International Federation of Gynecology and Obstetrics

Millennium Development Goal 5 (MDG 5)  

Two targets:

Reduce by three quarters, between 1990 and 2015, the maternal mortality ratio

Achieve, by 2015, universal access to reproductive health

BACKGROUND

Each year, nearly 350,000 women die of causes related to pregnancy and childbirth.  

Women's mortality and morbidity related to pregnancy, and the ensuing impact on perinatal mortality, remains unacceptably high, particularly in low resource countries across sub-Saharan Africa and South Asia where almost all these deaths occur and where a high percentage of women deliver at home or outside a health facility without immediate recourse to emergency obstetric care or a skilled birth attendant. It is widely acknowledged that post-partum haemorrhage (PPH) is the most significant contributor to maternal mortality and morbidity worldwide with, according to WHO statistics, approximately 25 per cent of maternal deaths resulting from severe post-partum bleeding. 

The most common cause of PPH is uterine atony, or failure of the uterus to contract after delivery. In health care facilities, Active Management of the Third Stage of Labour (AMTSL), including the use of uterotonics, is the recommended standard practice for all births in order to prevent and treat PPH. The gold-standard uterotonic for PPH is oxytocin. For optimum use oxytocin requires refrigeration, intravenous or intramuscular infusion, and skilled providers. These factors can hinder its use in low resource settings. In some countries, hospitals or health regions, uterotonics require a specific order by a physician. These requirements may create dangerous delays in appropriate management by skilled birth attendants.  

Originally developed to treat gastric ulcers, misoprostol has since attracted great interest in sexual and reproductive health circles and is increasingly used ad hoc for PPH prevention and treatment. Seen as a potential alternative to standard injectable oxytocics, misoprostol, a synthetic E1 prostaglandin analogue, is relatively heat-stable, inexpensive and available in tablet form. It is well absorbed orally and sublingually, has the potential to be used more widely than would be possible with injectable uterotonics alone, and is considered potentially lifesaving, particularly in low-resource settings. However, until recently, evidence has been insufficient to lend full support to recommendations for its widespread use in the prevention and treatment of PPH.

ABOUT THE FIGO INITIATIVE 

FIGO is dedicated to the improvement of women’s health and rights, the reduction of disparities in health care available to women and newborns, and the advancement of the science and practice of obstetrics and gynaecology.

In September 2010, FIGO signed an agreement with Gynuity Health Projects to collaborate in the second phase of a project funded by the Bill & Melinda Gates Foundation which sets out to answer a host of scientific, operational, and policy questions regarding the use of misoprostol for PPH care. The project partners include: Aga Khan Development Fund, Family Care International (FCI), FIGO, Guttmacher Institute, Gynuity Health Projects, PATH, Population Services International (PSI), University of Liverpool, University of Illinois, Chicago/UCSF, World Health Organization (WHO), Ministries of Health, hospitals, providers, advocates and networks globally.  

Project Team

Project Director - (FIGO Chief Executive) Hamid Rushwan

Project Manager - Clare Waite

Financial Administrator - Raj Waghela 

Project Period

Phase I: September 2010 – October 2012

Phase II: November 2012 – October 2014  

Project Purpose

To advocate for and disseminate evidence-based information on misoprostol for PPH for providers and clinical policy makers  

Project Objectives

Objective 1 – To act as a ‘guiding’ organisation for advocacy among the medical community and health professionals; 

Objective 2 – To disseminate information on strong evidence-based results related to the effectiveness and greater use of misoprostol;

Objective 3 – To develop materials for dissemination, including guidelines and protocols for professional groups on the use of misoprostol for PPH.  

Working closely with the FIGO Committee for Safe Motherhood and Newborn Health, professional associations, and other like-minded organisations, FIGO’s project activities will include conducting expert panel sessions at regional meetings of obstetricians and gynaecologists to highlight the findings of evidence-based clinical studies and to introduce planned operational studies; publishing scientific articles in the International Journal of Gynecology and Obstetrics (IJGO); producing an IJGO supplement; conducting a half-day session at the 2012 FIGO World Congress in Rome; developing user-friendly education and training materials for professional associations and health personnel; offering assistance in the development of guidelines, protocols, and other materials for professional groups at the national level; and conducting national workshops in support of national activities. 

