Postpartum Haemorrhage

African pregnant mother holding her belly

Every six minutes, a mother dies from losing too much blood while giving birth. The tragedy is that this is almost always preventable. Research shows that 99% of maternal deaths occur in low- and middle-income countries (LMICs), with very few deaths in high-income countries like the UK.

Our projects

The E-MOTIVE Trial

Sparked by the postpartum haemorrhage global challenge, researchers at Birmingham are leading a global effort to tackle bleeding after childbirth, called the E-MOTIVE programme. The E-MOTIVE study is supported by the Institute of Global Innovation of the University of Birmingham and a $10.9M grant from the Bill & Melinda Gates Foundation.EMOTIVE logo

The E-MOTIVE programme is exploring a package of interventions that could save mothers around the world. The aim is to implement an early detection strategy and a ‘first response’ bundle of care for cutting down deaths and complications related to PPH by 25%. The programme will use a robust implementation strategy that focusses on simulation-based training, peer-assisted learning and local champions.

The E-MOTIVE team will work with international partners and co-ordinating centres in Kenya, Tanzania, Nigeria, South Africa, and Sri Lanka to test the E-MOTIVE intervention in a large randomised trial across 80 health facilities, involving over 300,000 women. The trial is focussing in women giving birth vaginally, but the team will also develop a similar strategy for women giving birth by caesarean section.​

The ReAct Trial

We are optimistic and believe that for most women, if healthcare providers detect the problem early and treat it efficiently, the bleeding will stop and the mother will be safe. If, however, the treatment does not succeed and a woman continues to bleed despite the first response treatment, then her life is at risk.

This condition is called refractory PPH and would now require life-saving specialist treatment and invasive surgical procedures to ensure survival of the mother. The Birmingham team are also developing, with funding from the Medical Research Council in the UK, a provisional management package for these women who continue to bleed despite first response treatment. This programme, called the 'PPH ReAct' package, is due to be field-tested and piloted in five health facilities in Nigeria.

The WHO CHAMPION Trial

The WHO Champion Trial compared heat-stable carbetocin with the standard therapy of oxytocin for the prevention of postpartum haemorrhage. This trial involved 29,645 women across Argentina, Egypt, India, Kenya, Nigeria, Singapore, SA, Thailand, Uganda and the UK. Our team led the study in the UK for this WHO trial. The trial concluded that carbetocin is non-inferior to (i.e. not worse than) oxytocin for preventing blood loss of at least 500ml or need for additional uterotonic medication at the time of vaginal birth.

PPH Evidence Synthesis

Excessive bleeding after childbirth (postpartum haemorrhage; PPH) is a major concern for every pregnant woman. It can lead to long-term ill health and death. The World Health Organisation (WHO) recommends the uterus-contracting (‘uterotonic’) drug oxytocin for prevention of PPH. In high-income countries, oxytocin is given as standard practice to halve a woman’s risk of PPH  but in LMIC oxytocin is often ineffective because it is heat labile (i.e. effectiveness reduced at higher temperatures) and facilities for refrigerated storage and transport are generally not available. PPH during childbirth kills around 100,000 mothers and 80,000 babies each year in LMIC. Lack of an effective uterotonic medication is a major contributor to high maternal mortality in these countries. A heat-stable alternative would be more effective and potentially save many lives.​

There are at least seven uterotonic medicines for preventing PPH, including the heat-stable drug carbetocin. In 2015, the National Institute for Health Research (NIHR) funded Coomarasamy (principal investigator), Gallos, Roberts, Deeks and Price at the University of Birmingham (UoB) to identify the most effective uterotonic drug for preventing PPH with the fewest adverse effects, using network meta-analysis (NMA); a complex statistical method to analyse data for multiple treatments from multiple studies [R1]. ​

The NMA compared multiple drugs in a single coherent analysis. Gallos was the principal reviewer and Price and Deeks were statisticians on the study. They designed the NMA methods using a reputable Cochrane protocol and performed the statistical analysis of 140 randomised controlled trials involving 88,947 women. They reported the following key finding in April 2018 [R2]:​

KF1: Three uterotonic drugs, including carbetocin, are more effective for the prevention of PPH than oxytocin. ​

