Tranexamic acid for preventing postpartum haemorrhage after vaginal birth.

Postpartum haemorrhage (PPH) is common and potentially life-threatening. The antifibrinolytic drug tranexamic acid (TXA) is thought to be effective for treating PPH. There is growing interest in whether TXA is effective for preventing PPH after vaginal birth. In randomised controlled trials (RCTs), TXA has been associated with increased risk of seizures and unexplained increased mortality when given more than three hours after traumatic bleeding. Reliable evidence on the effects, cost-effectiveness and safety of prophylactic TXA is required before considering widespread use. This review updates one published in 2015. To assess the effects of TXA for preventing PPH compared to placebo or no treatment (with or without uterotonic co-treatment) in women following vaginal birth. We searched MEDLINE, Embase, CENTRAL, and WHO ICTRP (to 6 September 2024). We also searched reference lists of retrieved studies. We included RCTs evaluating TXA alone or in addition to standard care (uterotonics) for preventing PPH following vaginal birth. For this update, we required trials to be prospectively registered (before participant recruitment), and we applied a trustworthiness checklist. Critical outcomes were blood loss ≥ 500 mL and blood loss ≥ 1000 mL. Important outcomes included maternal death, severe morbidity, blood transfusion, receipt of additional surgical interventions to control PPH, thromboembolic events, receipt of additional uterotonics, hysterectomy, and maternal satisfaction. We used the Cochrane risk of bias tool (RoB 1) to assess the risk of bias in the studies. Two review authors independently selected trials, extracted data, assessed risk of bias, and assessed trial trustworthiness. We used random-effects meta-analysis to combine data. We assessed the certainty of the evidence using GRADE. We included three RCTs with 18,974 participants in total. The trials were conducted in both high- and low-resource settings and involved participants at both low and high risk of PPH. The trials compared intravenous TXA (1 g) and standard care versus placebo (saline) and standard care. After applying our trustworthiness checklist, we did not include any of the 12 trials in the previous version of this review. Prophylactic tranexamic acid in addition to standard care compared to placebo in addition to standard care TXA results in little to no difference in blood loss ≥ 500 mL (risk ratio (RR) 0.93, 95% confidence interval (CI) 0.81 to 1.06; 2 studies, 18,897 participants; 5 fewer per 1000, 95% CI 15 fewer to 5 more; high-certainty evidence). TXA likely results in little to no difference in blood loss ≥ 1000 mL (RR 0.86, 95% CI 0.69 to 1.07; 2 studies, 18,897 participants; 3 fewer per 1000, 95% CI 6 fewer to 1 more; moderate-certainty evidence). TXA likely results in little to no difference in severe morbidity (RR 0.88, 95% CI 0.69 to 1.12; 1 study, 15,066 participants; 2 fewer per 1000, 95% CI 6 fewer to 2 more; moderate-certainty evidence). TXA results in little to no difference in receipt of blood transfusion (RR 1.00, 95% CI 0.95 to 1.06; 3 studies, 18,972 participants; 0 fewer per 1000, 95% CI 10 fewer to 12 more; high-certainty evidence). TXA may result in little to no difference in receipt of additional surgical interventions to control PPH (RR 0.63, 95% CI 0.32 to 1.23; 2 studies, 18,972 participants; 1 fewer per 1000, 95% CI 2 fewer to 1 more; low-certainty evidence). In women with anaemia, TXA results in little to no difference in receipt of additional uterotonics (RR 1.02, 95% CI 0.94 to 1.10; 1 study, 15,066 participants; 3 more women per 1000, 95% CI 8 fewer to 24 more; high-certainty evidence). In women with no anaemia, TXA results in a slight reduction in receipt of additional uterotonics (RR 0.75, 95% CI 0.61 to 0.92; 1 study, 3891 participants; 24 fewer women per 1000, 95% CI 38 fewer to 8 fewer; high-certainty evidence). TXA likely results in little to no difference in maternal satisfaction. The evidence is very uncertain about the effect of TXA on maternal death, thromboembolic events, and hysterectomy (very low-certainty evidence): maternal death (RR 0.99, 95% CI 0.39 to 2.49; 2 studies, 15,081 participants; 0 fewer per 1000, 95% CI 1 fewer to 2 more); thromboembolic events (RR 0.25, 95% CI 0.03 to 