Implementation strategies for WHO guidelines to prevent, detect, and treat postpartum hemorrhage.

Despite World Health Organization (WHO) guidelines for preventing, detecting, and treating postpartum hemorrhage (PPH), effective implementation has lagged. To evaluate the clinical benefits and harms of implementation strategies used to promote adherence to WHO clinical guidelines for the prevention, detection, and treatment of PPH. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, CINAHL, and two trial registries, along with reference checking, citation searching, and contact with study authors. The latest search date was 25 April 2024. We included randomized controlled trials (RCTs), including cluster, pragmatic, and stepped-wedge designs, and non-randomized studies of interventions (NRSIs), including interrupted time series (ITS) studies, controlled before-after (CBA) studies, and follow-up (cohort) studies containing concurrent controls that focused on or described implementation strategies of WHO guidelines for the prevention, detection, and treatment of PPH. Participants were birth attendants and people giving birth in a hospital or healthcare facility. We excluded studies that did not implement a WHO PPH recommendation, had no comparator group, or did not report clinical/implementation outcomes. Our critical outcomes were: adherence to WHO-recommended guidelines for PPH prevention, detection, and treatment; PPH ≥ 500 mL; PPH ≥ 1000 mL; additional uterotonics within 24 hours after birth; blood transfusions; maternal death; severe morbidities (major surgery; admission to intensive care unit [ICU]); and adverse effects (variable and related to the clinical intervention) during hospitalization for birth. Our important outcomes were: breastfeeding at discharge; implementation outcomes such as acceptability, adoption, appropriateness, feasibility, fidelity, implementation cost, penetration, and sustainability of the implementation strategy; and health professional outcomes such as knowledge and skill. We used the RoB 2 and ROBINS-I tools to assess risk of bias in RCTs and NRSIs, respectively. Two review authors independently selected studies, performed data extraction, and assessed risk of bias and trustworthiness. Due to the nature of the data, we reported relevant results for each comparison and outcome but did not attempt quantitative synthesis. We used GRADE to assess the certainty of evidence. We included 13 studies (9 cluster-RCTs and 4 NRSIs) with a total of 1,027,273 births and more than 4373 birth attendants. The included studies were conducted in 17 different countries. Most trials were conducted in resource-limited settings. None of the included studies reported data on the use of additional uterotonics within 24 hours after birth or adverse effects. Single-component implementation strategies versus usual care for PPH prevention, detection, and treatment We do not know if single-component implementation strategies have any effect on adherence to WHO PPH prevention recommendations, PPH ≥ 500 mL, PPH ≥ 1000 mL, or blood transfusion (very low-certainty evidence). Low-certainty evidence suggests that single-component implementation strategies may have little to no effect on maternal death (86,788 births, 3 trials); may increase severe morbidity related to ICU admission (26,985 births, 1 trial); and may reduce severe morbidity related to surgical outcomes (26,985 births, 1 trial). No trials in this comparison measured the effect on adherence to WHO treatment guidelines. Multicomponent implementation strategies versus usual care for PPH prevention, detection, and treatment We do not know if multicomponent implementation strategies have any effect on adherence to WHO PPH treatment recommendations, PPH ≥ 500 mL, blood transfusion, or severe morbidity relating to surgical outcomes (very low-certainty evidence). Multicomponent implementation strategies may have little to no effect on maternal death (274,008 births, 2 trials; low-certainty evidence) compared to usual care. No trials in this comparison measured the effect on adherence to WHO PPH prevention recommendations, PPH ≥ 1000 mL, or severe morbidity (outcomes related to ICU admission). Multicomponent implementation strategies versus enhanced usual care for PPH prevention, detection, and treatment Low-certainty evidence suggests that multicomponent implementation strategies may improve adherence to WHO PPH prevention recommendations (14,718 births, 2 trials) and adherence to WHO PPH treatment recommendations (356,913 births, 2 trials) compared to enhanced usual care. Multicomponent implementation strategies probably have little to no effect on maternal death (224,850 births, 2 trials; moderate-certainty evidence), severe morbidity related to ICU admission (224,850 births, 2 trials; moderate-certainty evidence), and surgical morbidity (210,132 births, 1 trial; moderate-certainty evidence) compared to enhanced usual care. We do not know if multicomponent implementation strategies affect PPH ≥ 500 mL, PPH ≥ 1000 mL, or blood transfusion (very low-certainty evidence). Multicomponent implementation strategies may improve adherence to WHO PPH prevention and treatment recommendations, but they probably result in little to no difference in ICU admissions, surgical morbidity, or maternal death. The majority of available evidence is of low to very low certainty, thus we cannot draw any robust conclusions on the effects of implementation strategies for WHO guidelines to prevent, detect, and treat PPH. While all included studies used the implementation strategy of 'train and educate,' the effects seem to be limited when used as a single strategy. Additional research using pragmatic, hybrid effectiveness-implementation study designs that measure implementation outcomes simultaneously alongside clinical outcomes would be beneficial to understand contextual factors, barriers, and facilitators that affect implementation. This Cochrane review had no dedicated external funding. Dr Rose Molina, who is employed by Beth Israel Deaconess Medical Center, received funding from Ariadne Labs (Harvard T.H. Chan School of Public Health, Brigham and Women's Hospital) for her time. As a funder, Ariadne Labs had no involvement in the development of the protocol or conduct of the review. The views and opinions expressed therein are those of the review authors and do not necessarily reflect those of Ariadne Labs. Registration: PROSPERO (CRD42024563802) available via https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024563802.

