High dose versus low dose oxytocin for augmentation of
delayed labour (Review)
Mori R, Tokumasu H, Pledge D, Kenyon S
This is a reprint of a Cochrane review, prepared and maintained by The Cochrane Collaboration and published in The Cochrane Library2011, Issue 10
http://www.thecochranelibrary.com
High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
T A B L E O F C O N T E N T S
1HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
1ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
2BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
3METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
7RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
8ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
9REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
10CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
16DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
Analysis 1.1. Comparison 1 High versus low dose of oxytocin (all women), Outcome 1 Neonatal mortality. . . . . 16
Analysis 1.2. Comparison 1 High versus low dose of oxytocin (all women), Outcome 2 Caesarean section. . . . . 17
Analysis 1.3. Comparison 1 High versus low dose of oxytocin (all women), Outcome 3 Length of labour (hour; oxytocin to
delivery). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
Analysis 1.4. Comparison 1 High versus low dose of oxytocin (all women), Outcome 4 Spontaneous vaginal birth. . 18
Analysis 1.5. Comparison 1 High versus low dose of oxytocin (all women), Outcome 5 Incidence of hyperstimulation. 18
Analysis 1.6. Comparison 1 High versus low dose of oxytocin (all women), Outcome 6 Diagnosis of chorioamnionitis. 19
Analysis 1.7. Comparison 1 High versus low dose of oxytocin (all women), Outcome 7 Epidural analgesia. . . . . 19
Analysis 1.8. Comparison 1 High versus low dose of oxytocin (all women), Outcome 8 Neonatal admission to special care
baby units. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Analysis 1.9. Comparison 1 High versus low dose of oxytocin (all women), Outcome 9 Apgar score less than 7 at 5
minutes. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
Analysis 1.10. Comparison 1 High versus low dose of oxytocin (all women), Outcome 10 Umbilical cord (artery) pH. 21
21HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
21CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
21DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
21SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .
22DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . .
iHigh dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
[Intervention Review]
High dose versus low dose oxytocin for augmentation ofdelayed labour
Rintaro Mori1, Hironobu Tokumasu2 , Debbie Pledge3, Sara Kenyon4
1Collaboration for Research in Global Women’s and Children’s Health, Tokyo, Japan. 2Neonatology, Kagoshima City Hospital,
Kagoshima, Japan. 3National Collaborating Centre for Women’s and Children’s Health, London, UK. 4 School of Health and Population
Sciences, University of Birmingham, Edgbaston, UK
Contact address: Rintaro Mori, Collaboration for Research in Global Women’s and Children’s Health, 1-13-10 Matsunoki, Suginami-
ku, Tokyo, Tokyo, 166-0014, Japan. [email protected].
Editorial group: Cochrane Pregnancy and Childbirth Group.
Publication status and date: New, published in Issue 10, 2011.
Review content assessed as up-to-date: 23 August 2011.
Citation: Mori R, Tokumasu H, Pledge D, Kenyon S. High dose versus low dose oxytocin for augmentation of delayed labour.
Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD007201. DOI: 10.1002/14651858.CD007201.pub2.
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
A B S T R A C T
Background
A major cause of failure to achieve spontaneous vaginal birth is delay in labour caused by presumed inefficient uterine action. High
dose may potentially increase the number of spontaneous vaginal births, but as oxytocin can cause hyperstimulation of the uterus, there
is a possibility of increased adverse events.
Objectives
To compare starting dose and increment of amount of oxytocin for augmentation for women delayed in labour to determine whether
augmentation by high dose of oxytocin improves labour outcomes and the effect on both maternal/neonatal outcomes and women’s
birth experiences.
Search strategy
We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 February 2011) and reference lists of retrieved studies.
Selection criteria
We included all randomised and quasi-randomised controlled trials for women in delayed in labour requiring augmentation by oxytocin
comparing high starting and increment dose (defined as starting dose and increment of equal to or more than 4 mU per minute) with
low dose (defined as starting dose and an increment of less than 4 mU per minute. Increase interval: between 15 and 40 minutes. The
separation of low and high doses is based on an arbitrary decision.
Data collection and analysis
Three review authors undertook assessment of trial eligibility, risk of bias, and data extraction independently.
Main results
We included four studies involving 660 pregnant women. Three studies were randomised controlled trials and one trial was a quasi-
randomised study. A higher dose of oxytocin was associated with a significant reduction in length of labour reported from one trial
(mean difference (MD) -3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial, 40 women). There was a decrease in rate
1High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
of caesarean section (risk ratio (RR) 0.53; 95% CI 0.38 to 0.75, four trials, 650 women) and an increase in the rate of spontaneous
vaginal birth (RR 1.37; 95% CI 1.15 to 1.64, two trials, 350 women). There were no significant differences for neonatal mortality,
hyperstimulation, chorioamnionitis, epidural analgesia; or neonatal outcomes of Apgar scores, umbilical cord pH or admission to
special care baby unit. The following outcomes were not evaluated in the included studies: perinatal mortality, women’s satisfaction,
instrumental vaginal birth, uterine rupture, postpartum haemorrhage, abnormal cardiotocography, women’s pyrexia, dystocia and
neonatal neurological morbidity.
Authors’ conclusions
Higher dose of oxytocin starting and increment dose (4 mU per minute or more) was associated with a reduction in the length of
labour and in caesarean section, and an increase in spontaneous vaginal birth. However, there is insufficient evidence. The number
of studies and the quality of the available evidence is of concern. Additionally, there is insufficient evidence for other maternal and
neonatal outcomes, and how women feel about the higher doses of oxytocin. Therefore, no firm recommendation can be made. Further
research should evaluate the effect of high dose oxytocin for women delayed in labour and should include these outcomes.
P L A I N L A N G U A G E S U M M A R Y
Oxytocin in high versus low doses for augmentation of delayed labour
Women have different lengths of labour, with first labours lasting on average eight hours (and unlikely to last more than 18 hours)
and second and subsequent labours lasting an average of five hours and unlikely to last more than 12 hours. Progress in labour takes
into account not just cervical dilatation, but also descent and rotation of the fetal head and the strength, duration and frequency
of contractions. Some evidence suggests that up to one-third of women in their first labour experience delay. They are often given
a synthetic version of the hormone oxytocin to increase uterine contractions and shorten labour. Surprisingly for such a routine
treatment, the ideal dose at which it should be given is not known, although some comparisons suggest that higher doses of oxytocin
could shorten labour and reduce the chance of caesarean section with an increase in the numbers of women having a spontaneous
vaginal birth compared with a lower dose. However, there are potentially harmful side effects if oxytocin causes the uterus to contract
too quickly, and the baby becomes distressed. Clinicians therefore routinely adjust the dose of oxytocin to reduce the chances of the
baby being distressed in labour.