2.24; 3 studies, 18,774 participants; 3 fewer women per 10,000, 95% CI 4 fewer to 5 more); hysterectomy (RR 0.89, 95% CI 0.36 to 2.19; 1 study, 15,066 participants; 1 fewer women per 10,000, 95% CI 9 fewer to 16 more). Adding prophylactic TXA to standard care of women during vaginal birth makes little to no difference to blood loss ≥ 500 mL and likely makes little to no difference to blood loss ≥ 1000 mL or the risk of severe morbidity, compared to placebo and standard care. TXA may result in little to no difference in additional surgical interventions to control PPH and results in little to no difference in blood transfusions. One trial found that TXA reduced the use of additional uterotonics in women without anaemia, whereas the largest trial found little to no difference in the use of additional uterotonics in women with anaemia. Although there were very few serious adverse events reported, the evidence is insufficient to draw conclusions about the effect of TXA on maternal death, thromboembolic events, hysterectomy, or seizures. TXA likely results in little to no difference in maternal satisfaction. These findings are based mainly on two large trials. In the smaller of these, less than 30% of study participants were at high risk of PPH. In the largest trial, all participants had moderate to severe anaemia. Those making decisions about routine administration of prophylactic TXA for all women having vaginal births should consider that current evidence does not show a benefit of TXA for blood loss outcomes and related morbidity, and the evidence is very uncertain about serious adverse events. This review was partially funded by the World Health Organization (WHO). 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 AC ，Cluver C ，Ker K ，Hofmeyr GJ ... -  《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》

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》

Uterotonics for management of retained placenta.

Retained placenta is a significant cause of maternal death from postpartum haemorrhage. Traditionally, it is managed by manual removal under anaesthesia, which carries risks of haemorrhage, infection, and uterine perforation. Uterotonics may offer an alternative for delivering the retained placenta since they induce uterine contractions. However, evidence regarding uterotonic agents for retained placenta is still limited. To assess the benefits and harms of uterotonics for women with retained placenta after vaginal delivery for preventing postpartum haemorrhage. We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, and WHO ICTRP; and checked references of included studies and pertinent systematic reviews to identify additional studies. The latest search date was 25 April 2024. We included randomised controlled trials (RCTs) and non-randomised studies of interventions in women who underwent vaginal delivery with retained placenta comparing one uterotonic with another uterotonic, placebo, or no treatment. We excluded studies that compared different uterotonics administered by umbilical vein injection. Our main outcomes were manual removal of the placenta; postpartum haemorrhage of 1000 mL or more; adverse effects, such as shivering; blood transfusion; maternal death; severe morbidity (admission to the intensive care unit); and blood loss in millilitres. The primary time point of interest for all outcomes was the end of the study period. We used the Cochrane RoB 2 tool to assess bias in RCTs and the ROBINS-I tool to assess bias in non-randomised studies of interventions. We synthesised results for each outcome using a random-effects meta-analysis, where possible, employing Mantel-Haenszel with risk ratio (RR) or inverse variance with mean difference (MD), as appropriate. Where this was not possible due to the nature of the data, we synthesised results using narrative synthesis methods. We used GRADE to assess the certainty of evidence for each outcome. We included five studies with 560 women, comprising four RCTs and one non-randomised study. The studies were conducted in the Netherlands, Tanzania, and Egypt. Three RCTs compared uterotonics (sulprostone or misoprostol) with placebo or no treatment. One RCT compared oxytocin, intravenous carbetocin, and sublingual misoprostol. One non-randomised study compared intraumbilical oxytocin to oxytocin infusion. Systemic