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DOI: 10.1111/1471-0528.14417
Commentary
www.bjog.org
Postpartum haemorrhage: a single definition is no longer enough RS Kerr, AD Weeks Sanyu Research Unit, Department of Women’s and Children’s Health, University of Liverpool, Liverpool Women’s Hospital, Liverpool, UK Correspondence: R Kerr, Sanyu Research Unit, Department of Women’s and Children’s Health, University of Liverpool, Liverpool Women’s Hospital, Crown Street, Liverpool, L8 7SS, UK. Email [email protected] Accepted 28 September 2016. Published Online 24 November 2016. Please cite this paper as: Kerr RS, Weeks AD. Postpartum haemorrhage: a single definition is no longer enough. BJOG 2017;124:723–726.
Postpartum haemorrhage (PPH) is the leading cause of death in pregnancy globally, causing 187 deaths daily.1 In many more it leads to anaemia, blood transfusion, surgery and psychological morbidity. This burden of disease makes it a global priority to improve PPH management. Critical to this is the need to agree a simple fact: what exactly is a PPH?
Official definitions During a WHO ‘informal meeting of experts’ in 1989, PPH was defined as ‘the loss of 500mls or more of blood from the genital tract after delivery of the baby’.2 This definition has been widely cited, and has been relatively unchallenged until recently, despite the meeting’s report acknowledging 500 ml as ‘an arbitrary figure’ and ‘not always of great clinical significance’. In recent years, professional societies have developed definitions with more clinical significance. The Royal College of Obstetricians and Gynaecologists (RCOG) in 2011 endorsed the 500 ml threshold in their definition of ‘Minor PPH’, although it stated that 1000 ml (or a lesser volume with clinical shock), should be classed as ‘Major PPH’. They recommend ‘readiness for resuscitation’ in response to blood loss 500–1000 ml, but ‘a full protocol of measures’ when the blood loss reaches 1000 ml or there are clinical signs of shock.3 The American College of Obstetricians and Gynecologists (ACOG) held a modified Delphi vote of its members in 2014 to reach a consensus on a PPH definition. They dismissed the 500 ml cutoff, endorsing in its place a definition of ‘greater or equal to 1000 ml or blood loss with signs or symptoms of hypovolemia’.4 The WHO avoided a specific recommendation in their 2012 guidelines, instead commenting that ‘PPH is commonly defined as blood loss 500 ml or more’.5 The most recent WHOendorsed definition was instead for ‘Severe PPH’, defined
ª 2016 Royal College of Obstetricians and Gynaecologists
by the WHO Working Group on Maternal Mortality and Morbidity Classifications as ‘genital bleeding after delivery, with at least one of the following: perceived abnormal bleeding (1000 ml or more) or any bleeding with hypotension or blood transfusion’.6
Definitions based on the volume of blood loss A review of primary outcomes used in PPH prevention randomised controlled trials (RCTs) and systematic reviews (SRs) reported that ≥500 ml was the most common primary outcome in RCTs (24/82), whereas ≥1000 ml was preferred in SRs (10/77).7 The preference for 500 ml in trials but 1000 ml in systematic reviews most likely reflects trialists’ desire to maximise statistical power versus reviewers’ preference for outcomes more closely associated with morbidity. But definitions based on blood loss volume all suffer from the inaccuracies inherent in blood loss quantification —practitioners underestimate by 46–75%, with greater errors at higher losses.8 Diagnostic accuracy can be improved by direct measurement of blood in under-buttock calibrated drapes. Unfortunately, as routine use of calibrated drapes has not been associated with a decrease in severe PPH, their use at every delivery is hard to justify outside of research.9 Many clinicians compromise by using collection drapes for high-risk deliveries, and retrospectively weighing blood-soaked materials after PPH at other deliveries. In selecting a blood loss threshold, we are attempting to find a division between normal bleeding and abnormal bleeding. But what is normal bleeding? In 9348 low-risk vaginal deliveries with no third stage prophylaxis and no treatment until 700 ml of blood loss, the mean, mode and median of measured blood loss were between 200 and
723
Kerr, Weeks
300 ml.10 However, what is the upper limit of normal: the 75th centile (310 ml); the 90th centile (720 ml); or the 95th centile (900 ml)? The choice is arbitrary, with the resulting definition based, somewhat illogically, on those at the lowest risk of PPH. Indeed, the normal blood loss of any population varies hugely depending on the environment (e.g. altitude), ethnicity, the pregnancy itself (e.g. multiple pregnancy), and health care factors (including obstetric interventions and PPH prophylaxis).3 Importantly, an individual’s tolerance of blood loss will also vary widely. The presence of anaemia, endemic in many regions due to malaria, dietary deficiencies and intestinal worms, will be critical in determining the consequences of blood loss. Routine calculation of the blood loss as a percentage of total blood volume (using weight and height) would take account of the woman’s habitus, but the challenges of blood measurement persist.