From the four randomised controlled trials involving 660 pregnant women that we included in this review, results indicate that a higher
dose of oxytocin (4-7 mU per minute, compared with 1-2 mU per minute) reduced the length of labour and the rate of caesarean
sections with increased spontaneous vaginal births, but the studies did not provide enough evidence on possible differences between
the high and low doses in adverse events including hyperstimulation of the uterus and outcomes for the newborn infant. No trial
reported on how the women experienced the births. The overall quality of the included trials was not good, but this might reflect how
the clinical trials were reported.
While the evidence we have showed that the high doses reduced the length of labour and the rate of caesarean sections, the number
and quality of the studies is of concern and not enough is known about the effect on the baby or women’s birth experiences for the
higher dose oxytocin to be recommended as treatment for women delayed in labour. We recommend that more research is carried out.
B A C K G R O U N D
Description of the condition
Length of labour varies between women, with first labours lasting
on average eight hours (and unlikely to last more than 18) and
second and subsequent labours lasting on average five hours (and
unlikely to last more than 12 hours). Progress in labour should
take into account not just cervical dilatation, but also descent and
rotation of the fetal head and strength, duration and frequency of
contractions. The definition of delay varies, but cervical dilatation
of 2 cm in four hours is widely accepted as being normal (NICE
2007). The incidence of delay in labour is not accurately known.
2High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Some evidence suggests that up to one-third of women in their first
labours become delayed (Williams 1998). Other evidence suggests
the incidence of prolonged labour is more than 10% of women
(DOH 2004), and about 40% to 60% of these women have their
labour augmented with oxytocin due to slow progress or other
reasons in first stage of labour (Gottschall 1997; Impey 2000).
Many women would have already had their membranes ruptured
spontaneously, and amniotomy is not recommended as routine
practice (Smyth 2007).
Description of the intervention
Oxytocin has been widely used in obstetric practice and increases
both the frequency and strength of uterine contractions in labour.
In doses under 4 mU/min, it has been shown to shorten labour
but not alter mode of birth (Wei 2007).
How the intervention might work
It is plausible that increasing both the dose and speed of the oxy-
tocin will increase the number of women having a spontaneous
vaginal birth. It is currently routine treatment for women delayed
in labour, and while it does carry potentially harmful side effects,
clinicians routinely effectively titrate the dose against uterine con-
tractions.
Why it is important to do this review
Evidence suggests that high doses of oxytocin may increase spon-
taneous vaginal birth but not enough is known about neonatal
outcomes or how this might affect women’s birth experience. One
non-Cochrane systematic review included trials that compared
high versus low doses of oxytocin for augmentation of labour (Wei
2010) but some of the trials were undertaken in the context of
active management of labour.
This review intends to assess the risks and benefits of high and
low doses of oxytocin infusion for augmentation of labour due to
delayed first stage of labour. We have excluded trials undertaken
in the context of active management of labour (one-to-one con-
tinuous support, strict definition of established labour, early am-
niotomy, routine two-hourly vaginal examinations and oxytocin
if labour becomes slow) or as part of induction of labour.
O B J E C T I V E S
To compare starting dose as well as increment of amount of oxy-
tocin for augmentation in delayed labour to determine whether
augmentation by high dose of oxytocin improves labour outcomes
and women’s satisfaction.
M E T H O D S
Criteria for considering studies for this review
Types of studies
All randomised and quasi-randomised controlled trials. We in-
tended to include both published or unpublished trials.
Types of participants
Women in labour assessed as requiring augmentation by oxytocin
for delay or slow progress in labour. We only included women
with live fetuses.
Types of interventions
High starting and increment dose (4 micro unit (mU) per minute
or more) of oxytocin for augmentation in delayed labour compared
with low dose (less than 4 mU per minute). We defined amount
of oxytocin as below:
• high dose: defined as starting dose and increment of equal
to or more than 4 mU per minute;
• low dose: defined as starting dose and an increment of less
than 4 mU per minute;
• increase interval: between 15 and 40 minutes.
The separation of low and high doses is based on an arbitrary
decision.
Types of outcome measures
Primary outcomes
1. Perinatal mortality rate (as defined by trial authors)
2. Neonatal mortality rate
3. Caesarean section rate
4. Women’s satisfaction (measured quantitatively using
validated questionnaires)
5. Length of labour
Secondary outcomes
1. Spontaneous vaginal birth
2. Instrumental vaginal birth
3. Incidence of hyperstimulation
4. Incidence of ruptured uterus
5. Diagnosis of chorioamnionitis
6. Incidence of postpartum haemorrhage (blood loss more
than 500/1000 ml)
7. Use of epidural analgesia
3High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
8. Incidence of abnormal cardiotocography (considered only if
blindly assessed)
9. Incidence of women’s pyrexia
10. Incidence of dystocia
11. Neonatal outcomes of Apgar scores, umbilical cord pH,
neurological morbidity, admission to special care baby units
Search methods for identification of studies
Electronic searches
We contacted the Trials Search Co-ordinator to search the
Cochrane Pregnancy and Childbirth Group’s Trials Register (28
February 2011).
The Cochrane Pregnancy and Childbirth Group’s Trials Register
is maintained by the Trials Search Co-ordinator and contains trials
identified from:
1. quarterly searches of the Cochrane Central Register of
Controlled Trials (CENTRAL);
2. weekly searches of MEDLINE;
3. weekly searches of EMBASE;
4. handsearches of 30 journals and the proceedings of major
conferences;
5. weekly current awareness alerts for a further 44 journals
plus monthly BioMed Central email alerts.
Details of the search strategies for CENTRAL, MEDLINE and
EMBASE, the list of handsearched journals and conference pro-
ceedings, and the list of journals reviewed via the current aware-
ness service can be found in the ’Specialized Register’ section
within the editorial information about the Cochrane Pregnancy
and Childbirth Group.
Trials identified through the searching activities described above
are each assigned to a review topic (or topics). The Trials Search
Co-ordinator searches the register for each review using the topic
list rather than keywords.
Searching other resources
We searched the reference lists of retrieved studies.
We did not apply any language restrictions.
Data collection and analysis
We used the following methods when assessing the reports iden-
tified by the search.
Selection of studies
Rintaro Mori (RM), Hironobu Tokumasu (HT) and Sara Kenyon
(SK) independently assessed for inclusion all the potential studies
identified as a result of the search strategy. We intended to resolve
any disagreement through discussion or, if required, consult Deb-
bie Pledge (DP), though there was no disagreement found.
Data extraction and management
We designed a form to extract data prior to the review. For eligible
studies, RM and HT extracted the data using the agreed form,
which was checked by SK. We resolved discrepancies through dis-
cussion or, if required, we planned to consult DP (though we were
able to resolve all discrepancies by discussion). We entered data
into Review Manager software (RevMan 2011) and checked for
accuracy.
Assessment of risk of bias in included studies
RM, HT and SK independently assessed risk of bias for each study
using the criteria outlined in the Cochrane Handbook for SystematicReviews of Interventions (Higgins 2011). We resolved all disagree-
ment by discussion.