Semrau K ，Litman E ，Molina RL ，Marx Delaney M ，Choi L ，Robertson L ，Noel-Storr AH ，Guise JM ... -  《Cochrane Database of Systematic Reviews》

Transfusion of blood and blood products for the management of postpartum haemorrhage.

Postpartum haemorrhage (PPH) is commonly defined as blood loss of 500 mL or greater within 24 hours after birth. Intravenous transfusions of whole blood, red blood cells (RBC), or other blood components collected from a donor may be administered to manage PPH. Key questions remain regarding optimal timing for initiating blood and blood product transfusion in managing PPH and whether the use of fractionated blood products, either as replacement for or in addition to whole blood transfusion, could improve maternal outcomes. No systematic review has examined appropriate transfusion strategies for managing PPH. To assess the benefits and harms of transfusion of whole blood or other blood products for preventing morbidity and mortality among women with PPH. We searched CENTRAL, MEDLINE, Embase, and two trials registers, together with reference checking, citation searching, and contact with study authors to identify studies for inclusion in the review. The latest search was 18 July 2024. We considered randomised controlled trials (RCTs), cluster-randomised trials, or controlled non-randomised studies of interventions (NRSI) evaluating the efficacy and safety of blood transfusion for managing PPH, regardless of the mode of birth. Our critical outcomes were maternal death, severe maternal morbidity, and adverse effects. We assessed risk of bias in included studies using the Cochrane RoB 2 tool and the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tool. We synthesised results for each outcome within each comparison using meta-analysis where possible, and used GRADE to assess the certainty of evidence for each outcome. We included 12 studies with 17,868 participants. We excluded five NRSIs from outcome analyses due to critical risk of bias related to confounding. One threshold for initiating transfusion versus another threshold for initiating transfusion None of the studies assessed this comparison. One- to two-unit RBCs versus no transfusion Among women with moderate blood loss, low-certainty evidence from one NRSI found that transfusing 1 to 2 units of RBCs to treat PPH may increase severe maternal morbidity - composite excluding intensive care unit (ICU) admission (risk ratio (RR) 7.00, 95% confidence interval (CI) 2.75 to 17.80; 2130 women) and severe maternal morbidity - ICU admission (RR 2.12, 95% CI 1.20 to 3.75; 2130 women), though we have substantial concerns about the potential bias due to confounding as the volume of blood lost was not controlled for in the analysis. The study did not report maternal death or adverse effects. Packed RBCs versus whole blood versus combination of blood products One NRSI assessed this comparison but had critical risk of bias and was subsequently excluded from analysis. Fresh frozen plasma (FFP)/RBCs with fibrinogen concentrate versus FFP/RBCs alone One NRSI assessed this comparison but had critical risk of bias and was subsequently excluded from analysis. Fibrinogen concentrate versus placebo or no fibrinogen concentrate The evidence is very uncertain about the effect of fibrinogen concentrate on maternal death (0 events; 2 studies, 674 women; very low-certainty evidence). Fibrinogen concentrate probably results in little to no difference in severe maternal morbidity - ICU admission (RR 1.09,0 95% CI 0.80 to 1.49; 2 studies, 485 women; moderate-certainty evidence). The evidence is very uncertain about the effect of fibrinogen concentrate on severe maternal morbidity - arterial embolisation (1 study, 430 women; very low-certainty evidence). One RCT (430 women) and one NRSI (730 women) reported severe maternal morbidity - hysterectomy, each of which reported different directions of effect with low-certainty evidence. Fibrinogen concentrate may result in little to no difference in adverse effect - thromboembolic events (RR 0.19, 95% CI 0.01 to 3.95; 2 studies, 674 women; low-certainty evidence). The evidence is very uncertain about the effects of fibrinogen concentrate on additional adverse effects, such as shivering or fever (1 study, 244 women; very low-certainty evidence). Cryoprecipitate versus no cryoprecipitate The evidence is very uncertain about the effect of cryoprecipitate on maternal death. One RCT (0 deaths; 180 women; very low-certainty evidence) and one NRSI (0 deaths; 157 women; very low-certainty evidence) reported this outcomes. The evidence is also very uncertain about the effects of cryoprecipitate on severe maternal morbidity - ICU admission, severe maternal morbidity - any organ failure, severe maternal morbidity - laparotomy, or severe maternal morbidity - uterine artery embolisation (1 study, 180 women; very low-certainty evidence). One RCT (180 women; very low-certainty evidence) and one NRSI (157 women; very low-certainty evidence) reported severe maternal morbidity - hysterectomy and the evidence is very uncertain. The evidence is also very uncertain about the effects of cryoprecipitate on adverse effects, such as thromboembolic events or transfusion-related reactions (1 study, 180 women; very low-certainty evidence). Massive transfusion protocol versus no massive transfusion protocol Two NRSIs assessed this comparison but had critical risk of bias and were subsequently excluded from analysis. Overall, available evidence for the effects of blood and blood product transfusion on priority maternal outcomes is largely uncertain. Low-certainty evidence suggests that 1 to 2 units of RBC transfusion may increase the risk of severe maternal morbidity; however, we urge caution when interpreting this finding as the effect estimates are at serious risk of bias due to possible confounding. We are unable to comment on the effects of larger blood transfusion amounts on severe maternal morbidity. This review received no dedicated funding. This protocol for this Cochrane review is registered with PROSPERO. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024599608.

