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Objective: There are no globally agreed on strategies on early detection and first response management of postpartum haemorrhage (PPH) during and after caesarean birth. Our study aimed to develop an international expert's consensus on evidence-based approaches for early detection and obstetric first response management of PPH intraoperatively and postoperatively in caesarean birth., Design: Systematic review and three-stage modified Delphi expert consensus., Setting: International., Population: Panel of 22 global experts in PPH with diverse backgrounds, and gender, professional and geographic balance., Outcome Measures: Agreement or disagreement on strategies for early detection and first response management of PPH at caesarean birth., Results: Experts agreed that the same PPH definition should apply to both vaginal and caesarean birth. For the intraoperative phase, the experts agreed that early detection should be accomplished via quantitative blood loss measurement, complemented by monitoring the woman's haemodynamic status; and that first response should be triggered once the woman loses at least 500 mL of blood with continued bleeding or when she exhibits clinical signs of haemodynamic instability, whichever occurs first. For the first response, experts agreed on immediate administration of uterotonics and tranexamic acid, examination to determine aetiology and rapid initiation of cause-specific responses. In the postoperative phase, the experts agreed that caesarean birth-related PPH should be detected primarily via frequently monitoring the woman's haemodynamic status and clinical signs and symptoms of internal bleeding, supplemented by cumulative blood loss assessment performed quantitatively or by visual estimation. Postoperative first response was determined to require an individualised approach., Conclusion: These agreed on proposed approaches could help improve the detection of PPH in the intraoperative and postoperative phases of caesarean birth and the first response management of intraoperative PPH. Determining how best to implement these strategies is a critical next step., Competing Interests: Competing interests: Disclosure forms provided by the authors are available with the full text of this article., (© World Health Organization 2024. Licensee BMJ.)

Background: There is general agreement that oxytocin given either through the intravenous or intramuscular route is effective in reducing postpartum blood loss. However, it is unclear whether the subtle differences between the mode of action of these routes have any effect on maternal and infant outcomes. This review was first published in 2012 and last updated in 2018., Objectives: To determine the comparative effectiveness and safety of oxytocin administered intravenously or intramuscularly for prophylactic management of the third stage of labour after vaginal birth., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (19 December 2019), and reference lists of retrieved studies., Selection Criteria: Eligible studies were randomised trials comparing intravenous with intramuscular oxytocin for prophylactic management of the third stage of labour after vaginal birth. We excluded quasi-randomised trials., Data Collection and Analysis: Two review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the certainty of the evidence with the GRADE approach., Main Results: Seven trials, involving 7817 women, met the inclusion criteria for this review. The trials compared intravenous versus intramuscular administration of oxytocin just after the birth of the anterior shoulder or soon after the birth of the baby. All trials were conducted in hospital settings and included women with term pregnancies, undergoing a vaginal birth. Overall, the included studies were at moderate or low risk of bias, with two trials providing clear information on allocation concealment and blinding. For GRADE outcomes, the certainty of the evidence was generally moderate to high, except from two cases where the certainty of the evidence was either low or very low. High-certainty evidence suggests that intravenous administration of oxytocin in the third stage of labour compared with intramuscular administration carries a lower risk for postpartum haemorrhage (PPH) ≥ 500 mL (average risk ratio (RR) 0.78, 95% confidence interval (CI) 0.66 to 0.92; six trials; 7731 women) and blood transfusion (average RR 0.44, 95% CI 0.26 to 0.77; four trials; 6684 women). Intravenous administration of oxytocin probably reduces the risk of PPH ≥ 1000 mL, although the 95% CI crosses the line of no-effect (average RR 0.65, 95% CI 0.39 to 1.08; four trials; 6681 women; moderate-certainty evidence). In all studies but one, there was a reduction in the risk of PPH ≥ 1000 mL with intravenous oxytocin. The study that found a large increase with intravenous administration was small (256 women), and contributed only 3% of total events. Once this small study was removed from the meta-analysis, heterogeneity was eliminated and the treatment effect favoured intravenous oxytocin (average RR 0.61, 95% CI 0.42 to 0.88; three trials; 6425 women; high-certainty evidence). Additionally, a sensitivity analysis, exploring the effect of risk of bias by restricting analysis to those studies rated as 'low risk of bias' for random sequence generation and allocation concealment, found that the prophylactic administration of intravenous oxytocin reduces the risk for PPH ≥ 