(1) Random sequence generation (checking for possible
selection bias)
We describe for each included study the method used to generate
the allocation sequence in sufficient detail to allow an assessment
of whether it should produce comparable groups.
We assessed the method as:
• low risk of bias (any truly random process, e.g. random
number table; computer random number generator),
• high risk of bias (any non-random process, e.g. odd or even
date of birth; hospital or clinic record number) or,
• unclear risk of bias.
(2) Allocation concealment (checking for possible selection
bias)
We describe for each included study the method used to conceal
allocation to interventions prior to assignment and assess whether
intervention allocation could have been foreseen in advance of, or
during recruitment, or changed after assignment.
We assessed the methods as:
• low risk of bias (e.g. telephone or central randomisation;
consecutively numbered sealed opaque envelopes);
• high risk of bias (open random allocation; unsealed or non-
opaque envelopes, alternation; date of birth);
• unclear risk of bias.
(3) Blinding of participants, personnel and outcome
assessment (checking for possible performance bias)
We describe for each included study the methods used, if any, to
blind study participants and personnel from knowledge of which
4High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
intervention a participant received. We consider studies to be at
low risk of bias if they were blinded, or if we judge that the lack of
blinding would be unlikely to affect results. We assessed blinding
separately for different outcomes or classes of outcomes.
We assessed the methods as:
• low, high or unclear risk of bias for participants;
• low, high or unclear risk of bias for personnel;
• low, high or unclear risk of bias for outcome assessment.
(4) Incomplete outcome data (checking for possible attrition
bias due to the amount, nature and handling of incomplete
outcome data)
We describe for each included study, and for each outcome or class
of outcomes, the completeness of data including attrition and ex-
clusions from the analysis. We state whether attrition and exclu-
sions were reported and the numbers included in the analysis at
each stage (compared with the total randomised participants), rea-
sons for attrition or exclusion where reported, and whether miss-
ing data were balanced across groups or were related to outcomes.
Where sufficient information is reported, or was supplied by the
trial authors, we re-include missing data in the analyses which we
have undertaken.
We assessed methods as:
• low risk of bias (e.g. no missing outcome data; missing
outcome data balanced across groups);
• high risk of bias (e.g. numbers or reasons for missing data
imbalanced across groups; ‘as treated’ analysis done with
substantial departure of intervention received from that assigned
at randomisation);
• unclear risk of bias.
(5) Selective reporting (checking for reporting bias)
We describe for each included study how we investigated the pos-
sibility of selective outcome reporting bias and what we found.
We assessed the methods as:
• low risk of bias (where it is clear that all of the study’s pre-
specified outcomes and all expected outcomes of interest to the
review have been reported);
• high risk of bias (where not all the study’s pre-specified
outcomes have been reported; one or more reported primary
outcomes were not pre-specified; outcomes of interest are
reported incompletely and so cannot be used; study fails to
include results of a key outcome that would have been expected
to have been reported);
• unclear risk of bias.
(6) Other bias (checking for bias due to problems not
covered by 1 to 5 above)
We describe for each included study any important concerns we
have about other possible sources of bias.
We assessed whether each study was free of other problems that
could put it at risk of bias:
• low risk of other bias;
• high risk of other bias;
• unclear whether there is risk of other bias.
(7) Overall risk of bias
We will make explicit judgements about whether studies are at
high risk of bias, according to the criteria given in the Handbook(Higgins 2011). With reference to (1) to (6) above, we will assess
the likely magnitude and direction of the bias and whether we
consider it is likely to impact on the findings. We will explore the
impact of the level of bias through undertaking sensitivity analyses
- see ’Sensitivity analysis’.
Measures of treatment effect
We carried out statistical analysis using the Review Manager soft-
ware (RevMan 2011). We used fixed-effect meta-analysis for com-
bining data where trials examined the same intervention, and the
trials’ populations and methods were judged to be sufficiently sim-
ilar. Where we suspected clinical or statistical heterogeneity be-
tween studies, sufficient to suggest that treatment effects might
differ between trials, we carried out random-effects meta-analysis.
Dichotomous data
For dichotomous data, we presented results as summary risk ratio
with 95% confidence intervals.
Continuous data
For continuous data, we have used the mean difference if out-
comes are measured in the same way between trials. We used the
standardised mean difference to combine trials that measure the
same outcome, but used different methods.
Unit of analysis issues
Cluster-randomised trials
We did not identify any cluster-randomised trials for inclusion in
this review. However, if we identify cluster-randomised trials for
inclusion in future updates of this review we will include them
in the analyses along with individually randomised trials. We will
adjust their sample sizes using the methods described in the Hand-book using an estimate of the intracluster correlation co-efficient
(ICC) derived from the trial (if possible), from a similar trial or
from a study of a similar population. If we use ICCs from other
sources, we will report this and conduct sensitivity analyses to in-
vestigate the effect of variation in the ICC. If we identify both
5High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
cluster-randomised trials and individually randomised trials, we
plan to synthesise the relevant information. We will consider it
reasonable to combine the results from both if there is little het-
erogeneity between the study designs and the interaction between
the effect of intervention and the choice of randomisation unit is
considered to be unlikely.
Crossover trials
We did not include crossover trials.
Dealing with missing data
For included studies, we have noted levels of attrition. We have
explored the impact of including studies with high levels of missing
data (over 10% for outcomes where data were collected in labour)
in the overall assessment of treatment effect by using Sensitivity
analysis.
For all outcomes, we carried out analyses, as far as possible, on an
intention-to-treat basis, i.e. we attempted to include all partici-
pants randomised to each group in the analyses, and analysed all
participants in the group to which they were allocated, regardless
of whether or not they received the allocated intervention. The
denominator for each outcome in each trial was the number ran-
domised minus any participants whose outcomes were known to
be missing.
Assessment of heterogeneity
We assessed statistical heterogeneity in each meta-analysis using
the T², I² and Chi² statistics. We regarded heterogeneity as sub-
stantial if T² was greater than zero and either I² was greater than
30% or there was a low P value (less than 0.10) in the Chi² test
for heterogeneity.
Assessment of reporting biases
Where we suspected reporting biases (such as publication bias) we
attempted to contact study authors asking them to provide missing
outcome data.
In future updates of this review, if more data become available and
there are 10 or more studies in the meta-analysis we will investigate
reporting biases (such as publication bias) using funnel plots. We
will assess funnel plot asymmetry visually, and use formal tests for
funnel plot asymmetry. For continuous outcomes we will use the
test proposed by Egger 1997, and for dichotomous outcomes we
will use the test proposed by Harbord 2006. If we detect asymme-
try in any of these tests or by a visual assessment, we will perform
exploratory analyses to investigate it.
