the woman should be advised
to lie down for at least 30 minutes, followed by continuous electronic
monitoring of the fetal heart until fetal wellbeing is established. This need
not be initiated until contractions are detected or reported.8
When oxytocin is employed following prostaglandin agents, it should not be
started within six hours of the administration of prostaglandins. This is as a
result of the potential uterotonic effect of combining oxytocin with
prostaglandin agents.
CWherever induction of labour occurs, facilities should be available for
continuous uterine and FHR monitoring.
Care during induction of labour
19
Ia
III
Ia
III
III
III
Induction of Labour
20
CFetal wellbeing should be established immediately prior to induction
of labour.
CFollowing induction of labour with vaginal prostaglandins (PGE2) fetal
wellbeing should be established once contractions are detected or
reported.
CFor women who are healthy and have had an otherwise
uncomplicated pregnancy, the assessment of fetal wellbeing
following the administration of vaginal prostaglandins should
comprise an initial assessment with continuous electronic fetal
monitoring and, once normality is confirmed, intermittent monitoring
can be used.
CWhere oxytocin is being used for induction or augmentation of
labour, continuous electronic fetal monitoring should be used.
4.4 Uterine hypercontractility with induction agents
The management of suspicious or pathological CTGs is directly addressed
within the RCOG Evidence-based Clinical Guideline The Use of Electronic
Fetal Monitoring.10 Readers are referred to Section 8.3. in that Guideline.
The recommendations arising from this section are shown below and the
Guideline Development Group felt they were appropriate to include within
this section.
If prostaglandin only has been used, removal of the remainder of the agent
may help to alleviate the uterine hypercontractility. However, irrigation of
the cervix or vagina is not beneficial.
Uterine hypercontractility with or without FHR changes during oxytocin
infusions usually resolves with reduction or cessation of the infusion, but if
this fails then tocolysis should be considered using the regimen published in
The Use of Electronic Fetal Monitoring.16 Although discussed in further
detail in Section 5.6 of that Guideline, the frequency of contractions with
oxytocin use should not exceed three to four contractions in every ten-
minute interval.
CProlonged use of maternal facial oxygen therapy may be harmful to the
fetus and should be avoided. There is no research evidence evaluating
the benefits or risks associated with the short-term use of maternal
facial oxygen therapy in cases of suspected fetal compromise.
BIn cases of uterine hypercontractility with a suspicious or pathological
CTG secondary to oxytocin infusions, the oxytocin infusion should be
decreased or discontinued.
AIn the presence of abnormal FHR patterns and uterine
hypercontractility (not secondary to oxytocin infusion), tocolysis
should be considered.
A suggested regimen is subcutaneous terbutaline 0.25 milligrams.
BIn cases of suspected or confirmed acute fetal compromise, delivery
should be accomplished as soon as possible, taking account of the
severity of the FHR abnormality and relevant maternal factors. The
accepted standard has been that, ideally, this should be accomplished
within 30 minutes.
III
Ia
4.5 Care of higher-risk pregnancies
This section covers conditions of pregnancy where there may be a risk of
increased adverse maternal or neonatal outcomes when induction of labour
is undertaken.
4.5.1 Induction of labour of women with suspected fetal growth compromise
Risks associated with fetal growth compromise
Infants with fetal growth compromise are at a higher risk of perinatal death.
One study found an association with perinatal mortality and growth
restriction that was nearly five times that of normal weight infants.17 Infants
with growth compromise enter labour in an increased state of vulnerability
and are more likely to become acidotic because of:
uteroplacental insufficiency
lower metabolic reserves due to intrauterine malnutrition or pre-existing
hypoxia
an umbilical cord more prone to compression due to a reduction in
amniotic fluid volume.
Reduction of risks associated with suspected fetal growth compromise
The Guideline Development Group was unable to locate any studies that
considered induction of labour specifically in babies with suspected fetal
growth compromise.
4.5.2 Induction of labour of women with a previous caesarean section
Risks associated with induction of labour in women with a previous
caesarean section
There are small amounts of RCT data relating to induction of labour in
women with a previous caesarean section. The Guideline Development
Group is aware of only four RCTs that focused on or reported subgroup data
relating to this group of women.1821 These studies included only 137
patients and, hence, are underpowered to evaluate the risks associated with
induction in this group or to comment on the relative efficacy of the agents
considered.
One review of observational data focused on safety issues when undertaking
induction of labour of women with a history of a previous caesarean
section.22 The review focused on induction of labour in women with
previous caesarean section with vaginal prostaglandins in comparison with
other agents and reviewed evidence from seven studies. The authors
concluded that the rate of vaginal delivery in this group of patients was
similar to that quoted for spontaneous labour after a previous caesarean
section, about 75%. The rate of uterine rupture from the largest of these
observational studies was calculated as:
0.2% (00.6%) for symptomatic rupture
1.1% (0.12.1%) for asymptomatic dehiscence and symptomatic rupture.
The authors commented on the varied terminology used to define uterine
rupture and the difficulty this posed for collecting reliable data on the risk of
induction of women with a previous caesarean section.
Reduction of risk with induction of labour of women with a history of a
previous caesarean section
In view of the sparsity of data specifically reporting in this subgroup, it is
difficult to make specific recommendations for practice. Careful consideration
of the risks of an induction of labour versus the risks of an elective caesarean
Care during induction of labour
21
IIa
Ib
III
section should be made in light of the womans wishes and views. From the
review of observational data and extrapolation of the data relating to induction
of labour of women in other subgroups, vaginal prostaglandins appear to be
safe. If and when oxytocin is used, the dose schedules employed should be
carefully considered. Overall, induction of women with previous caesarean
section should follow the working algorithm presented in the next section with
careful consideration of cervical status and membrane status.
4.5.3 Induction of labour of women with a breech presentation
About 34% of all pregnancies reach term with a fetus in the breech
presentation.23 A recent trial24 provides information on the risks and benefits
of planned caesarean section compared with planned vaginal breech
delivery. The data within the trials relating to those women with a breech
presentation who underwent induction of labour are not reported separately
from the whole group who were randomised to a planned vaginal delivery.
The perinatal mortality was lower for planned caesarean section compared
with planned vaginal breech delivery (1.6% vs. 5.0%; RR 0.33; 95% CI
0.190.56; NNT 29). Hence, no conclusions can be reached from these data
regarding induction of labour with a breech presentation.
4.5.4 Induction of labour of women of high parity
Risks associated with induction of labour in women of high parity
Induction of labour in women of high parity may be associated with an
increased incidence of precipitate labour, uterine rupture and postpartum
haemorrhage. One casecontrol study examined the role of vaginal
prostaglandins in the induction of labour in women of high parity and with
unfavourable cervices. This study examined 101 grand multiparae with
unfavourable cervices who underwent induction of labour. The control
group consisted of 202 grand multiparae who went into labour
spontaneously. There was a reduction in the rates of vaginal delivery (88.1%
vs. 96.5%; OR 0.27; 95% CI 0.100.70) when induction was compared with
spontaneous labour.
Caesarean section rates were increased in the induction group (8.9% vs. 3%;
OR 3.20; 95% CI 1.109.25) when compared with the spontaneous group.
One fetal death and one ruptured uterus occurred in the induction group.
Although this study is small it does highlight the risks associated with
induction of labour in women of high parity.
The 5th CESDI report included a focus group on cases involving a ruptured
uterus.25 Of the 42 cases of ruptured uterus, 30 (71%) women had a previous
caesarean section (only one woman had more than one previous caesarean
section). Of the 12 women with no uterine scar, 11 were parous (three were
para 1, two were para 2, three were para 3 and three were para 4).
Reduction of risk with induction of labour in women of high parity
The Guideline Development Group found one randomised controlled trial
that examined the role of a fast versus slow incremental regimen of
intravenous oxytocin infusion for the induction of labour in women of high
parity.26 The trials included 90 women of parity five or more requiring
induction of labour for medical or obstetric reasons. Both groups had the
same starting dose of two milliunits per minute. In the control (fast) group
this was doubled every 15 minutes. In the experimental (slow) group it was
doubled every 45 minutes until the women were experiencing three
contractions every ten minutes. This rate was maintained until delivery, with
a maximum of 32 milliunits per minute. The results showed little difference
in mode of delivery in both groups.
Induction of Labour
22
Ib
IIa
III
Ib
There were 13 precipitate labours in the fast group and no instances of
precipitate labour in the slow group (OR 0.09; 95% CI 0.030.30).
There were 17 instances of uterine hypercontractility (FHR changes were
unspecified) in the fast group and five instances in the slow group (OR 0.23;
95% CI 0.090.59).
There were no uterine ruptures in the slow group and three in the fast group
(OR 0.12; 95% CI 0.011.22).
No fetal/neonatal outcomes were reported.
4.5.5 Summary
There are insufficient data to comment on the risks of induction of
labour of women with babies with known growth restriction.
Induction of labour with a history of a previous caesarean section is not
contraindicated but careful consideration of the mothers clinical
condition should be taken before induction is started.
Induction of labour with a history of previous caesarean section can be
undertaken with vaginal prostaglandins with or without the use of
oxytocin and/or amniotomy, although the safety data is limited.
There is an increased risk associated with planned vaginal breech
delivery. The risks associated with induction of labour with a breech
presentation cannot be quantified from the available trial literature.
Induction of labour in women of high parity with standard oxytocin
regimens may be associated with an increase in uterine rupture.
4.5.6 Practice recommendations
CWhen undertaking induction of labour in women, with recognised
risk factors (e.g. including suspected fetal growth compromise,
previous caesarean section and high parity) the clinical discussion
regarding the timing and method of induction of labour should be
undertaken at consultant level. The induction process should not
occur on an antenatal ward.
4.6 Future research recommendations
Adequately powered RCTs reporting relevant clinical outcomes in specific
clinical groups are needed to evaluate the risks and benefits of induction of
labour for women whose pregnancies are complicated by:
diabetes (divided according to aetiology of diabetes)
multifetal pregnancy
suspected fetal growth compromise
macrosomia.
Further research is also needed to investigate the role of outpatient cervical
ripening within a UK setting.
Diabetic pregnancy
See Section 5 Indications for Induction of Labour.
Multifetal pregnancy
See Section 5 Indications for Induction of Labour.
Care during induction of labour
23
Ib
5. Indications for
induction of labour
5.1 Introduction
Induction of labour is indicated when it is agreed that the fetus or mother
will benefit from a higher probability of a healthy outcome than if birth is
delayed. An exception to this is induction of labour at maternal request for
social reasons. In this section, specific indications for induction of labour are
considered.
The process of induction of labour should only be considered when vaginal
delivery is felt to be the appropriate route of delivery.9
Induction of labour should only follow informed consent by the woman. For
consent to be fully informed, it should include the reasons for induction, the
choice of method to be used and the potential risks and consequences for
accepting or refusing an offer of induction of labour. The Guideline
Development Group was unable to locate any current epidemiological data
regarding the numbers of women being induced for specific indications.
The list provided is not exhaustive. It covers:
prolonged pregnancy
diabetic pregnancy
breech presentation
multifetal pregnancy
high parity
prelabour rupture of membranes
macrosomia
the presence of fetal growth restriction
previous caesarean section
maternal request
history of precipitate labour
(See Section 4 for breech presentation, high parity, suspected fetal growth
restriction and previous caesarean section).