FIGO endorses the administration of misoprostol in situations when safe administration and/or appropriate storage conditions for injectable oxytocin and ergot alkaloids are not possible. 

PUBLISHED EVIDENCE – Clinical and Operational Studies 

Prevention Studies   Data from a randomized controlled trial comparing misoprostol to placebo in a home birth setting in rural Pakistan show that 600 mcg oral misoprostol reduces the rate of PPH (≥500 mL) by 24%, compared with placebo (Mobeen et al). The findings from the study corroborate those from seminal studies on misoprostol care at the community level in India (Derman et al).  

Article: Administration of misoprostol by trained traditional birth attendants to prevent postpartum haemorrhage in homebirths in Pakistan: a randomised placebo-controlled trial

Journal: British Journal of Obstetrics and Gynaecology, Volume 118, Issue 3, pages 353–361, February 2011. Article first published online: 23 December 2010

Authors: N Mobeen, J Durocher, NF Zuberi, N Jahan, J Blum, S Wasim, G Walraven, J Hatcher 

Article: Oral misoprostol in preventing postpartum haemorrhage in resource-poor communities: a randomised controlled trial

Journal: The Lancet 2006;368(9543):1248–53

Authors: Derman RJ, Kodkany BS, Goudar SS, Geller SE, Naik VA, Bellad MB, et al.

Treatment Studies   Two large randomised controlled trials, undertaken in hospitals in Burkina Faso, Ecuador, Egypt, Turkey, and Viet Nam, provide evidence on the effectiveness of misoprostol for the treatment of primary PPH. The purpose of the trials was to establish whether 800mcg sublingual misoprostol is as effective as a regimen of 40 IU oxytocin (IV) in stopping haemorrhage in tertiary care facilities. The data from these trials indicate that sublingual misoprostol (800mcg) might be a suitable first-line treatment alternative to IV oxytocin for PPH due to uterine atony.    

Article: 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

Journal: The Lancet, Volume 375, Issue 9710, Pages 210 - 216, 16 January 2010

Authors: Beverly Winikoff, Rasha Dabash, Jill Durocher, Prof Emad Darwish,  Nguyen Thi Nhu Ngoc, Wilfrido León, Sheila Raghavan, Prof Ibrahim Medhat, Huynh Thi Kim Chi, Gustavo Barrera, Jennifer Blum   

Article: Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial

Journal: The Lancet, Volume 375, Issue 9710, Pages 217 - 223, 16 January 2010

Authors: Jennifer Blum, Beverly Winikoff, Sheila Raghavan, Rasha Dabash, Mohamed Cherine Ramadan, Berna Dilbaz, Prof Blami Dao, Jill Durocher, Serdar Yalvac, Ayisha Diop, Ilana G Dzuba, Nguyen Thi Nhu Ngoc 

Article: Misoprostol as an adjunct to standard uterotonics for treatment of post-partum haemorrhage: a multicentre, double-blind randomised trial

Journal: The Lancet, Volume 375, Issue 9728 Pages 1808 - 1813, 22 May 2010

Authors: Mariana Widmer, Jennifer Blum, G Justus Hofmeyr, Guillermo Carroli, Prof Hany Abdel-Aleem, Prof Pisake Lumbiganon, Nguyen Thi Nhu Ngoc, Daniel Wojdyla, Prof Jadsada Thinkhamrop, Mandisa Singata, Luciano E Mignini, Mahmoud Ahmad Abdel-Aleem, Tran Son Thach, Beverly Winikoff 

Operations Studies

Article: Expanding uterotonic protection following childbirth through community-based distribution of misoprostol: operations research study in Nepal

Journal: International Journal of Gynecology and Obstetrics, 2010; 108(3):282–8  

Authors: Rajbhandari S, Hodgins S, Sanghvi H, McPherson R, Pradhan YV, Baqui AH; Misoprostol Study Group