Data synthesis
We carried out statistical analysis using the Review Manager soft-
ware (RevMan 2011). We used fixed-effect meta-analysis for com-
bining data where it was reasonable to assume that studies were
estimating the same underlying treatment effect: i.e. where trials
were examining the same intervention, and the trials’ populations
and methods were judged sufficiently similar. If there was clinical
heterogeneity sufficient to expect that the underlying treatment
effects differ between trials, or if substantial statistical heterogene-
ity was detected, we would use random-effects meta-analysis to
produce an overall summary if an average treatment effect across
trials was considered clinically meaningful. The random-effects
summary was treated as the average range of possible treatment
effects and we discussed the clinical implications of treatment ef-
fects differing between trials. If the average treatment effect was
not clinically meaningful we did not combine trials.
If we use random-effects analyses, we will present the results as the
average treatment effect with its 95% confidence interval, and the
estimates of T² and I².
Subgroup analysis and investigation of heterogeneity
We intended to conduct planned subgroup analysis using the
methods described by Deeks 2001 and set out in the CochraneHandbook for Systematic Reviews of Interventions (Higgins 2011).
We were unable to carry out any subgroup analysis due to insuffi-
cient data. In future updates of this review, as more data become
available, we will carry out the following planned subgroup anal-
yses.
1. By parity (nulliparous versus multiparous women).
2. By previous experience of caesarean section (women who
had a caesarean before this delivery versus those who had not).
We planned to use the following outcomes in subgroup analysis.
• Perinatal mortality rate.
• Neonatal mortality rate.
• Women’s satisfaction.
• Mode of birth.
For fixed-effect inverse variance meta-analyses we planned to assess
differences between subgroups by interaction tests. For random-
effects and fixed-effect meta-analyses using methods other than
inverse variance, we planned to assess differences between sub-
groups by inspection of the subgroups’ confidence intervals; with
non-overlapping confidence intervals indicative of a statistically
significant difference in treatment effect between the subgroups.
Sensitivity analysis
Although the quality of included studies varied such as allocation
concealment, considering lack of other available information and
general quality of the studies, we did not carry out sensitivity anal-
yses to explore the effect of trial quality for important outcomes
6High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
in the review. We plan to conduct the sensitivity analysis in the
next update when other information may be available.
R E S U L T S
Description of studies
See: Characteristics of included studies; Characteristics of excluded
studies.
Results of the search
The search of the Pregnancy and Childbirth Group’s Trials Reg-
ister found 18 reports. We also identified, and subsequently ex-
cluded, two additional reports from the reference lists of retrieved
studies (Cummiskey 1989; Satin 1994). In total, we initially con-
sidered 16 studies published in 20 articles/reports. From these, we
included four studies and excluded 12 studies. We identified no
unpublished trials. For further information on details of trial char-
acteristics, please refer to the Characteristics of included studies
and Characteristics of excluded studies tables.
Included studies
We included four studies, involving 660 women. Please refer to
Characteristics of included studies for the further details.
Among the included trials, three trials (Bidgood 1987; Jamal 2004;
Supajitkulchi 2003) were randomised controlled trial design and
one trial (Xenakis 1995) employed a quasi-randomised design,
where allocation of intervention was made on the basis of the day
of the week.
With the exception of one, three-armed trial (Bidgood 1987), all
of the included studies were two-armed trials. Data from one arm
of the three-arm trial were not used as it did not meet our inclusion
criteria.
One trial included only nulliparous women (Bidgood 1987), while
the other three trials included both nulliparous and parous women
(Jamal 2004; Supajitkulchi 2003; Xenakis 1995). Three trials
excluded women with previous caesarean section (Jamal 2004;
Supajitkulchi 2003; Xenakis 1995).
Maximum dose for oxytocin was reported by one trial (Bidgood
1987) as 40 mU/min.
Excluded studies
We excluded 12 studies. Please see Characteristics of excluded
studies for the further details.
One report (Alderman 1974) was a letter with no primary data.
Six trials (Arulkumaran 1989; Lazor 1993; Lowensohn 1990;
Majoko 2001; Satin 1994; Seitchik 1982) examined different rate
of oxytocin administration for augmentation of labour; their stated
doses are outside of the preset criteria of low and high doses.
One trial (Cummiskey 1989) compared pulsatile administration
of oxytocin for augmentation with continuous administration.
One trial (Parpas 1995) compared high and low doses of oxytocin
for augmentation and induction of labour but the two populations
were not reported separately.
One trial (Vorherr 1963) compared effectiveness of oxytocin for
augmentation with placebo.
One trial (Merrill 1999) included women with planned routine
augmentation of labour by oxytocin; hence these women were not
necessarily with delayed labour.
One trial (Akoury 1993) was excluded because it was carried out
in the context of active management of labour.
Risk of bias in included studies
Due to poor description of the included trials, we were not able
to assess risk of bias adequately.
We rated random sequence generation as ’high risk’ of bias in two
trials (which used consecutive sealed envelopes (Bidgood 1987)
and days of the week (Xenakis 1995). Supajitkulchi 2003 reported
using block randomisation but the details were ’unclear’. The other
trial (Jamal 2004) did not provide a detailed description of the
methods used for sequence generation and we have rated it as
’unclear’.
Allocation was concealed in two trials (Bidgood 1987; Jamal
2004). However, it was not used in the (Xenakis 1995) trial and
was ’unclear’ in Supajitkulchi 2003.
Blinding was not possible in three trials (Bidgood 1987;
Supajitkulchi 2003; Xenakis 1995), but one trial blinded care-
givers and pregnant women (Jamal 2004).
Lack of information, which would allow fuller assessment of risk
of bias, may reflect changes in reporting of trials.
Effects of interventions
Primary outcomes
There was a significant reduction in length of labour with higher
dose of oxytocin reported from one trial (mean difference (MD) -
3.50 hours; 95% confidence interval (CI) -6.38 to -0.62; one trial,
40 women (Analysis 1.3)). There was also evidence of reduction
in rates of caesarean section (risk ratio (RR) 0.53; 95% CI 0.38
to 0.75, four trials, 660 women (Analysis 1.2)). No significant
differences was seen in the incidence of neonatal mortality. None
of the included trials reported effects on perinatal mortality or
women’s birth experiences (satisfaction).
7High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Secondary outcomes
There was a significant evidence of increases in spontaneous vagi-
nal birth (RR 1.37; 95% CI 1.15 to 1.64, two trials, 350 women
(Analysis 1.4)). No significant difference was seen in the incidence
of ruptured uterus, dystocia, chorioamnionitis, epidural analgesia,
admission to neonatal units, Apgar score less than seven at five
minutes or umbilical cord pH. No trials reported instrumental
vaginal birth, incidences of ruptured uterus, postpartum haemor-
rhage, abnormal cardiotocography, women’s pyrexia and dystocia,
and neurological morbidities of the infants.
There were no significant differences for hyperstimulation,
chorioamnionitis, epidural analgesia, or neonatal outcomes of Ap-
gar scores, umbilical cord pH or admission to special care baby
unit.
