Abstract

OBJECTIVE To assess the benefits and safety of early human fibrinogen concentrate in postpartum haemorrhage (PPH) management. DESIGN Multicentre, double-blind, randomized placebo-controlled trial. SETTING 30 French hospitals. POPULATION patients with persistent PPH after vaginal delivery requiring a switch from oxytocin to prostaglandins. METHODS Within 30 min after introduction of prostaglandins, patients received either 3 g fibrinogen concentrate or placebo. MAIN OUTCOME MEASURES Failure as composite primary efficacy endpoint: at least 4 g/dL of haemoglobin decrease and/or transfusion of at least 2 units of packed red blood cells within 48h following investigational medicinal product administration. Secondary endpoints: PPH evolution, need for haemostatic procedures, and maternal morbidity-mortality within 6±2 weeks after delivery. RESULTS 437 patients were included : 224 received FC and 213 placebo. At inclusion, blood loss (877 ± 346mL) and plasma fibrinogen (4.1 ± 0.9g/L) were similar in both groups (mean ± SD). Failure rates were 40.0% and 42.4% in the Fibrinogen and placebo groups, respectively (OR=0.99) after adjustment for centre and baseline plasma fibrinogen; (95%CI: [0.66;1.47]; p=0.96). No significant differences in secondary efficacy outcomes were observed. The mean plasma FG was unchanged in the Fibrinogen group and decreased by 0.56 g/L in the placebo group. No thromboembolic or other relevant adverse effects were reported in the Fibrinogen group, versus two in the placebo group. CONCLUSIONS As previous placebo-controlled studies findings, early and systematic administration of 3 g fibrinogen concentrate did not reduce blood loss, transfusion needs, and postpartum anaemia, but prevented plasma fibrinogen decrease without any subsequent thromboembolic events.

Abstract

INTRODUCTION Postpartum hemorrhage (PPH) has remained the leading cause of maternal mortality. While anemia is a leading contributor to maternal morbidity, molecular, cellular and anemia-induced hypoxia, clinical studies of the relationship between prenatal-anemia and PPH have reported conflicting results. Therefore, our objective was to investigate the outcomes of studies on the relationships between prenatal anemia and PPH-related mortality. MATERIALS AND METHODS Electronic databases (MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE, and the Cochrane Central Register of Controlled Trials) were searched for studies published before August 2019. Keywords included "anemia," "hemoglobin," "postpartum hemorrhage," and "postpartum bleeding." Only studies involving the association between anemia and PPH were included in the meta-analysis. Our primary analysis used random effects models to synthesize odds-ratios (ORs) extracted from the studies. Heterogeneity was formally assessed with the Higgins' I(2) statistics, and explored using meta-regression and subgroup analysis. RESULTS We found 13 eligible studies investigating the relationship between prenatal anemia and PPH. Our findings suggest that severe prenatal anemia increases PPH risk (OR = 3.54; 95% CI: 1.20, 10.4, p-value = 0.020). There was no statistical association with mild (OR = 0.60; 95% CI: 0.31, 1.17, p-value = 0.130), or moderate anemia (OR = 2.09; 95% CI: 0.40, 11.1, p-value = 0.390) and the risk of PPH. CONCLUSION Severe prenatal anemia is an important predictive factor of adverse outcomes, warranting intensive management during pregnancy. PROSPERO Registration Number: CRD42020149184; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=149184.

