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1.
Tranexamic acid for the prevention and treatment of postpartum hemorrhage in resource-limited settings: a literature review
Gedeno Gelebo, K., Mulugeta, H., Mossie, A., Geremu, K., Darma, B.
Annals of medicine and surgery (2012). 2024;86(1):353-360
Abstract
INTRODUCTION Postpartum haemorrhage is a major cause of maternal morbidity and mortality worldwide. Early recognition and appropriate treatment are crucial for managing postpartum haemorrhage. OBJECTIVES This literature review aimed to evaluate the efficacy of tranexamic acid in the prevention and treatment of postpartum haemorrhage in resource-limited settings. SEARCH METHODS This literature review was conducted based on the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) guidelines. A computerized systematic search of the MEDLINE (PubMed), Google Scholar, and Cochrane databases using a combination of the following Medical Subject Headings (MeSH) terms for PubMed: [(obstetric haemorrhage OR postpartum haemorrhage OR massive obstetric haemorrhage) AND (tranexamic acid OR antifibrinolytic drugs) AND (prophylaxis OR prevention) AND (management OR treatment) AND (resource-limited settings OR resource-limited area OR developing countries)] to find articles published in English since 2010. SELECTION CRITERIA Studies on the obstetric population who underwent vaginal or caesarean delivery, comparing the use of tranexamic acid versus placebo (or no treatment) for treatment (or prevention) of postpartum haemorrhage with the outcome of postpartum haemorrhage rate, blood transfusion requirements, uterotonics requirements, hysterectomy, or mortality were included. RESULT In total, 5315 articles were identified. Following the elimination of duplicates, the methodological quality of 15 studies was evaluated independently, with eligibility determined based on the inclusion and exclusion criteria, as well as outcome variables. Finally, eight articles were included in the review. CONCLUSION This review provides evidence that the administration of tranexamic acid has the potential to decrease the need for blood transfusion, incidence of postpartum haemorrhage, demand for supplementary uterotonics, and maternal morbidity and mortality with marginal adverse effects. Healthcare systems must develop and implement interventions that involve the use of tranexamic acid for the treatment of postpartum haemorrhage in resource-limited settings.
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2.
Intravenous iron versus blood transfusion for postpartum anemia: a systematic review and meta-analysis
Caljé, E., Groom, K. M., Dixon, L., Marriott, J., Foon, R., Oyston, C., Bloomfield, F. H., Jordan, V.
Systematic reviews. 2024;13(1):9
Abstract
BACKGROUND Intravenous iron (IV-iron) is used as an alternative to, or alongside, red blood cell transfusion (RBC-T) to treat more severe postpartum anemia (PPA), although optimal treatment options remain unclear. No previous systematic reviews have examined IV-iron and RBC-T, including patient-reported outcomes and hematological responses. METHODS A systematic review and meta-analysis of randomized trials comparing IV-iron and RBC-T with each other, oral iron, no treatment, and placebo for the treatment of PPA. Key inclusion criteria were PPA (hemoglobin < 12 g/dL) and IV-iron or RBC-T as interventions. Key exclusion criteria were antenatal IV-iron or RBC-T. Fatigue was the primary outcome. Secondary outcomes included hemoglobin and ferritin concentrations, and adverse events. From 27th August 2020 to 26th September 2022, databases, registries, and hand searches identified studies. A fixed-effect meta-analysis was undertaken using RevMan (5.4) software. The quality of the studies and the evidence was assessed using the Cochrane Risk of Bias table, and Grading of Recommendations, Assessment, Development, and Evaluation. This review is registered with the Prospective Register of Systematic Reviews (CRD42020201115). RESULTS Twenty studies and 4196 participants were included: 1834 assigned IV-iron, 1771 assigned oral iron, 330 assigned RBC-T, and 261 assigned non-intervention. Six studies reported the primary outcome of fatigue (1251 participants). Only studies of IV-iron vs. oral iron (15 studies) were available for meta-analysis. Of these, three reported on fatigue using different scales; two were available for meta-analysis. There was a significant reduction in fatigue with IV-iron compared to oral iron (standardized mean difference - 0.40, 95% confidence interval (CI) - 0.62, - 0.18, I(2) = 0%). The direction of effect also favored IV-iron for hemoglobin (mean difference (MD) 0.54 g/dL, 95% confidence interval (CI) 0.47, 0.61, I(2) = 91%), ferritin, (MD 58.07 mcg/L, 95% CI 55.74, 60.41, I(2) = 99%), and total adverse events (risk-ratio 0.63, 95% CI 0.52, 0.77, I(2) = 84%). The overall quality of the evidence was low-moderate. DISCUSSION For all outcomes, the evidence for RBC-T, compared to IV-iron, non-intervention, or dose effects of RBC-T is very limited. Further research is needed to determine whether RBC-T or IV-iron for the treatment of PPA is superior for fatigue and hematological outcomes.
