Timing of prophylactic oxytocics for the third stage of labour after vaginal birth
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To assess the specific effect of the timing of administration of prophylactic oxytocics as part of the active management on the progress of the third stage of labour.
Background
The delivery of the placenta after childbirth can be a critical stage in relation to maternal and neonatal wellbeing. It is managed in a number of different ways, ranging from active (including early clamping and cutting of the umbilical cord, administration of oxytocic drugs and controlled cord traction) to totally physiological (expectant) with no interventions at all. Different aspects of the management may also be combined in a piecemeal way, which is not recommended based on the current available evidence (Gyte 1994).
The routine prophylactic use of oxytocics such as oxytocin or combined oxytocin/ergometrine (syntometrine) has been shown to reduce the risk of postpartum haemorrhage (PPH) (Cotter 2001; Prendiville 2000). The timing of the administration of oxytocic drugs, however, varies greatly among practitioners. The main recommended approach in the active management is to administer relevant drugs at the delivery of the anterior shoulder. This, however, can make the process complicated in many busy maternity units and increases the demand for having more than one healthcare professional present at the time of birth. In the practical setting, many clinicians use oxytocics immediately after the birth of the baby. There are others who administer the oxytocic drugs at the crowning of the head or even after the delivery of the placenta (Cotter 2001). The latter is mainly reported in the American literature and it is believed to reduce the risk of retention (Jackson 2001). The timing of oxytocic drugs can potentially impact on the blood perfusion to the baby and on the amount of maternal blood loss at the time of delivery. In addition, although there are no studies evaluating the transfusion of oxytocic drugs through the placenta or no reported evidence of any harmful effects on the baby, this may be a concern for some women. It is therefore pertinent to include outcome measures which reflect the immediate wellbeing of the neonate (Apgar scores) or haemodynamic indicators (for example, maternal blood pressure and haemoglobin changes). It is also important to note that there is a great deal of interaction between different components of the active third stage management. The outcomes such as PPH or neonatal haemoglobin level may be influenced by the combination of the timing of oxytocic administration as well as the timing of cord clamping. Therefore, when synthesising or interpreting the results, special attention should be given to these confounding factors.
A number of reviews have compared specific uterotonic agents or the whole package of different types of care (Cotter 2001; Prendiville 2000; Rabe 2004); however, evaluation of the individual aspects of the management of the third stage of labour rarely occurs. The timing of cord clamping is currently under evaluation (McDonald 2003) and the effects of cord drainage have been systematically reviewed by Soltani 2005. The results of the latter study showed a potential reduction in the length of the third stage of labour; however, the limited and heterogenous information available made it difficult to reach a conclusive statement. The timing of oxytocic administration, which can potentially influence maternal blood loss, neonatal blood volume or haemodynamics as well as the resources needed at the time of birth, has not been systematically evaluated. The aim of this review is, therefore, to examine the effect of the timing of the administration of oxytocics on various aspects of the third stage of labour and the postnatal period.
Objectives
To assess the specific effect of the timing of administration of prophylactic oxytocics as part of the active management on the progress of the third stage of labour.
Methods
Criteria for considering studies for this review
Types of studies
All randomised controlled trials examining the timing of prophylactic oxytocic drugs in the third stage of labour.
Types of participants
Women who had a spontaneous vaginal delivery.
Types of interventions
The administration of oxytocic drugs, given prophylactically at varying stages of the second or third stages of labour, to prevent postpartum haemorrhage.
Types of outcome measures
Maternal outcomes
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Postpartum haemorrhage (estimated or measured blood loss greater than 500 ml)
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Postpartum haemorrhage (estimated or measured blood loss greater than 1000 ml)
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Retained placenta (as defined by trials)
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Manual removal of placenta
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Length of third stage of labour
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Estimated or measured postpartum blood loss
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Changes in haemoglobin
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Blood transfusion
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Blood pressure
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Maternal pain during the third stage
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Maternal nausea and vomiting
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Use of additional uterotonics
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Secondary postpartum haemorrhage (after 24 hours and before six weeks)
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Death
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Breastfeeding rates
Neonatal outcomes
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Apgar score at birth and five minutes
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Admission to special care baby unit
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Jaundice (as defined by the authors)
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Respiratory distress
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Neonatal haemoglobin (after birth and at four to six weeks' postpartum)
Search methods for identification of studies
Electronic searches
We will contact the Trials Search Co‐ordinator to search the Cochrane Pregnancy and Childbirth Group's Trials Register.
The Cochrane Pregnancy and Childbirth Group's Trials Register is maintained by the Trials Search Co‐ordinator and contains trials identified from:
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quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);
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monthly searches of MEDLINE;
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handsearches of 30 journals and the proceedings of major conferences;
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weekly current awareness search of a further 37 journals.
Details of the search strategies for CENTRAL and MEDLINE, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the 'Search strategies for identification of studies' section within the editorial information about the Cochrane Pregnancy and Childbirth Group.
Trials identified through the searching activities described above are given a code (or codes) depending on the topic. The codes are linked to review topics. The Trials Search Co‐ordinator searches the register for each review using these codes rather than keywords.
