Global Health Interventions: A Review of the Evidence Background Methodology • Glossary

Overview: Maternal Hemorrhage

Background

Maternal hemorrhage – severe bleeding that occurs during pregnancy (ante-partum), labor, or post-partum – accounts for the majority of maternal deaths worldwide.[1] Post-partum hemorrhage (PPH) comprises the majority of maternal hemorrhage cases. The World Health Organization has defined PPH as 'blood loss from the birth canal in excess of 500 ml during the first 24 hours after delivery.[2] Clinical signs and symptoms of blood loss (also used for diagnosis) include weakness, sweating, and tachycardia, with hemodynamic collapse occurring at losses of between 35 and 45% of blood.[3] PPH can kill a healthy woman within 2 hours and is the quickest maternal killer.[4] Women with PPH in one pregnancy are at increased risk of PPH in subsequent pregnancies.

Epidemiology

• Maternal hemorrhage is the leading cause of maternal mortality in developing countries, accounting for 35% of maternal deaths in these regions.[5]
• According to the World Health Organization, at least 100,000 maternal deaths are caused by maternal hemorrhage annually.[6]
• PPH is estimated to occur in 6% of all deliveries, with 1.96% being severe cases.
• Common causes of PPH include: atonic uterus (failure of the uterus to contract adequately after birth; 90%); trauma to the genital tract (7%); and retention of placental tissue and failure in the coagulation system (3%). Atonic PPH is the leading cause of maternal death in low- and middle-income countries.[7]

The intervention assessments below summarize the information presented in the "Key Findings" table.

Prevention: What works?

There are four categories of interventions to prevent maternal hemorrhage: drugs, non-drug interventions, training, and active management (which is multifaceted). No studies on prevention evaluate changes in mortality but rather focus on reducing risk of severe blood loss and other indicators of adverse clinical developments, including manual removal of the placenta (curettage), use of uterotonics, vomiting, and pyrexia.

• Drugs. Oxytocin (a hormone with diverse actions) is an effective injected uterotonic, decreasing severe PPH by half to two-thirds and other disease indicators by one-third to half (very strong evidence). Its synthetic analog carbetocin appears to have similar benefit for PPH (weak evidence) and greater reduction of other adverse outcomes (moderately strong evidence). Tranexamic acid (an antifibrinolytic, i.e., helps with clotting) reduces PPH by half (moderate strength of evidence). Drug regimens containing ergometrine (which stimulates uterine muscle) appear slightly better than oxytocin at reducing bleeding, but with much higher rates of vomiting and other adverse events. Misoprostol (a prostaglandin) is an important option in resource poor settings, due to low cost and easier administration. In most formulations, it has worked poorly for PPH prevention (108% increased risk to 31% reduction, moderate strength evidence), with considerable side effects. However one specific formulation (600 mcg sublingual), studied in three trials (one recent[8]), appears better than oxytocin (11-52%, moderate evidence), though with increased fever (strong evidence).
• Non-drug interventions. Breast stimulation may reduce bleeding by more than half (moderately strong evidence). Other strategies appear ineffective: Uterine massage has no evidence of benefit for bleeding, one study found decreased need for uterotonic drugs (weak evidence). Supplementation with minerals or folic acid appears more likely to increase than decrease bleeding. Saline solutions have not been evaluated for bleeding and may slightly decrease the need for curettage (non-statistically significant).
• Training. Training traditional birth attendants reduces bleeding by about 40% (moderately strong evidence). The use of midwife-general practitioner managed care versus obstetrician-led shared care had a non-statistically significant benefit (moderately strong evidence).
• Active management. Active management of the third stage of labor is multifaceted, combining a uterotonic drug, early umbilical cord clamping, and controlled cord traction to aid delivery of the placenta. It may reduce bleeding even for low risk women, and when offered for all women reduces bleeding by two thirds (very strong evidence), albeit with increased risk of return visit for bleeding, prolonged vomiting, and blood pressure drop. These studies are predominantly from wealthy countries. One study of “holistic psychophysiological” third stage care found a 7-fold reduction in hemorrhage versus active management (very weak evidence, not in table).[9]

Treatment: What works?

We found evidence in three treatment categories: providing drugs, blocking or removing the source of bleeding, and maintaining core circulation. Importantly, we did not assess evidence for use of blood products (e.g., transfusion), because this is standard of practice with massive blood loss and risk of circulatory failure, regardless of cause or patient population.

• Drugs. Misoprostol reduces blood loss by half or more (moderately strong evidence).
• Blocking or removing source of bleeding. Evidence for the value of surgical (and radiologically-guided) methods is weak.
• Maintaining core circulation. An anti-shock garment (non-pneumatic) has been shown in two studies by one research time, in Nigeria and Egypt, to reduce mortality and severe morbidity for women with PPH by two thirds (weak evidence due to lack of RCTs).