uterotonic agents versus placebo or no treatment Sulprostone or misoprostol may result in little to no difference in the rate of manual removal of the placenta (RR 0.82, 95% confidence interval (CI) 0.54 to 1.27; 3 RCTs, 244 women; low-certainty evidence), and probably results in little to no difference in postpartum haemorrhage (RR 0.80, 95% CI 0.55 to 1.15; 2 RCTs, 194 women; moderate-certainty evidence), and blood transfusion (RR 0.72, 95% CI 0.43 to 1.22; 3 RCTs, 244 women; moderate-certainty evidence) compared to placebo or no treatment. We are very uncertain about the effect of misoprostol on shivering (RR 10.00, 95% CI 1.40 to 71.49; 1 RCT, 70 women; very low-certainty evidence) and the effects of uterotonic agents on mean blood loss (MD -205.26 mL, 95% CI -536.31 to 125.79; 3 RCTs, 244 women; very low-certainty evidence). No study assessed maternal death or severe morbidity. Intravenous carbetocin versus sublingual misoprostol Intravenous carbetocin probably does not reduce the need for manual removal of the placenta (RR 0.79, 95% CI 0.52 to 1.20; 1 RCT, 185 women; moderate-certainty evidence), and may not reduce blood transfusion (RR 0.48, 95% CI 0.09 to 2.58; 1 RCT, 185 women; low-certainty evidence) compared to sublingual misoprostol. The study did not assess postpartum haemorrhage of 1000 mL or more, adverse effects (shivering), maternal death, severe morbidity, and blood loss. Sublingual misoprostol versus oxytocin intraumbilical venous injection Sublingual misoprostol probably results in little to no difference in the rate of manual removal of the placenta (RR 1.09, 95% CI 0.73 to 1.61; 1 RCT, 187 women; moderate-certainty evidence) and may not reduce the need for blood transfusion (RR 1.05, 95% CI 0.27 to 4.09; 1 RCT, 187 women; low-certainty evidence) compared to oxytocin intraumbilical venous injection. The study did not assess postpartum haemorrhage of 1000 mL or more, adverse effects (shivering), maternal death, severe morbidity, and blood loss. Intravenous carbetocin versus oxytocin intraumbilical venous injection Intravenous carbetocin probably does not reduce the rate of manual removal of the placenta (RR 0.86, 95% CI 0.56 to 1.32; 1 RCT, 190 women; moderate-certainty evidence), and may result in little to no difference in reducing blood transfusions (RR 0.51, 95% CI 0.10 to 2.72; 1 RCT, 190 women; low-certainty evidence) compared to intraumbilical venous injection. The study did not assess postpartum haemorrhage of 1000 mL or more, adverse effects (shivering), maternal death, severe morbidity, and blood loss. Oxytocin infusion versus oxytocin intraumbilical venous injection The evidence from one non-randomised study is very uncertain about the effect of oxytocin infusion on manual removal of the placenta compared to oxytocin intraumbilical venous injection (RR 0.90, 95% CI 0.71 to 1.13; 1 study, 35 women; very low-certainty evidence). The study did not assess our other outcomes of interest. Current evidence suggests that uterotonic agents (such as misoprostol and sulprostone) may result in little to no difference in the rates of manual removal of the placenta, and probably result in little to no difference in postpartum haemorrhage and the need for blood transfusions, compared to placebo or no treatment in the management of retained placenta. The evidence is very uncertain about their effects on blood loss and the effect of misoprostol on shivering. There is probably little to no difference in effects and there may be no difference in safety between one uterotonic agent over another. We found no useable data for maternal death and admission to the intensive care unit. Further large-scale studies are necessary to evaluate uterotonics versus placebo, compare different uterotonic agents, or assess combined uterotonic regimens. Additional research should focus on identifying specific adverse effects, maternal satisfaction and well-being, breastfeeding rates at discharge, and postpartum anaemia. This Cochrane review was funded by UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP). Registration (13 July 2024): Prospero, CRD42024564386.

Sothornwit J ，Ngamjarus C ，Pattanittum P ，Waidee T ，Jampathong N ，Jongjakapun A ，Kongwattanakul K ，Lumbiganon P ... -  《Cochrane Database of Systematic Reviews》

Treatment for women with postpartum iron deficiency anaemia.

