Source: Spy Ghana
Mbarara University of Science and Technology (MUST) has announced research findings that will prevent maternal death in Uganda and other developing countries.
The research entitled 'Sublingual Misoprostol versus Intramuscular Oxytocin for Prevention of Postpartum Hemorrhage in Uganda: A Double-Blind Randomized Non-Inferiority Trial' was led by Esther Cathyln Atukunda, a PHD Scholar, in pharmaco epidemiology together with Dr. Mark J Siedner, a physician at Massechussettes General Hospital/ Harvard Medical School-Boston USA, Proffessor MJ, Celestino Obua, Vice Chancellor and professor of Pharmacology at MUST, Dr. Godfrey R Mugyenyi, a senior obstetrician/ Gynaecology at MUST, Dr. Marc Twagirumukiza, a clinical pharmacologist/physician at Ghent university Belgius and Proffessor Amon Ganaafa Agaba of MUST
The research, which is the first of its kind in the world in this field, was to establish whether misoprostol a drug that is not recommended by the World Health Organization (WHO) was not inferior to oxytocin, a drug that is currently recommended by (WHO) for use in preventing mothers from bleeding to death after giving birth.
Background
Every year, worldwide nearly 290,000 women die during pregnancy or labor or during the first six weeks after giving birth (the postpartum period). Most of the maternal deaths occur in low- or middle-income countries like Uganda. The deaths are caused by preventable or treatable conditions including postpartum hemorrhage (severe bleeding from the uterus within 24 hours of childbirth), post-delivery infections, unsafe abortion, obstructed (difficult) labor, and blood pressure disorders during pregnancy.
The leading cause of maternal deaths in the world is postpartum hemorrhage, which is responsible for 25%–30% of all maternal deaths. However, in Uganda this bleeding causes over 24% of all maternal deaths which currently stand at 17 deaths every day.
However, it is interesting to note that this postpartum hemorrhage can be prevented by giving the mother an intramuscular injection of oxytocin, a hormone that stimulates uterine contractions and limits uterine bleeding, immediately after her child is born.
Why was the study done?
This study was done because women from low and middle income countries like Uganda have continued to die from postpartum hemorrhage even when the drug oxytocin is available and the simple reasons are:
1. Oxytocin needs to be kept cool in a refrigerator (needing electricity) which is not readily available in clinics and hospitals where the majority of Ugandan women deliver. Over 40% of women deliver at home where oxytocin cannot be administered.
2. Administration of oxytocin requires skill of a trained personnel to administer the injection.
These limitations in low- and middle-income countries motivated the team to look for alternative safe treatment modalities to prevent this monster from killing our mothers.
According to WHO, oxytocin use is recommended to combat the bleeding of women after child birth, but the researchers noted that 97% of health facilities in Uganda are unable to provide emergency obstetric care and the reason is because of lack of electricity, laboratory services, sometimes lack of trained staff and also because most of the medicines like oxytocin which is recommended needs a cold chain for its storage and administration, said Dr. Esther Atukunda.
"'We also noted that 95% of women in Uganda will attend at least one antenatal visit, although 57% of the overall deliver in a health facility supervised by skilled personnel. And yet, postpartum hemorrhage, which is the bleeding after birth, occurs in 24 hours after delivery, and due to limited resources and the challenges faced with the use of oxytocin like requiring cold storage and use of skilled personnel that we cannot provide in some settings, there is an increasing use of an alternative which is misoprostol," she Atukunda said.
Dr. Atukunda added that the reason why misoprostol is increasingly being used is because of its advantages over oxytocin which include: A long shelf life meaning it can be kept normally at room temperature for at least 2 years without losing its efficacy. It can be administered as a pill which can be administered by anyone and does not need a skilled or trained health worker.
Atukunda said administration of misoprostol, a synthetic prostaglandin that has effects similar
to those of oxytocin, has been proposed as an alternative way to prevent postpartum hemorrhage in resource-limited settings due to its advantages; misoprostol is stable at room temperature and because it can be given sublingually (beneath the tongue), it acts very quickly.
The above advantages of misoprostol notwithstanding, the researchers noted that there is generally lack of data about misoprostol in terms of its registration in Uganda, how it is distributed, how it is used, but also its comparative efficacy with the standard oxytocin which is challenging to use in Uganda.
However, the comparative efficacy of sublingual misoprostol and intramuscular oxytocin for the prevention of postpartum hemorrhage has not been established making this Ugandan research the first of its kind in the world.
