new england
The
journal of medicine
established in 1812 July 6, 2023 vol. 389 no. 1
Randomized Trial of Early Detection and Treatment
of Postpartum Hemorrhage
I. Gallos, A. Devall, J. Martin, L. Middleton, L. Beeson, H. Galadanci, F. Alwy Al‑beity, Z. Qureshi, G.J. Hofmeyr,
N. Moran, S. Fawcus, L. Sheikh, G. Gwako, A. Osoti, A. Aswat, K.-M. Mammoliti, K.N. Sindhu, M. Podesek,
I. Horne, R. Timms, I. Yunas, J. Okore, M. Singata‑Madliki, E. Arends, A.A. Wakili, A. Mwampashi, S. Nausheen,
S. Muhammad, P. Latthe, C. Evans, S. Akter, G. Forbes, D. Lissauer, S. Meher, A. Weeks, A. Shennan,
A. Ammerdorffer, E. Williams, T. Roberts, M. Widmer, O.T. Oladapo, F. Lorencatto, M.A. Bohren, S. Miller,
F. Althabe, M. Gülmezoglu, J.M. Smith, K. Hemming, and A. Coomarasamy
a bs t r ac t
BACKGROUND
Delays in the detection or treatment of postpartum hemorrhage can result in com- The authors’ full names, academic de‑
plications or death. A blood-collection drape can help provide objective, accurate, grees, and affiliations are listed in the
Appendix. Dr. Devall can be contacted
and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of at a.j.devall@bham.ac.uk or at the Insti‑
effective interventions may be able to be addressed by a treatment bundle. tute of Metabolism and Systems Re‑
search, WHO Collaborating Centre on
METHODS Global Women’s Health, College of Med‑
We conducted an international, cluster-randomized trial to assess a multicomponent ical and Dental Sciences, University of
Birmingham, 4th Fl. E., Heritage Bldg.,
clinical intervention for postpartum hemorrhage in patients having vaginal delivery. Mindelsohn Way, Edgbaston, Birmingham
The intervention included a calibrated blood-collection drape for early detection of B15 2TH, United Kingdom.
postpartum hemorrhage and a bundle of first-response treatments (uterine massage, This article was published on May 9, 2023,
oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), at NEJM.org.
supported by an implementation strategy (intervention group). Hospitals in the con- This is the New England Journal of Medi-
trol group provided usual care. The primary outcome was a composite of severe cine version of record, which includes all
postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or mater- Journal editing and enhancements. The
Author Accepted Manuscript, which is the
nal death from bleeding. Key secondary implementation outcomes were the detec- author’s version after external peer review
tion of postpartum hemorrhage and adherence to the treatment bundle. and before publication in the Journal, is
available at PubMed Central.
RESULTS
A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tan- N Engl J Med 2023;389:11-21.
DOI: 10.1056/NEJMoa2303966
zania, in which 210,132 patients underwent vaginal delivery, were randomly assigned Copyright © 2023 Massachusetts Medical Society.
to the intervention group or the usual-care group. Among hospitals and patients with
data, a primary-outcome event occurred in 1.6% of the patients in the intervention CME
at NEJM.org
group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40;
95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was
detected in 93.1% of the patients in the intervention group and in 51.1% of those in
the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle
was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28).
CONCLUSIONS
Early detection of postpartum hemorrhage and use of bundled treatment led to
a lower risk of the primary outcome, a composite of severe postpartum hemor-
rhage, laparotomy for bleeding, or death from bleeding, than usual care among
patients having vaginal delivery. (Funded by the Bill and Melinda Gates Founda-
tion; E-MOTIVE ClinicalTrials.gov number, NCT04341662.)
n engl j med 389;1 nejm.org July 6, 2023 11
The New England Journal of Medicine
Downloaded from nejm.org on July 6, 2023. For personal use only. No other uses without permission.
Copyright © 2023 Massachusetts Medical Society. All rights reserved.