Conditions where there are specific risks attached to induction of labour are
discussed in Section 4: Care During Induction of Labour.
5.2 Prolonged pregnancy
5.2.1 Risk associated with prolonged pregnancy
Population studies indicate that, in women who are healthy and have
otherwise uncomplicated pregnancies, perinatal mortality and morbidity is
increased in pregnancies of more than 42 weeks. The risk of stillbirth
increases from one per 3000 continuing pregnancies at 37 weeks to three
per 3000 continuing pregnancies at 42 weeks to six per 3000 continuing
pregnancies at 43 weeks.27 A similar increase in neonatal mortality is also
reported. Further analysis of the same data attempted to clarify the gestation
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specific risk for unexplained stillbirth,28 the results obtained are
approximations from three sources of data but the methodology of this study
has been criticised.2932
5.2.2 Reduction of risk in prolonged pregnancy
One systematic review evaluates interventions aimed at preventing or
improving the outcome of delivery beyond term.33 The conclusions are
summarised below.
Early Ultrasound in Pregnancy
A policy of early pregnancy ultrasound reduced the induction of labour for
prolonged pregnancy (1.9% vs. 2.8%; RR 0.69; 95% CI 0.580.82; NNT
111).33 These data were extracted from four trials from a previous review,34
which focused on the use of ultrasound for early fetal assessment in
pregnancy.
Policy of offering induction of labour after 41 weeks
The benefit of a policy of active induction of labour compared with
expectant management is derived from the trials of routine induction of
labour after 41 weeks (0.02% vs. 0.23%; Peto OR 0.23; 95% CI 0.060.90;
NNT 476)33
The rate of caesarean section is reduced with a policy of routine induction
of labour in those trials comparing a policy of routine induction with
conservative management in pregnancies beyond 41 weeks (19.6% vs.
21.7%; RR 0.90; 95% CI 0.810.99; NNT 47). Similar findings were seen in
those trials restricted to induction in nulliparous women. No effect was
evident on caesarean section rates if the analysis was divided up by cervical
favourability or background caesarean section rates (either less or greater
than 10% in the populations in the included trials).33
There is no effect on instrumental delivery rates, use of epidural analgesia or
FHR abnormalities during labour with a routine policy of induction of
labour.
There is a reduction in meconium staining of the amniotic fluid with routine
induction (20.0% vs. 25.3%; RR 0.78; 95% CI 0.720.86; NNT 19).
However, this finding is probably related to the increase in meconium-
stained liquor seen with increasing gestation in the conservative
management arm of these trials.33
The Guideline Development Group was unable to find any reports or
surveys of practice on the current induction policies in the UK with regard
to the timing of routine induction for prolonged pregnancy.
Data from one cohort27 revealed that at 40 weeks of gestation only 58% of
women had delivered. This increased to 74% by 41 weeks and to 82% by
42 weeks. Hence, a policy of induction of labour prior to 41 weeks would
generate increases in workload but with no reduction in perinatal mortality.
Alternative policy of screening high/low risk pregnancies from 42 weeks
The review included data on one trial comparing complex antenatal fetal
monitoring (computerised cardiotocography, amniotic fluid index and
assessment of fetal breathing, tone and gross body movements) with more
simple monitoring (standard cardiotocography and ultrasound measurement
of maximum pool depth) for identification of high-risk pregnancies from 42
weeks. There was no difference between the two policies with respect to
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perinatal mortality or caesarean section. However, the number of included
patients in this trial was small (n= 145) and, hence, the trial was
underpowered to detect any significant differences in perinatal mortality.33
The Guideline Development Group was unable to locate any data
comparing simple or more complex monitoring packages with no
monitoring in prolonged pregnancy.
5.2.3 Economic considerations
Two published economic studies have examined the costs of induction of
labour versus expectant management of prolonged pregnancy, in different
settings.35,36 The first study, based on a Canadian multicentre trial, found
that expectant management was more costly than induction with
prostaglandin gel, due mainly to costs of additional monitoring and a higher
caesarean-section rate.35 The second study, based on the TERMPROM
international multicentre trial, found that there was no difference in cost
between expectant management and induction with prostaglandin.36 The
difference is largely due to assumptions made about the operative delivery
rate differential: the TERMPROM trial found only small and statistically
insignificant operative delivery rate differences between the treatment arms.
An important issue not dealt with by these published studies is that, in the
context of local staff shortages, increased numbers of women being induced
for prolonged pregnancy may have local opportunity costs in terms of delivery
suite workload. Other women and babies may be exposed to risk if the
induction of labour workload is increased. This is a matter for local discussion
and debate, since it depends crucially on local staffing circumstances.
5.2.4 Summary
A policy of offering routine early-pregnancy ultrasound reduces the
incidence of induction for perceived prolonged pregnancy.
A policy of offering routine induction of labour after 41 weeks reduces
perinatal mortality without an increase in caesarean section rates.
The type of antenatal monitoring in the identification of high-risk
pregnancies beyond 42 weeks is uncertain, but the simpler modalities
used have been as effective as the more complex.
5.2.5 Practice recommendations
AAn ultrasound to confirm gestation should be offered before 20 weeks
of gestation, as this reduces the need for induction for perceived post-
term pregnancy.
AWomen with uncomplicated pregnancies should be offered induction
of labour beyond 41 weeks.
AFrom 42 weeks, women who decline induction of labour should be
offered increased antenatal monitoring consisting of a twice weekly
CTG and ultrasound estimation of maximum amniotic pool depth.
5.3 Diabetes in pregnancy
5.3.1 Risk associated with diabetes in pregnancy
The complications associated with diabetes in pregnancy vary according to
the type and severity of the diabetes. Diabetes complicates 2.6% of
pregnancies.
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In women with pre-existing diabetes, major concerns during the third
trimester include:
a higher perinatal mortality rate, which incorporates an increased rate
of late fetal death. Three UK population studies show a four or fivefold
increase in perinatal mortality rate in diabetic pregnancies in
comparison with either the local or national population.3739 One of
the studies showed a stillbirth rate five times that of the general
population.38
increased rate of other complications necessitating preterm delivery
(e.g. pre-eclampsia)40.
increased potential for birth trauma associated with increased fetal
size.3840 Infants of diabetic mothers are particularly prone to brachial
plexus injury caused by shoulder dystocia.41 One population cohort
study showed that the mean birthweight in the sample was 1.3 standard
deviations greater than infants of mothers without diabetes, after
correction for gestational age.38
While there is insufficient data clarifying the gestation-specific risk for
unexplained stillbirth in diabetic pregnancy gestation, the Guideline
Development Group considered that it is currently usual practice in the UK
to induce women with insulin-dependent diabetes prior to 40 weeks.
Previously published guidelines have recommended that women with good
diabetic control and no complications of pregnancy could be delivered at
3940 weeks.42
5.3.2 Reduction of risk in diabetic pregnancies
Induction or elective delivery before full term has been proposed as a means
of improving maternal and neonatal outcome. However, the potential
benefits of induction need to be balanced against the potential to increase
the risk of pulmonary complications in the fetus.
One systematic review compared the policy of elective induction of labour
at 38 weeks with expectant management.43 Only one pragmatic RCT was
included in this review.44 This trial had 200 participants, none of whom had
type I diabetes. Three of the reviewerspre-specified outcomes were
reported upon. There was no difference in the risk of caesarean section
(either elective or in labour) between interventions (25% vs. 31%; RR 0.81;
95% CI 0.521.26). The risk of macrosomia (birthweight over 4000 g) was
reduced in those women who were actively induced (15% vs. 27%; RR
0.56; 95% CI 0.320.98; NNT 8). The trial is too small to draw conclusions
regarding the effect of this policy on perinatal mortality.
5.3.3 Summary
Induction of labour of term pregnancies in women with diabetes is
associated with a reduced risk of macrosomia.
Routine induction does not appear to increase the risk of caesarean
section or neonatal morbidity, cases of which were rare and mild.
5.3.4 Practice recommendations
CWomen who have pregnancies complicated by diabetes should be
offered induction of labour prior to their estimated date for delivery.
5.4 Multifetal pregnancy
The discussion below relates only to twin pregnancies and the Guideline
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Development Group was unable to locate any specific studies relating to
higher-order pregnancies.
5.4.1 Risk associated with twin pregnancy
Nearly 70% of multifetal pregnancies deliver between 35 and 37 weeks of
gestation.45 A proportion will deliver prior to this time because of
complications relating to chorionicity and growth restriction or are delivered
electively due to maternal request relating to discomfort. In the remaining
multifetal pregnancies there has been concern over potential increased risk
of adverse outcome according to duration of gestation.
A retrospective study of all singleton and multiple pregnancies in Japan
between 1989 and 1993 demonstrated that the risk of perinatal death was
increased for fetuses of multiple pregnancy compared with singleton
pregnancies born at 40 weeks (1.8% vs. 0.16%).45 The same study showed
that, in multiple pregnancies, the percentage of perinatal deaths between 37
and 39 weeks of gestation was 1.11.2%; at 40 weeks of gestation it was
1.8%, at 41 weeks it was 2.2% and at 42 or more weeks it was 3.7%.
5.4.2 Reduction of risk in twin pregnancies
One RCT examined the role of induction of labour in multiple pregnancies
in comparison with expectant management.46 The study examined 36 twin
pregnancies at 37 weeks of gestation and randomised them to immediate
induction with oral prostaglandins or expectant management with
continued surveillance (consisting of daily non-stress testing, twice weekly
ultrasound evaluation and cervical assessment).
There were 17 women in the immediate-induction arm of the trial and 19 in
the expectant-management arm. The study was underpowered to detect any
difference in perinatal mortality rates. There was no difference in caesarean
section rates (32% vs. 18%), birthweight, Apgar scores of less than seven at
five minutes or postpartum haemorrhage rates. There was an increase in
meconium-stained liquor in the expectant-management group (13% vs.
0%). This may be related to a higher gestational age at delivery.
5.4.3 Summary
The perinatal mortality rate in twin pregnancies is increased in
comparison with singleton pregnancies at term.
No conclusions can be drawn from the available trial evidence relating
to the merits of an active policy of induction of labour in uncomplicated
multifetal pregnancies.
5.5 Induction of labour in the presence of prelabour
rupture of the membranes
5.5.1 Risk associated with prelabour rupture of the membranes
Prelabour rupture of the membranes (PROM) occurs in 619% of term
pregnancies.47,48 The risks of PROM at term relate to maternal and neonatal
infection, prolapsed cord and fetal distress resulting in operative delivery or
low five-minute Apgar score.4959 Fetal distress may be caused by any of the
complications listed.
Epidemiological data on time interval from term PROM to spontaneous
labour demonstrates that most women go into spontaneous labour within 24
hours of rupturing their membranes.60
86% of women will labour within 1223 hours
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91% will labour within 2447 hours
94% will labour within 4895 hours.
6% of women will not be in spontaneous labour within 96 hours of
PROM.
As the time between the rupture of the membranes and the onset of labour
increases, so may the risks of maternal and fetal infection. Induction of
labour may reduce these risks47,48.
5.5.2 Reduction of risk in prelabour rupture of the membranes
A series of systematic reviews examined the outcome of pregnancies with
PROM at or near term.47,6163 Two of the reviews focused on outcome in
pregnancies where a policy of no intervention was compared with induction
with either prostaglandin62 or oxytocin.63 The operative delivery rates were
not different in the induction group compared with the no treatment group
in either review.