Scientific study design
So the research undertook a double-blinded, double-dummy randomized controlled non-inferiority trial to compare sublingual misoprostol and intramuscular oxytocin for the prevention of postpartum hemorrhage in Uganda, a country where there are more than 6000 maternal deaths every year.
A randomized controlled trial compares the outcomes of individuals assigned to different interventions through the play of chance. In a double-blinded trial, neither the researchers nor the participants know who is receiving which intervention.
In this particular trial, double-blinding is achieved by giving a dummy (placebo) sublingual pill to the women assigned to the oxytocin group and a dummy injection to the women assigned to the misoprostol group, as well as their assigned treatments. A non-inferiority trial investigates whether one treatment is not worse than another treatment.
What did the researchers find?
The researchers measured blood loss over the first 24 hours after delivery in 1,140 women admitted to a referral hospital in Uganda. The women were given either sublingual misoprostol or intramuscular oxytocin at the currently recommended doses along with matching placebos, immediately after the birth of their child.
Postpartum hemorrhage (defined as the loss of more than 500 ml of blood within 24 hours of delivery; the trial's primary outcome) occurred in 28.6% and 17.4% of the women in the misoprostol and oxytocin groups, respectively (an absolute risk difference of 11.2%). Severe postpartum hemorrhage (loss of more than 1,000 ml of blood within 24 hours of delivery) occurred in 3.6% and 2.7% of participants in the misoprostol and oxytocin groups, respectively, but this difference was not statistically significant (it could have happened by chance).
On average, women given misoprostol had lost slightly more blood by two and 24 hours after delivery than those given oxytocin. There were no significant differences between the groups in terms of death, the need for blood transfusion, or the use of additional drugs to prevent blood loss, but women given misoprostol experienced shivering and fever more often than those given oxytocin.
What do the findings mean?
In their study protocol, the researchers specified that sublingual misoprostol would be deemed non-inferior to intramuscular oxytocin if the absolute risk difference for postpartum hemorrhage between the misoprostol and oxytocin treatment groups was less than 6% (the "non-inferiority" margin). These findings therefore indicate that sublingual misoprostol given at the recommended dose is inferior to intramuscular oxytocin for the prevention of postpartum hemorrhage in women undergoing an uncomplicated birth at a regional referral hospital in Uganda.
Although several aspects of this study may affect the accuracy and generalizability of its findings (for example, women at high risk of birth complications were excluded from the study), the researchers conclude that oxytocin should remain the preferred agent for the prevention of postpartum hemorrhage where it is available.
They however, note that sublingual misoprostol remains important for the prevention of postpartum hemorrhage where oxytocin is unavailable or where its administration is not feasible to help curb maternal deaths due to bleeding.
How can these research findings be used to curb maternal death in Uganda?
Considering the fact that over 97% of health facilities in Uganda cannot administer oxytocin due to the challenges mentioned above, misoprostol should be encouraged in settings where oxytocin is not feasible to curb maternal death that have continued to rise despite various efforts by government and civil society.
According to Dr. Godfrey Mugyenyi one of the researchers and senior obstetrician/Gynecologist at MUST, the findings of this study need to be taken seriously by the reproductive health division of the ministry of health whose major goal is to reduce maternal mortality in Uganda. He adds that the distribution of this reasonably cheap drug that prevents women from dying while giving life should be scaled up in settings where the use of oxytocin is not feasible.
Guidelines for use of misoprostol
Uganda started using misoprostol in 2010 without guidelines for its use because some health workers saw how important it is in stopping women from bleeding to death.
But guidelines were released in 2012, although up to now they have not been availed to the health centers. Although misoprostol was registered for PPH prevention, the guidelines include the drug for other indications like induction of labor, treatment of post-patum hemorrhage and post abortion care.
Challenges
The drug misoprostol has been widely abused in Uganda because it is illegally used to do abortions by mostly the quark doctors without proper guidelines.
What other scholars say about these findings
Professor Celestino Obua, the Vice Chancellor of MUST, a seasoned scientific researcher and senior mentor to Dr. Atukunda said that such evidence should not be taken lightly. Mbarara University will always provide a favorable atmosphere for such ground breaking research that will positively impact the wellbeing of the community.
The findings of this study have been peer reviewed and published jointly by the Lancet and PlosMedicine, a rare occurrence. The results were also published and presented at the world health summit in Berlin, Germany October 2014 and have been widely recognized and published on websites of several scientific media houses referring to the study as well done and that the results will save very many mothers from death.
Jim Thornton, a Professor of Obstetrics and Gynecology at Nottingham University, UK and the editor of the resource center at the European Journal o f obstetrics and Gynecology noted that this as a key publication in the area of Obstetrics Gynecology.