​In 2017, WHO prioritised the update of their existing (2012) recommendations on the use of uterotonics for prevention of PPH. This was in order to inform changes to practice and to work toward reducing global maternal mortality by 2030, in line with target 3.1 of the third Sustainable Development Goal. WHO identified the detailed NMA [R2] in progress in Cochrane Library by the UoB researchers. They invited Gallos to serve on the Evidence Synthesis Group for the recommendations and asked the UoB team to update their NMA to include the new evidence from the CHAMPION trial [R3] and other recent trials relating to other uterotonics [S1(i), p.8]. The updated NMA, published in December 2018, included 196 randomised controlled trials conducted across 53 countries (across all income levels) and involving 134,414 women. The study provided effectiveness and safety estimates for each of the uterotonic agents, reported a ranking for each drug and described the following key findings [R4]: ​

KF3: Carbetocin is superior to oxytocin, preventing for all births (vaginal and caesarean​ section) one more PPH event out of three (30% reduction) without any greater undesirable effects. ​

KF4: Using carbetocin as the drug of choice worldwide, could save more than 4 million women from suffering PPH each year and reduce related complications including death that are a particularly significant risk for women in LMIC. ​

Heat-stable carbetocin has a higher unit cost than oxytocin (£17.64 vs. £0.91). To assess whether carbetocin could be recommended for general healthcare, its cost-effectiveness and affordability compared with other uterotonics had to be considered. Using pooled data from the NMA, Roberts developed a model-based cost-effectiveness analysis to compare from the perspective of the UK NHS as respresentative of a high-income country setting, the six different combinations of uterotonic drugs available [R5 & R6]. The study made the following key finding:​

KF5: In developed countries, where the cost of PPH is high, carbetocin is the most cost-effective drug for the prevention of PPH. 

The Postpartum Haemorrhage team 

Meet the team

Professor Arri Coomarasamy MBChB, MD, FRCOG, FMedSci

Professor of Gynaecology and Reproductive Medicine
Founding Director of the WHO Collaborating Centre for Global Women's Health
a.coomarasamy@bham.ac.uk
@arricoomarasamy

Professor Arri Coomarasamy

Dr Adam Devall, BMedSc (Hons), PhD

Lecturer in Maternal Health Clinical Trials​
Senior Clinical Trials Fellow, Tommy's National Centre for Miscarriage Research​a.j.devall@bham.ac.uk
@tommysbham

Adam_Devall_10.09.19-1

Dr Ioannis Gallos, DMS, MD, MRCOG

Senior Lecturer in Global Women's Health
Co-Director of WHO Collaborating Centre for Global Women's Health
i.d.gallos@bham.ac.uk
@IoannisGallos

Dr Ioannis Gallos
Kristie-Marie Mammoliti, Programme Manager 

 

Leanne Beeson, Trial Manager

 

Rebecca Timms, BSc, MRes

Data Manager for E-MOTIVE Trial
Institute of Applied Health Research
r.l.timms@bham.ac.uk 

Rebecca Timms

 

Rachel Lillywhite

Deputy Trials Management Team Leader
Institute of Applied Health Research
College of Medical and Dental Sciences
r.e.lillywhite@bham.ac.uk
@RE_Lilyewhite

Rachel Lillywhite

PhD Students

Eleanor Thomas MSc, MBPsS

PhD student
Institute of Metabolism and Systems Research
WHO Collaborating Centre for Global Women's Health
ERT825@student.bham.ac.uk
@_Ellie_Thomas_

Eleanor Thomas

Dr Argyro Papadopoulou MBChB

PhD student
Institute of Metabolism and Systems Research
WHO Collaborating Centre for Global Women's Health
axp1015@student.bham.ac.uk
@ArgyPapaUoB

Argyro Papadopoulou

Dr Francis Muriithi, MBChB, Mmed, O&G, MSc EBHC MRCOG

Doctoral Research Training Fellow in Global Women's Health
Institute of Metabolism and Systems Research
WHO Collaborating Centre for Global Women's Health
fgm911@student.bham.ac.uk
@EBMSavvyObsGyn

Francis Muriithi

Medical student

Eva Larkai​
Medical Student​
University of Bristol​
el16314@bristol.ac.uk

Eva Larkai