Alternative prophylactic therapies (acupuncture and/or moxibustion) for reducing blood loss in the third stage of labour

  • Protocol
  • Intervention

Authors


Abstract

This is the protocol for a review and there is no abstract. The objectives are as follows:

To systematically review the effectiveness and safety of all types of acupuncture and moxibustion for reducing blood loss in the third stage of labour for women who expected a vaginal singleton birth at 24 weeks' gestation or later.

Background

Description of the condition

Millennium Development Goal (MDG) 5 set out to reduce the maternal mortality rate by 75% between 1990 and 2015; however, according to WHO statistics (WHO 2012), only 10 countries achieved MDG5 in 2010. Postpartum haemorrhage (PPH) continues to be the leading cause of maternal deaths in low-income settings (Khan 2006) and accounts for 125,000 deaths per year, which makes up nearly 25% of all maternal deaths globally (Kent 2010; World Health Organization 2012). Furthermore, women who survive PPH have a relatively high risk of severe anaemia and morbidity (Abou-Zahr 2003). Given the mortality and morbidity caused by PPH, further reduction of this condition is necessary in order to significantly reduce the maternal mortality rate.

PPH describes blood loss occurring within 24 hours following delivery that is greater than or equal to 500 mL, while severe PPH describes blood loss greater than or equal to 1000 mL (WHO 2009). The leading cause of PPH is failure of the uterus to contract adequately. Since the International Confederation of Midwives (ICM) and the International Federation of Gynecology and Obstetrics (FIGO) (ICM&FIGO 2003) showed that active management of the third stage of labour (AMTSL) is effective in reducing the incidence of PPH due to uterine atony, timely and appropriate interventions should be given to pregnant women during the third stage of labour. The effectiveness of active management of the third stage of labour was also supported by a systematic review of randomised controlled trials (Begley 2015). According to the ICO-FIGO definition, active management of the third stage of labour commonly included uterotonic administration within one minute of delivery, controlled cord traction until complete delivery of the placenta, followed by fundal massage every 15 minutes for the first two hours immediately after placental delivery (ICM&FIGO 2003). Promoting strong uterine contractions and conducting faster retraction and placental separation and delivery are the most important effects of AMTSL for PPH prevention (Begley 2015; Sheldon 2013).

Description of the intervention

Acupuncture has been used in China for centuries and is now regarded as a useful form of complementary and alternative medicine (CAM) worldwide. Traditional acupuncture involves the insertion of needles into the skin and underlying tissues at specific points on the body known as 'acupoints'. Moxibustion is a special kind of acupuncture without needles. This technique uses moxa, a fluffy substance made from dried mugwort, placed at acupoints on the body to stimulate blood flow in these areas. The moxa is usually heated and applied to the skin in the form of small cones or a cigar-shaped stick. In traditional Chinese medicine, acupuncture and moxibustion have been used to regulate the female reproductive system and prevent massive bleeding during labour and delivery (Chen 1963; Maciocia 1997).

Acupuncture, as one of the key treatment modalities of traditional Chinese medicine, aims to achieve a state of health maintained by the balance of the whole body instead of only focusing on one partial symptom, and is reported as having few side effects (Xu 2013). In addition, although some kinds of acupuncture require needling skills, moxibustion and acupressure require only knowledge of the right acupuncture points, and could therefore be implemented by caregivers, the pregnant woman's family, or even pregnant women themselves.

The use of CAM including acupuncture and moxibustion is increasing worldwide, and is more commonly used by women of reproductive age (Eisenberg 1998). A recent study conducted in Australia showed that more than 90% of participants used CAM during their pregnancy (Frawley 2014). It is possible that a significant proportion of women who have previously experienced acupuncture plan to use acupuncture during pregnancy. Although side effects from acupuncture such as infections, pain, and injuries have been reported (Yamashita 1999), recent surveys conducted in Europe about acupuncture safety among regulated, qualified practitioners (White 2001; Witt 2011), confirmed that serious adverse events after acupuncture are uncommon among licensed practitioners.