Definitions based on physiological changes An alternative approach is to define PPH by a fall in haematocrit (by >10%) or haemoglobin concentration (>2 g/dl) on blood samples taken before and after delivery. While this has many advantages, it is markedly affected by intravascular fluid depletion (with pre-eclampsia or dehydration), infusions of fluid or blood, and the physiological postpartum rise. Furthermore, it requires laboratory facilities and only permits a retrospective diagnosis. Vital signs have been used by some authors and professional societies in their definitions to capture the effects of bleeding. Their measurement has the advantage of being standard management already, relatively easy, cheap and objective. A systematic review into the relation between blood loss and clinical signs highlighted that shock index (heart rate divided by systolic blood pressure) was the most promising clinical sign for this purpose.11 However, shock index alone has a low specificity for PPH, and there is insufficient evidence at present to recommend a cutoff to be used as part of a PPH definition.
Definitions based on need for intervention Interventions for PPH, for example the need for additional uterotonics, are a pragmatic way to define PPH. However, practitioners tend to commence treatment early in the bleeding, for example in response to a rapid rate of bleeding.8 Indeed, a secondary analysis of four large randomised trials found little correlation between additional uterotonic medication and final measured blood loss, with two trials finding the majority of women receiving uterotonics had a final blood loss of less than 500 ml.7 Identifying cases
724
retrospectively can also present a challenge, as it may be unclear whether medication was given as prophylaxis or as treatment. The aforementioned approaches are all unsatisfactory as they fail to measure what is most important to the woman —adverse outcomes. Postpartum bleeding may cause a new mother to be light-headed, weak and unable to feed her baby. But she may also develop organ dysfunction, require blood products, surgery, be admitted to intensive care, or even die as a result of PPH. Adverse clinical outcomes like these should be central when developing a consensus on PPH definition so that it accurately captures the morbidity caused by the disease.
The need for different definitions It is important to separate out the level of bleeding at which treatment is initiated, and that at which PPH, as an adverse outcome, is defined. Although previous definitions have tried to hold both together, a value of 500 ml satisfies neither requirement. After all, no clinician would sit back and watch a rapid atonic or traumatic PPH, waiting for it to reach an arbitrary value before initiating treatment. Consider the analogy of a town with a flood-prone river running through it. In heavy rainfall, shopkeepers are likely to lay sandbags across the front of their shops as soon as they see the water level rapidly rising. The official definition of ‘flooding’ may be that the river spills over the quay —but that doesn’t represent the point at which action should be taken. Nor does it adequately quantify the flood damage. It makes more sense to have two measures. One is an early measure based on underlying risk, vulnerability and rate of change, which indicates the point at which evasive action should be taken in order to prevent harm. The second quantifies the actual harm caused.
Creating different definitions for different purposes To decide when to start treatment Early treatment, when bleeding is first recognised to be abnormal, has relatively few risks and could stop bleeding progressing to coagulopathy. Proactive treatment to prevent adverse outcomes in these patients is entirely logical and should be supported. Therefore, we would suggest that initial measures are started as soon as the bleeding is noted to be abnormal or, failing that, causes symptoms or signs.