The following outcomes were not evaluated in the included stud-
ies: instrumental vaginal birth, uterine rupture, postpartum haem-
orrhage, abnormal cardiotocography, women’s pyrexia, dystocia,
and neonatal neurological morbidity.
Subgroup analyses
By parity
No trial considered only parous women, and therefore we did not
conduct subgroup analysis by parity.
Previous caesarean section
No trial considered women with previous caesarean section sep-
arately, and therefore we did not conduct subgroup analysis by
previous caesarean section.
D I S C U S S I O N
The overall quality of the included trials was not good and all the
included trials were published before 2005, but lack of informa-
tion which would allow fuller assessment may reflect changes in
reporting of trials. Available evidence showed that a higher dose of
oxytocin for augmentation of delayed labour reduced the length
of labour and the number of caesarean sections and increased the
number of spontaneous vaginal births. No trial reported any effect
on women’s birth experience. There was no evidence of difference
in incidence of adverse events, though this could be due to the
small number of included trials and women. Since this review is
comparing only higher versus lower doses with the same intervals,
we can draw no conclusion on the optimal intervals or doses out-
side the ranges that this review assessed. There is little information
on effect in the group of women with previous caesarean section
and with different parities.
A U T H O R S ’ C O N C L U S I O N S
Implications for practice
The available evidence shows that high dose oxytocin for women
delayed in labour both reduces caesarean section and increases
spontaneous vaginal birth, as well as accelerates the progress of
labour. However, the number and quality of available evidence is
of concern and not enough is known about other clinically impor-
tant outcomes, including neonatal outcomes and the effects on
women’s birth experience, for this to be recommended treatment
for women delayed in the first stage of labour.
Implications for research
Further research should be conducted to evaluate high dose oxy-
tocin for delay in labour and such research should include ro-
bust assessment of both labour effects (hyperstimulation) as well
as neonatal outcomes and any effect on women’s birth experience.
A C K N O W L E D G E M E N T S
The protocol of this review was developed with contributions from
Dr Roz Ullman and Mr Steven Walkinshaw.
As part of the pre-publication editorial process, this review has
been commented on by three peers (an editor and two referees
who are external to the editorial team), a member of the Pregnancy
and Childbirth Group’s international panel of consumers and the
Group’s Statistical Adviser.
We are grateful to Maria Kalousi for translating Parpas 1995, Tip-
pawan Liabsuetrakul for translating Supajitkulchi 2003 and Kate
Kaminski for translating Vorherr 1963.
8High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
R E F E R E N C E S
References to studies included in this review
Bidgood 1987 {published data only}∗ Bidgood KA, Steer PJ. A randomized control study of
oxytocin augmentation of labour. 1. Obstetric outcome.
British Journal of Obstetrics and Gynaecology 1987;94:512–7.
Bidgood KA, Steer PJ. A randomized control study of
oxytocin augmentation of labour. 2. Uterine activity.
British Journal of Obstetrics and Gynaecology 1987;94:
518–22.
Bidgood KA, Steer PJ. Oxytocin augmentation of labour.
Proceedings of the 24th British Congress of Obstetrics and
Gynaecology;1986 April 15-18; Cardiff, UK. 1986:239.
Jamal 2004 {published data only}
Jamal A, Kalantari R. High and low dose oxytocin in
augmentation of labor. International Journal of Gynecology
& Obstetrics 2004;87:6–8.
Supajitkulchi 2003 {published data only}
Supajitkulchi S, Sritongchai C. A comparison of high and
low oxytocin concentration in active phase of labor. Chon
Buri Hospital Journal 2003;28(1):11–5.
Xenakis 1995 {published data only}∗ Xenakis EM, Langer O, Piper JM, Conway D, Berkus
MD. Low-dose versus high-dose oxytocin augmentation of
labor--a randomized trial. American Journal of Obstetrics and
Gynecology 1995;173:1874–8.
Xenakis EMJ, Field N, Barshes D, Langer O. Efficacy of
high dose vs low dose oxytocin in labor augmentation.
American Journal of Obstetrics and Gynecology 1994;170:
378.
References to studies excluded from this review
Akoury 1993 {published data only}
Akoury H, Brodie G, Caddick R, Chandbry N, Pugh N,
Rowell Y. Oxytocin augmentation of labour: a comparison
between high and low dose protocol and perinatal outcome
a nulliparous women. Proceedings of 49th Annual Clinical
Meeting of the Society of Obstetricians and Gynaecologists
of Canada; 1993 June 22-26; Ottawa, Ontario, Canada.
1993:14.
Alderman 1974 {published data only}
Alderman B. Letter: Dangers of oxytocin-induced labour to
fetuses. BMJ 1974;4:44–5.
Arulkumaran 1989 {published data only}
Arulkumaran S, Yang M, Ingemarsson I, Singh P, Ratnam
SS. Augmentation of labour: does oxytocin titration to
achieve preset active contraction area values produce better
obstetric outcome?. Asia-Oceania Journal of Obstetrics and
Gynaecology 1989;15:333–7.
Cummiskey 1989 {published data only}
Cummiskey KC, Gall SA, Yusoff DM. Pulsatile
administration of oxytocin for augmentation of labor.
Obstetrics & Gynecology 1989;74(6):869–72.
Lazor 1993 {published data only}
Lazor LZ, Philipson EH, Ingardia CJ, Kobetitsch ES, Curry
SL. A randomized comparison of 15- and 40-minute dosing
protocols for labor augmentation and induction. Obstetrics
& Gynecology 1993;82:1009–12.
Lazor LZ, Philipson EH, Ingardia CJ, Kobetitsch ES, Curry
SL. A randomized prospective comparison of oxytocin
dosing protocols for labor augmentation in nulliparous
women. American Journal of Obstetrics and Gynecology 1993;
168:295.
Lowensohn 1990 {published data only}
Lowensohn RI, Jensen JT. Oxytocin use in induction
and augmentation of labor. Proceedings of 10th Annual
Meeting of Society of Perinatal Obstetricians; 1990 January
23-27; Houston, Texas, USA. 1991:76.
Majoko 2001 {published data only}
Majoko F. Effectiveness and safety of high dose oxytocin
for augmentation of labour in nulliparous women. Central
African Journal of Medicine 2001;47(11-12):247–50.
Merrill 1999 {published data only}
Merrill DC, Zlatnik FJ. Randomized, double-masked
comparison of oxytocin dosage in induction and
augmentation of labor. Obstetrics & Gynecology 1999;94:
455–63.
Parpas 1995 {published data only}
Parpas G, Gondry J, Verhoest P, Martinez C, Boulanger
JCh. Randomised trial of 2 dosages of oxytocin for labour
induction or augmentation [Utilisation de l’ocytocine
(syntocinon) dans le declenchement ou la direction du
travail: faible ou forte posologie, comparaison]. Journal deGynecologie, Obstetrique et Biologie de la Reproduction 1995;
24(8):873.