1000 mL, compared with intramuscular oxytocin (average RR 0.64, 95% CI 0.43 to 0.94; two trials; 1512 women). The two routes of oxytocin administration may be comparable in terms of additional uterotonic use (average RR 0.78, 95% CI 0.49 to 1.25; six trials; 7327 women; low-certainty evidence). Although intravenous compared with intramuscular administration of oxytocin probably results in a lower risk for serious maternal morbidity (e.g. hysterectomy, organ failure, coma, intensive care unit admissions), the confidence interval suggests a substantial reduction, but also touches the line of no-effect. This suggests that there may be no reduction in serious maternal morbidity (average RR 0.47, 95% CI 0.22 to 1.00; four trials; 7028 women; moderate-certainty evidence). Most events occurred in one study from Ireland reporting high dependency unit admissions, whereas in the remaining three studies there was only one case of uvular oedema. There were no maternal deaths reported in any of the included studies (very low-certainty evidence). There is probably little or no difference in the risk of hypotension between intravenous and intramuscular administration of oxytocin (RR 1.01, 95% CI 0.88 to 1.15; four trials; 6468 women; moderate-certainty evidence). Subgroup analyses based on the mode of administration of intravenous oxytocin (bolus injection or infusion) versus intramuscular oxytocin did not show any substantial differences on the primary outcomes. Similarly, additional subgroup analyses based on whether oxytocin was used alone or as part of active management of the third stage of labour (AMTSL) did not show any substantial differences between the two routes of administration., Authors' Conclusions: Intravenous administration of oxytocin is more effective than its intramuscular administration in preventing PPH during vaginal birth. Intravenous oxytocin administration presents no additional safety concerns and has a comparable side effects profile with its intramuscular administration. Future studies should consider the acceptability, feasibility and resource use for the intervention, especially in low-resource settings., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: There is general agreement that oxytocin given either through the intramuscular or intravenous route is effective in reducing postpartum blood loss. However, it is unclear whether the subtle differences between the mode of action of these routes have any effect on maternal and infant outcomes. This is an update of a review first published in 2012., Objectives: To determine the comparative effectiveness and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labour after vaginal birth., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (7 September 2017) and reference lists of retrieved studies., Selection Criteria: Randomised trials comparing intramuscular with intravenous oxytocin for prophylactic management of the third stage of labour after vaginal birth. We excluded quasi-randomised trials., Data Collection and Analysis: Two review authors independently assessed studies for inclusion and risk of bias, extracted data and checked them for accuracy. We assessed the quality of the evidence using the GRADE approach., Main Results: Three studies with 1306 women are included in the review and compared intramuscular versus intravenous oxytocin administered just after the birth of the anterior shoulder or soon after the birth of the baby. Studies were carried out in hospital settings in Turkey and Thailand and recruited women with singleton, term pregnancies. Overall, the included studies were at moderate risk of bias: none of the studies provided clear information on allocation concealment or attempted to blind staff or women. For GRADE outcomes the quality of the evidence was very low, with downgrading due to study design limitations and imprecision of effect estimates.Only one study reported severe postpartum haemorrhage (blood loss 1000 mL or more) and showed no clear difference between the intramuscular and intravenous oxytocin groups (risk ratio (RR) 0.11, 95% confidence interval (CI) 0.01 to 2.04; 256 women; very low-quality evidence). No woman required hysterectomy in either group in one study (no estimable data, very low-quality evidence), and in another study one woman in each group received a blood transfusion (RR 1.00, 95% CI 0.06 to 15.82; 256 women; very low-quality evidence). Other important outcomes (maternal death, hypotension, maternal dissatisfaction with the intervention and neonatal jaundice) were not reported by any of the included studies. There were no clear differences between groups for other prespecified secondary outcomes reported (postpartum haemorrhage 500 mL or more, use of additional uterotonics, retained placenta or manual removal of the placenta)., Authors' Conclusions: Very low-quality evidence indicates no clear difference between the comparative benefits and risks of intramuscular and intravenous oxytocin when given to prevent excessive blood loss after vaginal birth. Appropriately designed randomised trials with adequate sample sizes are needed to assess whether the route of prophylactic oxytocin after vaginal birth affects maternal or infant outcomes. Such studies could be large enough to detect clinically important differences in major side effects that have been reported in observational studies and should also consider the acceptability of the intervention to mothers and providers as important outcomes.