How the intervention might work

Acupuncture and moxibustion have long been used in traditional Chinese medicine to prevent and control blood loss during delivery. Although there is no clear-cut mechanism to explain the function of acupuncture, some hypotheses suggest that acupuncture performed at specific acupoints—usually acupoints in the Conception vessel, which is a part of the body's channel system in Chinese medicine—may promote uterine contractions and reduce blood loss associated with uterine atony by promoting delivery, regulating the female reproductive system and reducing pain (Ma 2006; Maciocia 1997).

Why it is important to do this review

As blood loss is the leading cause of maternal death, reducing maternal mortality and morbidity caused by blood loss in the third stage of labour is a major challenge for health workers. Acupuncture and moxibustion have been used for centuries in parts of Asia to reduce bleeding during delivery. However, no Cochrane systematic review has evaluated the effectiveness and safety of acupuncture and moxibustion for reducing blood loss in the third stage of labour. Consumers often regard complementary medicine as a more natural and potentially safer option than conventional medicine (Smith 2013). If acupuncture and moxibustion could be proven to be effective and safe in reducing PPH, these methods could be widely used as a low-risk, low-cost complementary treatment during pregnancy.

Objectives

To systematically review the effectiveness and safety of all types of acupuncture and moxibustion for reducing blood loss in the third stage of labour for women who expected a vaginal singleton birth at 24 weeks' gestation or later.

Methods

Criteria for considering studies for this review

Types of studies

We will include randomised controlled trials (RCTs) including cluster-RCTs and quasi-RCTs. We will exclude trials using a cross-over design.

Types of participants

Women who had normal vaginal delivery and who expected a singleton birth during the third stage of labour at 24 weeks' gestation or later.

Types of interventions

We will include trials that use acupuncture alone, or moxibustion alone, or any combination of acupuncture and moxibustion. All kinds of acupuncture or moxibustion in the third stage of labour which aimed to prevent blood loss will be regarded as interventions. We will include all kinds of acupunctures such as manual acupuncture, electroacupuncture, auricular acupuncture, acupuncture point injection therapy, plum-blossom needle therapy etc. Groups that use either or both acupuncture and moxibustion will be regarded as an intervention group. Any other treatments other than acupuncture or moxibustion, or no interventions, will be regarded as a comparable group. We will not include head-to-head comparison (e.g. electroacupuncture versus manual acupuncture).

Types of outcome measures

Primary outcomes
  1. Severe postpartum haemorrhage (PPH) > 1000 mL over the period of observation (as determined by the trial authors)

  2. Severe maternal morbidity (e.g. renal or respiratory failure, cardiac arrest or multiple-organ failure)

  3. Blood transfusion

Secondary outcomes
  1. PPH: defined as blood loss greater or equal to 500 mL over the period of observation (defined by the trial authors)

  2. Retained placenta

  3. Manual removal of placenta

  4. Length of third stage of labour

  5. Mean blood loss (mL)

  6. Postnatal anaemia (defined by trial authors, as a reduction of haemoglobin (Hb))

  7. Secondary PPH: abnormal or excessive vaginal bleeding between 48 hours and six weeks after delivery

  8. Maternal mortality

  9. Adverse effects of intervention (such as headache, vomiting, injury)

Search methods for identification of studies

The following methods section of this protocol is based on a standard template used by the Cochrane Pregnancy and Childbirth Group.

Electronic searches

We will the Cochrane Pregnancy and Childbirth Group’s Trials Register by contacting the Information Specialist.

The Register is a database containing over 21,000 reports of controlled trials in the field of pregnancy and childbirth. For full search methods used to populate the Pregnancy and Childbirth Group’s Trials Register including the detailed search strategies for CENTRAL, MEDLINE, Embase and CINAHL; the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service, please follow this link to the editorial information about the Cochrane Pregnancy and Childbirth Group in the Cochrane Library and select the ‘Specialized Register ’ section from the options on the left side of the screen.