Satin 1994 {published data only}
Satin AJ, Leveno KJ, Sherman L, McIntire D. High-dose
oxytocin: 20- versus 40-minute dosage interval. Obstetrics
& Gynecology 1994;83(2):238.
Seitchik 1982 {published data only}
Seitchik J, Castillo M. Oxytocin augmentation of
dysfunctional labor? I Clinical data. American Journal of
Obstetrics and Gynecology 1982;144:899–905.
Vorherr 1963 {published data only}
Von Vorherr H. Is there a pharmacological acceleration
of childbirth? [Gibt es eine medikamentose
Geburtsbeschleunigung?]. Deutsche MedizinischeWochenschrift 1963;88:1426–30.
Additional references
Deeks 2001
Deeks JJ, Altman DG, Bradburn MJ. Statistical methods
for examining heterogeneity and combining results from
several studies in meta-analysis. In: Egger M, Davey Smith
G, Altman DG editor(s). Systematic Reviews in Health Care:
Meta-Analysis in Context. London: BMJ Books, 2001.
9High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DOH 2004
Government Statistical Service for the Department of
Health. NHS Maternity Statistics. London: Department of
Health, 2004.
Egger 1997
Egger M, Davey Smith G, Schneider M, Minder C. Bias
in meta-analysis detected by a simple, graphical test. BMJ
1997;315(7109):629–34.
Gottschall 1997
Gottschall DS, Borgida AF, Mihalek JJ, Sauer F, Rodis JF.
A randomized clinical trial comparing misoprostol with
prostaglandin E2 gel for preinduction cervical ripening.
American Journal of Obstetrics and Gynecology 1997;177(5):
1067–70.
Harbord 2006
Harbord RM, Egger M, Sterne JA. A modified test for
small-study effects in meta-analyses of controlled trials
with binary endpoints. Statistics in Medicine 2006;25(20):
3443–57.
Higgins 2011
Higgins JPT, Green S, editors. Cochrane Handbook for
Systematic Reviews of Interventions Version 5.1.0 [updated
March 2011]. The Cochrane Collaboration, 2011.
Available from www.cochrane-handbook.org.
Impey 2000
Impey L, Hobson J, O’Herlihy C. Graphic analysis of
actively managed labor: prospective computation of
labor progress in 500 consecutive nulliparous women in
spontaneous labor at term. American Journal of Obstetricsand Gynecology 2000;183(2):438–43.
NICE 2007
National Collaborating Centre for Women’s and Children’s
Health. Intrapartum Care: Care of Healthy Women and
Their Babies During Childbirth. London: RCOG Press
2007.
RevMan 2011
The Nordic Cochrane Centre, The Cochrane Collaboration.
Review Manager (RevMan). 5.1. Copenhagen: The Nordic
Cochrane Centre, The Cochrane Collaboration, 2011.
Smyth 2007
Smyth RMD, Alldred SK, Markham C. Amniotomy
for shortening spontaneous labour. Cochrane Database
of Systematic Reviews 2007, Issue 4. [DOI: 10.1002/
14651858.CD006167.pub2]
Wei 2007
Wei SQ, Wo BL, Xu HR, Roy C, Turcot L, Fraser WD.
Early amniotomy and early oxytocin for delay in first stage
spontaneous labor compared with routine care. CochraneDatabase of Systematic Reviews 2007, Issue 4. [DOI:
10.1002/14651858.CD006794]
Wei 2010
Wei SQ, Luo ZC, Qi HP, Xu H, Fraser WD. High-dose vs
low-dose oxytocin for labor augmentation: a systematic
review. American Journal of Obstetrics and Gynecology 2010;
203:296–304.
Williams 1998
Williams FLR, Florey C du V, Ogston SA, Patel NB, Howie
PW, Tindall VR. UK study of intrapartum care of low
risk primigravidas: a survey of interventions. Journal of
Epidemiology and Community Health 1998;52:494–500.∗ Indicates the major publication for the study
10High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
C H A R A C T E R I S T I C S O F S T U D I E S
Characteristics of included studies [ordered by study ID]
Bidgood 1987
Methods A 3-arm randomised controlled trial.
Participants Nulliparous women in spontaneous labour with vertex at term (the high dose group: 19
women, the low dose group: 21 women).
Interventions Intervention: oxytocin started at 7 mU/min, increased by 7 mU/min every 15 minutes,
to a maximum of a frequency of 7 contractions in 15 minutes or by abnormality in the
fetal heart rate tracing.
Control: oxytocin started at 2 mU/min, increased by 2 mU/min every 15 minutes, to a
maximum of 40 mU/min until a table phase of uterine activity was detected or uterine
activity integral exceeded 1500 kPas/15 minutes.
Oxytocin was deferred for 8 hours for the third group. This review only included the
above 2 groups.
Outcomes Mode of delivery, incidence of hyperstimulation, length of labour, umbilical cord pH,
Apgar scores at 1 and 5 minutes.
Notes mU/min: 0.001 unit per minutes, kPas: kilo pascal.
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection
bias)
High risk Consecutive sealed envelopes means there is a
high risk of introducing bias.
Allocation concealment (selection bias) Low risk The allocation was concealed.
Blinding (performance bias and detection
bias)
All outcomes
High risk The assessment was not concealed.
Incomplete outcome data (attrition bias)
All outcomes
Low risk There is no loss of follow up reported.
Selective reporting (reporting bias) Unclear risk There is no information to make an appropriate
judgement on this.
11High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Jamal 2004
Methods A randomised controlled trial.
Participants Pregnant women with cervical dilatation of 3 cm or greater and gestational age 37 weeks
and more.
Both parous and nulliparous women were included. Women with previous caesarean
section were excluded.
ineffective uterine contraction in the beginning of active labour.
Amniotimy was performed in those with intact membrane
(the high dose group: 100 women, the low dose group: 100 women).
Interventions Intervention: 4.5 mU/min and increased by 4.5 mU/min every 30 minutes.
Control: 1.5 mU/min and increased by 1.5 mU/min every 30 minutes.
Outcomes Mode of delivery, length of labour.
Notes cm: centimetre
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection
bias)
Unclear risk No detailed description.
Allocation concealment (selection bias) Low risk The allocation was concealed.
Blinding (performance bias and detection
bias)
All outcomes
Low risk The assessment was concealed.
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk No description.
Selective reporting (reporting bias) Unclear risk No description.
Other bias Unclear risk No description.
Supajitkulchi 2003
Methods A randomised controlled trial.
Participants Pregnant women with singleton in spontaneous labour at term with cervical dilatation
of 3-5 cm, alive fetus and cephalic presentation. Unclear whether labour delayed or not
before augmentation.
Women with previous caesarean section, placenta praevia, parity of more than 5 times,
fetal distress, risk of dystocia (maternal height lower than 140 cm, maternal body weight
of less than 50 kg or more than 75 kg, abnormal pelvic bone or other complications)
were excluded.
