Randomized Trial of Early Detection and Treatment of Postpartum Hemorrhage.

BACKGROUND: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. METHODS: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. RESULTS: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned 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 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 hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.).

Differences in obstetric practices and outcomes of postpartum hemorrhage across Nigerian health facilities.

OBJECTIVE: To explore differences in obstetric practices and clinical outcomes of postpartum hemorrhage (PPH) in Nigerian facilities. METHODS: A descriptive cross-sectional study of public health facilities providing maternal healthcare services in Nigeria. Surveys were conducted across 38 purposively sampled facilities (January 2020-March 2021) to collect information on obstetric practices related to the management of the third stage of labor, treatment of postpartum hemorrhage, and clinical outcomes related to postpartum hemorrhage in the preceding 12 months. RESULTS: The median number of annual births per facility was 2230 (IQR, 1952-3283). The cesarean section rate was 21.6% (range 2.1%-52.6%). There was large variability in PPH rate (median 3%, range 0.4%-16.8%) and blood transfusions for PPH (median 2.8%, range 0.4%-48.6%) after vaginal birth. There was less variability for laparotomies (median 0.25%, range 0%-2.8%) and maternal deaths (median 0.11%, range 0%-0.64%) due to PPH after vaginal birth. The number of maternal deaths from all causes varied (median 0.27%, range 0%-3.5%). The rates of PPH and adverse maternal outcomes did not vary substantially between state or federal facilities, region, type of facility, and the number of clinical staff. CONCLUSION: Across the Nigerian facilities surveyed there was large variation in PPH rates and adverse maternal outcomes due to PPH. This variability remains largely unexplained and requires further insights and detailed data to gain a deeper understanding of the root causes and challenges to implement customized solutions to improve maternal outcomes.

Quality of oxytocin and tranexamic acid for the prevention and treatment of postpartum hemorrhage in Kenya, Nigeria, South Africa, and Tanzania.

OBJECTIVE: To check the quality of oxytocin and tranexamic acid-two recommended products for prevention and treatment of postpartum hemorrhage (PPH)-used in facilities taking part in an implementation research project to improve PPH diagnosis and management. METHODS: Between September 2020 and August 2021, oxytocin and tranexamic acid products used in the study facilities in Kenya, Nigeria, South Africa, and Tanzania were collected and transported in cold storage for analysis. Samples were analyzed according to the International (oxytocin) and British Pharmacopeia (tranexamic acid) standards. RESULTS: Of the 17 unique oxytocin products, 33 individual measurements were made. Only six unique products had adequate content and no related substances exceeding the recommended limits. Of 14 tranexamic acid samples, 10 showed adequate content. One product in Kenya and two products in Nigeria from different manufacturers had a high content of related substances, which classified them as substandard. CONCLUSION: While we were unable to investigate the origin regarding poor manufacturing or poor storage or both, the high number of substandard oxytocin samples is of great concern. Most of the tranexamic acid samples had adequate content but the presence of impurities in multiple products is worrying and requires further study.

Top-down or bottom-up regulation of intra-host blood-stage malaria: do malaria parasites most resemble the dynamics of prey or predator?

Knowledge of the factors that limit parasite numbers offers hope of improved intervention strategies as well as exposing the selective forces that have shaped parasite life-history strategies. We develop a theoretical framework with which to consider the intra-host regulation of malaria parasite density. We analyse a general model that relates timing and magnitude of peak parasite density to initial dose under three different regulatory processes. The dynamics can be regulated either by top-down processes (upgradable immune regulation), bottom-up processes (fixed immune response and red blood cell (RBC) limitation) or a mixture of the two. We define and estimate the following key parameters: (i) the rate of RBC replenishment; (ii) the rate of destruction of uninfected RBCs; and (iii) the maximum parasite growth rate. Comparing predictions of this model with experimental results for rodent malaria in laboratory mice allowed us to reject functional forms of immune upregulation and/or effects of RBC limitation that were inconsistent with the data. Bottom-up regulation alone was insufficient to account for observed patterns without invoking either localized depletion of RBC density or merozoite interference. By contrast, an immune function upregulated in proportion to either merozoite or infected RBC density was consistent with observed dynamics. An immune response directed solely at merozoites required twice the level of activation of one directed at infected RBCs.