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A successful multifaceted intervention to reduce postpartum hemorrhage (PPH) and maternal mortality (MM) in Sub-Saharan Africa — and the related confirmation of a link between prenatal anemia and PPH — may have global implications for improving maternal health outcomes. 

What Is the MM Rate, and What Roles Do PPH and Prenatal Anemia Play?

Maternal mortality rates vary widely across the globe. In Sub-Saharan Africa (SSA), MM is high, with an estimated 500-1000 maternal deaths per 100,000 live births — due mainly to nutritional deficiencies. In developed nations, the rate is 5-20 per 100,000 live births, rates in the United States vary widely by race, according to the Centers for Disease Control.

PPH is a major contributor to MM, and two recent large studies have identified a relationship between prenatal anemia — a correctable risk factor — and PPH. One study, the prospective evaluation of an intervention in SSA by Annette von Drygalski, MD, PharmD, director, Hemophilia and Thrombosis Center, University of California at San Diego, and her colleagues found a strong association between prenatal anemia and PPH.

A prospective cohort analysis of data from the World Maternal Antifibrinolytic-2 (WOMAN-2) trial, also identified the association.

What Was the Intervention in SSA, and What Were the Results?

Given the high MM rates in SSA and a lack of data on the contemporary incidence of PPH, its contribution to MM, and potential rescue interventions, von Drygalski and her colleagues collected data on MM, PPH, and associated risk factors from 8879 consecutive deliveries at a hospital in metropolitan Mozambique between February 2019 and January 2021.

Then, using a combined intervention strategy including the introduction of cryoprecipitate production capacity along with an early massive transfusion and standardized PPH care protocol, single-use hemorrhage boxes, and PPH education and simulations, they prospectively assessed postintervention outcomes for 6087 deliveries between October 2022 and April 2024.

Cryoprecipitate and tranexamic acid were used to intervene for PPH in 39.26% and 16.11% of cases in the pre- and postintervention phases, respectively.

The pre- and postintervention groups were similar with respect to demographic characteristics, and significant improvements were observed in MM and PPH in the postintervention group versus the preintervention group. MM rates were 1104/100,000 (1.10%) vs 279/100,000 (0.28%), and PPH rates were 14.01 vs 4.90% in the groups, respectively. Infant mortality also improved (3.44% vs 2.59%), von Drygalski, a professor of clinical medicine and director of the Hemophilia and Thrombosis Treatment Center at the University of California, San Diego, reported in an oral presentation at the 2024 American Society of Hematology conference.

Predominant factors significantly associated with PPH in both phases included eclampsia, parity greater than 4, preterm delivery, maternal age under 20 years, maternal age over 35 years, and pre-eclampsia. Uterine atony was rare, occurring in only about 1% of patients, but preceded PPH in nearly 92% of cases.

But another finding also caught the investigators’ attention: Laboratory data available from about 13% of women in the study revealed that anemia or thrombocytopenia were strongly associated with PPH both in the pre- and postintervention period, she noted.

Despite the sharp decline in postintervention PPH, moderate and severe anemia remained a strong PPH risk factor (adjusted odds ratio, 3.31), she explained.

The same was true for thrombocytopenia. The risk for PPH increased with increasing anemia and severity and was additive in the presence of thrombocytopenia, she added.

“Now, we have two studies, around the same time, that confirm the presence of this phenomenon,” she said in an interview, noting that her team communicated with the WOMAN-2 trial investigators regarding the finding. “But we don’t have a lot of explanation.”

How Do the Findings Apply Outside SSA, and Are There Implications for Future Research?

Although the rates of MM and anemia in the United States and other developed countries are low, they do occur, thus the findings have widespread applicability, von Drygalski said.

In the United States, the incidence of anemia is low and cases involving severe iron deficiency are rare. In the SSA study, those with prenatal anemia frequently had moderate or severe anemia, whereas cases in the United States tend to be milder, she explained, noting that the association between anemia and PPH was most evident when hemoglobin dropped below 10 g/dL, indicating moderate or severe anemia.

However, it is possible that anemia is underrecognized in the United States and other developed countries — and that the relationship between anemia and PPH has been missed due to the small numbers.

The SSA intervention and the WOMAN-2 trial both included very large populations, which provided the statistical power for identifying the link.

Attention to the prevention, diagnosis, and treatment of anemia in all women of reproductive age could lead to risk reduction and improved maternal health outcomes globally, she said, underscoring a need for more women’s health research in general.

Identifying the mechanism for the link between anemia and PPH is a priority, as well.

At this point, the findings “lead us to believe it is something to do with red cell physiology that we don’t really understand very well,” she noted. “Next, we have to ask, ‘Why?’”

For now, she has a message for clinicians: “P ay attention to iron deficiency in women, particularly during pregnancy.”

Nearly one in three US adults have an absolute or functional iron deficiency, but cases are often missed due to a lack of screening, according to a study published in JAMA Network Open in September. Another study, published in June in JAMA Network Open and reported by Medscape Medical News, also highlighted the underdiagnosis of nonanemic iron deficiency in women and the need for screening. 

“Iron deficiency can cause fatigue, poor functioning, and anemia, and it’s important to look for it, especially given our findings showing an association between anemia and maternal mortality — from something entirely preventable,” von Drygalski said. 

Von Drygalski reported relationships with Biomarin, Regeneron, Pfizer, Bioverativ/Sanofi, CSL-Behring, Novo Norkisk, Sparx Therapeutics, Takeda, Genentech, and Hematherix LLC. 

Sharon Worcester, MA, is an award-winning medical journalist based in Birmingham, Alabama, writing for Medscape Medical News, MDedge, and other affiliate sites. She currently covers oncology, but she has also written on a variety of other medical specialties and healthcare topics. She can be reached at sworcester@mdedge.com or on X @SW_MedReporter.