A definition for audit purposes Repeated studies show that estimated blood loss is too inaccurate and unreliable to be used as a measure of quality of care. Audits of treatment do allow insights into clinical practice (informing training and quality improvement),
ª 2016 Royal College of Obstetricians and Gynaecologists
PPH: a single definition is no longer enough
but they have limited value in monitoring PPH morbidity. Instead, measurement of PPH-related adverse outcomes should be prioritised, accepting that in many cases they will require the use of proxy outcomes such as transfusion or hysterectomy, which have their own problems of inconsistency.
Contribution to authorship RK conducted the literature review and wrote the commentary. ADW edited and contributed to the commentary.
Details of ethics approval No ethical approval was sought for this review.
A definition for use in research The very poor specificity of a 500 ml cutoff for maternal morbidity makes it virtually useless as a clinical research outcome. It only retains its popularity through researchers looking for frequently occurring adverse outcomes to give statistical power to small clinical trials. But the use of a 500 ml cutoff in this situation may be misleading, or even dangerous. A PPH treatment that shows benefit at 500 ml may have no benefit at all for important larger bleeds (e.g. due to abruption, or placenta praevia) and may thereby be recommended unjustifiably, wasting resources and time. Conversely, a negative study that was powered to detect changes at 500 ml may miss an important effect on major haemorrhage. It is critical, therefore, that clinical studies are powered (and funded) to detect changes in maternal morbidity, not just an arbitrary blood loss cutoffs, especially of 500 ml. A suitable morbidity outcome might be the WHO maternal near-miss criteria12 using the features relevant to PPH (shock, transfusion of over 5 units, hysterectomy, coagulopathy or oliguria). Those needing a blood loss cutoff should use a minimum of 1000 ml, reflecting a level more closely correlated with maternal morbidity. This is supported by consensus-building work already completed by ACOG and WHO as well as the ongoing work on core outcome sets by COMET. Our international working group reached a consensus on this approach for a definition of PPH for research.13 A large cohort study could identify the best proxy outcome for a PPH adverse event, by providing the sensitivity and specificity of numerous measures (e.g. 500 ml, 1000 ml, units of blood transfused, shock index). A proxy outcome may allow interventions to be compared without the need for huge sample sizes, although it will never replace the adverse event as an outcome in itself. It is time to stop the search for a universal definition for PPH and instead accept that we need different definitions for different purposes. We need one definition as a guide to when to start treatment, a second for audit purposes and a third for research outcomes. Now is the time for building consensus on these definitions, to encourage better data collection and synthesis, so that progress can be made to reduce the global burden of PPH.
Disclosure of interests Full disclosure of interests available to view online as supporting information.
ª 2016 Royal College of Obstetricians and Gynaecologists
Funding No funding was received for work contributing to this commentary.