Williams CR ，Huffstetler HE ，Nyamtema AS ，Larkai E ，Lyimo M ，Kanellopoulou A ，Robertson L ，Choi L ，Alwy Al-Beity FM ... -  《Cochrane Database of Systematic Reviews》

Perineal techniques during the second stage of labour for reducing perineal trauma and postpartum complications.

Postpartum haemorrhage (PPH) is responsible for around 27% of global maternal deaths. Perineal tears are common in vaginal births and a significant contributor to excessive blood loss. A diversity of perineal techniques are utilised to prevent perineal trauma and reduce the incidence of PPH; however, they lack evidence-based comparisons to understand their effects. To assess the effect of perineal techniques during the second stage of labour on the incidence of and morbidity associated with perineal trauma to prevent postpartum complications. We searched four databases and two trial registers up to 16 April 2024. We checked references, searched citations and contacted study authors to identify additional studies. We included randomised controlled trials (RCTs) of women in the second stage of labour who intended to give birth vaginally, comparing any perineal techniques with control or another perineal technique. We excluded studies that performed perineal techniques outside the second stage of labour. Our critical outcomes were second-, third- and fourth-degree tears measured immediately after birth, and PPH ≥ 500 mL measured within 24 hours after birth. We used the Cochrane risk of bias 2 tool to assess bias in the included RCTs. We synthesised results for each outcome within each comparison using meta-analysis where possible. Where this was not possible due to the nature of the data, we synthesised results narratively. We used GRADE to assess the certainty of evidence for each outcome. We included a total of 17 studies with 13,695 participants. Hands off (or poised) versus hands on Hands off (poised) may result in little to no difference in second-degree tears (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.32 to 1.64; 2 studies; low-certainty evidence) and third- or fourth-degree tears when data are combined (RR 1.27, 95% CI 0.81 to 1.99; 2 studies; low-certainty evidence). The evidence is very uncertain about the effect of hands off (poised) on third-degree tears and fourth-degree tears when reported separately (RR 0.50, 95% CI 0.05 to 5.27; 1 study; very low-certainty evidence and RR 3.00, 95% CI 0.13 to 71.22; 1 study; very low-certainty evidence). Hands off (poised) may result in little to no difference in PPH ≥ 500 mL (RR 1.16, 95% CI 0.92 to 1.47; 1 study; low-certainty evidence). Hands off (poised) probably results in little to no difference in breastfeeding two days after birth (RR 1.02, 95% CI 0.99 to 1.06; 1 study; moderate-certainty evidence) and perineal pain (RR 0.98, 95% CI 0.94 to 1.01; 1 study; moderate-certainty evidence). Vocalisation versus control Vocalisation may result in a reduction in second-degree tears (RR 0.56, 95% CI 0.23 to 1.38; 1 study; low-certainty evidence) and third-degree tears (RR 0.13, 95% CI 0.01 to 2.32; 1 study; low-certainty evidence), but the CIs are wide and include the possibility of no effect. No events were reported for fourth-degree tears (low-certainty evidence). Vocalisation may increase maternal satisfaction (RR 1.19, 95% CI 0.93 to 1.51; 1 study; low-certainty evidence). The evidence is very uncertain about the effect of vocalisation on perineal pain (RR 1.44, 95% CI 0.81 to 2.58; 1 study; very low-certainty evidence). Warm compress on the perineum versus control (hands off or no warm compress) Warm compress on the perineum may result in little to no difference in second-degree tears (RR 0.94, 95% CI 0.72 to 1.21; 2 studies; low-certainty evidence), but likely results in a reduction in third- or fourth-degree tears (RR 0.46, 95% CI 0.27 to 0.79; 3 studies; moderate-certainty evidence). Evidence from two smaller studies is very uncertain about the effect of warm compress on the perineum on third-degree tears (RR 0.51, 95% CI 0.04 to 7.05; 2 studies; very low-certainty evidence) or fourth-degree tears (RR 0.11, 95% CI 0.01 to 2.06; 2 studies; very low-certainty evidence) when reported separately. Warm compress likely results in a large reduction in