Ferric carboxymaltose versus standard-of-care oral iron to treat second-trimester anaemia in Malawian pregnant women: a randomised controlled trial
Lancet (London, England). 2023
BACKGROUND Anaemia affects 46% of pregnancies in Africa; oral iron is recommended by WHO but uptake and adherence are suboptimal. We tested a single dose of a modern intravenous iron formulation, ferric carboxymaltose, for anaemia treatment in Malawian pregnant women. METHODS In this open-label, individually randomised controlled trial, we enrolled women with a singleton pregnancy of 13-26 weeks' gestation in primary care and outpatient settings across two regions in southern Malawi. Women were eligible if they had capillary haemoglobin of less than 10·0 g/dL and negative malaria rapid diagnostic test. Participants were randomised by sealed envelope 1:1. Assessors for efficacy outcomes (laboratory parameters and birthweight) were masked to intervention; participants and study nurses were not masked. Participants were given ferric carboxymaltose up to 1000 mg (given once at enrolment in an outpatient primary care setting), or standard of care (60 mg elemental iron twice daily for 90 days), along with intermittent preventive malaria treatment. The primary maternal outcome was anaemia at 36 weeks' gestation. The primary neonatal outcome was birthweight. Analyses were performed in the intention-to-treat population for mothers and liveborn neonates, according to their randomisation group. Safety outcomes included incidence of adverse events during infusion and all adverse events from randomisation to 4 weeks' post partum. The trial is registered with ANZCTR, ACTRN12618001268235. The trial has completed follow-up. FINDINGS Between Nov 12, 2018, and March 2, 2021, 21 258 women were screened, and 862 randomly assigned to ferric carboxymaltose (n=430) or standard of care (n=432). Ferric carboxymaltose did not reduce anaemia prevalence at 36 weeks' gestation compared with standard of care (179 [52%] of 341 in the ferric carboxymaltose group vs 189 [57%] of 333 in the standard of care group; prevalence ratio [PR] 0·92, 95% CI 0·81 to 1·06; p=0·27). Anaemia prevalence was numerically lower in mothers randomly assigned to ferric carboxymaltose compared with standard of care at all timepoints, although significance was only observed at 4 weeks' post-treatment (PR 0·91 [0·85 to 0·97]). Birthweight did not differ between groups (mean difference -3·1 g [-75·0 to 68·9, p=0·93). There were no infusion-related serious adverse events or differences in adverse events by any organ class (including malaria; ≥1 adverse event: ferric carboxymaltose 183 [43%] of 430 vs standard of care 170 [39%] of 432; risk ratio 1·08 [0·92 to 1·27]; p=0·34). INTERPRETATION In this malaria-endemic sub-Saharan African setting, treatment of anaemic pregnant women with ferric carboxymaltose was safe but did not reduce anaemia prevalence at 36 weeks' gestation or increase birthweight. FUNDING Bill & Melinda Gates Foundation (INV-010612).