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3.
Preventing postpartum hemorrhage: A network meta-analysis on routes of administration of uterotonics
Papadopoulou, A., Tournas, G., Georgiopoulos, G., Antsaklis, P., Daskalakis, G., Coomarasamy, A., Devall, A. J.
European journal of obstetrics, gynecology, and reproductive biology. 2024;295:172-180
Abstract
1. OBJECTIVE To perform a network meta-analysis to specify the route of administration that maximises the effectiveness of each of the available prophylactic uterotonics without increasing the risk for side effects. 2. DATA SOURCES Literature searches on 12th September 2022 included: CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform. The reference lists of the retrieved study records were also searched. 3. STUDY ELIGIBILITY CRITERIA Population: Randomized controlled trials involving women in the third stage of labour after a vaginal or caesarean delivery in hospital or community settings. INTERVENTIONS Systemically administered prophylactic uterotonics of any route and dose for primary postpartum hemorrhage prevention. Comparison: Any other prophylactic uterotonic, or a different route or dose of a given uterotonic, or placebo, or no treatment. Outcomes (primary): postpartum hemorrhage ≥ 500 mL and ≥ 1000 mL. 4. STUDY APPRAISAL AND SYNTHESIS METHODS Risk of bias and trustworthiness assessments were performed, according to Cochrane's guidance. Direct, indirect and network meta-analyses were conducted, and results were summarized either as risk ratio or mean difference with 95% confidence intervals for dichotomous and continuous outcomes, respectively. The certainty of generated evidence was assessed according to the GRADE approach. Cumulative probabilities were calculated and the surface under the cumulative ranking curve was used to create a ranking of the available drugs. 5. RESULTS One hundred eighty-one studies involving 122,867 randomised women were included. Most studies were conducted in hospital settings in lower-middle income countries and involved women delivering vaginally. When compared with intramuscular oxytocin, carbetocin (RR 0.58, 95 % CI 0.40-0.84) and oxytocin (RR 0.75, 95 % CI 0.59-0.97) by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination (RR 0.71, 95 % CI 0.56-0.91) are probably more effective in preventing primary postpartum hemorrhage. Intramuscularly administered oxytocin and carbetocin by an intravenous bolus have a favourable side effects profile. 6. CONCLUSIONS Generated evidence was generally moderate and global inconsistency was low. Carbetocin and oxytocin by an intravenous bolus, and intramuscular ergometrine plus oxytocin combination are probably the top uterotonics for primary postpartum hemorrhage prevention. Large scale studies exploring different routes of administration for available prophylactic uterotonics, and women's views should be conducted.
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4.
Clinical outcome post treatment of anemia in pregnancy with intravenous versus oral iron therapy: a systematic review and meta-analysis
Pandey, A. K., Gautam, D., Tolani, H., Neogi, S. B.