perineal pain (mean difference (MD) -0.81, 95% CI -1.18 to -0.44; 1 study; moderate-certainty evidence). The evidence is very uncertain about the effect of warm compress on the perineum on maternal satisfaction and PPH ≥ 500 mL. Massage of the perineum versus control (hands off or no usual care) Massage of the perineum may have little to no effect on second-degree tears (RR 1.04, 95% CI 0.89 to 1.21; 4 studies; low-certainty evidence). The evidence is very uncertain about the effect of massage of the perineum on third-degree tears (RR 0.57, 95% CI 0.16 to 2.02; 4 studies; very low-certainty evidence). Massage of the perineum may reduce fourth-degree tears but the CIs are wide and include the possibility of no effect (RR 0.26, 95% CI 0.04 to 1.61; 4 studies; low-certainty evidence). The evidence suggests that massage likely results in little to no difference in perineal pain (RR 0.97, 95% CI 0.90, 1.05; 1 study; moderate-certainty evidence). One study reported 10 participants with postpartum haemorrhage across three interventions (warm compress, massage, control). Combined warm compress and massage of the perineum versus control Combined warm compress and massage of the perineum likely results in a reduction in second-degree tears when compared to a control (RR 0.63, 95% CI 0.46 to 0.86; 1 study; moderate-certainty evidence), but the evidence is very uncertain about the effect on third-degree tears (RR 2.92, 95% CI 0.12 to 70.72; 1 study; very low-certainty evidence). The intervention may result in a reduction in PPH ≥ 500 mL but the CIs are wide and include the possibility of no effect (RR 0.43, 95% CI 0.14 to 1.35; 1 study; low-certainty evidence). Combined warm compress and massage likely results in an increase in maternal satisfaction (MD 0.4, 95% CI -0.01 to 0.81; 1 study; moderate-certainty evidence). Combined warm compress and massage of the perineum versus massage alone Combined warm compress and massage of the perineum may result in little to no difference in second-degree tears (RR 0.95, 95% CI 0.86 to 1.06; 1 study; low-certainty evidence) when compared to massage alone, but the evidence is very uncertain about the effect on third- or fourth-degree tears (RR 0.98, 95% CI 0.06 to 15.49; 1 study; very low-certainty evidence). It may also result in little to no difference in PPH ≥ 500 mL (RR 1.10, 95% CI 0.59 to 2.07; 1 study; low-certainty evidence). The evidence suggests that combined warm compress and massage may result in little to no difference in maternal satisfaction (1 study; low-certainty evidence). Other perineal techniques We also assessed evidence on the following comparisons, but since they are used less frequently in global clinical practice to optimise birth outcomes, we have not presented the results summary here: Ritgen's manoeuvre versus standard care; primary delivery of posterior versus anterior shoulder; massage with enriched oil on the perineum versus massage with liquid wax; petroleum jelly on the perineum versus control; and perineal protection device versus control. Overall, the evidence for the effectiveness of perineal techniques to reduce perineal trauma and postpartum haemorrhage is very uncertain. Very few studies reported rates of postpartum haemorrhage, adverse events, women's or health workers' experience or other important outcomes that allow us to understand the effectiveness and acceptability of perineal techniques to reduce perineal trauma. Prior to any further large trials, research is needed to clarify the types of interventions, including a clear description of the process of development and involvement of relevant stakeholders. There is a need to clarify how the intervention is proposed to achieve its effects. Trials would benefit from process evaluation alongside, to explore context, mechanisms and effects. This Cochrane review was funded (in part) by WHO (APW 2024/1475460). TF, VL and the CIDG editorial base are funded by UK aid from the UK government for the benefit of low- and middle-income countries (project number 300342-104). The views expressed do not necessarily reflect the UK government's official policies. Registration and protocol: PROSPERO, CRD42024537252. Available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024537252.