Maternal infection was reduced in both reviews with a policy of active
management.
An active policy of induction of labour with oxytocin reduced the incidence
of chorioamnionitis (4.5% vs. 7.2%; RR 0.63; 95% CI 0.510.99; NNT 37).
An active policy of induction of labour with prostaglandins reduces the
incidence of chorioamnionitis (6.5% vs. 8.2%; RR 0.78; 95% CI 0.630.98;
NNT 56).62,63
Neonatal infection risks were reduced if induction was undertaken with
oxytocin (1.3% vs. 2.4%; RR 0.65; 95% CI 0.450.95; NNT 90)63 However,
there were insufficient patients in these reviews to draw any conclusions
regarding perinatal or maternal mortality.
The trials included in these reviews used a variety of protocols for
conservative management. One trial dominates the analysis. The trial
included a number of policies of induction of labour up to a maximum of
96 hours after membrane rupture.
The trials included in the systematic reviews include a mixture of inpatient
and outpatient management policies with expectant management. There is
insufficient evidence to base a recommendation on the effect of place on
outcome for mother or baby that is dependent on the place that expectant
management occurs.
The systematic reviews do not specifically address any difference between
those groups who received or who did not receive screening for
microbiological organisms. In view of this, the Guideline Development
Group did not feel able to make recommendations regarding the use of
vaginal swabs with PROM, regardless of the subsequent management.
5.5.3 Summary
There is no difference in operative delivery rates between induction
versus a conservative approach in women with prelabour rupture of the
membranes.
A policy of induction of labour is associated with a reduction in
infective sequelae for mother and baby.
5.5.4 Practice recommendations
AWomen with prelabour rupture of the membranes at term (over 37
weeks) should be offered a choice of immediate induction of labour
or expectant management.
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AExpectant management of women with prelabour rupture of the
membranes at term should not exceed 96 hours following
membrane rupture.
5.6 Induction of labour for suspected fetal macrosomia
5.6.1 Risk associated with suspected fetal macrosomia
It has been postulated that induction of labour for suspected fetal
macrosomia will avoid caesarean section or difficult instrumental vaginal
delivery. However, for a policy to be effective, fetal size needs to be
estimated accurately and all methods currently used to estimate fetal size
especially for large fetuses are poorly predictive.64
5.6.2 Reduction of risk associated with suspected fetal macrosomia
One systematic review addressed the question of whether a policy of active
induction versus expectant management in cases of suspected fetal
macrosomia had any impact on maternal or neonatal outcomes.65 The
review included two trials involving 313 women. Both trials included an
active induction arm for babies estimated to weigh more than 4000 g in
pregnant women who were not diabetic. In both trials, the mean gestational
age at birth in both experimental and control groups was similar, despite one
group being managed expectantly.
Overall perinatal mortality and morbidity were similar for both policies.
However, in total there were two babies who had brachial plexus injuries
and four who had fractures. These all occurred in the control groups. There
was no difference in rates of caesarean section or instrumental vaginal
delivery between the two groups.
5.6.3 Summary
Currently, the evidence is inconclusive that a policy of induction of labour
for suspected fetal macrosomia in women who are not diabetic can reduce
maternal or neonatal morbidity.
5.7 Induction of labour for maternal request prior
to 41 weeks
5.7.1 Reasons why women request induction of labour
One study examined womens motives for opting for elective induction of
labour.66 The study reported that, within a series of 237 women offered
elective induction, 50% accepted. Womens reasons for accepting this
option included increased feelings of safety and a desire to shorten the
duration of pregnancy.
Women who requested induction were more likely to have had problems
during their current pregnancy, complications in their previous pregnancies,
problematic menstrual periods, and to be more anxious about their labours
than those women who chose a spontaneous onset of labour.
5.7.2 Risk associated with induction of labour for maternal request
The Guideline Development Group has not formally addressed the risks
associated with induction of labour for maternal request. Assuming that the
woman is healthy, with an uncomplicated pregnancy, the risks of continuing
the pregnancy should be equivalent to that of the general population. The
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risks of induction of labour for the mother will also be equivalent to those of
the general population. However, any potential benefits accrued are less
easy to quantify. There is an increased risk of respiratory distress syndrome
in the baby if labour is induced before term. Therefore, it is important that
these risks are highlighted in any discussions regarding induction prior to
term.
5.7.3 Economic considerations
A policy of routinely offering electiveinduction for psychological or social
reasons would have resource implications. However, no published study has
examined these costs. The costs would include both the immediate costs of
drugs, equipment and staff time, and the indirect costs due to an increased
risk of operative delivery. These costs would then have to be set against the
benefits from the womans point of view of having the freedom to choose
electiveinduction. One key uncertainty is how many women would in fact
opt for electiveinduction if this were routinely offered on the NHS.
Further economic evaluation research is therefore needed to evaluate both
the costs and the benefits of a policy of routinely offering electiveinduction
of labour for psychological or social reasons.
5.7.4 Summary
There is insufficient evidence to allow comment on the risks associated with
elective induction of labour for maternal request.
5.7.5 Practice recommendations
Where resources allow, maternal request for induction of labour
should be considered when there are compelling psychological or
social reasons and the woman has a favourable cervix.
5.8 Induction of labour of women with a history of
precipitate labour
Precipitate labour has been defined as labour having a duration of two hours
or less.67
5.8.1 Risk associated with induction of labour of women with a history
of precipitate labour
One cohort study included 4976 women who gave birth over a period of
two years. Among these women, there were 106 women who had non-
augmented spontaneous labours of two hours or less.67 The incidence of
spontaneous precipitate labour was 2.1%. Two controls were selected for
every woman in the precipitate labour group. There were no perinatal
deaths in the study and operative delivery rates were not reported. The
babies born in the precipitate group did not suffer any adverse neonatal
outcomes.
The Guideline Development Group was unable to identify any studies
highlighting potential problems relating to the place of birth in women with
a history of precipitate labour. The hypothesis is that induction of labour in
these women will avoid birth outside of hospital, in cases where this is the
preferred place of birth for that woman.
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5.8.2 Reduction of risk with induction of labour of women with a history
of precipitate labour
The Guideline Development Group was unable to locate any specific
studies that examined the reduction of risk associated with precipitate
labour.
5.8.3 Summary
No conclusions can be drawn from the available evidence in relation to the
timing of induction of labour of women with a history of precipitate labour.
5.9 Future research recommendations
Adequately powered RCTs reporting relevant clinical outcomes in specific
clinical groups are needed to evaluate the risks and benefits of induction of
labour for women whose pregnancies are complicated by:
diabetes (divided according to aetiology of diabetes)
multifetal pregnancy
macrosomia.
Research is needed to evaluate screening in the UK for abnormal vaginal
colonisation in cases of prelabour rupture of the membranes at term.
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6. Method of induction
6.1 Introduction
Induction of labour is indicated when it is agreed that the fetus or mother
will benefit from a higher probability of a healthy outcome than if birth is
delayed. The process of induction of labour should only be considered
when vaginal delivery is felt to be the appropriate route of delivery.9
Induction of labour should only follow informed consent by the woman. For
consent to be fully informed it should include the reasons for induction, the
choice of method to be used, and the potential risks and consequences for
accepting or refusing an offer of induction of labour.
Recommendations are based on evidence from the series of Cochrane
reviews on induction of labour. Pooled data from the reviews are presented
and, where it is available, evidence relating to clinical subgroups (parity,
membrane status and cervical favourability) is presented.
6.2 Membrane sweeping
6.2.1 Performance
Sweeping the membranes in women at term reduced the delay between
randomisation and spontaneous onset of labour, or between randomisation
and birth, by a mean of three days.68
Sweeping the membranes increased the likelihood of both:
spontaneous labour within 48 hours (63.8% vs. 83.0%; RR 0.77; 95%
CI 0.700.84; NNT 5)
birth within one week (48.0% vs. 66.0%; RR 0.73; 95% CI 0.660.80;
NNT 5).
Sweeping the membranes performed as a general policy from 3840 weeks
onwards decreased the frequency of prolonged pregnancy:
over 42 weeks: 3.4% vs. 12.9%; RR 0.27; 95% CI 0.150.49; NNT 11
over 41 weeks: 18.6% vs. 29.87%; RR 0.62; 95% CI 0.490.79; NNT 8.
Membrane sweeping reduced the frequency of using other methods to
induce labour (formal induction of labour). The overall risk reduction in the
available trials was 15%. This risk reduction of a formal induction of labour
was 21.3% vs. 36.3% (RR 0.59; CI 0.500.70; NNT 7).
The risk of operative delivery is not changed by the intervention. There was
no difference in other measures of effectiveness or adverse maternal
outcomes.
Sweeping the membranes was not associated with an increase in maternal
infection or fever rates (4.4% vs. 4.5%; RR 0.97; 95% CI 0.601.57).
Similarly, there was no increase in neonatal infection (1.4% vs. 1.3%; RR
0.92; 95% CI 0.302.82).
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No major maternal adverse effects were reported in the trials. A trial that
systematically assessed minor adverse effects and womens discomfort
during the procedure found that women in the sweeping group reported
more discomfort during vaginal examination. Median pain scores were
higher in women allocated to sweeping of membranes. Pain was assessed by
the Short Form of the McGill Pain Questionnaire,69 which included three
scales:
a visual analogue scale (010 cm)
the present pain index (05)
a set of 15 descriptors of pain scoring 03.
In addition, more women allocated to sweeping experienced vaginal
bleeding and painful contractions not leading to the onset of labour during
the 24 hours following the intervention. There was no difference in any fetal
outcome between the membrane sweeping and the non-membrane
sweeping groups. These results must be interpreted with caution due to the
presence of heterogeneity. The trials included in this review did not report
in relevant clinical subgroups.
6.2.2 Summary
Membrane sweeping is associated with a reduction in the length of
time between treatment and spontaneous labour.
Sweeping of the membranes reduces the incidence of prolonged
pregnancy.
Sweeping of the membranes reduces the need for the use of formal
methods of induction of labour.
Sweeping of the membranes is associated with an increase in maternal
discomfort.
6.2.3 Practice recommendations
APrior to formal induction of labour, women should be offered
sweeping of the membranes.
AWhen membrane sweeping is proposed, discussions should include
information that informs women that membrane sweeping:
is not associated with an increase in maternal or neonatal
infection
is associated with increased levels of discomfort during the
examination and bleeding.
6.3 Comparison of oxytocin and prostaglandins for
induction of labour
Oxytocin and prostaglandins are currently the main agents used for formal
induction of labour in the UK. Oxytocin was considered in two of the
current systematic reviews on induction of labour in the Cochrane Library.
One of these70 considered the use of oxytocin alone (i.e. included trials
where induction of labour was undertaken in the presence of ruptured
membranes or where oxytocin had not been used within two hours of
amniotomy). The other71 examined the use of oxytocin with amniotomy (i.e.
included trials where induction of labour was undertaken with oxytocin with
immediate amniotomy or within two hours of amniotomy).
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Within the systematic reviews, there were often few data reported in the
clinical subgroups. This was especially true with regard to comparisons of
oxytocin and prostaglandin agents in women with intact membranes. For the
purpose of this Guideline, data from the oxytocin alone and the oxytocin
with amniotomy reviews were conflated.70,71 The additional groups formed
and details of the sources of the data are shown in Appendix 3.
