Postpartum hemorrhage: Making maternal mortality history.

Introduction: Uterotonic drugs are recommended for the prevention and treatment of postpartum hemorrhage (PPH), and oxytocin is considered the gold standard for both indications due to its established efficacy and safety. Unfortunately, access to oxytocin is still limited in many low-resource settings due to the need for cool storage, sterile equipment and administration by skilled personnel. Misoprostol, an E1 prostaglandin analog, has therefore been explored as an alternative for such settings due to its proven ability to induce uterine contractions, low cost, stability at room temperature and ease of administration.Areas covered: This review covers evidence from 51 randomized controlled trials for both prevention and treatment of PPH. It discusses efficacy and side effects in the context of the various doses that have been studied using oral, sublingual or rectal routes of administration for both indications.Expert opinion: There is now a solid body of evidence to justify the use of misoprostol for postpartum hemorrhage indications in many settings. The evidence supports use of 600 μg orally for the prevention of PPH and 800 μg sublingually for the treatment of PPH. There is no evidence to support the adjunct use of misoprostol following administration of conventional uterotonics for prevention or treatment purposes.

Background : Postpartum haemorrhage (PPH) is a leading cause of maternal mortality especially in the developing world. Misoprostol, a highly effective drug is highly effective in inducing uterine contractions and has been proposed as a low-cost, easy-to-use intervention for PPH. Objective : This study assessed evidence of the effectiveness of misoprostol for the prevention and treatment of PPH. Method : Databases searched included MEDLINE, PUBMED, CINHAL, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL) and EMBASE. Reference lists and conference proceedings were also searched for more studies. Three studies included in the meta-analysis were limited to randomised controlled trials (RCT). Two reviewers independently screened all articles for methodological quality using a standardised instrument adapted from the Cochrane Collaboration website. Data were entered in Review Manager 5.1 software for analysis. Results : Three trials (n = 2346) compared misoprostol to a placebo. Misoprostol was shown not to be effective in reducing PPH (risk ratios [RR] 0.65; 95% confidence interval [CI] 0.40-1.06). Only one trial reported on the need for a blood transfusion (RR 0.14; 95% CI 0.02-1.15). Shivering (RR 2.75; 95% CI 2.26-3.34) and pyrexia (RR 5.34; 95% CI 2.86-9.96) were significantly more common with misoprostol than with a placebo. Conclusion : The use of misoprostol was not associated with any significant reduction in the incidence of PPH. Therefore, in order to verify the efficacious use of misoprostol in the treatment of PPH, specialised investigations of its dose and routes of administration for clinically significant effects and acceptable side effects are warranted.

The evidence that early tranexamic acid treatment reduces postpartum hemorrhage deaths has major implications for obstetrical care worldwide. Tranexamic acid may also have a role in the prevention of postpartum hemorrhage, but more evidence is needed on the balance of risks and benefits. Most deaths from postpartum hemorrhage are in low- and middle-income countries where tranexamic acid treatment is often unavailable. Several maternal health organizations including the Reproductive Health Supplies Coalition, Clinton Health Access Initiative, Concept Foundation, International Federation of Gynecology andObstetrics, and Unitaid are working to increase access. However, a wider view of the evidence on tranexamic acid and bleeding shows that it can improve maternal health in many other ways. An appreciation of these other health benefits could facilitate efforts to increase access. By reducing heavy menstrual bleeding, tranexamic acid could reduce the prevalence of maternal anemia, a common and important risk factor for postpartum hemorrhage and other maternal and neonatal outcomes. Further clinical trials of tranexamic acid for the treatment of menstrual bleeding are needed. By reducing surgical bleeding and the need for blood transfusion, tranexamic acid would increase the availability of blood in countries where there is blood shortage so that more blood is available for use in life-threatening bleeding including postpartum hemorrhage. In countries where there is no blood shortage, tranexamic acid use would reduce healthcare costs and prevent transfusion-transmitted infections and reactions. Trauma affects women and men, and violence is a leading cause of death in pregnancy. Increased use of tranexamic acid in trauma would significantly reduce trauma deaths. Efforts to increase the availability and use of tranexamic acid for obstetrical hemorrhage should acknowledge its other health benefits and aim to increase its use across health services more generally.