(the high dose group: 60 women, the low dose group: 50 women)
12High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Supajitkulchi 2003 (Continued)
Interventions Intervention: oxytocin started at 4.5 mU/min, increased by 4.5 mU/min every 30 min-
utes.
Control: oxytocin started at 1.5 mU/min, increased by 1.5 mU/min every 30 minutes.
Outcomes Length of labour, mode of delivery, Apgar scores at 1 and 5 minutes.
Notes Range for length of labour reported in this paper seems very small, considering the point
estimate. We tried to contact the authors, but they had already moved to a different
hospital and we were unable to reach them. We have decided not to use the range until
a clarification is made. kg: kilogram
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection
bias)
Unclear risk Block randomisation, though details are unclear, and
there was not enough information to make a judge-
ment.
Allocation concealment (selection bias) Unclear risk There was not enough information to make a judge-
ment.
Blinding (performance bias and detection
bias)
All outcomes
High risk The assessment was not blinded.
Incomplete outcome data (attrition bias)
All outcomes
Low risk There is no loss of follow-up.
Selective reporting (reporting bias) High risk Not an intention-to-treat analysis.
Xenakis 1995
Methods A quasi-randomised controlled trial.
Participants Pregnant women requiring augmentation at term.
Women with malpresentation, placenta praevia, previous caesarean section or multiple
gestation were excluded.
Both nulliparous and parous women were included
(the high dose group: 154 women, the low dose group: 156 women).
Interventions Intervention: oxytocin started at 4 mU/min, increased by 4 mU/min every 15 minutes.
Control: oxytocin started at 1 mU/min, increased by 1 mU/min every 30 minutes.
Outcomes Neonatal mortality, mode of delivery, incidence of hyperstimulation, incidence of
chorioamnionitis, epidural analgesia, incidence of dystocia, neonatal admission to spe-
cial care, Apgar scores at 5 and 10 minutes.
13High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Xenakis 1995 (Continued)
Notes
Risk of bias
Bias Authors’ judgement Support for judgement
Random sequence generation (selection
bias)
High risk The allocation was based upon days of week;
hence a quasi randomised controlled trial.
Allocation concealment (selection bias) High risk As above.
Blinding (performance bias and detection
bias)
All outcomes
High risk Neither caregivers nor pregnant women were
masked.
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk There was not enough information to make a
judgement.
Selective reporting (reporting bias) Unclear risk There was not enough information to make a
judgement.
Characteristics of excluded studies [ordered by study ID]
Study Reason for exclusion
Akoury 1993 Trial was carried out in the context of active management of labour. Relevant information is not available.
Alderman 1974 Letter, not a primary study.
Arulkumaran 1989 Both groups received 2.5 mu/min of oxytocin up to different criteria for an optimal dose.
Cummiskey 1989 Pulsatile administration was compared with continuous administration.
Lazor 1993 Both intervention and control were classified as low dose.
Lowensohn 1990 Both intervention and control were classified as high dose.
Majoko 2001 Both intervention and control were classified as high dose.
Merrill 1999 The study population was pregnant women with planned routine augmentation. This implies that the study
population were not women with a diagnosis of delayed labour.
Parpas 1995 The populations included both those for augmentation and those for induction. These were not separately
reported.
14High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
(Continued)
Satin 1994 Both intervention and control were classified as high dose.
Seitchik 1982 2 groups were classified as low dose and the third group was by a physician’s choice.
Vorherr 1963 Comparing oxytocin with placebo.
15High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
D A T A A N D A N A L Y S E S
Comparison 1. High versus low dose of oxytocin (all women)
Outcome or subgroup titleNo. of
studies
No. of
participants Statistical method Effect size
1 Neonatal mortality 2 510 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
2 Caesarean section 4 660 Risk Ratio (M-H, Fixed, 95% CI) 0.53 [0.38, 0.75]
3 Length of labour (hour; oxytocin
to delivery)
1 40 Mean Difference (IV, Fixed, 95% CI) -3.50 [-6.38, -0.62]
4 Spontaneous vaginal birth 2 350 Risk Ratio (M-H, Fixed, 95% CI) 1.37 [1.15, 1.64]
5 Incidence of hyperstimulation 3 550 Risk Ratio (M-H, Random, 95% CI) 1.71 [0.60, 4.87]
6 Diagnosis of chorioamnionitis 1 310 Risk Ratio (M-H, Fixed, 95% CI) 0.69 [0.43, 1.11]
7 Epidural analgesia 1 310 Risk Ratio (M-H, Fixed, 95% CI) 0.97 [0.83, 1.13]
8 Neonatal admission to special
care baby units
1 310 Risk Ratio (M-H, Fixed, 95% CI) 0.79 [0.30, 2.06]
9 Apgar score less than 7 at 5
minutes
3 504 Risk Ratio (M-H, Fixed, 95% CI) 0.37 [0.02, 8.50]
10 Umbilical cord (artery) pH 1 40 Mean Difference (IV, Fixed, 95% CI) 0.0 [-0.06, 0.06]
Analysis 1.1. Comparison 1 High versus low dose of oxytocin (all women), Outcome 1 Neonatal mortality.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 1 Neonatal mortality
Study or subgroup High dose Low dose Risk Ratio Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Jamal 2004 0/100 0/100 0.0 [ 0.0, 0.0 ]
Xenakis 1995 0/154 0/156 0.0 [ 0.0, 0.0 ]
Total (95% CI) 254 256 0.0 [ 0.0, 0.0 ]
Total events: 0 (High dose), 0 (Low dose)
Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
0.01 0.1 1 10 100
Favours high dose Favours low dose
16High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.2. Comparison 1 High versus low dose of oxytocin (all women), Outcome 2 Caesarean section.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 2 Caesarean section
Study or subgroup High dose Low dose Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Xenakis 1995 16/154 40/156 53.0 % 0.41 [ 0.24, 0.69 ]
Jamal 2004 5/100 9/100 12.0 % 0.56 [ 0.19, 1.60 ]
Supajitkulchi 2003 15/60 18/50 26.2 % 0.69 [ 0.39, 1.23 ]
Bidgood 1987 5/19 7/21 8.9 % 0.79 [ 0.30, 2.07 ]
Total (95% CI) 333 327 100.0 % 0.53 [ 0.38, 0.75 ]
Total events: 41 (High dose), 74 (Low dose)
Heterogeneity: Chi2 = 2.47, df = 3 (P = 0.48); I2 =0.0%
Test for overall effect: Z = 3.59 (P = 0.00033)
0.01 0.1 1 10 100
Favours high dose Favours low dose
Analysis 1.3. Comparison 1 High versus low dose of oxytocin (all women), Outcome 3 Length of labour
(hour; oxytocin to delivery).