6.3.1 All women
When comparing induction of labour using either oxytocin (alone or in
combination with amniotomy) or PGE2(vaginal or intracervical), overall,
induction with PGE2was associated with:
an increase in successful vaginal delivery within 24 hours
a reduction in caesarean-section rate
a reduction in the risk of the cervix remaining unfavourable/unchanged
at 2448 hours
a reduction in the use of epidural analgesia
an increase in the number of women satisfied with the method of
induction.
6.3.2 Evaluating the effect of parity
Induction of labour in women who are nulliparous
For induction of labour in nulliparous women comparing the use of either
oxytocin (alone or in combination with amniotomy) or PGE2(vaginal or
intracervical), overall, induction with PGE2was associated with:
an increase in successful vaginal delivery within 24 hours.
an increase in the number of women satisfied with the method of
induction.
no difference in caesarean section rate
no difference in the use of epidural analgesia.
The risk of the cervix remaining unfavourable or unchanged at 2448 hours
was not reported in this subgroup.
Induction of labour in women who are multiparous
For induction of labour in all multiparous women comparing the use of
either oxytocin (alone or in combination with amniotomy) or PGE2(vaginal
or intracervical), overall, induction with PGE2was associated with:
an increase in successful vaginal delivery within 24 hours
no difference in caesarean section rate
no difference in the use of epidural analgesia.
The risk of the cervix remaining unfavourable or unchanged at 2448 hours
and the number of women satisfied with the method of induction were not
reported in this subgroup.
6.3.3 Evaluating the effect of membrane status
Induction of labour in women with intact membranes
For induction of labour in women with intact membranes, comparing the
use of either oxytocin (alone or in combination with amniotomy) or PGE2
(vaginal or intracervical) in these women, overall induction with PGE2was
associated with:
an increase in successful vaginal delivery within 24 hours
a reduction in caesarean section rate
a reduction in the cervix remaining unfavourable/unchanged at 2448
hours
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an increase in the number of women satisfied with the method of
induction
there was no reduction in the use of epidural analgesia.
To evaluate the effect of parity for induction of labour in women with intact
membranes, the data were further subdivided into nulliparous and
multiparous women. For nulliparous women with intact membranes there
was no difference in the proportion of women achieving successful vaginal
delivery in 24 hours or in the caesarean section rates. The risk of the cervix
remaining unfavourable or unchanged at 2448 hours, the use of epidural
analgesia or the number of women satisfied with the method of induction
were not reported in this subgroup.
There were no data in the reviews on multiparous women with intact
membranes and so no conclusions have been drawn.
To evaluate the effect of cervical favourability on the choice of method of
induction of labour in women with intact membranes, the data were
subdivided into groups of women with favourable or unfavourable cervices.
For induction of labour of women with intact membranes and an
unfavourable cervix comparing the use of either oxytocin (alone or in
combination with amniotomy) or PGE2(vaginal or intracervical), overall,
induction with PGE2was associated with:
an increase in successful vaginal delivery within 24 hours
a reduction in caesarean section rate
a reduction in the cervix remaining unfavourable/unchanged at 2448
hours
no difference in the number of women satisfied with the method of
induction.
The use of epidural analgesia was not reported in this subgroup.
For induction of labour of women with intact membranes and an
unfavourable cervix comparing the use of either oxytocin (alone or in
combination with amniotomy) or PGE2(vaginal or intracervical), overall,
induction with PGE2was associated with:
an increase in successful vaginal delivery within 24 hours
no difference in caesarean section rate
no difference in the risk of the cervix remaining
unfavourable/unchanged at 2448 hours.
The use of epidural analgesia and the number of women satisfied with the
method of induction were not reported in this subgroup.
Induction of labour in women with ruptured membranes
In women with ruptured membranes, comparing the use of oxytocin to PGE2
(vaginal or intracervical), the use of prostaglandins resulted in:
an increase in successful vaginal delivery within 24 hours
no difference in caesarean section rate
no difference in the risk of the cervix remaining
unfavourable/unchanged at 2448 hours.
a reduction in the use of epidural analgesia
no difference in the number of women satisfied with the method of
induction.
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Further consideration should also be given to the results presented in Section
5.5 on the management of ruptured membranes at term, which showed that
induction with oxytocin in preference to vaginal PGE2reduced the rate of
some infective sequelae such as chorioamnionitis.47
To evaluate if this effect varies by parity, for both nulliparous and multiparous
women with ruptured membranes, the use of vaginal PGE2was associated
with an increase successful vaginal delivery within 24 hours. There was no
difference in caesarean-section rates or the use of epidural analgesia.
6.3.4 The effect of cervical favourability
Within the systematic reviews, the data were extracted and divided
according to cervical status where possible. Cervical status was divided into
three groups: cervix unfavourable, cervix favourable and cervix variable or
undefined. The cervix was assessed using a variety of cervical scoring
systems. The two main systems used were the original and modified Bishops
score (see Appendix 1). For the purposes of the reviews, a cervix was viewed
as unfavourable if the derived score was less than six.
Women with an unfavourable cervix
When comparing oxytocin (alone or in combination with amniotomy) with
PGE2(vaginal or intracervical), in women with an unfavourable cervix, the
use of prostaglandins was associated with:
an increase in successful vaginal delivery within 24 hours
a reduction in caesarean section rate
a reduction in the risk of the cervix remaining unfavourable/unchanged
at 2448 hours
no difference in the use of epidural analgesia
no difference in the number of women satisfied with the method of
induction.
Women with a favourable cervix
When comparing oxytocin (alone or in combination with amniotomy) with
PGE2(vaginal or intracervical), in women with a favourable cervix, the use
of prostaglandins was associated with:
an increase in successful vaginal delivery within 24 hours
no difference in caesarean section rate
no difference in the risk of the cervix remaining
unfavourable/unchanged at 2448 hours
no difference in the use of epidural analgesia
a reduction in the number of women satisfied with the method of
induction.
When these data were further divided according to parity there were
insufficient data to draw any further meaningful conclusions.
6.3.5 Economic considerations
One main study examined the costs of oxytocin compared with
prostaglandin as first-line method of labour induction.72 Based on earlier
Cochrane review data, this study found that prostaglandin was cost neutral
or cost saving compared with oxytocin, once non-medicine costs were taken
into account. Although the medicines cost was higher with use of
prostaglandin, this cost was offset by savings associated with a reduced rate
of caesarean section, a reduced rate of postpartum haemorrhage requiring
blood transfusion and reduced monitoring costs.
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A more recent study found that oxytocin may not be more costly than
prostaglandin. However, this conclusion may not be generally applicable, as
it was based on the findings of the TERMPROM multicentre trial, which
found no significant differences in operative delivery rates between the two
methods of induction.36
6.3.6 Summary
Overall, induction of labour using prostaglandins seem to improve the rate
of successful vaginal delivery, lower the rate of caesarean section, lower
epidural usage and to be associated with improved maternal satisfaction.
The benefits of prostaglandin are less marked in women with ruptured
membranes in comparison with women with intact membranes.
Unfortunately, there were insufficient data to evaluate fully the possible
differential effects of parity or cervical favourability.
6.3.7 Practice recommendations
AProstaglandins should be used in preference to oxytocin when
induction of labour is undertaken in either nulliparous or
multiparous women with intact membranes, regardless of their
cervical favourability.
AEither prostaglandins or oxytocin may be used when induction of
labour is undertaken in nulliparous or multiparous women who
have ruptured membranes, regardless of cervical status, as they are
equally effective.
6.4 A comparison of intracervical and intravaginal
prostaglandins (PGE2)
The two most commonly used preparations and routes of administration of
prostaglandins are intravaginal or intracervical PGE2. Methods of
administration, doses and intervals between doses, are discussed in the
subsequent sections. It should be noted, however, that intracervical PGE2is
no longer available in the UK for induction of labour.
There were no differences between operative delivery rates when
intracervical and vaginal prostaglandins were compared, irrespective of
patient group.73
There was no difference in any of the other defined outcomes between
intracervical and intravaginal prostaglandins.73
6.4.1 Summary
There was no difference in relation to outcome between the use of
intravaginal or intracervical prostaglandins.
6.4.2 Practice recommendations
AWhen induction of labour is undertaken with prostaglandins,
intravaginal PGE2should be used in preference to intracervical
preparations, as they are equally effective and administration of
vaginal PGE2is less invasive.
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6.5 A comparison of different preparations of vaginal
prostaglandin (PGE2)
6.5.1 Method of administration
In the current Cochrane systematic review,74 the varying formulations of
vaginal PGE2were evaluated. Comparisons were made between vaginal
PGE2gel, tablet, pessary or suppository and sustained-release formulations.
For the purpose of this Guideline and within the current structure of
systematic reviews, the term suppositoryor pessaryrefers to older
formulations where the PGE2formulation was often made in-houseinto a
pessary. These should not be confused with sustained-release formulations.
In the four trials comparing PGE2gel with PGE2tablets:
there was no difference between operative delivery rates between the
groups
oxytocin augmentation was reduced with the use of gel formulations
compared with tablet (50% vs. 59.7%; RR 0.84; 95% CI 0.720.99;
NNT 10). However, there was significant heterogeneity between the
trials and, hence, this result must be interpreted with caution
There was no difference in uterine hypercontractility or in the risk of
the cervix remaining unchanged/unfavourable at 2448 hours.
Two trials compared PGE2gel with either pessary or suppository
formulations. Operative delivery rates were not different between the three
formulations. Uterine hypercontractility with FHR changes was reduced
with the use of gel formulations in comparison with suppositories (1.3% vs.
11.2%; RR 0.16; 95% CI 0.030.87; NNT 9). However, there was no
difference in hypercontractility without FHR changes.
Three trials compared PGE2tablets with PGE2pessary or suppository. There
was no difference between caesarean-section rates between tablets and
pessaries. Instrumental vaginal delivery rates were increased with the use of
PGE2tablets compared with pessaries (17.8% versus 10.2%; RR 1.72; 95%
CI 1.092.70; NNT 13). There were insufficient data to comment on uterine
hypercontractility, epidural usage or maternal adverse effects.
Four trials compared PGE2slow-release formulations with any other route of
administration of PGE2. Operative delivery rates were not different between
the formulations. Uterine hypercontractility was not different between the
two groups. Oxytocin augmentation was reduced with the use of sustained-
release formulations (23.3% vs. 41.3%; RR 0.55; 95% CI 0.350.88; NNT
6). However, there was significant heterogeneity between the results of the
trials.
6.5.2 Dose comparisons of vaginal PGE2preparations
There are limited data available regarding comparisons of different dosage
regimens for vaginal prostaglandins. In the current Cochrane review, the
authors have made an arbitrary comparison of lowand highdose
regimens. Of the seven included trials, all used varying dosages and
methods of administration.
One trial included nearly two-thirds of the total women in this section of the
review (n= 995).75 This trial compared a policy of one versus two doses of
vaginal PGE2gel (2 milligrams). Overall there was no difference in operative
delivery rates between single or repeated doses. A reduction in the need for
amniotomy or oxytocin augmentation was seen in parous women who
received two doses of PGE2. This reduction was not seen in nulliparous
women.