Dwan K ，Fox T ，Lutje V ，Lavender T ，Mills TA ... -  《Cochrane Database of Systematic Reviews》

Cell salvage for the management of postpartum haemorrhage.

Postpartum haemorrhage (PPH), defined as a blood loss of 500 mL or more within 24 hours of birth, is the leading global cause of maternal morbidity and mortality. Allogenic blood transfusions are a critical component of PPH management, yet are often unfeasible, particularly in resource-poor settings where maternal morbidity is highest. Autologous cell salvage in the management of PPH has been proposed to combat limitations in access to allogenic blood and potential transfusion-related risks. This review examines the benefits and harms of using cell salvage for pregnant women during birth. To assess the benefits and harms of cell salvage when used during birth. We searched the CENTRAL, MEDLINE, Ovid Embase, and Global Index Medicus databases and the ICTRP and ClinicalTrials.gov trials registers. We also carried out reference checking and citation searching, and contacted study authors to identify all relevant studies. The latest search date was 8 February 2024. We included randomised controlled trials (RCTs) in pregnant women (24 weeks or more gestation) comparing use of cell salvage following caesarean or vaginal birth with routine care (defined as no cell salvage). We did not place any restrictions on mode of birth, ethnicity, race, socioeconomic status, education level, or place of residence. Critical outcomes for this review were risk of allogenic blood transfusion, risk of transfusion-related adverse reactions, risk of haemorrhage, transfer to higher level of care, length of hospitalisation, length of operation, and risk of sepsis. Important outcomes were estimated blood loss, blood loss ≥ 500 mL, blood loss ≥ 1000 mL, use of additional uterotonics or tranexamic acid, maternal death, postpartum haemoglobin concentration, change in haemoglobin, major surgery including hysterectomy, future major surgery, end-organ dysfunction or failure, amniotic fluid embolism, side effects, clotting abnormalities, maternal experience/satisfaction, maternal well-being, and breastfeeding. We assessed risk of bias using the Cochrane risk of bias tool (RoB 1) for each critical outcome from each RCT. We conducted a meta-analysis for each outcome where data were available from more than one study using a random-effects model. If data could not be analysed using meta-analysis, we synthesised results narratively using the Synthesis Without Meta-analysis (SWiM) guidance. We used GRADE to assess the certainty of evidence for each outcome. We included six RCTs with 3476 participants. All trials involved pregnant women having a caesarean birth. Three trials were conducted in high-income countries, and three were conducted in an upper-middle-income country. Allogenic blood transfusion Intraoperative cell salvage at caesarean birth may reduce the need for allogenic transfusions received by participants, although the 95% confidence interval (CI) includes the possibility of an increase in effect. Low-certainty evidence from three studies found the risk of donor transfusions was possibly lower in participants with cell salvage (risk ratio (RR) 0.45, 95% CI 0.15 to 1.33; P = 0.15, I2 = 33%; 3 RCTs, 3115 women; low-certainty evidence). The absolute risk of transfusion was very low in the studies (4% in women not treated with cell salvage and 2% in women treated with cell salvage). Transfusion-related adverse reactions The evidence is very uncertain about the risk of transfusion-related adverse reactions in participants with intraoperative cell salvage (RR 0.48, 95% CI 0.09 to 2.62; P = 0.39; 4 RCTs, 3304 women; very low-certainty evidence). Haemorrhage Two studies reported risk of haemorrhage and found that there was probably no difference between arms (RR 0.88, 95% CI 0.67 to 1.15; P = 0.36, I² = 0%; 2 RCTs, 3077 women; moderate-certainty evidence). Length of hospitalisation The evidence is very uncertain about whether interoperative cell salvage at caesarean birth affects length of hospitalisation. Three studies reported length of hospitalisation (MD -2.02 days, 95% CI -4.73 to 0.70; P = 0.15, I2 = 100%; 3 RCTs, 3174 women; very low-certainty evidence). Length of operation Two studies reported on length of operation. However, meta-analysis was not possible due to statistical heterogeneity and divergence of study findings; the direction of effect could not be determined. We evaluated the evidence as very low certainty. Sepsis One study reported risk of sepsis, finding that there was possibly no difference between arms (RR 1.00, 95% CI 0.43 to 2.29; P = 0.99; 1 RCT, 2990 women; low-certainty evidence). Estimated blood loss Cell salvage at caesarean birth may reduce blood loss. Two studies reported that estimated blood loss was possibly lower in women who had cell salvage compared to those who did not (MD -113.59 mL, 95% CI -130.41 to -96.77; P < 0.00001, I2 = 0%; 2 RCTs, 246 women; low-certainty evidence). Postpartum haemoglobin concentration Cell salvage at caesarean birth may increase day one postpartum haemoglobin. Three studies reported day one postpartum haemoglobin levels (MD 6.14 g/L, 95% CI 1.62 to 10.65; P = 0.008, I2 = 97%; 3 RCTs, 3070 women; low-certainty evidence). Amniotic fluid embolism Three trials reported risk of amniotic fluid embolism and no cases were observed (n = 3226 women). Cell salvage may reduce the need for allogenic blood transfusion, may reduce blood loss, and may increase day one postpartum haemoglobin in pregnant women having caesarean birth (low certainty). Cell salvage may make little to no difference to the risk of sepsis (low certainty) and probably makes little to no difference to the risk of haemorrhage (moderate certainty). The effect of cell salvage on risk of transfusion-related adverse reactions is very uncertain. The effect of cell salvage on the length of hospital stay was both clinically and statistically heterogenous, with a very low certainty of evidence. The effect of cell salvage on length of operation is divergent and meta-analysis was not possible due to significant statistical heterogeneity; the evidence is of very low certainty. No cases of amniotic fluid embolism were reported among the included trials. Studies in low- and middle-income settings are needed. This review had no dedicated funding. This review was registered with PROSPERO (CRD42024554204).