, The n e w e ng l a n d j o u r na l of m e dic i n e
P
ostpartum hemorrhage, defined as strategy for the detection and treatment of post-
blood loss of at least 500 ml after birth, partum hemorrhage after vaginal delivery.
accounts for 27% of maternal deaths world-
wide.1,2 The World Health Organization (WHO) Me thods
has published and updated several evidence-
A Quick Take
is available at informed recommendations for the prevention Trial Design and Oversight
NEJM.org and treatment of postpartum hemorrhage.3,4 De- The E-MOTIVE trial was an international, parallel
spite strong efforts to adopt and scale up the use cluster-randomized trial that included a baseline
of these recommendations, postpartum hemor- control phase, along with mixed-methods evalu-
rhage remains the leading cause of maternal ation. A cluster design was necessary because the
complications and death worldwide.1,2 Three key intervention was delivered at the hospital level,
challenges contribute to this lack of progress. targeting health care providers. The trial was
The first challenge is that postpartum hemor- approved by the University of Birmingham, the
rhage is often undetected or detected late; thus Ethics Review Committee of the World Health
lifesaving treatment is not promptly initiated. In Organization (WHO) (for the formative phase),
a large, international, randomized trial of pro- and the relevant ethics and regulatory review com-
phylaxis for postpartum hemorrhage in 29,645 mittees in each country.
participants,5 only 53% of the participants in Between August and October 2021, all the
whom postpartum hemorrhage developed received participating hospitals entered a 7-month base-
a diagnosis and were treated with a uterotonic line period during which they provided usual care
drug. The current approach for blood-loss as- for postpartum hemorrhage. After this 7-month
sessment at birth is visual estimation, which is baseline period, hospitals were randomly as-
widely recognized to be inaccurate and tends to signed, in a 1:1 ratio, in a sequential manner as
underestimate blood loss.6 they approached the end of their assigned base-
The second challenge is delayed or inconsis- line phase either to continue providing usual care
tent use of interventions for the management of or to receive the trial intervention for 7 months,
postpartum hemorrhage. Treatments for post- with an allowance of 2 months for transition in
partum hemorrhage are often administered in a order to conduct training and to implement and
sequential manner; a health care provider ad- embed the intervention in practice. A minimiza-
ministers an intervention and waits to see wheth- tion algorithm that was generated by an inde-
er it has had an effect before another intervention pendent statistician was used to ensure balance
is administered.7 However, postpartum hemor- between the intervention hospitals and usual-
rhage is a time-critical condition, and delays in care hospitals within each country for key prog-
the use of lifesaving interventions can result in nostic variables, including the number of vaginal
loss of life. Some effective interventions may not births per hospital (dichotomized with the use
be used at all. For example, a survey of hospitals of the median value obtained during the base-
in Kenya, Nigeria, South Africa, and Tanzania line phase), the prevalence of primary-outcome
showed that tranexamic acid was used late and events during the baseline phase (dichotomized
most often as a last resort in women in whom with the use of the median value obtained during
surgery for postpartum hemorrhage was indi- the baseline phase), the quality of oxytocin (di-
cated.8 chotomized as high or low quality on the basis
The third challenge is that despite the avail- of the percent of active ingredient contained in
ability of clear recommendations regarding post- the product),10 and the number of hospitals per
partum hemorrhage and their wide dissemina- country (count). During the 7-month implemen-
tion, uptake is poor at the point of care.9 In tation phase, we conducted mixed-methods pro-
previous work, we identified several barriers to cess evaluations to assess implementation out-
implementation, including limited staffing, lack comes.
of relevant knowledge and skills, lack of engage- Trial oversight and monitoring were provided
ment from health care providers, and profes- by a trial steering committee and an independent
sional attitudes that discouraged task sharing.9 data monitoring committee. The first two and
To address these challenges, we designed a clus- last two authors vouch for the accuracy and com-
ter-randomized trial to assess a multicomponent pleteness of the data and for the fidelity of the
12 n engl j med 389;1 nejm.org July 6, 2023
The New England Journal of Medicine
Downloaded from nejm.org on July 6, 2023. For personal use only. No other uses without permission.
Copyright © 2023 Massachusetts Medical Society. All rights reserved.