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Within the review, comparisons did not reveal any difference between PGE2
formulations when compared with placebo. The data were divided into
three subgroups: once-only administration, repeated administration and
sustained release formulations. There was a marked increase in uterine
hypercontractility (with and without FHR changes) with sustained-release
formulations when compared with the once-only and repeated-dose
regimens.
In the absence of compelling clinical evidence from the systematic review,
the Guideline Development Group considered that the manufacturers
recommendations should be used for the administration of vaginal PGE2
preparations.
CRecommended regimens for vaginal PGE2preparations include:
PGE2tablets: 3 milligrams PGE268 hourly.
The maximum total dose is 6 milligrams for all women.
PGE2gels: 2 milligrams PGE2in nulliparous women with an
unfavourable cervix (Bishops score less than 4), 1 milligram for
all other women.
In either, a second dose of 12 milligrams can be administered
six hours later.
The maximum dose is 4 milligrams PGE2for nulliparous women
with an unfavourable cervix and 3 milligrams for all other women.
6.5.3 Timing of administration
One trial compared a policy of administration of endocervical PGE2in the
evening (followed by amniotomy the following morning if the cervix was
favourable) with endocervical PGE2in the morning (with amniotomy later
that day). The outcomes assessed were time of birth (daytime, evening or
night) and patient satisfaction. Regarding time of birth, the hypothesis was
that administration of prostaglandins in the evening would reduce the
number of evening and night-time deliveries.
Overall, no difference was seen between the two policies with regard to
time of birth. Women preferred administration of PGE2in the morning. This
trial is, however, small (n= 126) and no details are given regarding the
format of the patient questionnaire used to assess maternal preference. As
such, the results should be interpreted with caution.
6.5.4 Failed induction
The Guideline Development Group was unable to locate any evidence that
specifically addressed the issues surrounding failed induction. In the
absence of evidence, the Guideline Development Group considered that the
induction process should follow the manufacturers recommendations for
the administration of prostaglandin agents.
According to the recommendations made regarding the administration of
induction agents in Section 6.3, if the cervix is favourable, induction can be
undertaken with amniotomy and oxytocin. If vaginal prostaglandins are used
instead and labour does not ensue after the maximum dose of vaginal
prostaglandin has been used then amniotomy can be considered and
oxytocin started.
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If the woman has an unfavourable cervix and intact membranes and
induction has been undertaken with vaginal PGE2, it may not be possible to
perform amniotomy following a course of this treatment. In these cases,
consideration must be given to the administration of further prostaglandin
agents. However, the suggested time interval between courses of
prostaglandin agents is not known.
The decisions made regarding the management of a failed inductionmust
be made in accordance with maternal wishes but must be made clinically at
consultant level.
6.5.5 Economic considerations
One study examined the economic considerations of comparing a regimen
of one versus two doses of prostaglandin gel for induction of labour.76 It
found that, once a full range of costs was taken into account, the two-dose
regimen was slightly cheaper. This was largely due to savings associated
with a slightly lower rate of assisted deliveries in the two-dose group.
However, there is a degree of uncertainty surrounding this estimate,
because, in this study, any necessary augmentation with amniotomy and
oxytocin infusion was delayed in the one-dose group until 1420 hours after
initial application of prostaglandin. Further research is therefore needed, to
examine outcomes when augmentation in the one-dose regimen is
commenced at an earlier stage.
No published study has examined cost effectiveness of slow-release pessary
versus gel or tablets. An unpublished economic study submitted by a slow-
release pessary manufacturer comparing their product with gel was
considered not to provide convincing evidence of cost effectiveness. The
drug cost of the slow-release pessary is considerably higher: about £15 per
induction more costly than gel and £40 per induction more costly than
tablets. However, there was no statistically significant difference in any of
the main clinical outcomes, apart from a slightly reduced need for oxytocin
augmentation by about 20% in absolute terms. This may be an
overestimate of any differential in routine practice since, in the trial, only
one dose of gel was used in many cases rather than the normal practice of
using two or more doses and a 10-milligram pessary was used (only the 5-
milligram pessary is available in the UK). Even if this estimate is accepted,
however, the cost savings from reduced oxytocin augmentation only
partially offset the higher drug cost. The cost per oxytocin augmentation is
approximately £12 to £21 (see calculations below) and 20% of this yields an
offset of £2.50 to £4.50 per induction.
No published study has examined costs of vaginal tablets versus vaginal gel.
It was therefore considered appropriate to conduct a simple costing exercise
to examine this, which is summarised below. The basic conclusion of this
simple costing exercise is that vaginal tablets are more cost effective than
vaginal gel. This costing exercise assumes, in line with the clinical evidence
presented above, that both preparations are equally effective in terms of all
neonatal outcomes, apart from a slightly greater need for oxytocin
augmentation in the case of vaginal tablets. There are no major cost
uncertainties that could alter this conclusion in particular, the existing trial
evidence shows that it is highly unlikely that there is a substantial difference
in the caesarean-section rate between the two preparations.
Method of induction of labour in specific clinical conditions
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IV
IV
Drug-only cost saving of using vaginal tablets rather than vaginal gel
Assuming an average of two doses are used, the drug-only cost per
induction is:
about £15.53 for vaginal tablets, compared with £27.74 to £30.56
for vaginal gel.
In terms of drug cost alone, therefore, there is a saving of about
£12 to £15 per induction from using tablets rather than gel.
These costs are based on the following prices quoted in the British
National Formulary, March 2001 (page 371):
Vaginal tablets dinoprostone 3mg £15.53 for two doses
(Prostin E2®; Pharmacia & Upjohn) (£62.11 for 8-tab pack, i.e.
£7.76 per tab)
Vaginal gel dinoprostone 3mg £27.74 to £30.56 for two doses
(Prostin E2®; Pharmacia & Upjohn) (£13.87 for one 1-mg dose;
£15.28 for one 2-mg dose
required for unfavourable
nulliparous)
Oxytocin augmentation cost of using tablets rather than gel
In addition to the drug cost, the costs of oxytocin augmentation must
also be taken into account, since vaginal gel is slightly more effective
than vaginal tablets in preventing the need for oxytocin
augmentation. Based on analysis of four trials with a pooled sample
of 504 women, the use of vaginal gel leads to a 9.3% lower rate of
oxytocin augmentation than use of vaginal tablets; 50.4% required
oxytocin augmentation with vaginal tablets and 59.7% with vaginal
gel a 9.3% difference in absolute terms.
Based on the assumptions set out below, the cost per oxytocin
augmentation is £12 to £21. Thus, the oxytocin-augmentation cost of
using tablets rather than gel is 9.3% of £12 to £21 = £1.15 to £2.01
per induction.
Details of the oxytocin augmentation cost calculations
The estimated cost per oxytocin augmentation was based on the
following costings:
Extra staff time £6.16 to £14.18
Equipment £0
Disposables £5.00 to £6.00 (estimate)
Drug cost £1.23 to £1.40
Total £12.00 to £21.00 (estimate)
Notes
Staff time
If one-to-one care during induction is available, there is no extra staff
time required for oxytocin infusion. If one-to-one care is otherwise
not available, however, then the time it takes to set up the oxytocin
drip should be accounted for (although not the time taken to perform
checks, since these can be done beside standard checks of vital
signs). This has been estimated as varying between 10 minutes and 23
minutes per oxytocin augmentation, with estimates varying
depending on whether retrospective reports or concurrent time
records are used. This assumes that a midwife is not otherwise
available to perform this task and, as such, may be an overestimate of
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the true opportunity cost. The cost per hour of contact time for a
midwife is approximately £37 (see more detailed calculations below);
thus, this time cost per oxytocin infusion is between and £6.17 and
£14.18.
Equipment
It is assumed that spare infusion equipment would be available. If it
is not, then the cost per augmentation would increase by a matter of
pence (roughly the cost of buying new equipment divided by the large
number of uses over a working lifetime).
Oxytocin drug cost
Based on price quoted in the British National Formulary March 2001
(page 372), oxytocin (Syntocinon; Alliance®) for intravenous infusion
is £1.23 for 5 units/ml, 1-ml ampoule; £1.40 for 10 units/ml, 1-ml
ampoule.
Net cost saving from using tablets rather than gel
Taking into account both drug and oxytocin augmentation costs, the net
cost saving from using tablets rather than gel is £11.07 to £13.03 per
induction. This represents a saving per 1000 inductions of about
£11,000 to £13,000 (1000 is roughly the number of inductions expected
in a typical sized maternity unit dealing with 5000 women a year).
The opportunity cost in terms of midwifery services foregone
The cost of vaginal gel represents only about 1.3% of the average costs
to the NHS of a single delivery. This is based on a total cost of NHS
maternity services in 199778 of £1,343m (NHS Executive, Leeds)
divided by 600 000 deliveries per year yields an estimated cost of
£2,238 per delivery. Although this represents a small fraction of total
maternity costs, there is a real opportunity cost of using gel rather than
tablets. This can be expressed, for example, in terms of what midwifery
services the NHS could otherwise purchase (see notes below).
The NHS could thus buy approximately 3550% of one E-grade
midwife (including all associated costs) for every 1000 inductions
performed using vaginal tablets rather than vaginal gel. Alternatively,
one extra hour of midwife contact time with a mother could be
purchased for every three inductions performed using tablets rather
than gel.
Notes on the estimated cost of midwifery services
The total annual cost of an E-grade midwife, including on-costs and
training costs, can be estimated at £29,203. This cost was estimated
using the Ready Reckoner software developed by the Personal Social
Sciences Research Unit, 1998 version.77 In the estimation, default
parameter values were used (e.g. for training and work patterns) and
salary costs updated to 200001 using the midpoint of the salary scale
from the Royal College of Midwivesweb site. On the basis of 50%
contact time, the cost per hour with the mother for this midwife is
estimated at £37.
Potential total NHS saving
The NHS volume of inductions is approximately 120 000 per year.
This is on the basis that 20% of women are induced, out of 600 000
deliveries per year. Assuming a scenario in which all women were
induced using PGE2gel, the potential total cost saving to the NHS
through switching all women to PGE2vaginal tablets would therefore
be 120 000 £11.07 to £13.03, or £1,300,000 to £1,600,000 per
Method of induction of labour in specific clinical conditions
43
year. This is an overestimate of the likely actual saving of switching
patterns of usage towards vaginal tablets, however, since not all
inductions are currently performed using prostaglandin gel (although
unfortunately the precise baseline pattern of usage is not known).
Summary of economic considerations
Economic variable Estimate
NHS financial saving of using £11.07 to £13.03 per induction
tablets rather than gel
£11,000 to £13,000 per 1000
inductions
Examples of the NHS opportunity Approximately 3550% of one
cost of using tablets rather than gel E-grade midwife per year per
1000 inductions
Approximately 1 hour of
midwife contact time per 3
inductions
Potential total NHS financial £1.3m to £1.6m per annum
saving of using tablets rather than gel
6.5.6 Summary
Vaginal PGE2tablets seem to be as effective as gel formulations.
In the absence of clinical benefit, prostaglandins PGE2tablets offer
financial savings when compared with PGE2gel.
Vaginal PGE2gel and tablets appear to be more effective than pessary
formulations.
Sustained-release formulations of PGE2do not appear to be more
effective than other PGE2preparations.
There are limited data regarding the use of different dose regimens and
the timing of administration of prostaglandins.