Abstract

INTRODUCTION Postpartum hemorrhage (PPH) is the most important concern after delivery. Tranexamic acid (TXA), an anti-fibrinolytic agent, has been suggested for prevention and treatment of PPH. OBJECTIVE The purpose of the present study was to find the effects of TXA on the amount of bleeding following vaginal delivery and its adverse effects. MATERIALS AND METHODS The study was performed as a randomized double blind placebo controlled clinical trial on low risk pregnant women who delivered vaginally. The patients were randomly assigned into two groups. Women in the intervention group received 10 mg/kg infusion of TXA in 100 mL normal saline and the control group received one vial of distilled water (as placebo) in 100 mL normal saline. The primary outcome was amount of bleeding after delivery. The secondary outcomes were decreased in hemoglobin level, need for additional uterotonic agents and need for blood transfusion. All were evaluated 6 h after delivery and compared in the two groups. Participants were followed up to six weeks after delivery for any TXA side effects. RESULTS Two hundred and seven women finished the study. There were no significant differences between the two groups in terms of demographic data and risk factors for bleeding. Mean blood loss and need to misoprostol was more in the control group (p=.033 and p=.000, respectively). Hemoglobin level was higher in the TXA group 6 h after delivery. None of the subjects needed blood transfusion, uterine balloon tamponade or emergency hysterectomy. Adverse effects were higher in the TXA group, however, there were no side effects between weeks 3 and 6 in both groups. There were no thromboembolic events during six weeks after delivery. CONCLUSIONS Tranexamic acid can reduce the amount of bleeding after vaginal delivery in low risk women without having serious complications. Also, it may decrease the need for additional uterotonic agents. Trial registration number and registry website: IRCT20091023002624N22.

Abstract

BACKGROUND Postpartum hemorrhage (PPH) is responsible for nearly one quarter of maternal deaths. A 2017 multicountry trial found that incorporating tranexamic acid (TXA) into the PPH management package was effective in reducing maternal death due to bleeding. OBJECTIVE To systematically review studies assessing the cost-effectiveness of tranexamic acid for PPH treatment. SEARCH STRATEGY Nine databases were searched using variations of keywords 'tranexamic acid', 'postpartum hemorrhage' and 'cost effectiveness'. SELECTION CRITERIA Eligible studies were any type of economic or effectiveness evaluation studies on tranexamic acid for treating women with PPH. DATA COLLECTION AND ANALYSIS Two reviewers independently screened citations and extracted data on cost effectiveness measures. Quality was assessed using the Consensus on Health Economic Criteria list. MAIN RESULTS Four studies were included, of which two were abstracts. Three studies concluded that early administration of TXA was cost-saving or cost-effective. One abstract reported TXA was not cost-effective in the USA unless the probability of death due to hemorrhage is higher. CONCLUSION Available evidence (four studies in three countries) suggests that this life-saving intervention may be below willingness to pay thresholds (cost-effective) or cost saving. Further studies conducted in different populations and settings are needed to inform health policy decision-making to reduce PPH-associated morbidity and mortality.

Abstract

OBJECTIVES To explore how childbirth-related blood loss is evaluated and excessive bleeding recognised; and develop and test a theory of postpartum haemorrhage (PPH) diagnosis. DESIGN Two-phase, exploratory, sequential mixed methods design using focus groups, interviews and a pilot, randomised crossover study. SETTING Two hospitals in North West England. SAMPLE Women (following vaginal birth with and without PPH), birth partners, midwives and obstetricians. METHODS Phase 1 (qualitative): 8 focus groups and 20 one-to-one, semi-structured interviews were conducted with 15 women, 5 birth partners, 11 obstetricians, 1 obstetric anaesthetist and 19 midwives (n=51). Phase 2 (quantitative): 11 obstetricians and 10 midwives (n=21) completed two simulations of fast and slow blood loss using a high-fidelity childbirth simulator. RESULTS Responses to blood loss were described as automatic, intuitive reactions to the speed, nature and visibility of blood flow. Health professionals reported that quantifying volume was most useful after a PPH diagnosis, to validate intuitive decisions and guide on-going management. During simulations, PPH treatment was initiated at volumes at or below 200ml (fast mean blood loss 79.6ml, SD 41.1; slow mean blood loss 62.6ml, SD 27.7). All participants treated fast, visible blood loss, but only half treated slow blood loss, despite there being no difference in volumes (difference 18.2ml, 95% CI -5.6 to 42.2ml, p=0.124). CONCLUSIONS Experience and intuition, rather than blood loss volume, inform recognition of excessive blood loss after birth. Women and birth partners want more information and open communication about blood loss. Further research exploring clinical decision-making and how to support it is required.

