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Meta-Analysis
. 2014 Feb 13;2014(2):CD003249.
doi: 10.1002/14651858.CD003249.pub3.

Treatment for primary postpartum haemorrhage

Hatem A Mousa  1 , Jennifer Blum, Ghada Abou El Senoun, Haleema Shakur, Zarko Alfirevic
Affiliations
Meta-Analysis

Treatment for primary postpartum haemorrhage

Hatem A Mousa et al. Cochrane Database Syst Rev. .

Abstract

Background: Primary postpartum haemorrhage (PPH) is one of the top five causes of maternal mortality in both developed and developing countries.

Objectives: To assess the effectiveness and safety of any intervention used for the treatment of primary PPH.

Search methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 August 2013).

Selection criteria: Randomised controlled trials comparing any interventions for the treatment of primary PPH.

Data collection and analysis: We assessed studies for eligibility and quality and extracted data independently. We contacted authors of the included studies to request more information.

Main results: Ten randomised clinical trials (RCTs) with a total of 4052 participants fulfilled our inclusion criteria and were included in this review.Four RCTs (1881 participants) compared misoprostol with placebo given in addition to conventional uterotonics. Adjunctive use of misoprostol (in the dose of 600 to 1000 mcg) with simultaneous administration of additional uterotonics did not provide additional benefit for our primary outcomes including maternal mortality (risk ratio (RR) 6.16, 95% confidence interval (CI) 0.75 to 50.85), serious maternal morbidity (RR 0.34, 95% CI 0.01 to 8.31), admission to intensive care (RR 0.79, 95% CI 0.30 to 2.11) or hysterectomy (RR 0.93, 95% CI 0.16 to 5.41). Two RCTs (1787 participants) compared 800 mcg sublingual misoprostol versus oxytocin infusion as primary PPH treatment; one trial included women who had received prophylactic uterotonics, and the other did not. Primary outcomes did not differ between the two groups, although women given sublingual misoprostol were more likely to have additional blood loss of at least 1000 mL (RR 2.65, 95% CI 1.04 to 6.75). Misoprostol was associated with a significant increase in vomiting and shivering.Two trials attempted to test the effectiveness of estrogen and tranexamic acid, respectively, but were too small for any meaningful comparisons of pre-specified outcomes.One study compared lower segment compression but was too small to assess impact on primary outcomes.We did not identify any trials evaluating surgical techniques or radiological interventions for women with primary PPH unresponsive to uterotonics and/or haemostatics.

Authors' conclusions: Clinical trials included in the current review were not adequately powered to assess impact on the primary outcome measures. Compared with misoprostol, oxytocin infusion is more effective and causes fewer side effects when used as first-line therapy for the treatment of primary PPH. When used after prophylactic uterotonics, misoprostol and oxytocin infusion worked similarly. The review suggests that among women who received oxytocin for the treatment of primary PPH, adjunctive use of misoprostol confers no added benefit.The role of tranexamic acid and compression methods requires further evaluation. Furthermore, future studies should focus on the best way to treat women who fail to respond to uterotonic therapy.

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Conflict of interest statement

Haleema Shakur and Zarko Alfirevic are investigators in the currently ongoing WOMAN trial. Jennifer Blum was a principal investigator in the Blum 2010, Winikoff 2010, Widmer 2010 and Zuberi 2008 trials. Hatem Mousa has received financial support from Novo Nordisk to investigate recombinant activated factor VII (rFVIIa) as a potential treatment for massive postpartum haemorrhage.