Postpartum haemorrhage (PPH) is an obstetric emergency. While PPH-related deaths are relatively rare in high-resource settings, PPH continues to be the leading cause of maternal mortality in limited-resource settings. We undertook a systematic review to identify, assess, and synthesise cost-effectiveness evidence on postpartum interventions to prevent, diagnose, or treat PPH. This systematic review was prospectively registered on PROSPERO (CRD42023438424). We searched Medline, Embase, NHS Economic Evaluation Database (NHS EED), EconLit, CINAHL, Emcare, Web of Science, and Global Index Medicus between 22 June 2023 and 11 July 2024 with no date or language limitations. Full economic evaluations of any postpartum intervention for prevention, detection, or management of PPH were eligible. Study screening, data extraction, and quality assessments (using the CHEC-E tool) were undertaken independently by at least 2 reviewers. We developed narrative syntheses of available evidence for each intervention. From 3,993 citations, 56 studies were included: 33 studies of preventative interventions, 1 study assessed a diagnostic method, 17 studies of treatment interventions, 1 study comparing prevention and treatment, and 4 studies assessed care bundles. Twenty-four studies were conducted in high-income countries, 22 in upper or lower middle-income countries, 3 in low-income countries, and 7 studies involved countries of multiple income levels. Study settings, methods, and findings varied considerably. Interventions with the most consistent findings were the use of tranexamic acid for PPH treatment and using care bundles. In both cases, multiple studies predicted these interventions would either result in better health outcomes and cost savings, or better health outcomes at acceptable costs. Limitations for this review include that no ideal setting was chosen, and therefore, a transferability assessment was not undertaken. In addition, some sources of study uncertainty, such as effectiveness parameters, were interrogated to a greater degree than other sources of uncertainty. In this systematic review, we extracted, critically appraised, and summarised the cost-effectiveness evidence from 56 studies across 16 different interventions for the prevention, diagnosis, and treatment of PPH. Both the use of tranexamic acid as part of PPH treatment, and the use of comprehensive PPH bundles for prevention, diagnosis, and treatment have supportive cost-effectiveness evidence across a range of settings. More studies utilizing best practice principles are required to make stronger conclusions on which interventions provide the best value. Several high-priority interventions recommended by World Health Organization (WHO) such as administering additional uterotonics, non-pneumatic anti-shock garment, or uterine balloon tamponade (UBT) for PPH management require robust economic evaluations across high-, middle-, and low-resource settings.

Postpartum hemorrhage (PPH) remains a common cause of maternal mortality worldwide, mainly caused by uterine atony. Medical intervention plays an important part in prevention and therapies of PPH. Prophylactic interventions include the use of uterotonic drugs. We elaborated the consistency of national and international guidelines on those medical approaches. Medical approaches in PPH were extracted from recent publications. Furthermore, the current guidelines of the World Health Organization, the FIGO and of the American, British, Canadian and German Societies of Obstetricians and Gynecologists on PPH were analyzed. Oxytocin is considered as therapy of first choice. However, the examined guidelines fail to give unequivocal recommendations on further uterotonics in PPH, which may partially be attributed to differing publication dates of the guidelines. International guidelines on PPH are characterized by differing recommendations. However, recent publications suggest that adhering to local guidelines significantly reduces the prevalence of severe PPH.

With its headquarters situated in The Hague, the membership in ICM consists of over 83 professional autonomous midwifery associations from 65 countries.The Confederation's structure of representation and governance is built around four regions: Africa, Americas, Asia-Pacific, and Europe, the members from which elect representatives to function as a channel of communication to the headquarters office and the Board of Management.These representatives meet twice in every 3-year period.Once in each such triennium, a meeting of the International Council is also held.This is the full governing body of the Confederation with two delegates from every member association; here, they elect their officers and establish the policy that will guide the work-plan of ICM.As with many other membership confederations, the ongoing work of the ICM is delicately balanced between direct support for the members, especially those from developing countries and those where the midwifery profession is only tentatively emerging in its own right; campaigning and fund-raising; and programme work, usually input to the planning of new national initiatives in maternity, which often involves partners, such as the World Health Organisation (WHO), one of the UN agencies such as UNICEF, UNAIDS, or UNFPA, or another worldwide professional confederation such as the International Federation of Gynaecologists and Obstetricians (FIGO).The campaign banner of the ICM for the past 14 years has read 'Safe Motherhood.'The more chilling words beneath it say, "Every year about 600,000 women die in pregnancy or childbirth, hundreds of thousands more are left with long-term sickness or disability.The majority of this mortality and morbidity can be avoided with good midwifery care."Every 3 years, each strand of this interwoven work is brought together in a series of meetings and an open conference for midwives and all those interested in midwifery, the ICM's Triennial International Congress.These congresses date back to 1900 when the first was held in Berlin with over 1,000 participants from nine European countries.These early meetings, although clearly popular, were not held in regular succession.It was 1919 before they began to recur on an approximately triennial cycle, and then the pattern was broken again by the Second World War.Finally, 1954 saw a new base in London for the ICM, a new constitution, and a congress which brought midwives from around the world, not just Europe, to a meeting which started the triennial progression.The 26th ICM Triennial Congress will take place April 14 -18, 2002, in Vienna.The title is "Midwives and women together for the family of the world."This will not be the first ICM Congress to take place in Austria.In 1928, also in April, the second International Congress of Midwives took place in Vienna; delegates attended from Belgium, Great Britain, Bulgaria, Hungary, Germany, and other countries.Some of the issues raised by the participants then are still current 73 years later.Midwives are still fighting for better working conditions and better remuneration of their work; many of them struggling to keep ante-and postnatal care in their hands.Before the Congress itself starts, there will be a Pre-Congress Collaborative Workshop for invited midwives only on "Violence against girls and women."This important topic illustrates the underlying theme of the conference, which is the recognition of human rights and equality.The five themes of the programme will be education, research, midwifery practice, special issues in midwifery, and social, cultural and political issues.