Scientific reports. 2024;14(1):179
Abstract
Oral iron therapy is often the most common way of treating anaemia; however intravenous iron is considered effective due to rapid iron replenishment. We have dearth of evidence on clinical outcomes post treatment of anaemia. We have searched studies published in English in PubMed, Cochrane, Scopus, ProQuest, and Google Scholar. Our study analysed the clinical outcomes amongst neonates and mother and the adverse events post treatment and assessed the mean change in maternal haemoglobin concentration in both the groups. Forest plots for the clinical outcomes are presented. From a total of 370 studies, 34 Randomized and quasi experimental studies comparing clinical outcomes post-treatment of anaemia in pregnancy were included for quantitative evidence synthesis. Pooled results of maternal clinical outcomes using random effect model [OR: 0.79 (95% CI 0.66; 0.95); 10 outcomes; 17 studies] showed statistically significant difference among both the groups [Moderate quality evidence]; however no significant difference [OR: 0.99 (95% CI 0.86; 1.14); 7 outcomes; 8 studies] have been observed for neonatal complications [Low quality evidence]. The study found that pregnant women receiving IV iron were significantly less likely to experience adverse events as compared with those receiving oral iron [OR 0.39; (95% CI 0.26-0.60)]; 34 studies; 13,909 women; [Low quality evidence]. Findings from meta-regression analysis showed that IV iron is more likely to reduce maternal complications by 21% compared to oral iron. Increase in odds of adverse maternal outcomes was observed due to increase in gestational age and publication year but no effect for the type of drug used. IV iron increases Hb more and at a higher pace than oral iron. Intravenous iron is more likely to avert adverse maternal outcomes and adverse reactions. However, there is no conclusive evidence on its effectiveness on individual maternal outcome or neonatal outcome/s. Protocol registered with PROSPERO CRD42022368346).
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5.
Tranexamic acid for the prevention of postpartum bleeding: Protocol for a systematic review and individual patient data meta-analysis
Ker, K., Shakur-Still, H., Sentilhes, L., Pacheco, L. D., Saade, G., Deneux-Tharaux, C., Brenner, A., Mansukhani, R., Ageron, F. X., Prowse, D., et al
Gates open research. 2023;7:3
Abstract
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.
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6.
Utilization of non-pneumatic anti-shock garment for treating obstetric hemorrhage and associated factors among obstetric care providers in Ethiopia: A systematic review and meta-analysis
Addisu, D., Gebeyehu, N. A., Belachew, Y. Y., Mekie, M.
PloS one. 2023;18(11):e0294052
Abstract
BACKGROUND The non-pneumatic anti-shock garment (NASG) is a life-saving device that can help to avoid delays and prevent further complications in the case of obstetric hemorrhage. Although there are many fragmented primary studies on the NASG utilization in Ethiopia, the pooled utilization rate is unknown. In addition, a disagreement was observed among those studies while reporting the associated factors. Therefore, this study was intended to determine the pooled level of NASG utilization and its associated factors among obstetric care providers in Ethiopia. METHODS A total of 51 studies were retrieved from PubMed, Google Scholar, the African Journal of Online, direct open-access journals, and Ethiopian universities' institutional repositories. This study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. The quality of studies was evaluated using the modified Newcastle-Ottawa quality assessment tool. The data were extracted by two authors independently using Microsoft Excel and analyzed by Stata version 11. A random-effects model was applied to calculate the pooled level of NASG utilization and its associated factors. The PROSPERO registration number for the review is CRD42023414043. RESULT A total of 8 studies comprising 2,575 study participants were involved in this meta-analysis. The pooled utilization rate of NASG was found to be 39.56%. Having NASG training (pooled odds ratio (OR) = 3.99, 95%CI = 2.35, 6.77), good knowledge about NASG (OR = 2.92, 95%CI = 2.04, 4.17), a positive attitude towards NASG (OR = 3.17, 95%CI = 2.10, 4.79), and having ≥ 2 NASGs in the health facility (OR = 10.59, 95%CI = 6.59, 17.01) were significantly associated with NASG utilization. CONCLUSION Utilization of NASG for the treatment of obstetric hemorrhage was low in Ethiopia. To increase its utilization, Ministry of Health should improve the accessibility of NASG at each health facility and increase the Health professionals' knowledge and attitude through in-service and pre-service training.
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7.