Ulipristal acetate versus levonorgestrel-releasing intrauterine system for heavy menstrual bleeding (UCON): a randomised controlled phase III trial
BACKGROUND Heavy menstrual bleeding affects one in four women and negatively impacts quality of life. Ulipristal acetate is prescribed to treat symptoms associated with uterine fibroids. We compared the effectiveness of ulipristal acetate and the levonorgestrel-releasing intrauterine system at reducing the burden of heavy menstrual bleeding, irrespective of the presence of fibroids. METHODS This randomised, open-label, parallel group phase III trial enrolled women over 18 years with heavy menstrual bleeding from 10 UK hospitals. Participants were centrally randomised, in a 1:1 ratio, to either three, 12-week treatment cycles of 5 mg ulipristal acetate daily, separated by 4-week treatment-free intervals, or a levonorgestrel-releasing intrauterine system. The primary outcome, analysed by intention-to-treat, was quality of life measured by the Menorrhagia Multi-Attribute Scale at 12 months. Secondary outcomes included menstrual bleeding and liver function. The trial is registered with ISRCTN, 20426843. FINDINGS Between June 5th, 2015 and February 26th, 2020, 236 women were randomised, either side of a recruitment suspension due to concerns of ulipristal acetate hepatoxicity. Subsequent withdrawal of ulipristal acetate led to early cessation of recruitment but the trial continued in follow-up. The primary outcome substantially improved in both groups, and was 89, (interquartile range [IQR] 65 to 100, n = 53) and 94, (IQR 70 to 100, n = 50; adjusted odds ratio 0.55, 95% confidence interval [CI] 0.26-1.17; p = 0.12) in the ulipristal and levonorgestrel-releasing intrauterine system groups. Rates of amenorrhoea at 12 months were higher in those allocated ulipristal acetate compared to levonorgestrel-releasing intrauterine system (64% versus 25%, adjusted odds ratio 7.12, 95% CI 2.29-22.2). Other outcomes were similar between the two groups and there were no cases of endometrial malignancy or hepatotoxicity due to ulipristal acetate use. INTERPRETATION Our findings suggested that both treatments improved quality of life. Ulipristal was more effective at inducing amenorrhoea. Ulipristal has been demonstrated to be an effective medical therapeutic option but currently its use has restrictions and requires liver function monitoring. FUNDING UK Medical Research Council and National Institute of Health Research EME Programme (12/206/52).
Effect of preoperative prophylactic intravenous tranexamic acid on perioperative blood loss control in patients undergoing cesarean delivery: a systematic review and meta-analysis
BMC pregnancy and childbirth. 2023;23(1):420
BACKGROUND Postpartum hemorrhage (PPH) is one of the important risk factors leading to maternal mortality and intervention is essential. Oxytocin therapy is widely used clinically, but the effect is unsatisfactory. The efficacy of tranexamic acid (TXA) in hemostasis is notable, whereas its use in preventing PPH warrants exploration. AIMS To evaluate the effect of prophylactic administration of TXA on perioperative blood loss in women undergoing cesarean section by systematic review and meta-analysis of published studies. METHODS Bibliographic databases were screened from their inception to December 2022 to retrieve relevant studies. Study outcomes including blood loss during cesarean section, 2-h postpartum blood loss, total blood loss (during cesarean section and 2-h postpartum), and 6-h postpartum, as well as hemoglobin changes were extracted and compared. RESULTS A total of 21 studies, nine randomized clinical trials and 12 cohort studies, involving 1896 patients given TXA prophylactically and 1909 patients given placebo or no treatment, were analyzed. Compared with the control group, the preoperative prophylactic intravenous administration of TXA significantly reduced the intraoperative (RCT: P < 0.00001, cohort studies: P < 0.00001), 2-h postpartum (RCT: P = 0.02, cohort studies: P < 0.00001) and total blood loss (RCT: P < 0.00001, cohort studies: P = 0.0002), and reduced the decline in hemoglobin (RCT: P < 0.00001, cohort studies: P = 0.0001), but did not significantly affect blood loss at 6-h postpartum (P = 0.05). CONCLUSION Prophylactic intravenous TXA before cesarean section is helpful in preventing perioperative bleeding in women. TRIAL REGISTRATION http://www.crd.york.ac.uk/PROSPERO , identifier: CRD 42022363450.
