high dose versus low dose oxytocin for augmentation of ... · with low dose (less than 4 mu per...

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.

http://www.thecochranelibrary.com

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)


[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.


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)


mailto:[email protected]

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.



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



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);


(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



http://www.mrw.interscience.wiley.com/cochrane/clabout/articles/PREG/frame.html





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.


• 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);


(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.


• 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);


(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



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



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).



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.



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.



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



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.



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)

Unclear risk No detailed description.

Allocation concealment (selection bias) Low risk The allocation was concealed.


bias)

All outcomes

Low risk The assessment was concealed.


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)



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)

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.


bias)

All outcomes

High risk The assessment was not blinded.


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.



Xenakis 1995 (Continued)

Notes

Risk of bias



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.


bias)

All outcomes

High risk Neither caregivers nor pregnant women were

masked.


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.



(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.



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



Analysis 1.2. Comparison 1 High versus low dose of oxytocin (all women), Outcome 2 Caesarean section.



Outcome: 2 Caesarean section

Study or subgroup High dose Low dose Risk Ratio Weight Risk Ratio


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 ]


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


Analysis 1.3. Comparison 1 High versus low dose of oxytocin (all women), Outcome 3 Length of labour

(hour; oxytocin to delivery).



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


-100 -50 0 50 100




Analysis 1.4. Comparison 1 High versus low dose of oxytocin (all women), Outcome 4 Spontaneous vaginal

birth.



Outcome: 4 Spontaneous vaginal birth



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 ]




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.



Outcome: 5 Incidence of hyperstimulation


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 ]


Heterogeneity: Tau2 = 0.43; Chi2 = 4.30, df = 2 (P = 0.12); I2 =54%


0.01 0.1 1 10 100




Analysis 1.6. Comparison 1 High versus low dose of oxytocin (all women), Outcome 6 Diagnosis of

chorioamnionitis.



Outcome: 6 Diagnosis of chorioamnionitis



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 ]




0.01 0.1 1 10 100


Analysis 1.7. Comparison 1 High versus low dose of oxytocin (all women), Outcome 7 Epidural analgesia.



Outcome: 7 Epidural analgesia



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 ]




0.01 0.1 1 10 100




Analysis 1.8. Comparison 1 High versus low dose of oxytocin (all women), Outcome 8 Neonatal admission

to special care baby units.



Outcome: 8 Neonatal admission to special care baby units



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 ]




0.01 0.1 1 10 100


Analysis 1.9. Comparison 1 High versus low dose of oxytocin (all women), Outcome 9 Apgar score less than

7 at 5 minutes.



Outcome: 9 Apgar score less than 7 at 5 minutes

Study or subgroup High dose Low dose Risk Ratio Risk Ratio


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 ]




0.01 0.1 1 10 100




Analysis 1.10. Comparison 1 High versus low dose of oxytocin (all women), Outcome 10 Umbilical cord

(artery) pH.



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 ]



-100 -50 0 50 100


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.



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.



high dose versus low dose oxytocin for augmentation of ... · with low dose (less than 4 mu per...

Documents