Postpartum hemorrhage

POSTPARTUM HEMORRHAGE

OVERVIEW

Postpartum hemorrhage (PPH) is the leading cause of maternal death globally, accounting for more than one quarter of all such deaths in low-resource regions of the world.

Gynuity Health Projects collaborates with partners to conduct programmatic and clinical research, generate and synthesize evidence to inform policy and practice, and provide technical assistance to governments and other key stakeholders to address gaps in PPH care.

We apply clinical evidence and programmatic experience to design and evaluate service delivery and program approaches to:
a) Improve the availability and use of technologies for the management of PPH and

b) Facilitate timely and effective PPH treatment across multiple levels of care.

We focus on simple technologies and interventions that are appropriate and useful in low-resource environments and community settings.

RESEARCH

The Role of Misoprostol in PPH Management

Uterotonic drugs stimulate contractions of the uterus after delivery and help to control bleeding caused by uterine atony, the most common cause of PPH. Misoprostol, a readily-available and inexpensive drug, comes in tablet form, is stable at room temperature, and does not require any special skills, equipment, or facilities for its use. These factors make it an important component of an integrated package of PPH interventions, especially in resource-poor and community settings. It is a valuable alternative to oxytocin (the gold standard uterotonic that requires cold storage, intravenous or intramuscular administration, and skilled providers).

Clinical evidence: Prevention and treatment of PPH with misoprostol

Evidence generated through a series of clinical trials that evaluated the use of misoprostol for PPH has helped to advance knowledge about the drug’s safety, efficacy and programmatic effectiveness.

Misoprostol for PPH: Evidence-Based Regimens
Prevention: Single dose 600mcg oral (3 tablets)
Treatment: Single dose 800mcg sublingual (4 tablets)

Translating the clinical evidence into practice: Models of PPH care using misoprostol

Research is underway at the community level to clarify the different ways for integrating misoprostol into PPH programs. Models of care using misoprostol at the community level include:

Policy and advocacy
We work with partners to advocate evidence-based changes in policy and practice at a country and international level. Our activities include:

Guidance clarifying the role of misoprostol

WHO: Recommendations for the prevention and treatment of PPH, 2012

FIGO: Prevention and treatment of PPH in low resource settings, 2012

ICM & FIGO: Misoprostol for the treatment of PPH in low resource settings, 2014

WHO Model List of Essential Medicines (19th Edition, 2015): Misoprostol listed for both PPH indications

European Medicines Agency: Approval of the first misoprostol product, Hemoprostol, for the treatment of PPH, 2014

When Uterotonics Are Not Enough: Additional Strategies to Address Gaps in PPH Care

Uterotonics alone will not eliminate PPH morbidity and mortality. We conduct collaborative research to understand the role of additional strategies and interventions that could fill gaps in PPH care. We are evaluating:

TECHNICAL ASSISTANCE

Evaluating What Works in National Scale-Up

We engage with governments to assist in the design, implementation and evaluation of service delivery innovations and policies. Our collaborations have allowed us to share lessons learned from national program evaluations in countries like Nepal, Niger and Senegal. In addition, our evaluations provide important guidance for other countries interested in improving the quality of their PPH programs.

GLOBAL PARTNERS

We work in partnership with government stakeholders (including Ministries of Health), experts and agencies to achieve the goals set forth in this program. Key partners include:

RELATED RESOURCES

We produce materials on PPH in multiple languages and targeted to various audiences, including policymakers, program implementers, health care providers, women’s health advocates, and women. This program brief is accompanied by an insert listing over 25 articles on PPH that have been published in peer-reviewed journals since 2005. Additional resources on PPH, as well as on other women’s health topics, are available from our website at www.gynuity.org and YouTube. You can also follow us on Twitter @Gynuity.

Updated April 2016

Gynuity Health Projects: Peer-Reviewed Publications on Postpartum Hemorrhage (2005-2016)

Additional resources, including educational and informational materials, Instructions for Use pamphlets and meeting reports, are available from our website at www.gynuity.org

Raghavan S, Geller S, Miller S, Goudar S, Anger H, Yadavannavar M, Dabash R, Bidri S, Gudadinni M, Udgiri R, Koch A, Bellad M, Winikoff B. Misoprostol for primary versus secondary prevention of postpartum haemorrhage: a cluster-randomised non-inferiority community trial. BJOG 2016; 123(1): 120–7.

Diop A, Daff B, Sow M, Blum J, Diagne M, Sloan NL, Winikoff B. Oxytocin in Uniject™ versus misoprostol for prevention of postpartum hemorrhage at the community level: A cluster randomized controlled trial. Lancet Global Health 2016; 4(1): e37–44.

Weeks AD, Ditai J, Ononge S, Faragher B, Frye LJ, Durocher J, Mirembe FM, Byamugisha J, Winikoff B, Alfirevic Z. The MamaMiso study of self-administered misoprostol to prevent bleeding after childbirth in the community: A placebo controlled trial. BMC Pregnancy Childbirth 2015; 15: 219.