Figures

1
1
Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies.
2
2
Risk of bias summary: review authors' judgements about each risk of bias item for each included study.
1.1
1.1. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 1 Maternal death.
1.2
1.2. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 2 Serious maternal morbidity.
1.3
1.3. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 3 Admission to intensive care unit.
1.4
1.4. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 4 Hysterectomy.
1.5
1.5. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 5 Average blood loss after enrolment in millilitres.
1.6
1.6. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 6 Blood loss 500 mL or more after enrolment.
1.7
1.7. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 7 Blood transfusion.
1.8
1.8. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 8 Blood loss 1000 mL or more after enrolment.
1.9
1.9. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 9 Additional uterotonics.
1.10
1.10. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 10 Manual removal of the placenta after enrolment.
1.11
1.11. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 11 Uterine tamponade after enrolment.
1.12
1.12. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 12 Artery ligation (uterine and/or hypogastric arteries) after enrolment.
1.13
1.13. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 13 Arterial embolisation after enrolment.
1.14
1.14. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 14 Uterine compression stitch after enrolment.
1.15
1.15. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 15 Evacuation of retained product of conception.
1.16
1.16. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 16 Any surgical co‐interventions (uterine tamponade, artery ligations, arterial embolisation) excluding hysterectomy after enrolment.
1.17
1.17. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 17 Nausea.
1.18
1.18. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 18 Vomiting.
1.19
1.19. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 19 Diarrhoea.
1.20
1.20. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 20 Maternal pyrexia 38 degrees or more.
1.21
1.21. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 21 Maternal pyrexia 40 degrees or more.
1.22
1.22. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 22 Headache.
1.23
1.23. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 23 Shivering.
1.24
1.24. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 24 Feeling faint or fainting.
1.25
1.25. Analysis
Comparison 1 Misoprostol (any route) versus placebo or no additional treatment given to women simultaneously treated with conventional uterotonics, Outcome 25 Allergy.
2.1
2.1. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 1 Maternal mortality.
2.2
2.2. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 2 Serious maternal morbidity.
2.3
2.3. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 3 Admission to intensive care.
2.4
2.4. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 4 Hysterectomy.
2.5
2.5. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 5 Blood loss 500 mL or more after enrolment.
2.6
2.6. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 6 Mean blood loss after enrolment.
2.7
2.7. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 7 Blood loss 1000 mL or more after enrolment.
2.8
2.8. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 8 Blood transfusion within 24 hours.
2.9
2.9. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 9 Duration from randomisation till cessation of bleeding or satisfactory response.
2.10
2.10. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 10 Additional uterotonics after enrolment.
2.11
2.11. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 11 Examination under anaesthesia.
2.12
2.12. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 12 Uterine tamponade after enrolment.
2.13
2.13. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 13 Bimanual compression.
2.14
2.14. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 14 Artery ligation (uterine and/or hypogastric arteries) after enrolment.
2.15
2.15. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 15 Arterial embolisation after enrolment.
2.16
2.16. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 16 Uterine tamponade after enrolment.
2.17
2.17. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 17 Unsatisfactory response after enrolment after enrolment.
2.18
2.18. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 18 Uterine compression stitch after enrolment.
2.19
2.19. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 19 Any surgical co‐interventions (uterine tamponade, artery ligations, arterial embolisation) excluding hysterectomy after enrolment.
2.20
2.20. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 20 Nausea.
2.21
2.21. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 21 Vomiting.
2.22
2.22. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 22 Diarrhoea.
2.23
2.23. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 23 Headache.
2.24
2.24. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 24 Shivering.
2.25
2.25. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 25 Feeling faint or fainting.
2.26
2.26. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 26 Maternal pyrexia 38 degrees or more.
2.27