The
journal of medicine
established in 1812 July 6, 2023 vol. 389 no. 1
Randomized Trial of Early Detection and Treatment
of Postpartum Hemorrhage
I. Gallos, A. Devall, J. Martin, L. Middleton, L. Beeson, H. Galadanci, F. Alwy Al‑beity, Z. Qureshi, G.J. Hofmeyr,
N. Moran, S. Fawcus, L. Sheikh, G. Gwako, A. Osoti, A. Aswat, K.-M. Mammoliti, K.N. Sindhu, M. Podesek,
I. Horne, R. Timms, I. Yunas, J. Okore, M. Singata‑Madliki, E. Arends, A.A. Wakili, A. Mwampashi, S. Nausheen,
S. Muhammad, P. Latthe, C. Evans, S. Akter, G. Forbes, D. Lissauer, S. Meher, A. Weeks, A. Shennan,
A. Ammerdorffer, E. Williams, T. Roberts, M. Widmer, O.T. Oladapo, F. Lorencatto, M.A. Bohren, S. Miller,
F. Althabe, M. Gülmezoglu, J.M. Smith, K. Hemming, and A. Coomarasamy
a bs t r ac t
BACKGROUND
Delays in the detection or treatment of postpartum hemorrhage can result in com- The authors’ full names, academic de‑
plications or death. A blood-collection drape can help provide objective, accurate, grees, and affiliations are listed in the
Appendix. Dr. Devall can be contacted
and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of at a.j.devall@bham.ac.uk or at the Insti‑
effective interventions may be able to be addressed by a treatment bundle. tute of Metabolism and Systems Re‑
search, WHO Collaborating Centre on
METHODS Global Women’s Health, College of Med‑
We conducted an international, cluster-randomized trial to assess a multicomponent ical and Dental Sciences, University of
Birmingham, 4th Fl. E., Heritage Bldg.,
clinical intervention for postpartum hemorrhage in patients having vaginal delivery. Mindelsohn Way, Edgbaston, Birmingham
The intervention included a calibrated blood-collection drape for early detection of B15 2TH, United Kingdom.
postpartum hemorrhage and a bundle of first-response treatments (uterine massage, This article was published on May 9, 2023,
oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), at NEJM.org.
supported by an implementation strategy (intervention group). Hospitals in the con- This is the New England Journal of Medi-
trol group provided usual care. The primary outcome was a composite of severe cine version of record, which includes all
postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or mater- Journal editing and enhancements. The
Author Accepted Manuscript, which is the
nal death from bleeding. Key secondary implementation outcomes were the detec- author’s version after external peer review
tion of postpartum hemorrhage and adherence to the treatment bundle. and before publication in the Journal, is
available at PubMed Central.
RESULTS
A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tan- N Engl J Med 2023;389:11-21.
DOI: 10.1056/NEJMoa2303966
zania, in which 210,132 patients underwent vaginal delivery, were randomly assigned Copyright © 2023 Massachusetts Medical Society.
to the intervention group or the usual-care group. Among hospitals and patients with
data, a primary-outcome event occurred in 1.6% of the patients in the intervention CME
at NEJM.org
group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40;
95% confidence interval [CI], 0.32 to 0.50; P<0.001). Postpartum hemorrhage was
detected in 93.1% of the patients in the intervention group and in 51.1% of those in
the usual-care group (rate ratio, 1.58; 95% CI, 1.41 to 1.76), and the treatment bundle
was used in 91.2% and 19.4%, respectively (rate ratio, 4.94; 95% CI, 3.88 to 6.28).
CONCLUSIONS
Early detection of postpartum hemorrhage and use of bundled treatment led to
a lower risk of the primary outcome, a composite of severe postpartum hemor-
rhage, laparotomy for bleeding, or death from bleeding, than usual care among
patients having vaginal delivery. (Funded by the Bill and Melinda Gates Founda-
tion; E-MOTIVE ClinicalTrials.gov number, NCT04341662.)
n engl j med 389;1 nejm.org July 6, 2023 11
The New England Journal of Medicine
Downloaded from nejm.org on July 6, 2023. For personal use only. No other uses without permission.
Copyright © 2023 Massachusetts Medical Society. All rights reserved.