Effects of misoprostol in reducing blood loss during abdominal myomectomy in Nigeria
Nigerian journal of clinical practice. 2023;26(4):454-462
BACKGROUND Despite using a tourniquet to reduce bleeding during abdominal myomectomy, the procedure is still complicated by significant intraoperative bleeding. AIM: To determine whether misoprostol and tourniquet compared with tourniquet alone would significantly reduce bleeding during abdominal myomectomy at two tertiary hospitals in Enugu. MATERIALS AND METHODS This study is an open-label randomized controlled trial. A total of 126 consenting participants were recruited from women booked for abdominal myomectomy at the study centers over 7 months. They were randomized into groups A (vaginal misoprostol 400 μg) and B (no misoprostol) one hour before surgery. Intraoperatively, all participants had a tourniquet application. Intraoperative and postoperative blood loss was compared between the two groups. Descriptive and inferential analyses were carried out using IBM SPSS Version 22.0. A P- value of < 0.05 was considered statistically significant. RESULTS An intention-to-treat analysis was carried out. All 63 participants (100%) and 56 (90%) completed the study according to the protocol in groups A and B, respectively. Socio-demographic characteristics were not significantly different in both groups. The mean intraoperative blood loss in the "misoprostol group" (522.6 ± 127.91 ml) was significantly lower than in the "no-misoprostol group" (583.5 ± 186.20 ml), with P = 0.028. The difference in mean hemoglobin (g/dl) was lower in the "misoprostol group" than in the "no-misoprostol group" (1.3 ± 0.79 vs. 1.9 ± 0.89, P < 0.001). The mean 48 hours postoperative blood loss (ml) between the two groups was 323.8 ± 221.44 vs. 549.4 ± 519.72), with P = 0.001. CONCLUSION Among women receiving tourniquet during myomectomy in Enugu, the additional use of vaginal misoprostol 400 μg significantly reduced intraoperative blood loss.
The effect of uterine massage after vaginal delivery on the duration of placental delivery and amount of postpartum hemorrhage
Archives of gynecology and obstetrics. 2023
OBJECTIVE The aim of this study was to investigate the effects of uterine massage performed before placental delivery on the third stage of labor and postpartum hemorrhage after vaginal delivery. MATERIALS AND METHODS The study was designed as a prospective randomized controlled study. Between June 2018 and June 2019, 242 women who gave birth in Istanbul Kanuni Sultan Suleyman Training and Research Hospital were included in the study. The women were divided into two groups; group 1 received uterine massage after vaginal delivery before placental delivery (n: 128) and group 2 did not receive massage (n: 114). Demographic characteristics, delivery times of the baby and placenta, duration of uterine massage, amount of postpartum hemorrhage and postpartum hemoglobin values of both groups were recorded. RESULTS Baseline characteristics were similar in both groups. Placental output time after delivery was 8.3 ± 4.2 min in group 1 and 13.5 ± 6.3 min in group 2. The third stage of labor was significantly shorter in group 1 (p = 0.012). The amount of blood loss of 500 mL or more after delivery was higher in group 2 but not statistically different (p > 0.05). Hemoglobin value measured within 12-24 h after delivery was significantly lower in group 2 (hemoglobin < 8 g/dL after 12-24 h p = 0.003; hemoglobin < 10 g/dL after 12-24 h p = 0.001). Delta hb value was also significantly lower in group 2 (p = 0.03). With this result, it was determined that bleeding intense enough to require transfusion was more common in group 2. CONCLUSION In patients delivering vaginally, uterine massage before placental delivery shortens the placental delivery time and reduces postpartum hemorrhage. In addition to oxytocin and controlled cord traction to reduce postpartum blood loss, uterine massage should be routinely used in the active management of the third stage of labor. CLINICAL TRIALS NUMBER NCT03858569.