In the absence of data regarding dose and timing of administration the
Guideline Development Group recommend adherence to the
manufacturers instructions.
6.5.7 Clinical practice recommendations
AGiven that they are clinically equivalent, when induction of labour
is undertaken with vaginal PGE2preparations, vaginal tablets should
be considered in preference to gel formulations.
6.6. A comparison of different regimens of oxytocin
administration
6.6.1 Method of administration
Data from the systematic reviews does not address the question of whether
oxytocin used in women with intact membranes should be used in
combination with amniotomy.
In the systematic review that focused on the use of oxytocin with
amniotomy, two trials compared the use of oxytocin alone to that of
oxytocin with amniotomy in women with intact membranes.71 They showed
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no difference in caesarean-section rates but an increase in successful vaginal
birth rates if oxytocin was used in combination with amniotomy. The small
number of included women in these trials make meaningful conclusions
difficult.
In trials where oxytocin alone is compared with vaginal or intracervical
PGE2an increase in caesarean-section rates and unsuccessful vaginal birth
rates was seen.70 These increases were not apparent in those trials
comparing oxytocin with amniotomy to the same prostaglandin agents.71
This indirect evidence suggests that oxytocin when used in women with
intact membranes should be used in combination with amniotomy. It should
be noted that these data are only reported in the all womengroups in the
relevant reviews and are not reported in specific subgroups.
6.6.2 Timing of administration and dose comparisons for oxytocin
Within the current structure of Cochrane reviews, oxytocin dose regimens
have not been compared. The Guideline Development Group examined
dose regimens used for induction of labour in 11 RCTs that studied the use
of oxytocin with or without immediate amniotomy.26,86,87 No formal meta-
analysis of these trials has been undertaken and the results of these trials are
summarised in Appendix 4.
The trials use a variety of regimens with differing starting doses of oxytocin
and different incremental rises and intervals of increase. The maximum dose
used varied in a similar fashion. Furthermore, the maximum dose of
oxytocin used was titrated against frequency of contractions or uterine
pressures via an intrauterine pressure catheter.
Comparing lower-doseregimens of oxytocin (lower starting doses, slower
incremental rises and lower maximal doses of oxytocin) with higher-dose
regimens, the conclusions drawn were:
lower-doseregimens were not associated with an increase in operative
delivery rates
oxytocin regimens with incremental rises in oxytocin dose more
frequently than every 30 minutes were associated with a increase in
uterine hypercontractility
lower-doseregimens were not associated with an increase in specified
delivery intervals
higher-doseoxytocin regimens were associated with an increase in the
incidence of precipitate labours.
Two current sets of guidelines currently recommend low-doseoxytocin
regimens.8,9,88 Both of these guidelines refer to a number of the trials
reviewed above.
From the above evidence, a suggested regimen for the administration of
oxytocin is outlined below.
The licensed maximum dose is currently 20 milliunits per minute. Trials
have used regimens up to 32 milliunits per minute. Most found that
adequate contractions can be achieved at 12 milliunits per minute.
Once a regular pattern of contractions is established, the rate of the infusion
can often be reduced. The manufacturers recommend that, if regular
contractions are not established after a total of 5 iu then the induction should
be stopped. They also recommend that the infusion can be recommenced
the following day.
For the administration of oxytocin, the infusion should be in accordance
with manufacturersrecommendations and should be delivered through an
infusion pump. The Guideline Development Group considered that delivery
Method of induction of labour in specific clinical conditions
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could also be via a syringe driver and the infusion set should include a non-
return valve.
6.6.3 Summary
From the available evidence when oxytocin with or without amniotomy is
used for induction of labour, a regimen with a slow incremental rise and low
maximum dose is appropriate.
When induction of labour of women with intact membranes is undertaken
with oxytocin, it should be used in combination with amniotomy.
6.6.4 Clinical practice recommendations
COxytocin should not be started for six hours following
administration of vaginal prostaglandins.
CIn women with intact membranes, amniotomy should be performed
where feasible prior to commencement of an infusion of oxytocin.
CWhen induction of labour is undertaken with oxytocin the
recommended regimen is:
a starting dose of 12 milliunits per minute
increased at intervals of 30 minutes or more.
The minimum dose possible of oxytocin should be used and this
should be titrated against uterine contractions aiming for a maximum
of three to four contractions every ten minutes.
Adequate contractions may be established at 12 milliunits per minute.
In the summary of product characteristics the licensed maximum dose
is 20 milliunits per minute.
If higher doses are used the maximum dose used should not exceed
32 milliunits per minute.
CLocal protocols for delivery of oxytocin for induction of labour
should:
specify and use the dose of oxytocin being delivered (milliunits
per minute) in preference to the volume of fluid being infused
(millilitres per minute)
be delivered through an infusion pump or via a syringe driver
with a non-return valve.
CTo reduce error, a standard dilution should always be used.
Suggested standardised dilutions and dose regimens include:
30 iu in 500 ml of normal saline; hence 1ml/hr = 1milliunits
oxytocin per minute
10 iu oxytocin in 500 ml of normal saline;
hence 3 ml/hr = 1milliunits oxytocin per minute.
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C
6.7. Other methods of induction of labour
Twenty-three methods of induction of labour were examined within the
series of systematic reviews on induction of labour. Most of these methods
are not commonly used in current clinical practice and, hence, the results
are not presented here. Many of the reviews contain very small amounts of
trial evidence.
The other interventions considered are:
mechanical methods89
extra amniotic prostaglandins90
intravenous prostaglandins91
oral prostaglandins92
mifepristone93
oestrogen with/without amniotomy94
corticosteroids95
relaxin96
hyaluronidase.97
For further information regarding these interventions, readers are referred to
the Cochrane Library.
A number of these methods represent methods used outside of current UK
practice or were not in current clinical use. All but mechanical methods are
currently not licensed for use in the UK.
A number of the methods discussed in these new Cochrane reviews
included reviews of alternative methods of induction of labour that have
traditionally been used by women and midwives to induce labour naturally.
6.7.1 Castor oil, bath or enema
There was one included trial in this review98 and involved the
administration of castor oil to one group of women and no treatment in the
other arm. The trial was small and no conclusion on the effectiveness of
castor oil in induction of labour could be drawn. All women who ingested
castor oil felt nauseous.
Method of induction of labour in specific clinical conditions
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Table 6.1 Oxytocin infusion
Time after Oxytocin dose
starting (milliunits Volume infused (ml/hour)
(minutes) per minute) Dilution 30 iu Dilution 10 iu
in 500 ml in 500 ml
0 113
30 226
60 4 4 12
90 8 8 24
120 12 12 36
150 16 16 48
180 20 20 60
210 24 24 72
240 28 28 84
270 32 32 96
Doses highlighted are quantities above those referred to in the summary of
product characteristics of 20 milliunits per minute
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6.7.2 Breast stimulation
The review included data from six trials of breast stimulation.99 Four trials
assessed the impact of breast stimulation compared with no intervention. In
these trials there was no difference in the caesarean-section rate or the rates
of meconium staining between the groups. The rates of postpartum
haemorrhage were reduced in the breast stimulation group (0.7% vs. 6%; RR
0.16; 95% CI 0.030.87). Two trials compared breast stimulation with
oxytocin alone. No difference in the caesarean-section rate was reported.
One of the RCTs was stopped after there were three perinatal deaths in the
breast stimulation group and one in the oxytocin group. The trial was the
only study that included a high-risk population.
6.7.3 Sexual intercourse
This review included data from one randomised controlled trial.100 The trial
compared one group who had regular sexual intercourse with vaginal semen
deposition to another group who refrained from sexual intercourse. Breast
stimulation was prohibited in both groups. There was no benefit from having
sexual intercourse as an induction agent. There were no adverse outcomes
encountered.
6.7.4 Acupuncture and homeopathic methods
There were no trials of acupuncture101 or homeopathic methods102 included
in these systematic reviews and hence the use of these interventions for
induction of labour has not been assessed.
6.8 Future research recommendations
Adequately powered RCTs reporting relevant clinical outcomes in
specific clinical groups are needed to evaluate further the effectiveness
of different vaginal PGE2formulations for induction of labour.
Future trials in induction of labour should attempt to standardise the
definitions of the outcomes collected.
Future trials should attempt to use recommended doses of prostaglandins
and oxytocin to allow meaningful comparisons between studies.
Where possible, in future studies on induction of labour, where
interventions are compared, consideration should be given to the
collection of relevant economic outcomes.
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7. Vaginal or oral
misoprostol (PGE1):
research to date
7.1 Background
Misoprostol has been widely investigated as an agent for induction of labour.
There are two current systematic reviews that focus on the use of both oral
and vaginal misoprostol.103,104
According to the evidence currently available, misoprostol appears to be
more effective than vaginal prostaglandins and oxytocin in the presence of
ruptured membranes (either spontaneous or artificial) for induction of
labour.
There are safety aspects of misoprostol that have not been fully evaluated
and it is not currently licensed for obstetric use. Its use must therefore be
restricted to RCTs.
7.2 Misoprostol compared with other induction agents
When comparing vaginal misoprostol with PGE2(either intracervical or
vaginal) or oxytocin alone:
caesarean-section rates were reduced when vaginal misoprostol was
compared with oxytocin alone
the rate of successful vaginal delivery in 24 hours was increased with
misoprostol
the cervix was less likely to remain unfavourable or unchanged after
2448 hours when vaginal misoprostol was used
uterine hypercontractility with FHR changes was increased when
vaginal misoprostol was compared with intracervical PGE2
uterine hypercontractility without FHR changes was increased with
vaginal misoprostol, compared with all three interventions.
7.3 Method of administration of misoprostol
Oral and vaginal misoprostol were compared in one review.104 The studies
included in the review used varying oral misoprostol regimens, ranging from
50-microgram tablets every four hours to 200-microgram tablets every six
hours. Oral misoprostol appeared to be less effective than vaginal
misoprostol. More women in the oral misoprostol group failed to achieve
vaginal birth within 24 hours of randomisation. The caesarean-section rate
was not different between oral and vaginal preparations.
Oral misoprostol resulted in fewer cases of hypercontractility without FHR
changes. There was no difference in uterine hypercontractility with FHR
Induction of Labour
49
Evidence level
Ia
Ia
Ia
Ia
changes. Meconium-stained liquor was more common following oral
administration. There are only limited data available on the combination of
vaginal and oral misoprostol.
7.4 Safety issues
As highlighted above, the use of misoprostol is associated with an increase
in uterine hypercontractility. This is not translated into an increase in
operative delivery rates. The safety issues surrounding the use of misoprostol
have not been fully evaluated.
There has been one maternal death due to amniotic fluid embolus in one
trial.105 This trial also reported two cases of caesarean hysterectomy for
atonic uterine haemorrhage.105 A trial examining the use of vaginal
misoprostol for induction of labour of women, limited to women with a
previous caesarean section, reported two cases of uterine rupture.21
What is unclear at present is whether misoprostol is associated with an
increase in adverse events or whether they represent chance sporadic
adverse events. Such adverse outcomes may be potentially under-reported
in trials examining other induction agents.
Misoprostol tablets are currently available only in 200-microgram
formulations. Trials examining 50-microgram and 25-microgram doses of
misoprostol have involved cutting tablets or making up suspensions of the
drug. Uniform concentration of the active drug thus cannot be guaranteed
in individual pieces. This may result in variable amounts of the active drug
being delivered. To allow further research on the use of lower doses of
vaginal misoprostol, commercially available 25-microgram and 50-
microgram tablets would be needed.