The primary objective of postpartum haemorrhage (PPH) prevention and treatment is to reduce maternal deaths. Misoprostol has the major public health advantage over injectable medication that it can more easily be distributed at community level. Because misoprostol might have adverse effects unrelated to blood loss which might impact on mortality or severe morbidity, it is important to continue surveillance of all relevant evidence from randomised trials. This is particularly important as misoprostol is being introduced on a large scale for PPH prevention in low-income countries, and is commonly used for PPH treatment in well-resourced settings as well. To review maternal deaths and severe morbidity in all randomised trials of misoprostol for prevention or treatment of PPH. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (11 January 2013). We included randomised trials including pregnant women who received misoprostol in the postpartum period, versus placebo/no treatment or other uterotonics for prevention or treatment of PPH, and reporting on maternal death, severe morbidity or pyrexia.We planned to include cluster- and quasi-randomised trials in the analysis, as a very large number of women will be needed to obtain robust estimates of maternal mortality but we did not identify any for this version of the review. In future updates of this review we will include trials reported only as abstracts if sufficient information is available from the abstract or from the authors. Two review authors independently assessed trials for inclusion and extracted data. We included 78 studies (59,216 women) and excluded 34 studies.There was no statistically significant difference in maternal mortality for misoprostol compared with control groups overall (31 studies; 11/19,715 versus 4/20,076 deaths; risk ratio (RR) 2.08, 95% confidence interval (CI) 0.82 to 5.28); or for the trials of misoprostol versus placebo: 10 studies, 6/4626 versus 1/4707 ; RR 2.70; 95% CI 0.72 to 10.11; or for misoprostol versus other uterotonics: 21 studies, 5/15,089 versus 3/15,369 (19/100,000); RR 1.54; 95% CI 0.40 to 5.92. All 11 deaths in the misoprostol arms occurred in studies of misoprostol ≥ 600 µg.There was a statistically significant difference in the composite outcome 'maternal death or severe morbidity' for the comparison of misoprostol versus placebo (12 studies; average RR 1.70, 95% CI 1.02 to 2.81; Tau² = 0.00, I² = 0%) but not for the comparison of misoprostol versus other uterotonics (17 studies; average RR 1.50, 95% CI 0.50 to 4.52; Tau² = 1.81, I² = 69%). When we excluded hyperpyrexia from the composite outcome in exploratory analyses, there was no significant difference in either of these comparisons.Pyrexia > 38°C was increased with misoprostol compared with controls (56 studies, 2776/25,647 (10.8%) versus 614/26,800 (2.3%); average RR 3.97, 95% CI 3.13 to 5.04; Tau² = 0.47, I² = 80%). The effect was greater for trials using misoprostol 600 µg or more (27 studies; 2197/17,864 (12.3%) versus 422/18,161 (2.3%); average RR 4.64; 95% CI 3.33 to 6.46; Tau² = 0.51, I² = 86%) than for those using misoprostol 400 µg or less (31 studies; 525/6751 (7.8%) versus 185/7668 (2.4%); average RR 3.07; 95% CI 2.25 to 4.18; Tau² = 0.29, I² = 58%). Misoprostol does not appear to increase or reduce severe morbidity (excluding hyperpyrexia) when used to prevent or treat PPH. Misoprostol did not increase or decrease maternal mortality. However, misoprostol is associated with an increased risk of pyrexia, particularly in dosages of 600 µg or more. Given that misoprostol is used prophylactically in very large numbers of healthy women, the greatest emphasis should be placed on limiting adverse effects. In this context, the findings of this review support the use of the lowest effective dose. As for any new medication being used on a large scale, continued vigilance for adverse effects is essential and there is a need for large randomised trials to further elucidate both the relative effectiveness and the risks of various dosages of misoprostol.