Acknowledgements We thank the other members of the Brighton Collaboration Post Partum Haemorrhage Working Group (Linda Eckert, Beverly Winikoff, Jill Durocher, Shireen Meher, Sue Fawcus, Shuchita Mundle, Ben Mol, Sabaratnam Arulkumaran, Khalid Khan and Julius Wandwabwa) for discussions that helped form this commentary. We also thank Beverley Winikoff and Jill Durocher for access to their primary data (reference 10) and Justus Hofmeyr for helpful feedback. &
References € Moller A-B, Daniels J, et al. 1 Say L, Chou D, Gemmill A, Tuncßalp O, Global causes of maternal death: a WHO systematic analysis. Lancet Global Health 2014;2:e323–33. 2 World Health Organization. The Prevention and Management of Postpartum Haemorrhage: Report of a Technical Working Group, 3– 6 July 1989. Geneva: WHO, 1990. 3 RCOG. RCOG Green-top Guideline No 52: Prevention and management of postpartum haemorrhage. 2009, updated 2011. 4 Menard MK, Main EK, Currigan SM. Executive Summary of the reVITALize Initiative. Obstet Gynecol 2014;124:150–3. 5 World Health Organization. WHO Recommendations for the Prevention and Treatment or Postpartum Haemorrhage. Geneva: WHO, 2012. 6 World Health Organization. Evaluating the Quality of Care for Severe Pregnancy Complications: the WHO Near-miss Approach for Maternal Health. Geneva: WHO, 2011. 7 Alfaifel N. Postpartum haemorrhage: new insights from published trials and the development of novel management options. PhD Thesis, University of Liverpool, 2015. 8 Hancock A, Weeks AD, Lavender DT. Is accurate and reliable blood loss estimation the ‘crucial step’ in early detection of postpartum haemorrhage: an integrative review of the literature. BMC Pregn Childbirth 2015;15:230. 9 Zhang WH, Deneux-Tharaux C, Brocklehurst P, Juszczak E, Joslin M, Alexander S. Effect of a collector bag for measurement of postpartum blood loss after vaginal delivery: cluster randomised trial in 13 European countries. BMJ 2010;340:c293. n W, 10 Winikoff B, Dabash R, Durocher J, Darwish E, Ngoc NTN, Leo et al. Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial. Lancet 2010;375:210–6.
725
Kerr, Weeks
11 Pacagnella RC, Souza JP, Durocher J, Perel P, Blum J, Winikoff B, et al. A systematic review of the relationship between blood loss and clinical signs. PLoS One 2013;8:e57594. 12 Say L, Souza JP, Pattinson RC. Maternal near miss—towards a standard tool for monitoring quality of maternal health care. Best Pract Res Clin Obst Gynaecol 2009;23:287–96.
726
13 Kerr R, Eckert LO, Winikoff B, Durocher J, Meher S, Fawcus S, et al. Postpartum haemorrhage: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2016;pii:S0264-410X(16)30022-6.
ª 2016 Royal College of Obstetricians and Gynaecologists
Commentary
www.bjog.org
Postpartum haemorrhage: a single definition is no longer enough RS Kerr, AD Weeks Sanyu Research Unit, Department of Women’s and Children’s Health, University of Liverpool, Liverpool Women’s Hospital, Liverpool, UK Correspondence: R Kerr, Sanyu Research Unit, Department of Women’s and Children’s Health, University of Liverpool, Liverpool Women’s Hospital, Crown Street, Liverpool, L8 7SS, UK. Email [email protected] Accepted 28 September 2016. Published Online 24 November 2016. Please cite this paper as: Kerr RS, Weeks AD. Postpartum haemorrhage: a single definition is no longer enough. BJOG 2017;124:723–726.
Postpartum haemorrhage (PPH) is the leading cause of death in pregnancy globally, causing 187 deaths daily.1 In many more it leads to anaemia, blood transfusion, surgery and psychological morbidity. This burden of disease makes it a global priority to improve PPH management. Critical to this is the need to agree a simple fact: what exactly is a PPH?