Recent articles have highlighted the large amount of trial data available
presenting persuasive evidence of efficacy regarding the use of misoprostol
as an induction agent. It also highlighted a number of the issues raised
above, including those relating to the non-availability of misoprostol tablets
in low-dose formulations due to the reluctance of the manufacturers to
promote the use of misoprostol as an induction agent.106108
7.5 Economic considerations
Misoprostol is considerably cheaper than both intravaginal and intracervical
PGE2. With reference to the recommended regimen of vaginal PGE2tablet
in this Guideline, the relative costs compared with vaginal misoprostol
would be £0.18 for one 200-microgram tablet of misoprostol compared with
£8.13 for a 3-milligram PGE2tablet. In addition, there would be further
indirect cost savings to the NHS, given the reduced rate of operative
delivery.
Further data are needed about the theoretical risks of misoprostol. Therefore,
until these are available there will remain considerable uncertainty about its
overall cost effectiveness.
7.6 Summary
Vaginal misoprostol appears to be a more effective induction agent than
either intravaginal or intracervical PGE2or oxytocin.
Misoprostol is significantly cheaper than currently recommended PGE2
preparations.
Induction of Labour
50
Ia
Ia
Ia
Ia
Ia
The safety issues concerning the use of vaginal misoprostol are unclear.
Further clinical trials are warranted in order to evaluate further the issues
of safety regarding the use of vaginal and oral misoprostol for induction
of labour using commercially produced low-dose tablets.
Vaginal or oral misoprostol (PGE1): research to date
51
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intravenous oxytocin in prelabor rupture of membranes with unripe cervix at term. Clin Exp Obstet
Gynecol 2001;25:468.
139. Malik N, Gittens L, Gonzalez D, Bardeguez A, Ganesh V, Apuzzio J. Clinical amnionitis and endometritis
in patients with premature rupture of membranes: endocervical prostaglandin E2gel versus oxytocin for
induction of labor. Obstet Gynecol 1996;88:5403.
140. Magann EF, Perry KG, Jr., Dockery JR Jr, Bass JD, Chauhan SP, Morrison JC. Cervical ripening before
medical induction of labor: a comparison of prostaglandin E2, estradiol, and oxytocin. Am J Obstet
Gynecol 1995;172:17026.
141. Jackson GM, Sharp HT, Varner MW. Cervical ripening before induction of labor: a randomized trial of
prostaglandin E2gel versus low-dose oxytocin. Am J Obstet Gynecol 1994;171:10926.
142. Papageorgiou I, Tsionou C, Minaretzis D, Michalas S, Aravantinos D. Labor characteristics of
uncomplicated prolonged pregnancies after induction with intracervical prostaglandin E2gel versus
intravenous oxytocin. Gynecol Obstet Invest 1992;34:926.
143. Goeschen K. Premature rupture of membranes near term: induction of labor with endocervical
prostaglandin E2gel or intravenous oxytocin. Am J Perinatol 1989;6:1814.
144. Egarter C, Schurz B, Wagner G, Grunberger W, Husslein P. [Comparison between prostaglandin E2gel
and oxytocin in medically indicated labor induction]. [German]. Geburtshilfe und Frauenheilkunde
1987;47:33740.
145. Wiqvist I, Norstrom A, Wiqvist N. Induction of labor by intra-cervical PGE2in viscous gel. Mechanism of
action and clinical treatment routines. Acta Obstet Gynecol Scand 1986;65:48592.
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intracervical administration of a new PGE2gel in labor induction]. [German]. Geburtshilfe und
Frauenheilkunde 1986;46:937.
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147. Ulmsten U, Wingerup L, Andersson KE. Comparison of prostaglandin E2and intravenous oxytocin for
induction of labor. Obstet Gynecol 1979;54:5814.
148. Parazzini F, Benedetto C, Danti L, Zanini A, Facchinetti F, Ettore G, et al. A randomized comparison of
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intermediately ripe cervices. Eur J Obstet Gynecol Reprod Biol 1998;81:1520.
149. Orhue AA. Induction of labour at term in primigravidae with low Bishops score: a comparison of three
methods. Eur J Obstet Gynecol Reprod Biol 1995;58:11925.
150. Lamont RF, Neave S, Baker AC, Steer PJ. Intrauterine pressures in labours induced by amniotomy and
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1991;98:4417.
151. Melchior J, Bernard N, Andre-David F. [Artificial induction of labor at term for medical reasons.
Comparison of two techniques for labour induction, oxytocin plus early artificial rupture of the
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Gynecol Obstet 1989;84:74752.
152. MacLennan A, Fraser I, Jakubowicz D, Murray-Arthur F, Quinn M, Trudinger B. Labour induction with
low dose PGE2vaginal gel: result of an Australian multicentre randomized trial. Aust N Z J Obstet
Gynaecol 1989;29:1248.
153. Dommisse J, Wild JM. Assessment of a new prostaglandin E2gel in labour induction. S Afr Med J
1987;71:5067.
154. Kennedy JH, Stewart P, Barlow DH, Hillan E, Calder AA. Induction of labour: a comparison of a single
prostaglandin E2vaginal tablet with amniotomy and intravenous oxytocin. Br J Obstet Gynaecol
1982;89:7047.
155. MacLennan AH, Green RC. The effect of intravaginal prostaglandin F2alpha on labour after spontaneous
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156. Taylor A, Sellers S, Ah-Moye M, MacKenzie IZ. A prospective random allocation trial to compare vaginal
prostaglandin E2with intravenous oxytocin for labour induction in women previously delivered by
caesarean section. J Obstet Gynaecol 1993;13:3336.
157. Thompson JH. Induction of labour: a comparison between intravaginal prostaglandin E2gel and oxytocin
infusion with low amniotomy. Proceedings of 21st International Congress of International Confederation
of Midwives, The Hague, Netherlands, 1987.
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Prostaglandins 1978;15:16973.
References
57
Appendix 1
Cervical scoring systems
Bishop’s score109
Cervical feature Pelvic score
01 23
Dilatation (cm) 0 123456
Effacement (%) 030 4060 6070 80+
Station (cm)a321/0 +1/+2
Consistency Firm Medium Soft
Position Posterior Mid-position Anterior
Modified Bishop’s score (Calder score)1
Cervical feature Pelvic score
01 23
Dilatation (cm) <1 1224>4
Length of cervix (cm) >4 2412<1
Station (cm)a321/0 +1/+2
Consistency Firm Average Soft
Position Posterior Mid; ––
Anterior
aIn both systems, station is measured in cm relative to the ischial spines.
For the purpose of this Guideline, the modified Bishop’s score is used to
assess the cervical condition.
Induction of Labour
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Appendix 2
Methodology of collaboration
between CESU and Cochrane
Pregnancy and Childbirth
group
Background
There are large numbers of agents currently employed in clinical practice to
promote cervical ripening and initiate labour. The research base focusing on
induction of labour is extensive. Systematic reviews published in the
literature tend to compare specific agents with all other available agents,
often without common or prespecified outcome measures. The Cochrane
Library currently hold a limited number of induction of labour reviews on its
database. The main bulk of systematic reviews focusing on other methods of
induction have not been available since 1995.
In a bid to produce an up-to-date and structured series of reviews on
induction of labour a collaboration between the RCOG Clinical
Effectiveness Support Unit (CESU) and Cochrane Collaborations Pregnancy
and Childbirth group was formed. The members of this group included
members of the Guideline Development Group, members of the RCOG
CESU and experienced Cochrane reviewers with an interest in the subject of
induction of labour.
The methodology used for these series of systematic reviews is highlighted
below. In the later sections, evidence is presented relating to different
methods of induction of labour and finally the evidence relating to induction
of labour in specific clinical situations is presented.
The Cochrane Pregnancy and Childbirth
Group/CESU collaboration
A generic protocol was developed by the group and published on the
Cochrane Library. The protocol discussed below outlines the methodology
used for all the reviews and standard outcome measures to be presented.
Clinically relevant outcomes for trials of methods of cervical ripening and
labour induction were developed from previously published systematic
reviews on induction of labour. These outcomes attempt to reflect both
measures of success and failure of induction. Due to the nature of the
reporting of outcomes within studies focusing on induction of labour,
measures of failure are more commonly reported.
Induction of Labour
59
Primary outcomes
Five primary outcomes were chosen as being most representative of the
clinically important measures of effectiveness and complications.
1. Vaginal delivery not achieved within 24 hours.
2. Uterine hyperstimulation with FHR changes.
3. Caesarean section.
4. Serious neonatal morbidity or perinatal death (e.g. seizures, birth
asphyxia defined by trialists, neonatal encephalopathy, disability in
childhood).
5. Serious maternal morbidity or death (e.g. uterine rupture, admission
to intensive care unit, septicaemia).
Perinatal and maternal morbidity and mortality are composite outcomes.
This is not an ideal solution because some components are clearly less
severe than others. It is possible for one intervention to cause more deaths
but less severe morbidity. However, in the context of labour induction at
term this is unlikely. All these events will be rare, and a modest change in
their incidence will be easier to detect if composite outcomes are presented.
The incidence of individual components were explored as secondary
outcomes (see below).
Secondary outcomes
These outcomes related to measures of effectiveness, complications and
satisfaction.
Measures of effectiveness
6. Cervix unfavourable/unchanged after 1224 hours.
7. Oxytocin augmentation.
Complications
8. Uterine hyperstimulation without FHR changes
9. Uterine rupture
10. Epidural anaesthesia
11. Instrumental vaginal delivery
12. Meconium stained liquor
13. Apgar score of less than seven at five minutes
14. Neonatal intensive care unit admission
15. Neonatal encephalopathy
16. Perinatal death
17. Disability in childhood
18. Maternal adverse effects (all)
19. Nausea (maternal)
20. Vomiting (maternal)
21. Diarrhoea (maternal)
22. Other (e.g. pyrexia)
23. Postpartum haemorrhage (as defined by the trial authors)
24. Serious maternal complications (e.g. intensive care unit admission,
septicaemia but excluding uterine rupture)
25. Maternal death
Measures of satisfaction
26. Woman not satisfied
27. Caregiver not satisfied
While all the above outcomes were sought, only those where these data
have been reported in the trials appear in the analysis tables.
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60
The terminology of uterine hyperstimulation is problematic. In the reviews,
the term uterine hyperstimulation without FHR changesincluded uterine
tachysystole (more than five contractions per ten minutes for at least 20
minutes) and uterine hypersystole/hypertonus (a contraction lasting at least
two minutes) and uterine hyperstimulation with FHR changesdenoted
uterine hyperstimulation syndrome (tachysystole or hypersystole with FHR
changes such as persistent decelerations, tachycardia or decreased short term
variability). However, due to varied reporting of this outcome there is the
possibility of subjective bias in interpretation. Also, it was not always clear
from trials if these outcomes are reported in a mutually exclusive manner.
Outcomes were included in the analysis if reasonable measures were taken
to minimise observer bias and data were available for analysis according to
original allocation.
Search strategy for identification of studies
This review drew on the search strategy developed for the Pregnancy and
Childbirth Group as a whole. The search was performed simultaneously for
all reviews of methods of inducing labour.