Dey T ，Brown D ，Cole MG ，Hill RA ，Chaplin M ，Huffstetler HE ，Curtis F ... -  《Cochrane Database of Systematic Reviews》

Tranexamic acid for preventing postpartum haemorrhage after caesarean section.

Postpartum haemorrhage (PPH) is common and potentially life-threatening. The antifibrinolytic drug tranexamic acid (TXA) is recommended for treating PPH; it reduces the risk of death from haemorrhage by one-third when given soon after bleeding onset, but not overall risk of death. Interest in whether TXA may be effective in preventing PPH is growing. Evidence indicates that TXA given more than three hours after injury to bleeding trauma patients increases mortality. Potential harm becomes critical in prophylactic use of TXA. Reliable evidence of the effect and safety profile of TXA is required before widespread prophylactic use can be considered. To assess the effects of TXA for preventing PPH compared to placebo or no treatment (with or without uterotonic co-treatment) in women during caesarean birth. We searched CENTRAL, MEDLINE, Embase, and WHO ICTRP to 20 February 2024 and searched reference lists of retrieved studies. We included randomised controlled trials (RCTs) evaluating the use of TXA alone or plus uterotonics during caesarean birth for preventing PPH. Trials needed to be prospectively registered (i.e. before starting recruitment). We applied a trustworthiness checklist. The critical outcome was blood loss ≥ 1000 mL, measured using estimated or calculated methods. Important outcomes included maternal death, severe morbidity, blood transfusion, the use of additional surgical interventions to control PPH, thromboembolic events, use of additional uterotonics, hysterectomy, maternal satisfaction, and breastfeeding at discharge. We assessed risk of bias in the included studies using Cochrane's RoB 1 tool. Two review authors independently selected trials, extracted data, and assessed risk of bias and trial trustworthiness. We pooled data using random-effects meta-analysis. We assessed the certainty of the evidence using GRADE. We included six RCTs with 15,981 participants. All 12 trials in the previous version of this review were not included after review of trial registrations and trustworthiness checklists. Most included studies involved women at low risk of PPH and were conducted in high-resource settings. Prophylactic TXA in addition to standard care compared to placebo in addition to standard care or standard care alone TXA results in little to no difference in estimated blood loss ≥ 1000 mL (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.79 to 1.11; 4 RCTs; n = 13,042; high certainty evidence), resulting in 8 fewer per 1000 women having estimated blood loss ≥ 1000 mL (from 30 fewer to 16 more). TXA likely results in a slight reduction in calculated blood loss ≥ 1000 mL (RR 0.83, 95% CI 0.76 to 0.92; 2 RCTs; n = 4327; moderate certainty evidence), resulting in 53 fewer per 1000 having calculated blood loss ≥ 1000 mL (from 75 fewer to 25 fewer). The evidence is very uncertain about the effect of TXA on maternal death (one event in placebo group, none in TXA group). No trials measured severe morbidity. TXA likely results in little to no difference in blood