Official definitions During a WHO ‘informal meeting of experts’ in 1989, PPH was defined as ‘the loss of 500mls or more of blood from the genital tract after delivery of the baby’.2 This definition has been widely cited, and has been relatively unchallenged until recently, despite the meeting’s report acknowledging 500 ml as ‘an arbitrary figure’ and ‘not always of great clinical significance’. In recent years, professional societies have developed definitions with more clinical significance. The Royal College of Obstetricians and Gynaecologists (RCOG) in 2011 endorsed the 500 ml threshold in their definition of ‘Minor PPH’, although it stated that 1000 ml (or a lesser volume with clinical shock), should be classed as ‘Major PPH’. They recommend ‘readiness for resuscitation’ in response to blood loss 500–1000 ml, but ‘a full protocol of measures’ when the blood loss reaches 1000 ml or there are clinical signs of shock.3 The American College of Obstetricians and Gynecologists (ACOG) held a modified Delphi vote of its members in 2014 to reach a consensus on a PPH definition. They dismissed the 500 ml cutoff, endorsing in its place a definition of ‘greater or equal to 1000 ml or blood loss with signs or symptoms of hypovolemia’.4 The WHO avoided a specific recommendation in their 2012 guidelines, instead commenting that ‘PPH is commonly defined as blood loss 500 ml or more’.5 The most recent WHOendorsed definition was instead for ‘Severe PPH’, defined
ª 2016 Royal College of Obstetricians and Gynaecologists
by the WHO Working Group on Maternal Mortality and Morbidity Classifications as ‘genital bleeding after delivery, with at least one of the following: perceived abnormal bleeding (1000 ml or more) or any bleeding with hypotension or blood transfusion’.6
Definitions based on the volume of blood loss A review of primary outcomes used in PPH prevention randomised controlled trials (RCTs) and systematic reviews (SRs) reported that ≥500 ml was the most common primary outcome in RCTs (24/82), whereas ≥1000 ml was preferred in SRs (10/77).7 The preference for 500 ml in trials but 1000 ml in systematic reviews most likely reflects trialists’ desire to maximise statistical power versus reviewers’ preference for outcomes more closely associated with morbidity. But definitions based on blood loss volume all suffer from the inaccuracies inherent in blood loss quantification —practitioners underestimate by 46–75%, with greater errors at higher losses.8 Diagnostic accuracy can be improved by direct measurement of blood in under-buttock calibrated drapes. Unfortunately, as routine use of calibrated drapes has not been associated with a decrease in severe PPH, their use at every delivery is hard to justify outside of research.9 Many clinicians compromise by using collection drapes for high-risk deliveries, and retrospectively weighing blood-soaked materials after PPH at other deliveries. In selecting a blood loss threshold, we are attempting to find a division between normal bleeding and abnormal bleeding. But what is normal bleeding? In 9348 low-risk vaginal deliveries with no third stage prophylaxis and no treatment until 700 ml of blood loss, the mean, mode and median of measured blood loss were between 200 and
723
Kerr, Weeks
300 ml.10 However, what is the upper limit of normal: the 75th centile (310 ml); the 90th centile (720 ml); or the 95th centile (900 ml)? The choice is arbitrary, with the resulting definition based, somewhat illogically, on those at the lowest risk of PPH. Indeed, the normal blood loss of any population varies hugely depending on the environment (e.g. altitude), ethnicity, the pregnancy itself (e.g. multiple pregnancy), and health care factors (including obstetric interventions and PPH prophylaxis).3 Importantly, an individual’s tolerance of blood loss will also vary widely. The presence of anaemia, endemic in many regions due to malaria, dietary deficiencies and intestinal worms, will be critical in determining the consequences of blood loss. Routine calculation of the blood loss as a percentage of total blood volume (using weight and height) would take account of the woman’s habitus, but the challenges of blood measurement persist.
Definitions based on physiological changes An alternative approach is to define PPH by a fall in haematocrit (by >10%) or haemoglobin concentration (>2 g/dl) on blood samples taken before and after delivery. While this has many advantages, it is markedly affected by intravascular fluid depletion (with pre-eclampsia or dehydration), infusions of fluid or blood, and the physiological postpartum rise. Furthermore, it requires laboratory facilities and only permits a retrospective diagnosis. Vital signs have been used by some authors and professional societies in their definitions to capture the effects of bleeding. Their measurement has the advantage of being standard management already, relatively easy, cheap and objective. A systematic review into the relation between blood loss and clinical signs highlighted that shock index (heart rate divided by systolic blood pressure) was the most promising clinical sign for this purpose.11 However, shock index alone has a low specificity for PPH, and there is insufficient evidence at present to recommend a cutoff to be used as part of a PPH definition.