Relevant trials were identified in the Groups Specialised Register of
Controlled Trials. The Cochrane Controlled Trials Register was searched and
the reference lists of trial reports and reviews were searched by hand. These
searches were cross-referenced with systematic searches of Medline and
Embase performed by the research staff at CESU.
Method of the reviews
A strategy was developed to deal with the large volume and complexity of
trial data relating to labour induction. Many methods of induction have been
studied, in many different clinical situations. Most trials are intervention-
driven, comparing two or more methods in various clinical situations.
Clinicians and women need the information arranged by specific clinical
situations in order to aid decision making. To extract these type of data from
several hundred trial reports in a single step would not be feasible. A two-
stage method of data extraction was developed. The initial data extraction
was performed in a series of primary reviews arranged by methods of
induction of labour, following a standardised methodology. The data were
then extracted from the primary reviews into a series of secondary reviews,
arranged by specific clinical scenarios.
To avoid duplication of data in the primary reviews, the labour induction
methods have been listed in a specific order, from 1 to 23. Each primary
review includes comparisons between one of the methods (from 2 to 23)
with those methods above it on the list. Thus, the review of intravenous
oxytocin (4) will include only comparisons with intracervical prostaglandins
(3), vaginal prostaglandins (2) or placebo (1). Methods identified in the
future will be added to the end of the list. The current list is as follows:
1. Placebo/no treatment
2. Vaginal prostaglandins
3. Intracervical prostaglandins
4. Intravenous oxytocin alone
5. Amniotomy alone
6. Intravenous oxytocin with amniotomy
7. Vaginal misoprostol
8. Oral misoprostol
Appendix 2
61
9. Mechanical methods
10. Membrane sweeping
11. Extra-amniotic prostaglandins
12. Intravenous prostaglandins
13. Oral prostaglandins
14. Mifepristone
15. Oestrogen with or without amniotomy
16. Corticosteroids
17. Relaxin
18. Hyaluronidase
19. Castor oil, bath, with or without enema
20. Acupuncture
21. Breast stimulation
22. Sexual intercourse
23. Homoeopathic methods.
The primary reviews included the following subgroup analysis:
1. Previous caesarean section or not
2. Nulliparity or multiparity
3. Membranes intact or ruptured
4. Cervix favourable, unfavourable or undefined.
The secondary reviews included all methods of labour induction for each of
the subgroups based on clinical scenarios performed in the primary reviews.
Originally, six reviews were proposed, divided by the above subgroups but
due to the small amount of data available additional secondary reviews have
been developed. There are therefore eight secondary reviews of methods of
labour induction in the following clinical scenarios:
1. All women (not divided by membrane status or cervical status)
2. All women intact membranes (unfavourable cervix, favourable
cervix, cervix not defined)
3. All women ruptured membranes (unfavourable cervix, favourable
cervix, cervix not defined)
4. Nulliparous women, intact membranes (unfavourable cervix,
favourable cervix, cervix not defined)
5. Nulliparous women, ruptured membranes (unfavourable cervix,
favourable cervix, cervix not defined)
6. Parous women, intact membranes (unfavourable cervix, favourable
cervix, cervix not defined)
7. Parous women, ruptured membranes (unfavourable cervix,
favourable cervix, cervix not defined)
8. Previous caesarean section (not divided by membrane status or
cervical status).
Data extraction
The trials included in the primary reviews were extracted from an initial set
of trials covering all interventions used in induction of labour (currently
approximately 700 RCTs). The data extraction process was conducted
centrally from the RCOG Clinical Effectiveness Support Unit, in co-
operation with the Cochrane Collaborations Pregnancy and Childbirth
Group. This process allowed the data extraction process to be standardised
across all the reviews.
The trials were initially reviewed on eligibility criteria, using a standardised
form and the basic selection criteria specified above. Following this, data
were extracted to a standardised data extraction form, which was piloted for
consistency and completeness.
Induction of Labour
62
Individual outcome data were included in the analysis if they met the
prestated criteria in Types of outcome measures. Included trial data were
processed as described in the Cochrane Collaboration Handbook. Data
extracted from the trials were analysed on an intention to treat basis (when
this was not done in the original report, re-analysis was performed if
possible). Where data were missing, clarification was sought from the
original authors. If the attrition was such that it might significantly affect the
results, these data were excluded from the analysis. These decisions rested
with the reviewers of the primary reviews and was clearly documented.
Due to the large number of trials, double data extraction was not feasible
and agreement between the three data extractors was therefore assessed on
a random sample of trials.
Once the data had been extracted, they were distributed to individual
reviewers for entry on to the Review Manager computer software, checked
for accuracy and analysed as above using the same software. For
dichotomous data, relative risks and 95% confidence intervals were
calculated and, in the absence of heterogeneity, results were pooled using a
fixed effects model.
The predefined criteria for sensitivity analysis included all aspects of quality
assessment, including aspects of selection, performance and attrition bias.
Primary analysis was limited to the prespecified outcomes and sub-group
analyses. In the event of differences in unspecified outcomes or subgroups
being found, these were analysed post hoc but clearly identified as such to
avoid drawing unjustified conclusions.
Appendix 2
63
Appendix 3
Conflated Oxytocin vs.
prostaglandin E2 data
The data presented below represent individual trials data from two Cochrane reviews
focusing on the use of oxytocin in comparison with PGE2(vaginal or intracervical).70,71
The data relate to the discussions and conclusions in Section 6.2. The data were derived
from the reviews below and their corresponding comparison groups:
Oxytocin alone Versus vaginal PGE2 110136
Versus intracervical PGE2 137147
Oxytocin with amniotomy71 Versus vaginal PGE2 148157
Versus intracervical PGE2 158
1. Any oxytocin vs. any PGE2(all women)
Includes all women:
oxytocin alone vs. vaginal PGE2
oxytocin alone vs. intracervical PGE2
oxytocin with amniotomy vs. intravaginal PGE2
oxytocin with amniotomy vs. intracervical PGE2
Outcome Trials Women Experimental Control Relative 95% Heterogeneity
(n)(n) group group risk Confidence (Pvalue)
intervals
Vaginal delivery 7 660 168/328 106/332 1.61 1.331.94
not achieved
within 24 hours
Caesarean section 51 7093 459/3533 395/3560 1.17 1.031.32
Cervix unfavourable 9 952 102/476 57/476 1.73 1.292.32 0.0001
or unchanged
after 2448 hours
Epidural analgesia 14 3796 916/1898 828/1898 1.11 1.031.18
Women not satisfied 5 2861 119/1430 79/1431 1.50 1.141.97 0.001
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64
2. Any oxytocin vs. any PGE2all women, intact membranes
Includes all women intact membranes:
oxytocin alone vs. vaginal PGE2with cervix: variable/undefined, unfavourable,
favourable
oxytocin alone vs. intracervical PGE2with cervix: variable/undefined, unfavourable,
favourable
oxytocin with amniotomy vs. intravaginal PGE2: variable/undefined, favourable
Outcome Trials Women Experimental Control Relative 95% Heterogeneity
(n)(n) group group risk Confidence (Pvalue)
intervals
Vaginal delivery 3 400 102/200 72/200 1.42 1.131.78
not achieved within
24 hours
Caesarean section 23 2278 196/1131 158/1147 1.25 1.041.51
Cervix unfavourable 5 574 67/289 45/285 1.45 1.032.03 0.0003
or unchanged after
2448 hours
Epidural analgesia 5 522 92/265 87/257 1.03 0.821.30
Women not satisfied 2 198 30/99 11/99 2.65 1.375.13 0.0001
3. Any oxytocin vs. any PGE2all women, ruptured
membranes
Includes all women intact membranes:
oxytocin alone vs. vaginal PGE2with cervix: variable/undefined, unfavourable
oxytocin alone vs. intracervical PGE2with cervix: variable/undefined, unfavourable
Outcome Trials Women Experimental Control Relative 95% Heterogeneity
(n)(n) group group risk Confidence (Pvalue)
intervals
Vaginal delivery not 2 120 31/60 14/60 2.21 1.333.68
achieved within
24 hours
Caesarean section 20 4172 217/2082 197/2090 1.10 0.921.32
Cervix unfavourable 1 90 6/46 7/44 0.82 0.302.25
or unchanged after
2448 hours
Epidural analgesia 9 3274 824/1633 741/1641 1.11 1.041.19
Women not satisfied 1 2517 74/1258 64/1259 1.16 0.841.60
Appendix 3
65
4. Any oxytocin vs. any PGE2all nulliparae
Includes all nulliparae:
oxytocin alone vs. vaginal PGE2
oxytocin alone vs. intracervical PGE2
oxytocin with amniotomy vs. intravaginal PGE2
Outcome Trials Women Experimental Control Relative 95% Heterogeneity
(n)(n) group group risk Confidence (Pvalue)
intervals
Vaginal delivery 1 100 22/50 10/50 2.20 1.164.16
not achieved within
24 hours
Caesarean section 7 1438 34/728 29/710 1.13 0.70,1.81
Cervix unfavourable ––
or unchanged after
2448 hours
Epidural analgesia 3 204 16/106 17/98 0.84 0.461.53
Women not satisfied 1 100 26/50 0/50 53.00 3.32,846.51
5. Any oxytocin vs. any PGE2all multiparae
Includes all multiparae:
oxytocin alone vs. vaginal PGE2
oxytocin alone vs. intracervical PGE2
oxytocin with amniotomy vs. intravaginal PGE2
Outcome Trials Women Experimental Control Relative 95% Heterogeneity
(n)(n) group group risk Confidence (Pvalue)
intervals
Vaginal delivery 2 120 31/60 18/60 1.72 1.102.70
not achieved within
24 hours
Caesarean section 12 2212 167/1100 163/1112 1.04 0.851.27
Cervix unfavourable
or unchanged after
2448 hours
Epidural analgesia 3 182 61/90 52/92 1.18 0.941.49
Women not satisfied
Induction of Labour
66
6. Any oxytocin vs. any PGE2all primiparae intact
membranes
Includes all nulliparae intact membranes:
oxytocin alone vs. intracervical PGE2unfavourable cervix and favourable cervix
Outcome Trials Women Experimental Control Relative 95% Heterogeneity
(n)(n) group group risk Confidence (Pvalue)
intervals
Vaginal delivery 1 100 22/50 14/50 1.57 0.912.71
not achieved
within 24 hours
Caesarean section 1 98 14/49 8/49 1.75 0.813.79
Cervix unfavourable
or unchanged after
2448 hours
Epidural analgesia
Women not satisfied
7. Any oxytocin vs. any PGE2all multiparae intact
membranes
Includes all multiparae intact membranes:
No available trial evidence.
8. Any oxytocin vs. any PGE2all primiparae ruptured
membranes
Includes all nulliparae ruptured membranes:
oxytocin alone vs. vaginal PGE2with cervix: variable/undefined or unfavourable
Outcome Trials Women Experimental Control Relative 95% Heterogeneity
(n)(n) group group risk Confidence (Pvalue)
intervals
Vaginal delivery 3 278 73/135 50/143 1.55 1.182.04
not achieved within
24 hours
Caesarean section 8 1887 136/942 141/945 0.97 0.781.20
Cervix unfavourable
or unchanged after
2448 hours
Epidural analgesia 3 182 61/90 52/90 1.18 0.941.49
Women not satisfied
Appendix 3
67