Briefly, the Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Information Specialist and contains trials identified from:

  1. monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL);

  2. weekly searches of MEDLINE (Ovid);

  3. weekly searches of Embase (Ovid);

  4. monthly searches of CINAHL (EBSCO);

  5. handsearches of 30 journals and the proceedings of major conferences;

  6. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts.

Search results are screened by two people and the full text of all relevant trial reports identified through the searching activities described above is reviewed. Based on the intervention described, each trial report is assigned a number that corresponds to a specific Pregnancy and Childbirth Group review topic (or topics), and is then added to the Register. The Information Specialist searches the Register for each review using this topic number rather than keywords. This results in a more specific search set which has been fully accounted for in the relevant review sections (Included, Excluded, Awaiting classification and Ongoing).

In addition, we will search ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) for unpublished, planned and ongoing trial reports (see: Appendix 1 for terms we plan to use).

We also plan to search the following Chinese databases:

  1. Chinese databases Sino-Med (previously called the Chinese Biomedical Database).

  2. Chinese National Knowledge Infrastructure.

  3. VIP Database for Chinese Technical Periodicals.

We will describe the search methods in full for these databases in an appendix in the full review.

Searching other resources

We will check references cited in papers identified through the above search strategy to retrieve additional relevant studies. We will include reports that are in abstract form and plan to contact authors for further information where necessary.

We will not apply any language or date restrictions.

Data collection and analysis

The following methods section of this protocol is based on a standard template used by the Cochrane Pregnancy and Childbirth Group.

Selection of studies

Two review authors (YL and EO) will independently assess for inclusion all the potential studies we identify as a result of the search strategy. We will resolve any disagreement through discussion or, if required, we will consult with a third author (KC).

We will create a study flow diagram to map out the number of records identified, included and excluded.

Data extraction and management

We will design a form to extract data. For eligible studies, two review authors (YL and EO) will extract the data using the agreed form. We will resolve discrepancies through discussion or, if required, we will consult with RM. We will enter data into Review Manager software (RevMan 2014) and check for accuracy.

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 risk of bias in included studies

Two review authors (YL and EO) will independently assess risk of bias for each study using the criteria outlined in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011). We will resolve any disagreement by discussion or by involving a third assessor (RM).

(1) Random sequence generation (checking for possible selection bias)

We will 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 will assess 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);

  • unclear risk of bias.

(2) Allocation concealment (checking for possible selection bias)

We will describe for each included study the method used to conceal allocation to interventions prior to assignment and will assess whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment.

We will assess 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.

(3.1) Blinding of participants and personnel (checking for possible performance bias)

We will describe for each included study the methods used, if any, to blind study participants and personnel from the knowledge of the allocated intervention during the study, and knowledge of which intervention a participant received. For “Blinding”, we will assign sham-controlled trials a judgment of “unclear”, unless we felt certain that the sham control was sufficiently credible in fully blinding participants to the treatment being evaluated (Manheimer 2007; Manheimer 2010). We will assign the “Yes” score to sham-controlled trials that either 1) evaluated the credibility of the sham and found the sham to be indistinguishable from true acupuncture or 2) used a penetrating needle or a previously validated sham needle (i.e. Streitberger needle). We will consider that studies are at low risk of bias if the participants and personnel were blinded, or if we judge that the lack of blinding would be unlikely to affect results. We will assess blinding separately for different outcomes or classes of outcomes.

We will assess the methods as:

  • low, high or unclear risk of bias for participants;

  • low, high or unclear risk of bias for personnel.

(3.2) Blinding of outcome assessment (checking for possible detection bias)

We will describe for each included study the methods used, if any, to blind outcome assessors from knowledge of which intervention a participant received. We will assess blinding separately for different outcomes or classes of outcomes.

We will assess methods used to blind outcome assessment as:

  • low, high or unclear risk of bias.