Summary / Future Directions

Prevention. The use of uteronic and other drugs (importantly misoprostol), breast stimulation, training, and active management substantially reduce the likelihood of life-threatening maternal hemorrhage. Novel approaches such as holistic care may improve outcomes.

Treatment. Misoprostol is the mainstay of treatment. Surgery may provide limited benefit. Anti-shock garments show promise in reducing mortality.

Advances in maternal hemorrhage prevention and treatment in recent years have included improved recognition of when normal blood loss during pregnancy becomes dangerous, active management of the third stage of labor, and the use of uteronics to prevent uterine atony.[10] Low-tech strategies (breast massage, anti-shock garment) are also valuable options in the intervention toolbox. Misoprostol is an essential drug for resource-poor settings, administered orally and lower cost than the uterotonics; further assessment of its prevention benefit is needed.

As demonstrated above, there are multiple effective interventions to prevent and manage maternal hemorrhage. With 99% of maternal deaths occurring in developing countries, the challenge lies in creating access to skilled birth attendants and emergency obstetric and newborn care services in resource poor settings. Existing facilities can often, with modest investments, be upgraded to provide such services. Major barriers to access for women in developing countries include a lack of services where they live, the inability to afford services or transportation to the nearest facility, and the perception that care at a large facility may be poor or ineffective.[11]

Reduction of maternal mortality by 75% between 1990 and 2015 is the first target of the fifth United Nations Millennium Development Goals (MDGs). However, according to WHO this target is critically off track, and the short-fall is particularly acute in sub-Saharan Africa.[12],[13] To meet MDG 5, governments, donors and policymakers must focus on the systemic barriers to access for emergency obstetric care if they hope to curb maternal hemorrhage and other major causes of maternal mortality.

References

1. United Nations Department of Economic and Social Affairs.  The Millennium Development Goals Report 2010. New York, 2010. Pgs. 30-38. Available from: http://mdgs.un.org/unsd/mdg/Resources/Static/Products/Progress2010/MDG_Report_2010_En_low%20res.pdf

2. WHO. WHO guidelines for the management of postpartum haemorrhage and retained placenta. 2009. Available from: http://whqlibdoc.who.int/publications/2009/9789241598514_eng.pdf

3. Bonnar J. Massive obstetric haemorrhage. Baillieres Clin Obstet Gynaecol. 2000; 14:1–18.

4. WHO. World Health Report 2005: Chap 4 – Make Every Mother and Child Count; 61-78. Available from: http://www.who.int/whr/2005/chap4-en.pdf

5. United Nations Department of Economic and Social Affairs.  The Millennium Development Goals Report 2010. New York, 2010. Pgs. 30-38. Available from: http://mdgs.un.org/unsd/mdg/Resources/Static/Products/Progress2010/MDG_Report_2010_En_low%20res.pdf

6. Abouzahr C. Antepartum and postpartum haemorrhage. In: Murray CJ, Lopez AD, eds. Health Dimensions of Sex and Reproduction. Boston, Mass: Harvard University Press; 1998:172-4.

7. Carroli G, Cuesta C, Abalos E, Gulmezoglu AM. Epidemiology of postpartum haemorrhage: a systematic review. Best Practice & Research Clinical Obstetrics and Gynaecology. 2008 Dec; 22(6):999-1012. doi:10.1016/j.bpobgyn.2008.08.004.

8. Singh G et al. Comparison of sublingual misoprostol, intravenous oxytocin, and intravenous methylergometrine in active management of the third stage of labor. International Journal of Gynecology and Obstetrics. 2009; 107, 130–134.

9. Fahy K, Hastie C, Bisits A, Marsh C, Smith L, Saxton A. Holistic physiological care compared with active management of the third stage of labour for women at low risk of postpartum haemorrhage: A cohort study. Women Birth. 2010 Mar 10. [Epub ahead of print]

10. UCSF Bixby Center for Global Reproductive Health. Safe Motherhood. Available from: http://bixbycenter.ucsf.edu/research/researchareas/safe_motherhood.html.

11. WHO. Maternal Mortality Fact Sheet. 2008. Available from: http://www.who.int/making_pregnancy_safer/events/2008/mdg5/factsheet_maternal_mortality.pdf

12.  Cross, S., J. S. Bell, et al. What you count is what you target: the implications of 3 maternal death classifications for tracking progress towards reducing maternal mortality in developing countries. Bull World Health Organ, 2010; 88(2): 147-153.

13. WHO. Maternal mortality in 2005: Estimates developed by WHO, UNICEF, UNFPA, and the World Bank. 2007. Available from: http://www.who.int/whosis/mme_2005.pdf

-- Updated June 2011