Abstract

Hemolytic disease of fetus and newborn (HDFN) imposes great healthcare burden being associated with maternal alloimmunization against parental-inherited fetal red blood cell antigens causing fetal anemia or death. Noninvasive prenatal analysis (NIPT) provides safe fetal RHD genotyping for early identification of risk pregnancies and proper management guidance. We aimed to conduct systematic review and meta-analysis on NIPT's beneficial application, in conjunction with quantitative maternal alloantibody analysis, for early diagnosis of pregnancies at risk. Search for relevant articles was done in; PubMed/Medline, Scopus, and Ovid (January 2006April 2020), including only English-written articles reporting reference tests and accuracy data. Nineteen eligible studies were critically appraised. NIPT was estimated highly sensitive/specific for fetal RHD genotyping beyond 11-week gestation. Amplifications from ≥2 exons are optimum to increase accuracy. NIPT permits cost-effectiveness, precious resources sparing, and low emotional stress. Knowledge of parental ethnicity is important for correct NIPT result interpretations and quantitative screening. Cut-off titer ≥8-up-to-32 is relevant for anti-D alloantibodies, while, lower titer is for anti-K. Alloimmunization is influenced by maternal RHD status, gravida status, and history of adverse obstetrics. In conclusion, NIPT allows evidence-based provision of routine anti-D immunoprophylaxis and estimates potential fetal risks for guiding further interventions. Future large-scale studies investigating NIPT's non-RHD genotyping within different ethnic groups and in presence of clinically significant alloantibodies are needed.

Abstract

OBJECTIVE This study was aimed to determine if confirmation bias affects diagnoses in obstetrics, specifically estimation of blood loss and amniotic fluid volume. STUDY DESIGN We performed a randomized simulation-based trial. Participants went through the following three consecutive scenarios: (1) the first involved estimating the volume of blood (actually a blood-like substance) in a container at the simulation model's perineum. The actual volume was either 500 or 1,500 mL. Participants were told it was blood seen after a vaginal delivery. One group was told that the "patient" was normotensive, the other was told that the "patient" was hypotensive. (2) The second scenario involved estimation of amniotic fluid from an ultrasound picture of four quadrants, with one group told that the patient was normotensive and the other group told that the patient had chronic hypertension. (3) The third scenario was a "negative image" of the first (i.e., if they had been randomized to the 500 mL/normotensive in scenario one, then they would be presented with the 1,500 mL/hypotensive). They also filled a survey including demographics and tolerance of ambiguity and confirmation bias scales. RESULTS From April 2018 through May 2018, a convenience sample of 85 providers was recruited. Participants were more likely to overestimate blood loss when they were told that the patient was hypotensive (p = 0.024), in comparison to when they were told the patient had normal blood pressure. They were also less likely to estimate the amniotic fluid as normal when they were told that the patient was hypertensive (p = 0.032). CONCLUSION Confirmation bias affects estimates of blood loss and amniotic fluid.

Abstract

BACKGROUND The American Academy of Blood Banks recommends single-unit red cell transfusion protocols across medicine to reduce transfusion complications and use of a scarce resource. There is minimal data regarding single-unit protocols within obstetrics. OBJECTIVE We aimed to compare a single- vs. multiple-unit transfusion protocol for treatment of hemodynamically stable postpartum anemia. STUDY DESIGN We performed a randomized trial comparing initial transfusion with 1 unit of packed red blood cells [pRBCs] (single-unit protocol) to 2 units of pRBCs (multiple-unit protocol) from 3/2018-7/2019. Postpartum women >6 hours from delivery who required transfusion were approached for consent. Unstable vital signs, hemoglobin(Hb)< 5g/dL, hemoglobinopathy, and cardiomyopathy were enrollment exclusions. Hemoglobin assessment and standardized clinical evaluation were performed 4-6 hours post-transfusion; additional pRBCs were given if indicated. The primary outcome was total units transfused. Secondary outcomes include length of stay, endometritis, wound separation/infection, venous thromboembolism, and intensive care unit admission within 30 days postpartum. Breastfeeding, depression, maternal attachment, and fatigue scores were assessed at 4-9 weeks postpartum. 66 women were required to detect a 20% reduction in units transfused with a single-unit protocol (power=80%; alpha=0.05). RESULTS 66 women were randomized (33/arm). There were no differences between groups in demographic or clinical characteristics, including delivery mode, blood loss, and randomization Hb. Mean number of units transfused was lower in the single- compared to the multiple-unit protocol (1.2u vs. 2.1u, p< 0.001). Only 18.2% of women in the single-unit arm required additional pRBCs. At post-transfusion assessment, women in the single-unit arm had lower Hb (7.8g/dL vs. 8.7g/dL, p< 0.001), but there were no differences in vital signs or symptoms between groups. There were also no differences in length of stay, 30-day complications, or 4-9 week postpartum outcomes. CONCLUSION In women with hemodynamically stable postpartum anemia, a single-unit protocol avoids a second unit of pRBCs in >80% of women without significant impact on morbidity. Our work supports use of single-unit initial transfusion in this population.

