Pregnancy and childbirth involve significant health risks, even for women with no pre-existing health problems. Approximately 40 per cent of the pregnant women experience pregnancy-related health problems, while 15 per cent of all pregnant women are prone to long-term or life-threatening complications. A woman living in a developing country is much more likely to receive antenatal care than she is to have skilled care during childbirth, or the postpartum period. According to World Health Organisation (WHO), United Nations Children's Fund (UNICEF) and United Nations Population Fund (UNFPA) the maternal deaths are considerably high, while postpartum haemorrhage (PPH) claims 125,000 lives each year all over the world.
PPH is excessive bleeding experienced by the mother after giving birth. The condition can result from failure of the uterus to contract after separation of the placenta or from lacerations of uterus and or tears in the vagina. Two-thirds of women who haemorrhage to death have no identifiable risk factors and PPH can take place unpredictably. If active intervention is not available at the site of delivery, within two hours of its occurrence, the mortality and morbidity will continue to remain high.
A July 2006 report of UNICEF reveals that in every five minutes a woman dies in India during childbirth. The risk factor is so much that the maternal mortality and morbidity (MMR) is 540 per 100,000 births. Report also shows that India accounts for 20 per cent of global maternity deaths. It is estimated that the lifetime risk of maternal death during pregnancy and childbirth is 1 in 48 in India, compared to 1 in 2800 in the developed countries.
Even in this twenty first century, India continues to be an agrarian economy and more than half of our population still live in rural areas. This very factor poses a big challenge to the 'safe motherhood and child survival programs' and national and international agencies' efforts to make pregnancy safer and enjoyable.
Preventive strategies
Active management of the third stage of labour is the recommended strategy for prevention of PPH. This strategy comprises of giving an uterotonic drug within one minute of birth of the newborn, clamping and cutting the umbilical cord soon after birth and applying controlled cord traction for delivery of placenta.
In contrast, expectant management, which is the norm in the majority of home births in developing countries, involves waiting for signs of separation of placenta from the uterine wall and allowing it to deliver spontaneously. Active management is shown to be associated with reduced maternal blood loss, reduced postpartum anaemia and decreased need for blood transfusion. It is also associated with a reduced risk of prolonged third stage of labour and less use of additional therapeutic uterotonic drugs.
The feasibility of widespread use of active management in developing countries requires consideration of costs as well as the storage and distribution requirements of drugs and supplies, the availability of skilled birth attendants at delivery and the quality of the health care facilities. However, administration of an uterotonic injection immediately after delivery is one of the most important interventions used to prevent PPH. But the fact is that only about half of the pregnant women in developing countries deliver with the help of a skilled attendant, and only 40 per cent deliver in a hospital or health centre.
Uterotonic agents
The drug of choice for prevention of PPH is injection oxytocin 10 IU. It reduces the incidence of PPH by 70 per cent. Based on literature review and a large multicenter trial, WHO has identified benefits of oxytocin over other uterotonic drugs. Injection ergometrine 0.2 mg is less stable at room temperature and tends to lose its potency more rapidly, especially in tropical climates. Women with high blood pressure cannot use ergometrine. While injection syntometrine (ergometrine combined with oxytocin) appears to be even more effective than oxytocin or ergometerine alone, it has side effects similar to ergometrine, including headache, nausea, increased blood pressure and vomiting.
Recently, injection prostaglandins have been found effective in controlling bleeding, but the side effects, cost factor and the requirement of rigid temperature control are some of its negative aspects. Oral misoprostol, a prostaglandin E1 analogue, though less effective at reducing PPH than oxytocin, appears to be the best choice in settings where injectible uterotonics like oxytocin may not be feasible. Misoprostol can be administered sub lingually and rectally as well. The choice of uterotonic drug for prevention of PPH depends on the clinical scenario, judgment of the provider, availability of drug options, cold chain storage facilities and assessment of the trade-offs between the anticipated benefits and side effects.