Definitions based on need for intervention Interventions for PPH, for example the need for additional uterotonics, are a pragmatic way to define PPH. However, practitioners tend to commence treatment early in the bleeding, for example in response to a rapid rate of bleeding.8 Indeed, a secondary analysis of four large randomised trials found little correlation between additional uterotonic medication and final measured blood loss, with two trials finding the majority of women receiving uterotonics had a final blood loss of less than 500 ml.7 Identifying cases
724
retrospectively can also present a challenge, as it may be unclear whether medication was given as prophylaxis or as treatment. The aforementioned approaches are all unsatisfactory as they fail to measure what is most important to the woman —adverse outcomes. Postpartum bleeding may cause a new mother to be light-headed, weak and unable to feed her baby. But she may also develop organ dysfunction, require blood products, surgery, be admitted to intensive care, or even die as a result of PPH. Adverse clinical outcomes like these should be central when developing a consensus on PPH definition so that it accurately captures the morbidity caused by the disease.
The need for different definitions It is important to separate out the level of bleeding at which treatment is initiated, and that at which PPH, as an adverse outcome, is defined. Although previous definitions have tried to hold both together, a value of 500 ml satisfies neither requirement. After all, no clinician would sit back and watch a rapid atonic or traumatic PPH, waiting for it to reach an arbitrary value before initiating treatment. Consider the analogy of a town with a flood-prone river running through it. In heavy rainfall, shopkeepers are likely to lay sandbags across the front of their shops as soon as they see the water level rapidly rising. The official definition of ‘flooding’ may be that the river spills over the quay —but that doesn’t represent the point at which action should be taken. Nor does it adequately quantify the flood damage. It makes more sense to have two measures. One is an early measure based on underlying risk, vulnerability and rate of change, which indicates the point at which evasive action should be taken in order to prevent harm. The second quantifies the actual harm caused.
Creating different definitions for different purposes To decide when to start treatment Early treatment, when bleeding is first recognised to be abnormal, has relatively few risks and could stop bleeding progressing to coagulopathy. Proactive treatment to prevent adverse outcomes in these patients is entirely logical and should be supported. Therefore, we would suggest that initial measures are started as soon as the bleeding is noted to be abnormal or, failing that, causes symptoms or signs.
A definition for audit purposes Repeated studies show that estimated blood loss is too inaccurate and unreliable to be used as a measure of quality of care. Audits of treatment do allow insights into clinical practice (informing training and quality improvement),
ª 2016 Royal College of Obstetricians and Gynaecologists
PPH: a single definition is no longer enough
but they have limited value in monitoring PPH morbidity. Instead, measurement of PPH-related adverse outcomes should be prioritised, accepting that in many cases they will require the use of proxy outcomes such as transfusion or hysterectomy, which have their own problems of inconsistency.
Contribution to authorship RK conducted the literature review and wrote the commentary. ADW edited and contributed to the commentary.
Details of ethics approval No ethical approval was sought for this review.
A definition for use in research The very poor specificity of a 500 ml cutoff for maternal morbidity makes it virtually useless as a clinical research outcome. It only retains its popularity through researchers looking for frequently occurring adverse outcomes to give statistical power to small clinical trials. But the use of a 500 ml cutoff in this situation may be misleading, or even dangerous. A PPH treatment that shows benefit at 500 ml may have no benefit at all for important larger bleeds (e.g. due to abruption, or placenta praevia) and may thereby be recommended unjustifiably, wasting resources and time. Conversely, a negative study that was powered to detect changes at 500 ml may miss an important effect on major haemorrhage. It is critical, therefore, that clinical studies are powered (and funded) to detect changes in maternal morbidity, not just an arbitrary blood loss cutoffs, especially of 500 ml. A suitable morbidity outcome might be the WHO maternal near-miss criteria12 using the features relevant to PPH (shock, transfusion of over 5 units, hysterectomy, coagulopathy or oliguria). Those needing a blood loss cutoff should use a minimum of 1000 ml, reflecting a level more closely correlated with maternal morbidity. This is supported by consensus-building work already completed by ACOG and WHO as well as the ongoing work on core outcome sets by COMET. Our international working group reached a consensus on this approach for a definition of PPH for research.13 A large cohort study could identify the best proxy outcome for a PPH adverse event, by providing the sensitivity and specificity of numerous measures (e.g. 500 ml, 1000 ml, units of blood transfused, shock index). A proxy outcome may allow interventions to be compared without the need for huge sample sizes, although it will never replace the adverse event as an outcome in itself. It is time to stop the search for a universal definition for PPH and instead accept that we need different definitions for different purposes. We need one definition as a guide to when to start treatment, a second for audit purposes and a third for research outcomes. Now is the time for building consensus on these definitions, to encourage better data collection and synthesis, so that progress can be made to reduce the global burden of PPH.