(4) Incomplete outcome data (checking for possible attrition bias due to the amount, nature and handling of incomplete outcome data)

We will describe for each included study, and for each outcome or class of outcomes, the completeness of data including attrition and exclusions from the analysis. We will state whether attrition and exclusions were reported and the numbers included in the analysis at each stage (compared with the total randomised participants), reasons for attrition or exclusion where reported, and whether missing data were balanced across groups or were related to outcomes. Where sufficient information is reported, or can be supplied by the trial authors, we will re-include missing data in the analyses which we undertake.

We will assess 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 will describe for each included study how we investigated the possibility of selective outcome reporting bias and what we found.

We will assess 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 will describe for each included study any important concerns we have about other possible sources of bias.

We will assess 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.

Assessing the quality of the body of evidence using the GRADE approach

We will assess the quality of the evidence using the GRADE approach as outlined in the GRADE handbook in order to assess the quality of the body of evidence relating to the following outcomes for the main comparisons.

  1. Severe postpartum haemorrhage (PPH) > 1000 mL over the period of observation (as determined by the trial authors)

  2. Severe maternal morbidity (e.g. renal or respiratory failure, cardiac arrest or multiple-organ failure)

  3. Blood transfusion

  4. PPH: defined as blood loss greater or equal to 500 mL over the period of observation (defined by the trial authors)

We will use the GRADEpro Guideline Development Tool to import data from Review Manager 5.3 (RevMan 2014) in order to create ’Summary of findings’ tables. A summary of the intervention effect and a measure of quality for each of the above outcomes will be produced using the GRADE approach. The GRADE approach uses five considerations (study limitations, consistency of effect, imprecision, indirectness and publication bias) to assess the quality of the body of evidence for each outcome. The evidence can be downgraded from 'high quality' by one level for serious (or by two levels for very serious) limitations, depending on assessments for risk of bias, indirectness of evidence, serious inconsistency, imprecision of effect estimates or potential publication bias.

Measures of treatment effect

Dichotomous data

For dichotomous data, we will present results as summary risk ratio with 95% confidence intervals.

Continuous data

For continuous data, we will use the 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.

Unit of analysis issues

Cluster-randomised trials

We will include cluster-randomised trials in the analyses along with individually-randomised trials. We will adjust their sample sizes using the methods described in the Handbook with an estimate of the intracluster correlation co-efficient (ICC) derived from the trial if possible, or 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 investigate 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 heterogeneity between the study designs and the interaction between the effect of intervention and the choice of randomisation unit is considered to be unlikely.

We will also acknowledge heterogeneity in the randomisation unit and perform a sensitivity analysis to investigate the effects of the randomisation unit.

Other unit of analysis issues

Trials with multiple arms will be included. If there are two acupuncture groups, data from both treatment arms will be combined into one group. For studies with a sham control and no treatment control group, the shared intervention will be divided evenly between groups as described in the Cochrane Handbook for Systematic Reviews of Interventions (Higgins 2011).

Dealing with missing data

For included studies, we will note levels of attrition. We will explore the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis.

For all outcomes, we will carry out analyses, as far as possible, on an intention-to-treat basis, i.e. we will attempt to include all participants randomised to each group in the analyses, and all participants will be analysed 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 will be the number randomised minus any participants whose outcomes are known to be missing.

Assessment of heterogeneity

We will assess statistical heterogeneity in each meta-analysis using the T², I² and Chi² statistics. We will regard heterogeneity as substantial if a I² is greater than 30% and either a T² is greater than zero, or there is a low P value (less than 0.10) in the Chi² test for heterogeneity.

Assessment of reporting biases

If 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. If asymmetry is suggested by a visual assessment, we will perform exploratory analyses to investigate it.

Data synthesis

We will carry out statistical analysis using the Review Manager software (RevMan 2014). We will use fixed-effect meta-analysis for combining data where it is reasonable to assume that studies are estimating the same underlying treatment effect: i.e. where trials are examining the same intervention, and the trials’ populations and methods are judged sufficiently similar. If there is clinical heterogeneity sufficient to expect that the underlying treatment effects differ between trials, or if substantial statistical heterogeneity is detected, we will use random-effects meta-analysis to produce an overall summary, if an average treatment effect across trials is considered clinically meaningful. The random-effects summary will be treated as the average range of possible treatment effects and we will discuss the clinical implications of treatment effects differing between trials. If the average treatment effect is not clinically meaningful, we will not combine trials.