Abstract

BACKGROUND Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more after birth, is the leading cause of maternal death worldwide. The World Health Organization (WHO) recommends that all women giving birth should receive a prophylactic uterotonic agent. Despite the routine administration of a uterotonic agent for prevention, PPH remains a common complication causing one-quarter of all maternal deaths globally. When prevention fails and PPH occurs, further administration of uterotonic agents as 'first-line' treatment is recommended. However, there is uncertainty about which uterotonic agent is best for the 'first-line' treatment of PPH. OBJECTIVES To identify the most effective uterotonic agent(s) with the least side-effects for PPH treatment, and generate a meaningful ranking among all available agents according to their relative effectiveness and side-effect profile. SEARCH METHODS We searched the Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (5 May 2020), and the reference lists of all retrieved studies. SELECTION CRITERIA All randomised controlled trials or cluster-randomised trials comparing the effectiveness and safety of uterotonic agents with other uterotonic agents for the treatment of PPH were eligible for inclusion. DATA COLLECTION AND ANALYSIS Two review authors independently assessed all trials for inclusion, extracted data and assessed each trial for risk of bias. Our primary outcomes were additional blood loss of 500 mL or more after recruitment to the trial until cessation of active bleeding and the composite outcome of maternal death or severe morbidity. Secondary outcomes included blood loss-related outcomes, morbidity outcomes, and patient-reported outcomes. We performed pairwise meta-analyses and indirect comparisons, where possible, but due to the limited number of included studies, we were unable to conduct the planned network meta-analysis. We used the GRADE approach to assess the certainty of evidence. MAIN RESULTS Seven trials, involving 3738 women in 10 countries, were included in this review. All trials were conducted in hospital settings. Randomised women gave birth vaginally, except in one small trial, where women gave birth either vaginally or by caesarean section. Across the seven trials (14 trial arms) the following agents were used: six trial arms used oxytocin alone; four trial arms used misoprostol plus oxytocin; three trial arms used misoprostol; one trial arm used Syntometrine® (oxytocin and ergometrine fixed-dose combination) plus oxytocin infusion. Pairwise meta-analysis of two trials (1787 participants), suggests that misoprostol, as first-line treatment uterotonic agent, probably increases the risk of blood transfusion (risk ratio (RR) 1.47, 95% confidence interval (CI) 1.02 to 2.14, moderate-certainty) compared with oxytocin. Low-certainty evidence suggests that misoprostol administration may increase the incidence of additional blood loss of 1000 mL or more (RR 2.57, 95% CI 1.00 to 6.64). The data comparing misoprostol with oxytocin is imprecise, with a wide range of treatment effects for the additional blood loss of 500 mL or more (RR 1.66, 95% CI 0.69 to 4.02, low-certainty), maternal death or severe morbidity (RR 1.98, 95% CI 0.36 to 10.72, low-certainty, based on one study n = 809 participants, as the second study had zero events), and the use of additional uterotonics (RR 1.30, 95% CI 0.57 to 2.94, low-certainty). The risk of side-effects may be increased with the use of misoprostol compared with oxytocin: vomiting (2 trials, 1787 participants, RR 2.47, 95% CI 1.37 to 4.47, high-certainty) and fever (2 trials, 1787 participants, RR 3.43, 95% CI 0.65 to 18.18, low-certainty). According to pairwise meta-analysis of four trials (1881 participants) generating high-certainty evidence, misoprostol plus oxytocin makes little or no difference to the use of additional uterotonics (RR 0.99, 95% CI 0.94 to 1.05) and to blood transfusion (RR 0.95, 95% CI 0.77 to 1.17) compared with oxytocin. We cannot rule out an important benefit of using the misoprostol plus oxytocin combination over oxytocin alone, for additional blood loss of 500 mL or more (RR 0.84, 95% CI 0.66 to 1.06, moderate-certainty). We also cannot rule out important benefits or harms for additional blood loss of 1000 mL or more (RR 0.76, 95% CI 0.43 to 1.34, moderate-certainty, 3 trials, 1814 participants, one study reported zero events), and maternal mortality or severe morbidity (RR 1.09, 95% CI 0.35 to 3.39, moderate-certainty). Misoprostol plus oxytocin increases the incidence of fever (4 trials, 1866 participants, RR 3.07, 95% CI 2.62 to 3.61, high-certainty), and vomiting (2 trials, 1482 participants, RR 1.85, 95% CI 1.16 to 2.95, high-certainty) compared with oxytocin alone. For all outcomes of interest, the available evidence on the misoprostol versus Syntometrine® plus oxytocin combination was of very low-certainty and these effects remain unclear. Although network meta-analysis was not performed, we were able to compare the misoprostol plus oxytocin combination with misoprostol alone through the common comparator of oxytocin. This indirect comparison suggests that the misoprostol plus oxytocin combination probably reduces the risk of blood transfusion (RR 0.65, 95% CI 0.42 to 0.99, moderate-certainty) and may reduce the risk of additional blood loss of 1000 mL or more (RR 0.30, 95% CI 0.10 to 0.89, low-certainty) compared with misoprostol alone. The combination makes little or no difference to vomiting (RR 0.75, 95% CI 0.35 to 1.59, high-certainty) compared with misoprostol alone. Misoprostol plus oxytocin compared to misoprostol alone are compatible with a wide range of treatment effects for additional blood loss of 500 mL or more (RR 0.51, 95% CI 0.20 to 1.26, low-certainty), maternal mortality or severe morbidity (RR 0.55, 95% CI 0.07 to 4.24, low-certainty), use of additional uterotonics (RR 0.76, 95% CI 0.33 to 1.73, low-certainty), and fever (RR 0.90, 95% CI 0.17 to 4.77, low-certainty). AUTHORS' CONCLUSIONS The available evidence suggests that oxytocin used as first-line treatment of PPH probably is more effective than misoprostol with less side-effects. Adding misoprostol to the conventional treatment of oxytocin probably makes little or no difference to effectiveness outcomes, and is also associated with more side-effects. The evidence for most uterotonic agents used as first-line treatment of PPH is limited, with no evidence found for commonly used agents, such as injectable prostaglandins, ergometrine, and Syntometrine®.