transfusion (RR 0.88, 95% CI 0.72 to 1.08; 5 RCTs; n = 15,740; moderate certainty evidence), resulting in 4 fewer per 1000 women requiring a blood transfusion (from 10 fewer to 3 more). TXA results in little to no difference in additional surgical interventions to control PPH (RR 1.02, 95% CI 0.86 to 1.22; 4 RCTs; n = 15,631; high certainty evidence), resulting in 1 more per 1000 women requiring additional surgical intervention (from 4 fewer to 7 more). The evidence is very uncertain about the effect of TXA on thromboembolic events (RR 1.40, 95% CI 0.22 to 8.90; 4 RCTs; n = 14,480; very low certainty evidence), resulting in 1 more per 1000 women having a thromboembolic event (from 2 fewer to 17 more). TXA results in little to no difference in the need for additional uterotonics (RR 0.88, 95% CI 0.78 to 1.00; 4 RCTs; n = 15,728; high certainty evidence), resulting in 15 fewer per 1000 women requiring additional uterotonics (from 27 fewer to 0 fewer). The evidence is very uncertain about the effect of TXA on hysterectomy (RR 0.80, 95% CI 0.20 to 3.29; 2 RCTs; n = 4546; very low certainty evidence), resulting in 3 fewer per 10,000 women requiring a hysterectomy (from 11 fewer to 31 more). One trial measuring maternal satisfaction reported no difference between groups at day two postpartum. No data were available on breastfeeding. Overall, studies had low risk of bias. We downgraded the certainty of evidence mainly for imprecision. Prophylactic TXA in addition to standard care during caesarean birth results in little to no difference in estimated blood loss ≥ 1000 mL and likely results in a slight reduction in calculated blood loss ≥ 1000 mL compared to placebo. There were no data for severe morbidity due to PPH. Event rates for further interventions to control PPH were low and similar across groups. Prophylactic TXA thus results in little to no difference between groups for additional surgical interventions (32 versus 31 per 1000), and likely results in little to no difference between groups for blood transfusions (31 versus 36 per 1000) and use of additional uterotonics (107 versus 121 per 1000). There were very few events for the outcomes maternal death (1 in placebo group), thromboembolic events (2 versus 3 per 1000), and hysterectomy (1 per 1000 in each group). Evidence for these serious adverse events is therefore very uncertain. Decisions about implementing routine prophylactic TXA during caesarean birth should not only consider outcomes related to blood loss, but also the relatively low rates of PPH morbidity and uncertainty of serious adverse events. Most studies included women at low risk of PPH, thereby precluding any conclusions about women at high risk of PPH. Cost associated with routine use of an additional drug for all caesarean births needs to be considered. This Cochrane review was funded in part by the World Health Organization. The published protocol and updates to the review can be accessed: Protocol (2009) DOI: 10.1002/14651858.CD007872 Original Review (2010) DOI: 10.1002/14651858.CD007872.pub2 Review Update (2015) DOI: 10.1002/14651858.CD007872.pub3.

Rohwer C ，Rohwer A ，Cluver C ，Ker K ，Hofmeyr GJ ... -  《Cochrane Database of Systematic Reviews》