, The n e w e ng l a n d j o u r na l of m e dic i n e
P
ostpartum hemorrhage, defined as strategy for the detection and treatment of post-
blood loss of at least 500 ml after birth, partum hemorrhage after vaginal delivery.
accounts for 27% of maternal deaths world-
wide.1,2 The World Health Organization (WHO) Me thods
has published and updated several evidence-
A Quick Take
is available at informed recommendations for the prevention Trial Design and Oversight
NEJM.org and treatment of postpartum hemorrhage.3,4 De- The E-MOTIVE trial was an international, parallel
spite strong efforts to adopt and scale up the use cluster-randomized trial that included a baseline
of these recommendations, postpartum hemor- control phase, along with mixed-methods evalu-
rhage remains the leading cause of maternal ation. A cluster design was necessary because the
complications and death worldwide.1,2 Three key intervention was delivered at the hospital level,
challenges contribute to this lack of progress. targeting health care providers. The trial was
The first challenge is that postpartum hemor- approved by the University of Birmingham, the
rhage is often undetected or detected late; thus Ethics Review Committee of the World Health
lifesaving treatment is not promptly initiated. In Organization (WHO) (for the formative phase),
a large, international, randomized trial of pro- and the relevant ethics and regulatory review com-
phylaxis for postpartum hemorrhage in 29,645 mittees in each country.
participants,5 only 53% of the participants in Between August and October 2021, all the
whom postpartum hemorrhage developed received participating hospitals entered a 7-month base-
a diagnosis and were treated with a uterotonic line period during which they provided usual care
drug. The current approach for blood-loss as- for postpartum hemorrhage. After this 7-month
sessment at birth is visual estimation, which is baseline period, hospitals were randomly as-
widely recognized to be inaccurate and tends to signed, in a 1:1 ratio, in a sequential manner as
underestimate blood loss.6 they approached the end of their assigned base-
The second challenge is delayed or inconsis- line phase either to continue providing usual care
tent use of interventions for the management of or to receive the trial intervention for 7 months,
postpartum hemorrhage. Treatments for post- with an allowance of 2 months for transition in
partum hemorrhage are often administered in a order to conduct training and to implement and
sequential manner; a health care provider ad- embed the intervention in practice. A minimiza-
ministers an intervention and waits to see wheth- tion algorithm that was generated by an inde-
er it has had an effect before another intervention pendent statistician was used to ensure balance
is administered.7 However, postpartum hemor- between the intervention hospitals and usual-
rhage is a time-critical condition, and delays in care hospitals within each country for key prog-
the use of lifesaving interventions can result in nostic variables, including the number of vaginal
loss of life. Some effective interventions may not births per hospital (dichotomized with the use
be used at all. For example, a survey of hospitals of the median value obtained during the base-
in Kenya, Nigeria, South Africa, and Tanzania line phase), the prevalence of primary-outcome
showed that tranexamic acid was used late and events during the baseline phase (dichotomized
most often as a last resort in women in whom with the use of the median value obtained during
surgery for postpartum hemorrhage was indi- the baseline phase), the quality of oxytocin (di-
cated.8 chotomized as high or low quality on the basis
The third challenge is that despite the avail- of the percent of active ingredient contained in
ability of clear recommendations regarding post- the product),10 and the number of hospitals per
partum hemorrhage and their wide dissemina- country (count). During the 7-month implemen-
tion, uptake is poor at the point of care.9 In tation phase, we conducted mixed-methods pro-
previous work, we identified several barriers to cess evaluations to assess implementation out-
implementation, including limited staffing, lack comes.
of relevant knowledge and skills, lack of engage- Trial oversight and monitoring were provided
ment from health care providers, and profes- by a trial steering committee and an independent
sional attitudes that discouraged task sharing.9 data monitoring committee. The first two and
To address these challenges, we designed a clus- last two authors vouch for the accuracy and com-
ter-randomized trial to assess a multicomponent pleteness of the data and for the fidelity of the
12 n engl j med 389;1 nejm.org July 6, 2023
The New England Journal of Medicine
Downloaded from nejm.org on July 6, 2023. For personal use only. No other uses without permission.
Copyright © 2023 Massachusetts Medical Society. All rights reserved.