Tranexamic acid for the prevention of postpartum bleeding: Protocol for a systematic review and individual patient data meta-analysis
Gates open research. 2023;7:3
Tranexamic acid (TXA) reduces the risk of death and is recommended as a treatment for women with severe postpartum bleeding. There is hope that giving TXA shortly before or immediately after birth could prevent postpartum bleeding. Extending the use of TXA to prevent harmful postpartum bleeding could improve outcomes for millions of women; however we must carefully consider the balance of benefits and potential harms. This article describes the protocol for a systematic review and individual patient data (IPD) meta-analysis to assess the effectiveness and safety of TXA for preventing postpartum bleeding in all women giving birth, and to explore how the effects vary by underlying risk and other patient characteristics. Methods: We will search for prospectively registered, randomised controlled trials involving 500 patients or more assessing the effects of TXA in women giving birth. Two authors will extract data and assess risk of bias. IPD data will be sought from eligible trials. Primary outcomes will be life-threatening bleeding and thromboembolic events. We will use a one-stage model to analyse the data. Subgroup analyses will be conducted to explore whether the effectiveness and safety of TXA varies by underlying risk, type birth, maternal haemoglobin (Hb), and timing of TXA. This protocol is registered on PROSPERO (CRD42022345775). Conclusions: This systematic review and IPD meta-analysis will address important clinical questions about the effectiveness and safety of the use of TXA for the prevention of postpartum bleeding that cannot be answered reliably using aggregate data and will inform the decision of who to treat. PROSPERO registration: CRD42022345775 Keywords Anti-fibrinolytics; Tranexamic acid; childbirth; postpartum haemorrhage; meta-analysis.
The use of a short course of Ulipristal Acetate for acute abnormal uterine bleeding in women without uterine fibroids
Facts, views & vision in ObGyn. 2023;15(2):99-105
BACKGROUND Ulipristal Acetate (UPA) is a synthetic selective progesterone receptor modulator. It is used as emergency contraception and to reduce pain and blood loss in women of reproductive age with uterine fibroids. The first mechanism of action is myometrial apoptosis, the second is on the hypo-thalamic-pituitary-ovarian axis and the third action, is an anti-proliferative effect on the endometrium. Mainly based on the latter two, UPA is increasingly used off-label in women with abnormal uterine bleeding (AUB) without fibroids. OBJECTIVES The aim of this paper is to find evidence for a short course of UPA to treat acute AUB without fibroids, performing a systematic review as well as scrutinising literature data on the pharmacokinetics and on short term bleeding control in women with fibroids. MATERIALS AND METHODS A systematic electronic literature review was performed in February 2022. Inclusion criteria were UPA administered to women without myomas in a setting of acute uterine bleeding. Further criteria included papers describing early bleeding control using UPA, deemed independent of the presence of fibroids, with specific attention to the median time to amenorrhoea. MAIN OUTCOME MEASURES The main outcome measured was the bleeding control within 10 days. RESULTS One case report was identified. The data on symptomatic women with fibroids using 5 mg or 10 mg daily revealed bleeding control was reported within 10 days in 81% and 89% respectively, with amenorrhoea in 57% and in 78% respectively. CONCLUSION A short-term administration may prove effective in abnormal uterine bleeding irrespective of the presence of uterine fibroids. However, more randomised controlled trials are needed and should be performed before implementation in general clinical practice. WHAT IS NEW? A short course of Ulipristal acetate as promising treatment for acute uterine bleeding without fibroids.
Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery
The New England journal of medicine. 2023;388(15):1365-1375
BACKGROUND Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; Pâ€‰=â€‰0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).
Patients undergoing caesarean delivery at 31 U.S. hospitals (n= 11,000).
Tranexamic acid (n= 5,529).
Placebo (n= 5,471).
The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days postpartum, whichever came first. A primary-outcome event occurred in 201 of 5,525 participants (3.6%) in the tranexamic acid group and in 233 of 5,470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% CI [0.74, 1.07]). Estimated intraoperative blood loss of more than 1 litre occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI [0.79, 1.05]). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI [0.82, 0.97]); the change in the haemoglobin level was -1.8 g per decilitre and -1.9 g per decilitre, respectively (mean difference, -0.1 g per decilitre; 95% CI [-0.2, -0.1]); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI [1.02, 1.61]). The frequencies of thromboembolic events and other adverse events were similar in the two groups.