Postpartum iron deficiency anaemia is caused by antenatal iron deficiency or excessive blood loss at delivery and might affect up to 50% of labouring women in low- and middle-income countries. Effective and safe treatment during early motherhood is important for maternal well-being and newborn care. Treatment options include oral iron supplementation, intravenous iron, erythropoietin, and red blood cell transfusion. To assess the benefits and harms of the available treatment modalities for women with postpartum iron deficiency anaemia. These include intravenous iron, oral iron supplementation, red blood cell transfusion, and erythropoietin. A Cochrane Information Specialist searched for all published, unpublished, and ongoing trials, without language or publication status restrictions. We searched databases including CENTRAL, MEDLINE, Embase, CINAHL, LILACS, WHO ICTRP, and ClinicalTrials.gov, together with reference checking, citation searching, and contact with study authors to identify eligible studies. We applied date limits to retrieve new records since the last search on 9 April 2015 until 11 April 2024. We included published, unpublished, and ongoing randomised controlled trials (RCTs) that compared treatments for postpartum iron deficiency anaemia with placebo, no treatment, or alternative treatments. Cluster-randomised trials were eligible for inclusion. We included RCTs regardless of blinding. Participants were women with postpartum haemoglobin ≤ 12 g/dL, treated within six weeks after childbirth. We excluded non-randomised, quasi-randomised, and cross-over trials. The critical outcomes of this review were maternal mortality and fatigue. The important outcomes included persistent anaemia symptoms, persistent postpartum anaemia, psychological well-being, infections, compliance with treatment, breastfeeding, length of hospital stay, serious adverse events, anaphylaxis or evidence of hypersensitivity, flushing/Fishbane reaction, injection discomfort/reaction, constipation, gastrointestinal pain, number of red blood cell transfusions, and haemoglobin levels. We assessed risk of bias in the included studies using the Cochrane RoB 1 tool. Two review authors independently performed study screening, risk of bias assessment, and data extraction. We contacted trial authors for supplementary data when necessary. We screened all trials for trustworthiness and scientific integrity using the Cochrane Trustworthiness Screening Tool. We conducted meta-analyses using a fixed-effect model whenever feasible to synthesise outcomes. In cases where data were not suitable for meta-analysis, we provided a narrative summary of important findings. We evaluated the overall certainty of the evidence using GRADE. We included 33 RCTs with a total of 4558 postpartum women. Most trials were at high risk of bias for several risk of bias domains. Most of the evidence was of low or very low certainty. Imprecision due to few events and risk of bias due to lack of blinding were the most important factors. Intravenous iron versus oral iron supplementation The evidence is very uncertain about the effect of intravenous iron on mortality (risk ratio (RR) 2.95, 95% confidence interval (CI) 0.12 to 71.96; P = 0.51; I² = not applicable; 3 RCTs; 1 event; 572 women; very low-certainty evidence). One woman died of cardiomyopathy, and another developed arrhythmia, both in the groups treated with intravenous iron. Intravenous iron probably results in a slight reduction in fatigue within 8 to 28 days (standardised mean difference -0.25, 95% CI -0.42 to -0.07; P = 0.006; I² = 47%; 2 RCTs; 515 women; moderate-certainty evidence). Breastfeeding was not reported. Oral iron probably increases the risk of constipation compared to intravenous iron (RR 0.12, 95% CI 0.06 to 0.21; P < 0.001; I² = 0%; 10 RCTs; 1798 women; moderate-certainty evidence). The evidence is very uncertain about the effect of intravenous iron on anaphylaxis or hypersensitivity (RR 2.77, 95% CI 0.31 to 24.86; P = 0.36; I² = 0%; 12 RCTs; 2195 women; very low-certainty evidence). Three women treated with intravenous iron experienced anaphylaxis or hypersensitivity. The trials that reported on haemoglobin at 8 to 28 days were too heterogeneous to pool. However, 5 of 6 RCTs favoured intravenous iron, with mean changes