2.27. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 27 Maternal pyrexia 40 degrees or more.
2.28
2.28. Analysis
Comparison 2 Sublingual misoprostol versus intravenous oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 28 Allergy.
3.1
3.1. Analysis
Comparison 3 Rectal misoprostol versus combination of ergometrine and oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 1 Hysterectomy.
3.2
3.2. Analysis
Comparison 3 Rectal misoprostol versus combination of ergometrine and oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 2 Persistent haemorrhage.
3.3
3.3. Analysis
Comparison 3 Rectal misoprostol versus combination of ergometrine and oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 3 Additional uterotonics.
3.4
3.4. Analysis
Comparison 3 Rectal misoprostol versus combination of ergometrine and oxytocin therapy for primary PPH treatment among women who have not received any conventional uterotonic therapy, Outcome 4 Surgical co‐interventions (excluding hysterectomy).
4.1
4.1. Analysis
Comparison 4 Estrogen versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 1 Hysterectomy.
4.2
4.2. Analysis
Comparison 4 Estrogen versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 2 Mean blood loss within two hours.
4.3
4.3. Analysis
Comparison 4 Estrogen versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 3 Mean blood loss between two and 24 hours.
5.1
5.1. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 1 Maternal mortality.
5.2
5.2. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 2 Serious maternal morbidity (renal failure respiratory failure, cardiac arrest, multiple organ failure).
5.3
5.3. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 3 Admission to intensive care unit.
5.4
5.4. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 4 Hysterectomy.
5.5
5.5. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 5 Blood loss 500 mL or more after enrolment.
5.6
5.6. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 6 Blood loss 1000 mL or more after enrolment.
5.7
5.7. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 7 Total mean blood loss after enrolment.
5.8
5.8. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 8 Blood transfusion within 24 hours.
5.9
5.9. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 9 Additional uterotonics after enrolment.
5.10
5.10. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 10 Unsatisfactory response after enrolment.
5.11
5.11. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 11 Uterine compression stitch after enrolment.
5.12
5.12. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 12 Interventions to control bleeding for secondary postpartum haemorrhage.
5.13
5.13. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 13 Examination under anaesthesia.
5.14
5.14. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 14 Uterine tamponade after enrolment.
5.15
5.15. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 15 Artery ligation (uterine and/or hypogastric arteries) after enrolment.
5.16
5.16. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 16 Arterial embolisation after enrolment.
5.17
5.17. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 17 Headache.
5.18
5.18. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 18 Nausea.
5.19
5.19. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 19 Maternal pyrexia 38 degrees or more.
5.20
5.20. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 20 Maternal pyrexia 40 degrees or more.
5.21
5.21. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 21 Deep vein thrombosis.
5.22
5.22. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 22 Seizures.
5.23
5.23. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 23 Dizziness.
5.24
5.24. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 24 Phosphenes.
5.25
5.25. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 25 Secondary postpartum haemorrhage.
5.26
5.26. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 26 Surgical evacuation for secondary postpartum haemorrhage.
5.27
5.27. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 27 Intravenous iron therapy in the puerperium.
5.28
5.28. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 28 Hospital re‐admission for secondary postpartum haemorrhage.
5.29
5.29. Analysis
Comparison 5 Tranexamic acid versus placebo/no treatment among women receiving conventional uterotonics for primary PPH, Outcome 29 Postnatal depression at day 42 postpartum.
6.1
6.1. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 1 Maternal mortality.
6.2
6.2. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 2 Serious maternal morbidity.
6.3
6.3. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 3 Hysterectomy.
6.4
6.4. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 4 Blood loss 500 mL or more after enrolment.
6.5
6.5. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 5 Blood loss 1000 mL or more after enrolment.
6.6
6.6. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 6 Average blood loss after enrolment.
6.7
6.7. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 7 Blood transfusion.
6.8
6.8. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 8 Other surgical interventions to control bleeding (other than hysterectomy).
6.9
6.9. Analysis
Comparison 6 Lower uterine segment compression versus conventional treatment, Outcome 9 Unsatisfactory response after enrolment.
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Update of