Prophylactic Tranexamic Acid Prevents Postpartum Hemorrhage and Transfusions in Cesarean Deliveries: A Systematic Review and Meta-analysis
American journal of perinatology. 2023
INTRODUCTION Postpartum hemorrhage (PPH) is the leading cause of maternal mortality worldwide and PPH resulting in transfusion is the most common maternal morbidity in the United States. Literature demonstrates that tranexamic acid (TXA) can reduce blood loss in cesarean deliveries; however, there is little consensus on the impact on major morbidities like PPH and transfusions. OBJECTIVE We conducted a systematic review/meta-analysis of randomized controlled trials (RCTs) to evaluate if administration of prophylactic IV TXA prevents PPH and/or transfusions following low-risk cesarean delivery. METHODS PRISMA guidelines were followed. Five databases were searched: Cochrane, EBSCO, Ovid, PubMed, and ClinicalKey. RCTs published in English between January 2000 and December 2021 were included. Studies compared PPH and transfusions in cesarean deliveries between prophylactic IV TXA and control (placebo or no placebo). The primary outcome was PPH, and the secondary outcome was transfusions. Random effects models were used to calculate effect size (ES) of exposure in Mantel-Haenszel Risk Ratios (RR). All analysis was done at a confidence level (CI) of alpha=0.5. RESULTS Modeling showed that TXA led to significantly less risk of PPH than control (RR: 0.43, 95% CI: 0.28-0.67). The effect on transfusion was comparable (RR: 0.39, 95% CI: 0.21-0.73). Heterogeneity was minimal (I2 = 0%). CONCLUSION Due to the large sample sizes needed, many RCTs are not powered to interpret TXA's effect on PPH and transfusions. Pooling these studies in a meta-analysis allows for more power and analysis but is limited by the heterogeneity of studies. Our results minimize heterogeneity while demonstrating that prophylactic TXA reduces the risk for PPH and transfusion. This has the potential to address blood shortages, transfusion-associated risks, and healthcare costs. We suggest considering prophylactic IV TXA as the standard of care in low-risk cesarean deliveries.
Effect of Endometrial Ablation by Thermal Balloon vs. Hysteroscopy Ablation on Amenorrhea Rates in Patients with Abnormal Uterine Bleeding: A Randomized Clinical Trial
International journal of fertility & sterility. 2023;17(2):133-139
BACKGROUND Abnormal uterine bleeding (AUB) that is any irregularity in menstrual cycles causes women to refer to clinics. This study aimed to compare the efficacy, safety, and complications of endometrial ablation by the thermal balloon (Cavaterm) method with the hysteroscopy loop resection method in the treatment of AUB. MATERIALS AND METHODS The present study is an open-label, randomized clinical trial that was performed in the two hospitals, Shahid Akbarabadi and Hazrat Rasoul Akram, of Tehran, Iran, from December 2019 to October 2020. Patients were randomly allocated to the two groups of interventions by a simple randomization method. The proportion of amenorrhea (as primary outcome) and consequent hysterectomy and patient satisfaction (as secondary outcomes) was assessed using the Chi-square test and independent t test. RESULTS There was no significant difference between the two groups in the baseline characteristics. The percentage of intervention failure was statistically higher in the hysteroscopy group (24%) in comparison with the Cavaterm group [8.2%, P=0.03, relative risk (RR)=1.63, 95% confidence interval (CI): 1.13-2.36]. Mean ± standard deviation of satisfaction based on the Likert score in the Cavaterm group and hysteroscopy group were 4.3 ± 1.21 and 3.7 ± 1.56, respectively, that showed a significant difference (P=0.04). Assessing the procedural complications, the rate of spotting, bloody discharge, and malodor discharge was significantly higher in the Cavaterm group. In contrast, postoperative dysmenorrhea is more common in the hysteroscopy group. CONCLUSION Cavaterm ablation is accompanied by a higher success rate of amenorrhea and patients' satisfaction than hysteroscopy ablation (registration number: IRCT20220210053986N1).