Tranexamic acid versus misoprostol for management of postpartum hemorrhage: A systematic review and meta-analysis of randomized controlled trials
Abu-Zaid, A., Baradwan, S., Albouq, B., Ghazi, A., Khadawardi, K., Bukhari, I. A., Alyousef, A., Abdulmalik, N. A., Alblewi, H., Alsehaimi, S. O., et al
European journal of obstetrics, gynecology, and reproductive biology. 2023;291:61-69
Abstract
AIM: To conduct the first-ever systematic review and meta-analysis of randomized controlled trials (RCTs) on the antihemorrhagic utility and safety of tranexamic acid (TXA) versus misoprostol for management (prevention and/or treatment) of postpartum hemorrhage (PPH). METHODS Six databases were screened from inception until May 2023 and updated in September 2023. The RCTs were assessed for quality according to the Cochrane's risk of bias tool. The endpoints were summarized as mean difference (MD) or risk ratio (RR) with 95% confidence interval (CI) in a random-effects model. RESULTS Ten RCTs with 2121 patients (TXA = 1061 and misoprostol = 1060) were analyzed. There was no significant difference between TXA and misoprostol groups regarding the mean intraoperative blood loss (n = 9 RCTs, MD = 17.32 ml, 95% CI [-40.43, 75.07], p = 0.56), mean change in hemoglobin (n = 6 RCTs, MD = 0.11 mg/dl, 95% CI [-0.1, 0.31], p = 0.30), mean hospital stay (n = 2 RCTs, MD = -0.3 day, 95% CI [-0.61, 0.01], p = 0.06), blood transfusion rate (n = 4 RCTs, RR = 0.49, 95% CI [0.16, 1.47], p = 0.2), and rate of additional uterotonic agents (n = 4 RCTs, RR = 1.05, 95% CI [0.72, 1.53], p = 0.81). Leave-one-out sensitivity analysis showed robustness of the results, and there was no evidence of publication bias. Regarding safety endpoints, there was no significant difference between both groups regarding the rates of minor side effects, such as diarrhea, fever, nausea, and vomiting. No patient developed thromboembolic events in the TXA group. CONCLUSION There was no significant antihemorrhagic efficacy between adjunct TXA and misoprostol for the management of PPH. The safety profile was comparable between both agents.
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8.
Efficacy and safety of rectal misoprostol versus intravenous oxytocin on reducing blood loss in cesarean section: A PRISMA-compliant systematic review and meta-analysis of randomized clinical trials
Albazee, E., Soliman, A., Albakri, K., Elbanna, M., Moussa, N. A., Faragalla, H. M.
Turkish journal of obstetrics and gynecology. 2023;20(2):142-153
Abstract
Blood loss is an inevitable complication and a major contributor to maternal morbidity and mortality at cesarean deliveries. We detected a potential preference regarding the efficacy and safety of rectal misoprostol over oxytocin as a uterotonic agent. We searched PubMed, Scopus, Web of Science, Cochrane, and other databases for the relevant trials from inception to September 2022. We included randomized clinical trials (RCTs) that compared rectal misoprostol versus intravenous oxytocin to control bleeding in women undergoing cesarean delivery. Our primary outcomes were the intra- and postoperative blood loss, and hemoglobin drop after delivery. Secondary outcomes included the need for blood transfusion, need for additional uterotonics, difference in operative time, as well as safety outcomes such as the incidence of shivering, pyrexia, nausea, and vomiting. Our search strategy revealed 1007 unique records, of them we retrieved full texts of 19 articles to check their adherence to our eligibility criteria. Seven RCTs with 1,090 participants were included. We found a significant reduction in postoperative blood loss [MD: -27.9; 95% confidence interval (CI): (-53.85, -2.10); p=0.03], and Hb drop after delivery [MD: -11; 95% CI: (-0.19, -0.03); p=0.01]. There is no significant difference regarding intraoperative blood loss, operative time, need for blood transfusion, or need for additional uterotonics. We could not find a significant difference between the two groups regarding safety outcomes, except for a higher shivering incidence in the misoprostol group [RR: 0.33; 95% CI; (0.16, 0.70); p=0.004]. We found a significant reduction in postoperative blood loss with a potentially favorable safety profile in women who administrated rectal misoprostol compared with oxytocin administration. Our findings recommend and prefer rectal misoprostol as a cheaper and effective uterotonic agent over oxytocin, which is expensive and requires an adequate cold chain for transportation and storage.
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9.