If we use random-effects analyses, the results will be presented as the average treatment effect with 95% confidence intervals, and the estimates of T² and I².

Subgroup analysis and investigation of heterogeneity

If we identify substantial heterogeneity, we will investigate it using subgroup analyses and sensitivity analyses. We will consider whether an overall summary is meaningful, and if it is, use random-effects analysis to produce it.

We plan to carry out the following subgroup analyses.

  1. Spontaneous labour versus induced labour

  2. Primiparous versus multiparous

  3. Term versus preterm birth

  4. Blinded assessors versus objectively (unblinded) measured excessive blood loss

  5. Individual- or cluster-RCTs versus quasi-RCTs

Subgroup analysis will be restricted to the review's primary outcomes.

We will assess subgroup differences by interaction tests available within RevMan (RevMan 2014). We will report the results of subgroup analyses quoting the Chi2 statistic and P value, and the interaction test I² value.

Sensitivity analysis

We will perform sensitivity analyses on primary outcomes to look at the possible contribution of differences in methodological quality, with trials of high quality (low risk of bias) compared to all trials. We will conduct sensitivity analyses for trials with unclear or high risk of bias for allocation concealment, and trials with more than 20% of missing data, which should be considered as high risk of bias for incomplete outcome data. We will also undertake a sensitivity analysis to explore the effects of fixed-effect or random-effects analyses for outcomes with statistical heterogeneity and the effects of any assumptions made, such as the value of the ICC used for cluster-randomised trials.

Acknowledgements

We thank Emma Barber for her editorial support.

As part of the pre-publication editorial process, this protocol 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.

This project was supported by the National Institute for Health Research, via Cochrane Infrastructure funding to Cochrane Pregnancy and Childbirth. The views and opinions expressed therein are those of the authors and do not necessarily reflect those of the Systematic Reviews Programme, NIHR, NHS or the Department of Health.

Rintaro Mori's institution receives government funding from the Clinical Research Program for Child Health and Development, AMED, Japan to provide support for the Cochrane Pregnancy and Childbirth Satellite in Japan.

Appendices

Appendix 1. Search terms for additional author searching

ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP)

acupuncture AND labor

acupuncture AND labour

acupressure AND labor

acupressure AND labour

moxibustion AND labor

moxibustion AND labour

We will run each line separately and manually remove duplicates.

Contributions of authors

Yi Liao (YL) and Erika Ota (EO) wrote the draft protocol with input from Ke Cheng (KC) and Rintaro Mori (RM).

Declarations of interest

Yi Liao: none known.

Erika Ota: none known.

Ke Cheng: was supported by the National Basic Research Program of China (2012CB518502), National Natural Science Foundation of China (81320108028), Shanghai development office of Traditional Chinese Medicine (ZYSNXD-CC-ZDXK-07), Shanghai Key Laboratory of acupuncture mechanism and acupoint function (14DZ2260500), program of Shanghai Municipal Education Commission (2014YSN13) (11DZ1973300, ZYSNXD-CC-ZDXK-07) for acupuncture and moxibustion research on inflammatory pain.

Rintaro Mori's institution has received government funding from the Clinical Research Program for Child Health and Development, AMED Japan (Japan AMED No.27300101; Principal Investigator: Rintaro Mori), to provide support for the Cochrane Pregnancy and Childbirth Satellite in Japan. Rintaro Mori's Department has received internal research grant from the National Center for Child Health Development, Japan (NCCHD 26-5; Principal Investigator: Rintaro Mori) to provide support for the Cochrane Japan.

Sources of support

Internal sources

  • The Grant of National Center for Child Health and Development 26A-5, Japan.

External sources

  • Japan Agency for Medical Research and development, Japan.

    AMED No.27300101

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