References

References to studies included in this review

Blum 2010 {published data only}
    1. Blum J, Winikoff B, Raghavan S, Dabash R, Ramadan MC, Dilbaz B, et al. Treatment of post‐partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double‐blind, randomised, non‐inferiority trial. Lancet 2010;375(9710):217‐23. - PubMed
    1. Blum J, Winikoff B, Raghavan S, Dabash R, Ramadan MC, Dilbaz B, et al. Treatment of postpartum hemorrhage with sublingual misoprostol versus oxytocin: results from a randomized noninferiority trial among women receiving prophylactic oxytocin. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S22‐S23.
    1. Dao B, Blum J, Barrera G, Cherine Ramadan M, Dabash R, Darwish E, et al. Side effect profiles for misoprostol and oxytocin in the treatment of postpartum hemorrhage. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S150.
Chantrapitak 2009 {published data only}
    1. Chantrapitak W, Srijanteok K, Puangsa‐art S. Lower uterine segment compression for management of early postpartum hemorrhage after vaginal delivery at Charoenkrung Pracharak Hospital. Journal of the Medical Association of Thailand 2009;92(5):600‐5. - PubMed
Ducloy‐Bouthors 2011 {published data only}
    1. Ducloy‐Bouthers A, Broisin F, Keita H, Fontaine S, Depret S, Legoeff F, et al. Tranexamic acid reduces blood loss in postpartum haemorrhage. Critical Care 2010;14()(Suppl 1):S124. - PMC - PubMed
    1. Ducloy‐Bouthors AS, Duhamel A, Broisin F, Keita H, Fontaine S. Tranexamic acid reduces blood loss in post‐partum haemorrhage by reducing hyperfibrinolysis. British Journal of Anaesthesia 2012;108:ii191.
    1. Ducloy‐Bouthors AS, Duhamel A, Tournoys A, Prado‐Dupont A, Debize G, Peneau E, et al. Post‐partum haemorrhage induced hyperfibrinolysis. Thrombosis Research 2013;131(Suppl 1):S89‐90.
    1. Ducloy‐Bouthors AS, Jude B, Duhamel A, Broisin F, Huissoud C, Keita‐Meyer H, et al. High‐dose tranexamic acid reduces blood loss in postpartum haemorrhage. Critical Care (London, England) 2011;15(2):R117. - PMC - PubMed
Hofmeyr 2004 {published data only}
    1. Hofmeyr GJ, Ferreira S, Nikodem VC, Mangesi L, Singata M, Jafta Z, et al. Misoprostol for treating postpartum haemorrhage: a randomized controlled trial [ISRCTN72263357]. BMC Pregnancy and Childbirth 2004;4(1):16. - PMC - PubMed
    1. Maholwana B, Hofmeyr GJ, Nikodem C, Ferreira S, Singata M, Mangesi L, et al. Misoprostol for treating postpartum haemorrhage. Presented at: 21st Conference on Priorities in Perinatal Care in South Africa. 2002 March 5‐8; Eastern Cape, South Africa.
Lokugamage 2001 {published data only}
    1. Lokugamage AU, Moodley J, Sullivan K, Rodeck CH, Niculescu L, Tigere P. The Durban primary postpartum haemorrhage study. Women's Health—into the new millennium. Proceedings of the 4th International Scientific Meeting of the Royal College of Obstetricians and Gynaecologists; 1999 October 3‐6; Cape Town, South Africa. 1999:77‐8.
    1. Lokugamage AU, Sullivan KR, Niculescu I, Tigere P, Onyangunga F, Refaey H, et al. A randomized study comparing rectally administered misoprostol versus syntometrine combined with an oxytocin infusion for the cessation of primary post partum hemorrhage. Acta Obstetricia et Gynecologica Scandinavica 2001;80(9):835‐9. - PubMed
Walraven 2004 {published data only}
    1. Walraven G, Dampha Y, Bittaye B, Sowe M, Hofmeyr J. Misoprostol in the treatment of postpartum haemorrhage in addition to routine management: a placebo randomised control trial. BJOG: an international journal of obstetrics and gynaecology 2004;111:1014‐7. - PubMed
Widmer 2010 {published data only}
    1. Villar J. Misoprostol to treat postpartum hemorrhage (PPH): a randomized controlled trial (Argentina, Egypt, South Africa, Thailand and Viet Nam). Current Controlled Trials (www.controlled‐trials.com/mrct) (accessed 21 March 2006).
    1. Widmer M, Blum J, Hofmeyr GJ, Carroli G, Abdel‐Aleem H, Lumbiganon P, et al. Misoprostol as an adjunct to standard uterotonics for treatment of post‐partum haemorrhage: a multicentre, double‐blind randomised trial. Lancet 2010;375(9728):1808‐13. - PubMed
Winikoff 2010 {published data only}
    1. Winikoff B. Misoprostol for the treatment of postpartum hemorrhage. ClinicalTrials.gov (http://clinicaltrials.gov/) (accessed 20 February 2008).
    1. Winikoff B, Dabash R, Durocher J, Darwish E, Ngoc NTN, Leon W, et al. Treatment of postpartum hemorrhage with sublingual misoprostol versus oxytocin: results from a randomized, non‐inferiority trial among women not exposed to oxytocin during labor. International Journal of Gynecology & Obstetrics 2009;107(Suppl 2):S59.
    1. Winikoff B, Dabash R, Durocher J, Darwish E, Nguyen TN, Leon W, 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(9710):210‐6. - PubMed
Zhou 2006 {published data only}
    1. Zhou M, Yang CY, Zhao Y, Li P. Clinical value of adjuvant therapy with estrogen for postpartum hemorrhage. Journal of Southern Medical University 2006;26(6):865‐6. - PubMed
Zuberi 2008 {published data only}
    1. Zuberi NF, Durocher J, Sikander R, Baber N, Blum J, Walraven G. Misoprostol in addition to routine treatment of postpartum hemorrhage: a hospital‐based randomized‐controlled trial in Karachi, Pakistan. BMC Pregnancy and Childbirth 2008;8:40. - PMC - PubMed

References to studies excluded from this review

Deneux‐Tharaux 2010 {published data only}
    1. Deneux‐Tharaux C, Dupont C, Colin C, Rabilloud M, Touzet S, Lansac J, et al. Multifaceted intervention to decrease the rate of severe postpartum haemorrhage: the PITHAGORE6 cluster‐randomised controlled trial. BJOG: an international journal of obstetrics and gynaecology 2010;117(10):1278‐87. - PMC - PubMed
Khalil 2011 {published data only}
    1. Khalil MI, Al‐Dohami H, Aldahish MM. A method to improve the effectiveness of the Bakri balloon for management of postpartum haemorrhage at caesarean. International Journal of Gynaecology and Obstetrics 2011;115(2):198‐200. - PubMed
Khireddine 2012 {published data only}
    1. Khireddine I, Le C, Dupont C, Rudigoz R, Bouvier‐Colle M, Deneux‐Tharaux C. Induction of labor and risk of postpartum hemorrhage in low risk parturient women. Journal of Maternal‐Fetal and Neonatal Medicine 2012;25(S2):101.
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References to studies awaiting assessment

Lavigne‐Lissalde 2013 {published data only}
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Collins 2013 {published data only}
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