Efficacy and safety of tranexamic acid in prevention of postpartum hemorrhage: a systematic review and meta-analysis of 18,649 patients
Al-Dardery, N. M., Abdelwahab, O. A., Abouzid, M., Albakri, K., Elkhadragy, A., Katamesh, B. E., Hamamreh, R., Mohd, A. B., Abdelaziz, A., Khaity, A.
BMC pregnancy and childbirth. 2023;23(1):817
Abstract
BACKGROUND In this meta-analysis, we aimed to update the clinical evidence regarding the efficacy and safety of TXA in the prevention of PPH. METHODS A literature search of PubMed, Scopus, Web of Science, Google Scholar, and Cochrane Library from inception until December 2022 was conducted. We included randomized controlled trials (RCTs) comparing TXA with a placebo among pregnant women. All relevant outcomes, such as total blood loss, the occurrence of nausea and/or vomiting, and changes in hemoglobin, were combined as odds ratios (OR) or mean differences (MD) in the meta-analysis models using STATA 17 MP. RESULTS We included 59 RCTs (18,649 patients) in this meta-analysis. For cesarean birth, TXA was favored over the placebo in reducing total blood loss (MD= -2.11 mL, 95%CI [-3.09 to -1.14], P < 0.001), and occurrence of nausea or/and vomiting (OR = 1.36, 95%CI [1.07 to 1.74], P = 0.01). For vaginal birth, the prophylactic use of TXA was associated with lower total blood loss, and higher occurrence of nausea and/or vomiting (MD= -0.89 mL, 95%CI [-1.47 to -0.31], OR = 2.36, 95%CI [1.32 to 4.21], P = 0.02), respectively. However, there were no differences between the groups in changes in hemoglobin during vaginal birth (MD = 0.20 g/dl, 95%CI [-0.07 to 0.48], P = 0.15). The overall risk of bias among the included studies varies from low to high risk of bias using ROB-II tool for RCTs. CONCLUSIONS This meta-analysis suggested that TXA administration is effective among women undergoing cesarean birth or vaginal birth in lowering total blood loss and limiting the occurrence of PPH. Further clinical trials are recommended to test its efficacy on high-risk populations.
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10.
Desmopressin to prevent and treat bleeding in pregnant women with an inherited bleeding disorder: A systematic literature review
Al Arashi, W., Romano, L. G. R., Leebeek, F. W. G., Kruip, Mjha, van Galen, K. P. M., Turan, O., Kadir, R. A., Cnossen, M. H.
Journal of thrombosis and haemostasis : JTH. 2023
Abstract
BACKGROUND Although desmopressin (DDAVP) is an accessible and inexpensive hemostatic drug, its use in pregnancy is still debated due to safety uncertainties. OBJECTIVE We aim to review safety and effectiveness of DDAVP in women with an inherited bleeding disorder during pregnancy and delivery. METHODS Databases were searched for articles up to July 25(th) 2022, reporting maternal and/or neonatal outcomes. PRISMA methodology was followed (PROSPERO CRD42022316490). RESULTS Fifty-three studies were included, comprising 273 pregnancies. Regarding maternal outcomes, DDAVP was administered in 73 pregnancies during pregnancy and in 232 pregnancies during delivery. Safety outcome was reported in 245 pregnancies, with severe adverse event reported in two (1%; hyponatremia with neurological symptoms).Overall, DDAVP was used as monotherapy in 234 pregnancies with effectiveness reported in 153 pregnancies (82% effective; 18% ineffective). Regarding neonatal outcomes, out of 60 pregnancies with reported neonatal outcomes after DDAVP use during pregnancy, two children (3%) had a severe adverse event (preterm delivery n=1; fetal growth restriction n=1). Of the 232 deliveries, 169 neonates were exposed to DDAVP during delivery and in 114 neonates, safety outcome was reported. Two children (2%) experienced a moderate adverse event (low Apgar score n=1; transient hyperbilirubinemia not associated with DDAVP n=1). CONCLUSION DDAVP use during pregnancy and delivery seems safe for the mother with special attention to the occurrence of hyponatremia and for the child, especially during delivery. However, due to poor study designs and limited documentation of outcomes, a well-designed prospective study is warranted.