Research background
Dr. Derman and Kodkany in the 2006 October 7 issue of 'the Lancet' reported the first randomized placebo controlled double blind trial using oral misoprostol for prevention of postpartum haemorrhage in a community setting. The study was conducted amongst women in rural areas of Belgaum, Karnataka, India. It was funded by the global network for Women's and Children's Health Research, a public-private partnership between NIH's National Institute of Child Health and Human Development and the Bill and Melinda Gates Foundation. A total of 1620 women were randomized to receive oral misoprostol (n=812) or placebo (n=808) after the delivery. A total of 25 auxiliary nurse midwives conducted all deliveries, administered study drug, measured blood loss and received ongoing training and monitoring. The primary outcome was the rate of postpartum haemorrhage (= 500 ml bleeding) within two hours of delivery.
Oral misoprostol also resulted in a significant reduction in the incidence rate of acute postpartum haemorrhage (12.0 to 6.4%, p < 0.0001) and acute severe postpartum haemorrhage (1.2 to 0.2%, p < 0.0001). Among women receiving misoprostol, the relative risk of acute postpartum haemorrhage and acute severe postpartum haemorrhage was 0.53 (95% confidence interval 0.39, 0.74) and 0.20 (95% confidence interval 0.04, 0.91) respectively. One among every eighteen women treated could prevent postpartum haemorrhage. Misoprostol was also resulted in a decrease in mean postpartum blood loss (262.3 to 214.3 ml, p < 0.0001). Women who received misoprostol were less likely to require emergency transfer to a higher-level facility (0.5 vs. 1.5%) and need for blood transfusion (0.1 vs. 0.9%) or surgical interventions (0.1 vs. 1.0%). However, transitory symptoms of chill and fever increased in the misoprostol group.
Low cost, ease of administration, stability and positive safety profile make misoprostol an attractive option in resource-poor settings. An unanticipated benefit of this study was the implementation of a new method for objective estimation of blood loss - BRASSS-V Drape. The calibrated drape provided a method of blood collection that was accurate and easy to utilize. It also facilitated earlier detection of postpartum haemorrhage at a less cost.
Benefits of drug
Despite various measures taken by the Indian Ministry of Health and Family Welfare, the maternal mortality and morbidity in recent years, has shown no significant reduction. The need of the hour is to promote the use of oral misoprostol for preventing PPH in settings where majority of deliveries continue to occur at home and are attended by unskilled birth attendants. Use of oral misoprostol as an uterotonic drug to prevent PPH during delivery in such low-resource settings is an indispensable step towards achieving the goal of 'safe motherhood', a major focus of the National Rural Health Mission. In order to achieve the millennium development goal of 130 maternal deaths per 100,000 live births by the year 2015, India needed to concentrate on evidence based interventions such as oral misoprostol for prevention of PPH.
Implications for community efforts at preventing PPH
The Ministry of Health, Government of India has taken active measure in recommending the use of oral misoprostol 600 mcg by the ANMs for prevention of PPH. Although the ANMs is awaiting training in its use and supplies, its value in saving the lives of mothers has been well recognized. In many developing countries where misoprostol is not registered for PPH, it is used off-label, for prevention of PPH because of the overwhelming medical evidence.
The Ministries of Health of Tanzania, Ethiopia and Nigeria have already approved the use of Misoprostol for preventing PPH. It is envisaged that the drug will be included in the WHO essential drug list for the prevention of PPH, largely in settings where other injectible uterotonics are not feasible. An announcement to this effect is likely to be made at the forthcoming World Congress of Federation of International Obstetricians and Gynaecologists to be held at Kuala Lumpur, Malaysia in November 2006.
(Prof. Dr. Bhalchandra S Kodkany, senior foreign investigator (India), Dr Shivaprasad S Goudar, research coordinator, Global Network for Women's and Children's Health Research & Dr Mubashir Angolkar, research officer, Human Reproduction Research Collaborating Centre, Indian Council of Medical Research, New Delhi)