We will search the Cumulative Index in Nursing and Allied Health Library (CINAHL 1982 to present), and EMBASE (1974 to present). Due to the varying structure of each database, slightly different search strategies will be required but will include the following search terms: third stage; oxytocin; oxytocic; syntocinon; ergometrine; syntometrine; head; shoulder; placenta; timing; delivery: restricted to research studies.
We will also search the National Research Register (NRR) to identify new or ongoing trials within this area.
We will not apply any language restrictions.
Data collection and analysis
Selection of studies
We will assess for inclusion all potential studies we identify as a result of the search strategy. We will resolve any disagreement through discussion or, if required, consult an outside person.
Data extraction and management
We will design a form to extract data. At least two review authors will extract the data using the agreed form. We will resolve discrepancies through discussion. We will use the Review Manager software (RevMan 2003) to double enter all the data or a subsample. When information regarding any of the above is unclear, we will attempt to contact authors of the original reports to provide further details.
Assessment of methodological quality of included studies
We will assess the validity of each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2005). Methods used for generation of the randomisation sequence will be described for each trial.
(1) Selection bias (randomisation and allocation concealment)
We will assign a quality score for each trial, using the following criteria:
(A) adequate concealment of allocation: such as telephone randomisation, consecutively‐numbered, sealed, opaque envelopes;
(B) unclear whether adequate concealment of allocation: such as list or table used, sealed envelopes, or study does not report any concealment approach;
(C) inadequate concealment of allocation: such as open list of random‐number tables, use of case record numbers, dates of birth or days of the week.
We will also include quasi‐randomised trials in this review. However, we will carry out a sensitivity analysis by trial quality.
(2) Attrition bias (loss of participants, for example, withdrawals, dropouts, protocol deviations)
We will assess completeness to follow up using the following criteria:
(A) less than 5% loss of participants;
(B) 5% to 9.9% loss of participants;
(C) 10% to 19.9% loss of participants;
(D) more than 20% loss of participants.
Studies with more than 20% attrition will be excluded.
(3) Performance bias (blinding of participants, researchers and outcome assessment)
We will assess blinding using the following criteria:
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blinding of participants (yes/no/unclear);
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blinding of caregiver (yes/no/unclear);
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blinding of outcome assessment (yes/no/unclear).
Measures of treatment effect
We will carry out statistical analysis using the Review Manager software (RevMan 2003). We will use fixed‐effect meta‐analysis for combining data in the absence of significant heterogeneity if trials are sufficiently similar. If heterogeneity is found, this will be explored by sensitivity analysis followed by a random‐effects analysis if required.
Dichotomous data
For dichotomous data, we will present results as summary relative risks with 95% confidence intervals.
Continuous data
For continuous data, we will use the weighted mean difference if outcomes are measured in the same way between trials. We will use the standardised mean difference to combine trials that measure the same outcome but use different methods. If there is evidence of skewness, we will report this.
Unit of analysis issues
Cluster‐randomised trials
Due to the nature of this intervention, cluster‐randomisation is unlikely. If available, we will include cluster‐randomised trials in the analyses along with individually randomised trials. The meta‐analysis will be performed using 'inflated standard errors' as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2005), and combined by the generic inverse variance method. We will also acknowledge heterogeneity in the randomisation unit and perform a separate meta‐analysis.
Dealing with missing data
We will analyse data on all participants with available data in the group to which they are allocated, regardless of whether or not they received the allocated intervention. If in the original reports participants are not analysed in the group to which they were randomised, and there is sufficient information in the trial report, we will attempt to restore them to the correct group.
Assessment of heterogeneity
We will apply tests of heterogeneity between trials, if appropriate, using the I² statistic. If we identify high levels of heterogeneity among the trials (exceeding 50%), we will explore it by prespecified subgroup analysis and perform sensitivity analysis. A random‐effects meta‐analysis will be used as an overall summary if this is considered appropriate.
Subgroup analyses
We will conduct planned subgroup analyses classifying whole trials by interaction tests as described by Deeks 2001.
In addition to overall timing of oxytocic drugs, if the data are available we plan to carry out the following analyses:
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timing of oxytocin versus syntometrine versus ergometrine;
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timing of oxytocics in women at high risk of postpartum haemorrhage (PPH) versus women at low risk of PPH (as defined by trials) versus mixed risk or risk not defined;
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timing of oxytocics accompanied by immediate cord clamping versus delayed cord clamping (as defined by trials) versus cord clamping time not defined;
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timing of oxytocics, data from developed countries versus developing countries versus multicentre trials in both categories of country.
Sensitivity analyses
We will carry out sensitivity analysis to explore the effect of trial quality. This will involve analysis based on an A, B, C, or D rating of selection bias and attrition bias. We will exclude studies of poor quality in the analysis (those rating B, C, or D) in order to assess for any substantive difference to the overall result.
If cluster‐randomised trials are available, additional sensitivity analysis will also be performed. If cluster trials have been incorporated with an estimate of the intracluster correlation coefficient (ICC) borrowed from a different trial, a sensitivity analysis will be carried out to see what the effect of different values of the ICC on the results of the analysis would be.