Postpartum hemorrhage (PPH) remains one of the main causes of maternal morbidity and mortality worldwide, despite the progress of medical science and the introduction of new methods of diagnosis and therapy of hemorrhagic complications during pregnancy, childbirth and the postpartum period. Aim - to familiarize the general public with the latest recommendations of the International Federation of Gynecology and Obstetrics (FIGO, 2022) and our own experience regarding the most effective and evidence-based methods of diagnosis, therapy and prevention of PPH. Postpartum hemorrhage is classified into primary (early), which occurs when more than 500 ml of blood is lost during the first 24 hours after childbirth, and secondary (late), which occurs after 24 hours and up to 6 weeks after childbirth. The initial examination of the patient should include a rapid clinical assessment and analysis of risk factors. In order to objectify the volume of blood loss according to FIGO recommendations, the shock index (SI) should be used. Treatment should be directed at the specific cause of PPH (uterine atony, genital trauma, retained placenta and/or coagulopathy), and therapeutic steps should move from a less invasive method to a more complex and radical approach. In the case of refractory PPH, it is necessary to use the most effective modern methods of surgical hemostasis: ligation of the main uterine vessels, compression sutures on the uterus, bilateral ligation of the internal iliac arteries, methods of remodeling the lower uterine segment (LUS-1,2). The paradigm of infusion-transfusion therapy for massive PPH has changed, which is based on the concept of damage control resuscitation (DCR), which is based on warming the parturient, limited use of crystalloids, permissive hypotension tactics, early initiation of blood product transfusion, use of massive blood transfusion protocols, and targeted correction of coagulopathy. PPH prevention strategies include prenatal identification of risk factors, correction of anemia during pregnancy, active management of the third stage of labor, and intravenous administration of tranexamic acid. Conclusions. The implementation of the latest FIGO recommendations for the prevention, diagnosis, and treatment of PPH in the practice of obstetric facilities in the country will contribute to reducing maternal morbidity and mortality. The authors declare no conflict of interest.

Variation in adherence to recommendations for management of the third stage of labor

Misoprostol, a synthetic prostaglandin E1 has wider application in obstetrics gynaecology. It has been recommended in the prophylaxis and treatment of Post Partum Haemorrhage (PPH) by Federation of Obstetrics and Gynaecology (FIGO), World Health Organisation (WHO) and American College of Obstetrics and Gynaecology (ACOG). It is a very safe drug associated with transient side-effects like fever, chills, nausea, vomiting, diarrhoea and abdominal pain. In the present case report patient had an unusual side effect of hyperpyrexia and convulsion after use of misoprostol for prophylaxis against PPH.

Effectiveness of care bundles for prevention and treatment of postpartum hemorrhage: a systematic review

Proteolytic Cleavage of the CD44 Adhesion Molecule in Multiple Human Tumors

ObjectiveAccess to quality, effective lifesaving uterotonics in low and middle-income countries (LMICs) remains a major barrier to reducing maternal deaths from postpartum haemorrhage (PPH). Our objective was to assess the costs of care for women who receive different preventative uterotonics, and with PPH and no-PPH so that the differences, if significant, can inform better resource allocation for maternal health care.MethodsThe costs of direct hospital care of women who received oxytocin or heat-stable carbetocin for prevention of PPH in selected tertiary care facilities in India, Kenya, Nigeria, and Uganda were assessed. We collected data from all women who had PPH, as well as a random sample of women without PPH. Cost data was collected for the cost of stay, PPH interventions, transfusions and medications for 2966 women. We analyzed the difference in cost of care at a facility level between women who experienced a PPH event and those who did not.Key findingsThe mean cost of care of a woman experiencing PPH in the study sites in India, Kenya, Nigeria, and Uganda exceeded the cost of care of a woman who did not experience PPH by between 21% and 309%. There was a large variation in cost across hospitals within a country and across countries.ConclusionOur results quantify the increased cost of PPH of up to 4.1 times that for a birth without PPH. PPH cost information can help countries to evaluate options across different conditions and in the formulation of appropriate guidelines for intrapartum care, including rational selection of quality-assured, effective medicines. This information can be applied to national assessment and adaptation of international recommendations such as the World Health Organization’s recommendations on uterotonics for the prevention of PPH or other interventions used to treat PPH. Trial registration HRP Trial A65870; UTN U1111-1162-8519; ACTRN12614000870651; CTRI/2016/05/006969, EUDRACT 2014–004445-26. Date of registration 14 August 2014Plain English summaryAccess to quality, effective lifesaving medicines in low and middle-income countries remains a major barrier to reducing maternal deaths from bleeding after childbirth. Information on to what extent treatments for bleeding increases the cost of care of women after childbirth is important for informed resource allocation.We collected data from all women who had bleeding after childbirth, as well as a random sample of women without bleeding in selected hospitals in India, Kenya, Nigeria, and Uganda. Cost data was collected for the cost of stay and interventions to manage bleeding for 2966 women. We compared the difference in cost of care between women who experienced a bleeding event and those who did not.The mean cost of care of a woman with bleeding in the study sites exceeded the cost of care of a woman who did not experience PPH by between 21% and 309%. There was a large variation in cost across hospitals within a country and across countries.Our results indicate an increased cost of bleeding of up to 4.1 times that for birth without bleeding. Effective prevention reduces the cost of care. Cost information can help countries to evaluate options across different conditions and in the formulation of appropriate guidelines for intrapartum care, including rational selection of quality-assured, effective medicines. This information can be applied to national assessment and adaptation of international recommendations such as the World Health Organization’s recommendations on medications for the prevention of bleeding after childbirth or other interventions used to treat bleeding.