Background: Almost 358,000 women die each year in childbirth, mainly in low-income countries. More than half of all maternal deaths occur within 24 hours of giving birth; severe bleeding in the postpartum period is the single most important cause. Depending on the rate of blood loss and other factors, such as pre-existing anaemia, untreated postpartum haemorrhage (PPH) can lead to hypovolaemic shock, multi-organ dysfunction, and maternal death, within two to six hours.This review investigated different methods for estimating blood loss. The most common method of measuring blood loss during the third stage of labour is visual estimation, during which the birth attendant makes a quantitative or semi-quantitative estimate of the amount of blood lost. In direct blood collection, all blood lost during the third stage of labour (except for the placenta and membranes) is contained in a disposable, funnelled, plastic collector bag, which is attached to a plastic sheet, and placed under the woman's buttocks. When the bleeding stops, there are two options: the bag can be weighed (also called gravimetric technique), or the bag can be calibrated, allowing for a direct measurement. A more precise measurement of blood loss is haemoglobin concentration (Hb) in venous blood sampling and spectrophotometry. With the dye dilution technique, a known quantity of dye is injected into the vein and its plasmatic concentration is monitored after the uterus stops bleeding. Using nuclear medicine, a radioactive tracer is injected, and its concentration is monitored after the uterus stops bleeding. Although hypothetically, these advanced methods could provide a better quantification of blood loss, they are difficult to perform and are not accessible in most settings., Objectives: To evaluate the effect of alternative methods to estimate blood loss during the third stage of labour, to help healthcare providers reduce the adverse consequences of postpartum haemorrhage after vaginal birth., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register (2 February 2018), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP; 21 March 2018), and reference lists of retrieved studies., Selection Criteria: All randomised trials, including cluster-randomised trials, evaluating methods for estimating blood loss after vaginal birth., Data Collection and Analysis: Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy., Main Results: The search retrieved 62 reports in total. Of these, we assessed 12 reports in full, corresponding to six trials. We included three trials and excluded one; two trials are ongoing.The included trials were conducted in hospital settings. Two trials were conducted in India; the third trial was a large cluster-randomised trial, which took place in 13 European countries. Overall, we judged the included trials to be at a low risk of bias. One study evaluated the use of calibrated drapes versus visual estimation, another evaluated the use of calibrated drapes versus the gravimetric technique (weight of blood-soaked materials), therefore, we were unable to pool the data from the two studies. The third study did not measure any of the outcomes of interest, so did not contribute data to the analyses.Direct measurement using calibrated drapes versus visual estimationOne cluster-randomised controlled trial in 13 western European countries, with over 25,000 women, examined this comparison.The trial did not report on postpartum anaemia (defined as Hb lower than 9 mg/dL), blood loss greater than 500 mL, or maternal infection.Moderate-quality evidence suggests there is probably little or no difference between groups in: severe morbidity (coagulopathy, organ failure, intensive care unit admission; adjusted risk ratio (RR) 0.82, 95% confidence interval (CI) 0.48 to 1.39); the risk of blood transfusion (adjusted RR 0.82, 95% CI 0.46 to 1.46); the use of plasma expanders (adjusted RR 0.77, 95% CI 0.42 to 1.42); and the use of therapeutic uterotonics (adjusted RR 0.87, 95% CI 0.42 to 1.76).Direct measurement using calibrated drapes (Excellent BRASSS-V Drape™) versus gravimetric techniqueOne randomised controlled trial in India, with 900 women, examined this comparison.The trial did not report on postpartum anaemia (defined as Hb lower than 9 mg/dL), severe morbidity, or maternal infection.High-quality evidence showed that using calibrated drapes improved the detection of blood loss greater than 500 mL when compared with the gravimetric technique (RR 1.86, 95% CI 1.11 to 3.11). Low-quality evidence suggests there may be little or no difference in the risk of blood transfusion between the two groups (RR 1.00, 95% CI 0.06 to 15.94), or in the use of plasma expanders, reported as intravenous fluids given for PPH treatment (RR 0.67; 95% CI 0.19 to 2.35). High-quality evidence showed little or no difference in the use of therapeutic uterotonics (RR 1.01, 95% CI 0.90 to 1.13), but the use of therapeutic uterotonics was extremely high in both arms of the study (57% and 56%)., Authors' Conclusions: Overall, the evidence in this review is insufficient to support the use of one method over another for blood loss estimation after vaginal birth. In general, the quality of evidence for our predefined outcomes ranged from low to high quality, with downgrading decisions due to imprecision. The included trials did not report on many of our primary and secondary outcomes.In trials that evaluate methods for estimating blood loss during vaginal birth, we believe it is important to measure their impact on clinical maternal and neonatal outcomes, along with their diagnostic accuracy. This body of knowledge needs further, well designed, appropriately powered, randomised controlled trials that correlate blood loss with relevant clinical outcomes, such as those listed in this review.

