Despite a significant reduction in maternal mortality over the last 30 years, global progress has stalled. Almost 300,000 women died as a result of pregnancy or childbirth in 2017.[1] Most of these deaths were preventable, and the vast majority occurred in low-and middle-income countries (LMICs). Given the current burden and slowing progress, maternal mortality targets set for the Sustainable Development Goals will not be reached on the current trajectory. A coordinated, integrated effort, with emphasis on expanded access to innovative health interventions, including new, lifesaving commodities, is needed to reach the 2030 targets and address the unacceptably high number of global maternal deaths.

The most common direct cause of maternal morbidity and death is PPH (excessive bleeding after birth), which is responsible for 20% of all maternal mortality.[2] Accelerated adoption and scale-up of tools to reduce maternal morbidity and mortality from PPH represents a near-term opportunity that would support efforts to progress toward targets in high burden countries.

Most cases of PPH are avoidable with appropriate tools. For prevention, WHO recommends the use of an effective uterotonic during the third stage of labor.[3] Studies suggest that for every 12 women who receive active management of third stage of labor, one case of PPH is averted.[4] Use of prophylactic uterotonics is critical to reducing the PPH burden; however, access barriers prevent uptake in many LMICs.

A key barrier lies in the quality of available uterotonics. Oxytocin, the recommended first-line drug for PPH prevention and treatment, requires cold-chain storage to remain effective. Given the challenges in ensuring cold-chain storage in many LMICs, it is often of poor quality. Oxytocin quality also suffers from manufacturing deficiencies, and poor regulatory oversight and procurement practices. In a WHO field test of essential medicines for women and children, 64% of oxytocin samples were non-compliant.[5] When cold-chain cannot be assured, misoprostol, a heat stable alternative is often used. However, like oxytocin, quality issues with misoprostol have also been documented.[6] Compromised product quality can occur at multiple stages along the complex drug supply chain, but monitoring is difficult given limited rapid screening tools that can analyze quality prior to administration.[7]

An additional challenge with oxytocin is that it is recommended for use only in the presence of a skilled birth attendant, as the drug needs to be administered through intravenous or intramuscular injection. Childbirth with a skilled birth attendant remains low in sub-Saharan Africa, restricting access for many women in the region.[8] Misoprostol is available in tablet form, and is recommended by the WHO when delivering outside of a health facility and without a skilled birth attendant, and most recently for distribution during antenatal care contacts for self-administration (with targeted monitoring and evaluation).[9] This recommendation is yet to be scaled.

When prevention is not effective, tranexamic acid is recommended by the WHO for management of all PPH cases as part of the standard PPH treatment package. Tranexamic acid is an old drug, but its recommendation for PPH is recent.[10] As a result, awareness and knowledge for this indication is limited, and uptake remains low. Furthermore, tranexamic acid requires an intravenous injection for administration, limiting its potential for use in many LMICs.

New drugs that respond to the access barriers to the current PPH standards-of-care are becoming available. For example, heat-stable carbetocin – a PPH preventive that does not require cold chain storage – is in early registration stage, and introduction efforts are underway in a few early adopter countries. In addition, new non-injectable, heat-stable formulations of oxytocin are in development. Efforts are also underway to evaluate non-injectable forms of tranexamic acid (e.g. oral, inhalable). These new drug formulations and delivery methods have the potential to overcome delivery barriers and expand access to the community level.

[1] WHO (2019) Trends in maternal mortality 2000 to 2017: estimates by WHO, UNICEF, UNFPA, World Bank Group, and the United Nations Population Division. Geneva: WHO.

[2] Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels JD, et al. Global Causes of Maternal Death: A WHO Systematic Analysis. Lancet Global Health. 2014;2(6): e323-e333.

[3] WHO (2018) WHO recommendations: uterotonics for the prevention of postpartum haemorrhage. Geneva: World Health Organization.

[4] USAID (2007). Prevention of Postpartum Hemorrhage: Implementing Active Management of the Third Stage of Labor (AMTSL) (Report – online). Available at: https://path.azureedge.net/media/documents/MCHN_popphi_amtsl_ref_man_1of3.pdf.

[5] WHO (2016). Survey of the Quality of Medicines Identified by the Commission on Life Saving Commodities for Women and Children (Online) Available at: https://apps.who.int/iris/bitstream/handle/10665/255550/9789241511117-eng.pdf.

[6] Torloni MR, Bonet M, Betrán AP, Ribeiro-do-Valle CC, Widmer M (2020) Quality of medicines for life-threatening pregnancy complications in low- and middle-income countries: A systematic review. PLoS ONE 15(7): e0236060.

[7] Lambert, P., McIntosh, M.P., Widmer, M., Evans, L., Rauscher, M., et al. (2020). Oxytocin quality: evidence to support updated global recommendations on oxytocin for postpartum hemorrhage. J of Pharm Policy and Pract 13, 14

[8] WHO (2020). Sexual and Reproductive Health – Skilled Birth Attendants. Online. Available at: https://www.who.int/reproductivehealth/topics/mdgs/skilled_birth_attendant/en/.

[9] WHO (2020) WHO recommendation on advance misoprostol distribution to pregnant women for prevention of postpartum haemorrhage. Geneva: World Health Organization

[10] WHO (2017). WHO recommendation on tranexamic acid for the treatment of postpartum haemorrhage. Geneva: World Health Organization.