Background & objective: Of the many pharmacological options for the management of postpartum hemorrhage, oxytocin is the first line of treatment. The newer drug carbetocin is getting popularity among obstetricians, although there is as yet not enough evidence about its safety and efficacy. The present study attempted to compare oxytocin with carbetocin for the routine prevention of postpartum hemorrhage (PPH) following caesarean section.
 Methods: The present comparative clinical trial was conducted in the Department of Obstetrics and Gynaecology in Rajshahi Medical College Hospital (RMCH), Rajshahi over a period of one year between March 2017 to February 2018. Pregnant women undergoing cesarean section under regional anaesthesia and do not have known hypersensitivity to oxytocin and carbetocin and known bleeding disorders were included in the study. A total of 96 such subjects were consecutively included and were randomly assigned to either Oxytocin (n = 48) and Carbetocin (n = 48) Groups. The outcome was evaluated in terms of incidence of PPH (loss of blood > 1000 ml), blood transfusion needed to compensate for lost blood, additional oxytocics needed to manage PPH and adverse effects encountered by the subjects.
 Result: The mean age of the subjects was around 25 years and the age distribution between the study groups was almost similar. In terms of obstetric characteristics multigravida was predominant in the Oxytocin group than that in the Carbetocin group. The current pregnancy profile like gestational age, ANC received, number of foetus in utero and placental position all were comparable between the groups. Antenatal conditions/diseases deemed to have influence on PPH were no different between the study groups. Past history of caesarean section was higher in Oxytocin group (43.8%) than that in the Carbetocin group (22.9%). There were negligible incidences of past PPH and myomectomy in either group. The mean haemoglobin level in the former and the latter groups were 9.5 and 10 gm/dl respectively with majority of the subjects being mildly anaemic. More than 80% of the subjects in either group underwent emergency caesarean section. The outcome showed that 83% in the Oxytocin group and 90% in the Carbetocin group did not develop PPH, but the difference was not significant. The mean blood lost was somewhat lower in the carbetocin group (630 ml) than that in the Oxytocin group (685 ml). The number of patients needed to be transfused and the mean amount of blood transfused to them in each group was fairly comparable. Oxytocin group received additional oxytocic drugs, such as, Metherspan and Misoprostol more frequently than the Carbetocin group did, but the differences did not turn significant. A few patients in both groups developed adverse effects but they were comparable. The mean 24-hours urine output was > 2000 ml in either group).
 Conclusion: The study concluded that the incidence of PPH, the amount of blood lost, number of patients transfused, amount of blood transfused and the additional amount of oxytocics required for the prevention and treatment of PPH were broadly comparable between the two study groups.
 Ibrahim Card Med J 2021; 11 (1): 71-78

The purpose of this review is to synthetize the latest evidence on the pharmacological management of postpartum hemorrhage (PPH) and apply it to the clinical context. The incidence of PPH in the developed world is rising. Oxytocin and its analogue carbetocin remain the number one choice as first-line uterotonics for the prevention of PPH due to excellent clinical efficacy and a favorable side effect profile. Doses of oxytocin and carbetocin currently recommended for prophylaxis are in excess to that required for clinical efficacy. There is no robust evidence suggesting that one second-line uterotonic drug is superior to another. Tranexamic acid is safe and highly effective and should be administered both for cases at high risk for PPH as well as early in established hemorrhage. Choosing a uterotonic drug strategy that uses the most appropriate agent in the clinical context at the minimal effective dose is essential for improving maternal safety and the quality of postpartum care.