Alfirevic A, Durocher J, Elati A, Leon W, Dickens D, Raedisch S, Box H, Siccardi M, Curley P, Xinarianos G, Ardeshana A, Owen A, Zhang JE, Pirmohamed M, Alfirevic Z, Weeks A, Winikoff B. Misoprostol-induced fever is related to genetic polymorphisms in drug transporters SLCO1B1 and ABCC4 in women of Latin American and European ancestry. Pharmacogenomics 2015; 16(9): 919–28.

Ambardekar S, Shochet T, Bracken H, Coyaji K, Winikoff B. Calibrated delivery drape versus indirect gravimetric technique for the measurement of blood loss after delivery: a randomized trial. BMC Pregnancy Childbirth 2014; 14: 276.

Sheldon WR, Blum J, Vogel JP, Souza JP, Gülmezoglu AM, Winikoff B. Postpartum haemorrhage management, risks, and maternal outcomes: findings from the World Health Organization Multicountry Survey on Maternal and Newborn Health. BJOG 2014; 121(Suppl 1): 5–13.

Mousa HA, Blum J, Abou El Senoun G, Shakur H, Alfirevic Z. Treatment for primary postpartum haemorrhage. Cochrane Database Syst Rev 2014; 2: CD003249.

Sheldon WR, Durocher J, Winikoff B, Blum J, Trussell J. How effective are the components of active management of the third stage of labor? BMC Pregnancy Childbirth 2013; 13: 46.

Pacagnella RC, Souza JP, Durocher J, Perel P, Blum J, Winikoff B, Gülmezoglu AM. A systematic review of the relationship between blood loss and clinical signs. PLoS One 2013; 8(3): e57594.

Sheldon WR, Blum J, Durocher J, Winikoff B. Misoprostol for the prevention and treatment of postpartum hemorrhage. Expert Opin Investig Drugs 2012; 21(2): 235–50.

Raghavan S, Abbas D, Winikoff B. Misoprostol for the prevention and treatment of postpartum hemorrhage: What do we know? What is next? Int J Gynaecol Obstet 2012; 119(Suppl 1): S35–8.

León W, Durocher J, Barrera G, Pinto E, Winikoff B. Dose and side effects of sublingual misoprostol for treatment of postpartum hemorrhage: what difference do they make? BMC Pregnancy Childbirth 2012; 12: 65.

Dabash R, Blum J, Raghavan S, Anger H, Winikoff B. Misoprostol for the management of postpartum bleeding: a new approach. Int J Gynaecol Obstet 2012; 119(3): 210–2.

Starrs A, Winikoff B. Misoprostol for postpartum hemorrhage: moving from evidence to practice. Int J Gynaecol Obstet 2012; 116(1): 1–3.

Oladapo OT, Fawole B, Blum J, Abalos E. Advance misoprostol distribution for preventing and treating postpartum haemorrhage. Cochrane Database Syst Rev 2012; 2: CD009336.

Mobeen N, Durocher J, Zuberi N, Jahan N, Blum J, Wasim S, Walraven G, Hatcher J. Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled trial. BJOG 2011; 118(3): 353–61.

Durocher J, Blum J, Walraven G, Zuberi NF, Mobeen N. Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in home births in Pakistan: randomised placebo-controlled trial [letter]. BJOG 2011; 118(8): 1018–9.

Durocher J, Bynum J, León W, Barrera G, Winikoff B. High fever following postpartum administration of sublingual misoprostol. BJOG 2010; 117(7): 845–52.

Winikoff B, Dabash R, Durocher J, Darwish E, Nguyen TN, León W, Raghavan S, Medhat I, Huynh TK, Barrera G, Blum J. 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.

Blum J, Winikoff B, Raghavan S, Dabash R, Ramadan MC, Dilbaz B, Dao B, Durocher J, Yalvac, S, Diop A, Dzuba IG, Ngoc NT. 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.

Widmer M, Blum J, Hofmeyr GJ, Carroli G, Abdel-Aleem H, Lumbiganon P, Nguyen TN, Wojdyla D, Thinkhamrop J, Singata M, Mignini LE, Abdel-Aleem MA, Tran ST, Winikoff B. 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.

Sloan NL, Durocher J, Aldrich T, Blum J, Winikoff B. What measured blood loss tells us about postpartum bleeding: a systematic review. BJOG 2010; 117(7): 788–800.

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 Childbirth 2008; 8: 40.

Blum J, Alfirevic Z, Walraven G, Weeks A, Winikoff B. Treatment of postpartum hemorrhage with misoprostol. Int J Gynaecol Obstet 2007; 99(Suppl 2): S202–5.

Alfirevic Z, Blum J, Walraven G, Weeks A, Winikoff B. Prevention of postpartum hemorrhage with misoprostol. Int J Gynaecol Obstet 2007; 99(Suppl 2): S198–201.

Walraven G, Blum J, Dampha Y, Sowe M, Morison L, Winikoff B, Sloan N. Misoprostol in the management of the third stage of labour in the home delivery setting in rural Gambia: a randomised controlled trial. BJOG 2005; 112(9): 1277–83.