Article: Prevention of postpartum haemorrhage at home birth in Afghanistan

Journal: International Journal of Gynecology and Obstetrics, 2010; 108(3):276-81  

Authors: Sanghvi H, Ansari N, Prata NJ, Gibson H, Ehsan AT, Smith JM

WHO MODEL LIST OF ESSENTIAL MEDICINES - 18th Expert Committee on the Selection and Use of Essential Medicines

The 18th Expert Committee on the Selection and Use of Essential Medicines took an important step when it approved the addition of misoprostol for the prevention of PPH to the WHO Model List of Essential Medicines. 

In its unedited report made public in May 2011 following a review of the efficacy, safety, and cost-effectiveness of this and other medicines, the Committee took the decision to move misoprostol from the Complementary List to the Core List and to amend the list to include “…and for the prevention of postpartum haemorrhage where oxytocin is not available or cannot be safely used.” The Committee noted that there is “some evidence that 600mcg given orally is effective and safe” and that new evidence submitted showed that “misoprostol can be safely administered to women to prevent post-partum haemorrhage by traditional birth attendants or assistants trained to use the products at home deliveries.” The Committee further noted that, although misoprostol was not added to the list for its treatment indication, current WHO guidelines recommend the use of misoprostol for prevention and treatment indications in settings where it is not possible to use oxytocin or another injectable uterotonic.

EVENTS

Plenary Session at the South Asia Federation Conference of Obstetrics and Gynaecology (SAFOG) – April 2011 

In April 400 delegates, mainly obstetricians and gynaecologists from Bangladesh, India, Nepal, Pakistan, and Sri Lanka, came together in Colombo for the joint 8th South Asia Federation Conference of Obstetrics and Gynaecology (SAFOG 2011) and the 44th Annual Scientific Sessions of the Sri Lanka College of Obstetricians and Gynaecologists (SLCOG).

At a plenary session sponsored by FIGO, the panel emphasised the important role of misoprostol in contributing to efforts to reduce the maternal mortality ratio by three quarters by 2015 (Millennium Development Goal 5), presented the findings of recent evidence-based clinical studies, and fostered a debate around the efficacy and use of misoprostol for PPH in settings where the gold-standard uterotonic, oxytocin, is neither available nor feasible.   

Dr Nadeem Zuberi (Aga Khan University, Karachi) opened with a presentation on studies in Pakistan that evaluate the efficacy and safety of 600 mcg oral misoprostol to prevent PPH, with an emphasis on a recent trial conducted in Chitral that investigated its use to prevent PPH when administered by trained traditional birth attendants at home deliveries (Mobeen et al., BJOG, December 2010). Dr MB Bellad (JNM College, Belgaum) summarised seminal studies on misoprostol care at the community-level in India (Derman et al., Lancet, 2006) and introduced new research to compare two key community-level preventative strategies for PPH management, namely primary and secondary prevention of PPH. Dina Abbas (Gynuity Health Projects, New York) focused on published evidence on the efficacy of misoprostol for treatment of PPH in a multi-country study (Blum et al., Lancet, 2010; Winikoff et al., Lancet, 2010) and discussed potential implications for service delivery programmes. Shafiq Mirzazada (Aga Khan Health Services, Kabul) discussed ongoing research assessing the programmatic effectiveness of an 800 mcg dose of sublingual misoprostol as a first-line treatment for PPH in community settings in Afghanistan, and the consequent implications of incorporating misoprostol into service delivery models in such settings.    

The session was moderated by Dr Shereen Bhutta, head of Pakistan’s largest public-funded obstetrics and gynecology department at Jinnah Postgraduate Medical Centre in Karachi and a member of FIGO’s Safe Motherhood and Newborn Health Committee, and is one of a series of sessions organised by FIGO at regional and international meetings as part of a joint initiative with Gynuity Health Projects to increase access to information among obstetricians and gynaecologists on misoprostol for its PPH indications in low resource settings.