Abstract

BACKGROUND The latest basic studies and clinical evidence have confirmed the safety and efficacy of intraoperative autologous blood cell transfusion in cardiac surgery and orthopaedics. However, in caesarean section, there are still concerns about the contamination of amniotic fluid and foetal components, and consequently the application of intraoperative autologous blood cell transfusion is not universal. Therefore, this study aimed to evaluate the clinical value of intraoperative autologous blood cell transfusion in obstetric surgery. METHODS A prospective, randomized, controlled, feasibility study was performed in women undergoing caesarean section. One hundred sixteen participants were randomly assigned at a 1:1 ratio into either the intraoperative cell salvage group or the control group. Allogeneic blood cells were transfused into patients with haemoglobin concentrations < 80 g/dL in both the intraoperative cell salvage group and the control group. RESULTS No significant differences were found between the two groups in age, weight, maternal parity, history of previous caesarean section, gestational weeks of delivery, etc. However, compared with the control group, patients in the intraoperative cell salvage group had a significantly lower amount of allogeneic blood cell transfusion, lower incidence of postoperative incision infection, delayed wound healing, perioperative allergy, adverse cardiovascular events, hypoproteinaemia and shorter hospital stay. CONCLUSION The results of this study suggest that the use of autologous blood cell transfusion is safe and effective for patients with obstetric haemorrhage. TRIAL REGISTRATION All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional and/or National Research Committee of Beijing Obstetrics and Gynecology Hospital, Capital Medical University (2016-XJS-003-01) as well as the 1964 Helsinki Declaration and its later amendments or other comparable ethical standards. The clinical trials were registered (ChiCTR-ICC-15,007,096) on September 28, 2015.