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 3 Length of labour (hour; oxytocin to delivery)
Study or subgroup High dose Low dose Mean Difference Weight Mean Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Bidgood 1987 19 7.8 (2.7) 21 11.3 (6.1) 100.0 % -3.50 [ -6.38, -0.62 ]
Total (95% CI) 19 21 100.0 % -3.50 [ -6.38, -0.62 ]
Heterogeneity: not applicable
Test for overall effect: Z = 2.38 (P = 0.017)
-100 -50 0 50 100
Favours high dose Favours low dose
17High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.4. Comparison 1 High versus low dose of oxytocin (all women), Outcome 4 Spontaneous vaginal
birth.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 4 Spontaneous vaginal birth
Study or subgroup High dose Low dose Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Bidgood 1987 6/19 5/21 5.6 % 1.33 [ 0.48, 3.65 ]
Xenakis 1995 110/154 81/156 94.4 % 1.38 [ 1.15, 1.65 ]
Total (95% CI) 173 177 100.0 % 1.37 [ 1.15, 1.64 ]
Total events: 116 (High dose), 86 (Low dose)
Heterogeneity: Chi2 = 0.00, df = 1 (P = 0.94); I2 =0.0%
Test for overall effect: Z = 3.45 (P = 0.00055)
0.01 0.1 1 10 100
Favours low dose Favours high dose
Analysis 1.5. Comparison 1 High versus low dose of oxytocin (all women), Outcome 5 Incidence of
hyperstimulation.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 5 Incidence of hyperstimulation
Study or subgroup High dose Low dose Risk Ratio Weight Risk Ratio
n/N n/N M-H,Random,95% CI M-H,Random,95% CI
Bidgood 1987 7/19 0/21 11.5 % 16.50 [ 1.01, 270.78 ]
Jamal 2004 14/100 8/100 46.9 % 1.75 [ 0.77, 3.99 ]
Xenakis 1995 7/154 8/156 41.5 % 0.89 [ 0.33, 2.38 ]
Total (95% CI) 273 277 100.0 % 1.71 [ 0.60, 4.87 ]
Total events: 28 (High dose), 16 (Low dose)
Heterogeneity: Tau2 = 0.43; Chi2 = 4.30, df = 2 (P = 0.12); I2 =54%
Test for overall effect: Z = 1.00 (P = 0.32)
0.01 0.1 1 10 100
Favours high dose Favours low dose
18High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.6. Comparison 1 High versus low dose of oxytocin (all women), Outcome 6 Diagnosis of
chorioamnionitis.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 6 Diagnosis of chorioamnionitis
Study or subgroup High dose Low dose Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Xenakis 1995 24/154 35/156 100.0 % 0.69 [ 0.43, 1.11 ]
Total (95% CI) 154 156 100.0 % 0.69 [ 0.43, 1.11 ]
Total events: 24 (High dose), 35 (Low dose)
Heterogeneity: not applicable
Test for overall effect: Z = 1.52 (P = 0.13)
0.01 0.1 1 10 100
Favours high dose Favours low dose
Analysis 1.7. Comparison 1 High versus low dose of oxytocin (all women), Outcome 7 Epidural analgesia.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 7 Epidural analgesia
Study or subgroup High dose Low dose Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Xenakis 1995 103/154 108/156 100.0 % 0.97 [ 0.83, 1.13 ]
Total (95% CI) 154 156 100.0 % 0.97 [ 0.83, 1.13 ]
Total events: 103 (High dose), 108 (Low dose)
Heterogeneity: not applicable
Test for overall effect: Z = 0.44 (P = 0.66)
0.01 0.1 1 10 100
Favours high dose Favours low dose
19High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.8. Comparison 1 High versus low dose of oxytocin (all women), Outcome 8 Neonatal admission
to special care baby units.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 8 Neonatal admission to special care baby units
Study or subgroup High dose Low dose Risk Ratio Weight Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Xenakis 1995 7/154 9/156 100.0 % 0.79 [ 0.30, 2.06 ]
Total (95% CI) 154 156 100.0 % 0.79 [ 0.30, 2.06 ]
Total events: 7 (High dose), 9 (Low dose)
Heterogeneity: not applicable
Test for overall effect: Z = 0.49 (P = 0.63)
0.01 0.1 1 10 100
Favours high dose Favours low dose
Analysis 1.9. Comparison 1 High versus low dose of oxytocin (all women), Outcome 9 Apgar score less than
7 at 5 minutes.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 9 Apgar score less than 7 at 5 minutes
Study or subgroup High dose Low dose Risk Ratio Risk Ratio
n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
Bidgood 1987 0/19 1/21 0.37 [ 0.02, 8.50 ]
Supajitkulchi 2003 0/82 0/72 0.0 [ 0.0, 0.0 ]
Xenakis 1995 0/154 0/156 0.0 [ 0.0, 0.0 ]
Total (95% CI) 255 249 0.37 [ 0.02, 8.50 ]
Total events: 0 (High dose), 1 (Low dose)
Heterogeneity: Chi2 = 0.0, df = 0 (P = 1.00); I2 =0.0%
Test for overall effect: Z = 0.63 (P = 0.53)
0.01 0.1 1 10 100
Favours high dose Favours low dose
20High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Analysis 1.10. Comparison 1 High versus low dose of oxytocin (all women), Outcome 10 Umbilical cord
(artery) pH.
Review: High dose versus low dose oxytocin for augmentation of delayed labour
Comparison: 1 High versus low dose of oxytocin (all women)
Outcome: 10 Umbilical cord (artery) pH
Study or subgroup High dose Low dose Mean Difference Weight Mean Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Bidgood 1987 19 7.27 (0.08) 21 7.27 (0.11) 100.0 % 0.0 [ -0.06, 0.06 ]
Total (95% CI) 19 21 100.0 % 0.0 [ -0.06, 0.06 ]
Heterogeneity: not applicable
Test for overall effect: Z = 0.0 (P = 1.0)
-100 -50 0 50 100
Favours high dose Favours low dose
H I S T O R Y
Protocol first published: Issue 3, 2008
Review first published: Issue 10, 2011
C O N T R I B U T I O N S O F A U T H O R S
Rintaro Mori (RM), Tokumasu Hironobu (TH) and Sara Kenyon (SK) reviewed the identified studies. RM wrote the first draft of the
review which was substantially commented on by SK. RM revised the document.
D E C L A R A T I O N S O F I N T E R E S T
None known.
S O U R C E S O F S U P P O R T
Internal sources
• Collaboration for Research in Global Women’s and Children’s Health, Japan.
21High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
External sources
• Ministry of Health. Labour and Welfare, Japan.
The study was partially funded by Ministry of Health, Labour and Welfare of Japan through a research grant.
D I F F E R E N C E S B E T W E E N P R O T O C O L A N D R E V I E W
We have updated the methods to reflect the latest Handbook (Higgins 2011). We have clarified that this review only includes women
whose labours were delayed, rather than routine augmentation in normal labour. We have removed the secondary outcome ’Assisted
vaginal delivery’ and added ’Spontaneous vaginal birth’ and ’Instrumental vaginal birth’ as secondary outcomes.
22High dose versus low dose oxytocin for augmentation of delayed labour (Review)
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.