Effect and safety of intravenous iron compared to oral iron for treatment of iron deficiency anaemia in pregnancy.

Intravenous iron is increasingly used to treat iron-deficient anaemia (IDA) in pregnancy. A previous network meta-analysis suggested that intravenous irons have a greater effect on haematological parameters than oral irons; however, the impact on serious pregnancy complications such as postpartum haemorrhage (PPH) or the need for blood transfusion was unclear. Since then, several new randomised controlled trials (RCTs) have been conducted. To evaluate the effect and safety of intravenous versus oral iron preparations for treating IDA in pregnancy. We searched CENTRAL, MEDLINE, Embase, and two trial registries (ClinicalTrials.gov and the WHO ICTRP) for eligible studies. The latest search was performed on 19 March 2024. We included RCTs in pregnant women with confirmed IDA (haemoglobin (Hb) level < 11 g/dL as per World Health Organization (WHO) criteria) comparing intravenous (iron sucrose, ferric carboxymaltose, ferric derisomaltose, ferumoxytol) and oral (ferrous sulfate, ferrous fumarate, ferrous gluconate) iron preparations. Our outcomes were antenatal and postnatal Hb levels, antenatal and postnatal anaemia status, PPH, blood transfusion, maternal satisfaction, maternal well-being, breastfeeding, maternal mortality, maternal morbidity, and adverse events (AEs). We used the Cochrane RoB 1 tool to assess risk of bias in the included RCTs. We followed standard Cochrane methods. Two review authors independently assessed studies for eligibility and scientific rigour, evaluated the risk of bias of included studies, and extracted data. Where appropriate, we pooled data using a fixed-effect model in the first instance. We reported dichotomous data as risk ratios (RRs) with 95% confidence intervals (CIs) and continuous data as mean differences (MDs) with 95% CIs. We assessed the certainty of the evidence using the GRADE approach. We included 13 RCTs (3939 participants) mainly conducted in India and Africa (8/13). Gestational age at baseline ranged from 13 to 37 weeks, and Hb levels ranged from 5.0 to just below 11.0 g/dL. The most frequently compared preparations were intravenous iron sucrose versus oral ferrous sulfate (5/13). Most RCTs were at low risk of bias, and the certainty of evidence ranged from moderate to very low, mainly due to concerns over attrition bias, imprecision, and inconsistency. Antenatal outcomes Compared with oral iron, intravenous iron likely slightly increases Hb level three to six weeks after treatment start (MD 0.49, 95% CI 0.28 to 0.69; 11 RCTs; 2935 participants; moderate-certainty evidence) and likely reduces anaemia status three to six weeks after treatment start (RR 0.81, 95% CI 0.77 to 0.86; 5 RCTs; 2189 participants; moderate-certainty evidence). Compared with oral iron, intravenous iron likely slightly increases Hb level around birth (MD 0.55, 95% CI 0.33 to 0.77; 6 RCTs; 1574 participants; moderate-certainty evidence) and likely reduces anaemia status around birth (RR 0.85, 95% CI 0.77 to 0.93; 4 RCTs; 1240 participants; moderate-certainty evidence). Postpartum outcomes Compared with oral iron, intravenous iron may slightly increase Hb level postpartum (MD 0.54, 95% CI 0.41 to 0.68; 3 RCTs; 1950 participants; low-certainty evidence). It may also reduce anaemia status (RR 0.66, 95% CI 0.59 to 0.73; 3 RCTs; 1950 participants; low-certainty evidence) and severe anaemia postpartum (RR 0.16, 95% CI 0.03 to 0.84; 2 RCTs; 1581 participants; very low-certainty evidence), although the evidence for the latter outcome is very uncertain. Compared with oral iron, intravenous iron may result in little to no difference in PPH (RR 1.44, 95% CI 0.50 to 4.20; 3 RCTs; 2251 participants; low-certainty evidence) and likely results in little to no difference in the need for blood transfusion (RR 0.97, 95% CI 0.58 to 1.60; 6 RCTs; 2592 participants; moderate-certainty evidence) or rates of breastfeeding (RR 1.04, 95% CI 0.97 to 1.12; 1 RCT; 404 participants; moderate-certainty evidence). No trials reported on maternal satisfaction or maternal well-being. Adverse outcomes Compared with oral iron, intravenous iron may have little to no effect on maternal mortality, but the evidence is very uncertain (RR 0.91, 95% CI 0.13 to 6.39; 4 RCTs; 2152 participants; very low-certainty evidence). Compared with oral iron, intravenous iron likely does not increase maternal morbidity: severe infections (RR 1.01, 95% CI 0.47 to 2.18; 1 RCT; 1881 participants; moderate-certainty evidence) and prolonged hospital stay (RR 0.86, 95% CI 0.62 to 1.21; 1 RCT; 1764 participants; moderate-certainty evidence) and may not increase admissions to the intensive care unit (ICU) (RR 1.99, 95% CI 0.18 to 21.87; 2 RCTs; 2069 participants; low-certainty evidence). Compared with oral iron, intravenous iron likely does not increase AEs (RR 1.05, 95% CI 0.82 to 1.35; 1 RCT; 349 participants; moderate-certainty evidence) and may not increase serious AEs (RR 1.25, 95% CI 0.61 to 2.59; 1 RCT; 1934 participants; low-certainty evidence). However, individual AEs were inconsistently reported across trials. Intravenous iron likely slightly increases Hb levels and likely reduces anaemia in pregnancy compared to oral iron. Hb levels postpartum may be slightly increased with intravenous iron, but the effect on postpartum severe anaemia status is very uncertain. Intravenous iron may result in little to no difference in PPH, and blood transfusion rates are likely unaffected by route of administration. Synthesis of adverse outcomes proved challenging due to their rarity and suboptimal reporting. The effects of intravenous iron on maternal mortality and admissions to the ICU are very uncertain, and there is likely little to no difference between groups in severe infections and prolonged hospital stay. Intravenous iron likely does not increase AEs and may not increase serious AEs; however, the 95% CIs in both cases include potential harm. Furthermore, this finding should be treated cautiously due to the varied adverse event profiles of both types of iron preparations. Data from the ongoing multicentre trials may address some of the identified evidence gaps. However, there is a clear need to strengthen the co-ordination of research efforts around clinically important time points of outcome measure, homogeneity of their definition, and safety reporting. This Cochrane Review was partially funded by the WHO and was supported by the UK Medical Research Council funding. Registration (2024): PROSPERO, CRD42024523791 via www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024523791.

Nicholson L ，Axon E ，Daru J ，Rogozińska E ... -  《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》

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》

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》

Fortification of condiments and seasonings with iron for preventing anaemia and improving health.

Jalal CS ，De-Regil LM ，Pike V ，Mithra P ... -  《Cochrane Database of Systematic Reviews》