in haemoglobin ranging from 0.73 to 2.10 g/dL (low-certainty evidence). Red blood cell transfusion versus intravenous iron No women died in the only trial that reported on mortality (1 RCT; 7 women; very low-certainty evidence). The evidence is very uncertain about the effect of red blood cell transfusion on fatigue at 8 to 28 days (mean difference (MD) 1.20, 95% CI -2.41 to 4.81; P = 0.51; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence) and breastfeeding more than six weeks postpartum (RR 0.43, 95% CI 0.12 to 1.57; P = 0.20; I² = not applicable; 1 RCT; 13 women; very low-certainty evidence). Constipation and anaphylaxis were not reported. Red blood cell transfusion may result in little to no difference in haemoglobin within 8 to 28 days (MD -1.00, 95% CI -2.02 to 0.02; P = 0.05; I² = not applicable; 1 RCT; 12 women; low-certainty evidence). Intravenous iron and oral iron supplementation versus oral iron supplementation Mortality and breastfeeding were not reported. One trial reported a greater improvement in fatigue in the intravenous and oral iron group, but the effect size could not be calculated (1 RCT; 128 women; very low-certainty evidence). Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone (RR 0.21, 95% CI 0.07 to 0.69; P = 0.01; I² = not applicable; 1 RCT; 128 women; low-certainty evidence). There were no anaphylaxis or hypersensitivity events in the trials (2 RCTs; 168 women; very low-certainty evidence). Intravenous iron and oral iron may result in little to no difference in haemoglobin (g/dL) at 8 to 28 days (MD 0.00, 95% CI -0.48 to 0.48; P = 1.00; I² = not applicable; 1 RCT; 60 women; low-certainty evidence). Red blood cell transfusion versus no transfusion Mortality, fatigue at day 8 to 28, constipation, anaphylaxis, and haemoglobin were not reported. Red blood cell transfusion may result in little to no difference in breastfeeding more than six weeks postpartum (RR 0.91, 95% CI 0.78 to 1.07; P = 0.24; I² = not applicable; 1 RCT; 297 women; low-certainty evidence). Oral iron supplementation versus placebo or no treatment Mortality, fatigue, breastfeeding, constipation, anaphylaxis, and haemoglobin were not reported. Two trials reported on gastrointestinal symptoms, but did not report results by study arm. Intravenous iron probably reduces fatigue slightly in the early postpartum weeks (8 to 28 days) compared to oral iron tablets, but probably results in little to no difference after four weeks. It is very uncertain if intravenous iron has an effect on mortality and anaphylaxis/hypersensitivity. Breastfeeding was not reported. Intravenous iron may increase haemoglobin slightly more than iron tablets, but the data were too heterogeneous to pool. However, changes in haemoglobin levels are a surrogate outcome, and treatment decisions should preferentially be based on patient-relevant outcomes. Iron tablets probably result in a large increase in constipation compared to intravenous iron. The effect of red blood cell transfusion compared to intravenous iron on mortality, fatigue, and breastfeeding is very uncertain. No studies reported on constipation or anaphylaxis/hypersensitivity. Red blood cell transfusion may result in little to no difference in haemoglobin at 8 to 28 days. The effect of intravenous iron and oral iron supplementation on mortality, fatigue, breastfeeding, and anaphylaxis/hypersensitivity is very uncertain or unreported. Intravenous iron and oral iron may result in a reduction in constipation compared to oral iron alone, and in little to no difference in haemoglobin. The effect of red blood cell transfusion compared to non-transfusion on mortality, fatigue, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. Red blood cell transfusion may result in little to no difference in breastfeeding. The effect of oral iron supplementation on mortality, fatigue, breastfeeding, constipation, anaphylaxis/hypersensitivity, and haemoglobin is unreported. This Cochrane review had no dedicated funding. Protocol and previous versions are available: Protocol (2013) [DOI: 10.1002/14651858.CD010861] Original review (2004) [DOI: 10.1002/14651858.CD004222.pub2] Review update (2015) [DOI: 10.1002/14651858.CD010861.pub2].

Jensen MCH ，Holm C ，Jørgensen KJ ，Schroll JB ... -  《Cochrane Database of Systematic Reviews》