Disclosure of interests Full disclosure of interests available to view online as supporting information.
ª 2016 Royal College of Obstetricians and Gynaecologists
Funding No funding was received for work contributing to this commentary.
Acknowledgements We thank the other members of the Brighton Collaboration Post Partum Haemorrhage Working Group (Linda Eckert, Beverly Winikoff, Jill Durocher, Shireen Meher, Sue Fawcus, Shuchita Mundle, Ben Mol, Sabaratnam Arulkumaran, Khalid Khan and Julius Wandwabwa) for discussions that helped form this commentary. We also thank Beverley Winikoff and Jill Durocher for access to their primary data (reference 10) and Justus Hofmeyr for helpful feedback. &
References € Moller A-B, Daniels J, et al. 1 Say L, Chou D, Gemmill A, Tuncßalp O, Global causes of maternal death: a WHO systematic analysis. Lancet Global Health 2014;2:e323–33. 2 World Health Organization. The Prevention and Management of Postpartum Haemorrhage: Report of a Technical Working Group, 3– 6 July 1989. Geneva: WHO, 1990. 3 RCOG. RCOG Green-top Guideline No 52: Prevention and management of postpartum haemorrhage. 2009, updated 2011. 4 Menard MK, Main EK, Currigan SM. Executive Summary of the reVITALize Initiative. Obstet Gynecol 2014;124:150–3. 5 World Health Organization. WHO Recommendations for the Prevention and Treatment or Postpartum Haemorrhage. Geneva: WHO, 2012. 6 World Health Organization. Evaluating the Quality of Care for Severe Pregnancy Complications: the WHO Near-miss Approach for Maternal Health. Geneva: WHO, 2011. 7 Alfaifel N. Postpartum haemorrhage: new insights from published trials and the development of novel management options. PhD Thesis, University of Liverpool, 2015. 8 Hancock A, Weeks AD, Lavender DT. Is accurate and reliable blood loss estimation the ‘crucial step’ in early detection of postpartum haemorrhage: an integrative review of the literature. BMC Pregn Childbirth 2015;15:230. 9 Zhang WH, Deneux-Tharaux C, Brocklehurst P, Juszczak E, Joslin M, Alexander S. Effect of a collector bag for measurement of postpartum blood loss after vaginal delivery: cluster randomised trial in 13 European countries. BMJ 2010;340:c293. n W, 10 Winikoff B, Dabash R, Durocher J, Darwish E, Ngoc NTN, Leo et al. Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women not exposed to oxytocin during labour: a double-blind, randomised, non-inferiority trial. Lancet 2010;375:210–6.
725
Kerr, Weeks
11 Pacagnella RC, Souza JP, Durocher J, Perel P, Blum J, Winikoff B, et al. A systematic review of the relationship between blood loss and clinical signs. PLoS One 2013;8:e57594. 12 Say L, Souza JP, Pattinson RC. Maternal near miss—towards a standard tool for monitoring quality of maternal health care. Best Pract Res Clin Obst Gynaecol 2009;23:287–96.
726
13 Kerr R, Eckert LO, Winikoff B, Durocher J, Meher S, Fawcus S, et al. Postpartum haemorrhage: case definition and guidelines for data collection, analysis, and presentation of immunization safety data. Vaccine 2016;pii:S0264-410X(16)30022-6.
ª 2016 Royal College of Obstetricians and Gynaecologists
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