Background: Postpartum haemorrhage (PPH) is the single leading cause of maternal mortality worldwide. Most of the deaths associated with PPH occur in resource-poor settings where effective methods of prevention and treatment - such as oxytocin - are not accessible because many births still occur at home, or in community settings, far from a health facility. Likewise, most of the evidence supporting oxytocin effectiveness comes from hospital settings in high-income countries, mainly because of the need of well-organised care for its administration and monitoring. Easier methods for oxytocin administration have been developed for use in resource-poor settings, but as far as we know, its effectiveness has not been assessed in a systematic review., Objectives: To assess the effectiveness and safety of oxytocin provided in non-facility birth settings by any way in the third stage of labour to prevent PPH., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, the WHO International Clinical Trials Registry Platform (ICTRP), ClinicalTrials.gov (12 November 2015), and reference lists of retrieved reports., Selection Criteria: All published, unpublished or ongoing randomised or quasi-randomised controlled trials comparing the administration of oxytocin with no intervention, or usual/standard care for the management of the third stage of labour in non-facility birth settings were considered for inclusion.Quasi-randomised controlled trials and randomised controlled trials published in abstract form only were eligible for inclusion but none were identified. Cross-over trials were not eligible for inclusion in this review., Data Collection and Analysis: Two review authors independently assessed studies for eligibility, assessed risk of bias and extracted the data using an agreed data extraction form. Data were checked for accuracy., Main Results: We included one cluster-randomised trial conducted in four rural districts in Ghana that randomised 28 community health officers (CHOs) (serving 2404 potentially eligible pregnant women) to the intervention group and 26 CHOs (serving 3515 potentially eligible pregnant women) to the control group. Overall, the trial had a high risk of bias. CHOs delivered the intervention in the experimental group (injection of 10 IU (international units) of oxytocin in the thigh one minute following birth using a prefilled, auto-disposable syringe). In the control group, CHOs did not provide this prophylactic injection to the women they observed. CHOs had no midwifery skills and did not in any way manage the birth. All other CHO activities (outcome measurement, data collection, and early treatment and referral when necessary) were identical across the control and oxytocin CHOs.Although only one of the nine cases of severe PPH (blood loss greater or equal to 1000 mL) occurred in the oxytocin group, the effect estimate for this outcome was very imprecise and it is uncertain whether the intervention prevents severe PPH (risk ratio (RR) 0.16, 95% confidence interval (CI) 0.02 to 1.30; 1570 women (very low-quality evidence)). Similarly, because of the lack of cases of severe maternal morbidity (e.g. uterine rupture) and maternal deaths, it was not possible to obtain effect estimates for those outcomes (both very low-quality evidence).Oxytocin compared with the control group decreased the incidence of PPH (> 500 mL) in both our unadjusted (RR 0.48, 95% CI 0.28 to 0.81; 1569 women) and adjusted (RR 0.49, 95% CI 0.27 to 0.90; 1174 women (both low-quality evidence)) analyses. There was little or no difference between the oxytocin and control groups on the rates of transfer or referral of the mother to a healthcare facility (RR 0.72, 95% CI 0.34 to 1.56; 1586 women (low-quality evidence)), stillbirths (RR 1.27, 95% CI 0.67 to 2.40; 2006 infants (low-quality evidence)); andearly infant deaths (0 to three days) (RR 1.03, 95% CI 0.35 to 3.07; 1969 infants (low-quality evidence)). There were no cases of needle-stick injury or any other maternal major or minor adverse event or unanticipated harmful event. There were no cases of oxytocin use during labour.There were no data reported for some of this review's secondary outcomes: manual removal of placenta, maternal anaemia, neonatal death within 28 days, neonatal transfer to health facility for advanced care, breastfeeding rates. Similarly, the women's or the provider's satisfaction with the intervention was not reported., Authors' Conclusions: It is uncertain if oxytocin administered by CHO in non-facility settings compared with a control group reduces the incidence of severe PPH (>1000 mL), severe maternal morbidity or maternal deaths. However, the intervention probably decreases the incidence of PPH (> 500 mL).The quality of the one trial included in this review was limited because of the risk of attrition and recruitment biases related to limitations in the follow-up of pregnant women in both arms of the trials and some baseline imbalance on the size of babies at birth. Additionally, there was serious imprecision of the effect estimates for most of the primary outcomes mainly because of the size of the trial, very few or no events and CIs around both relative and absolute estimates of effect that include both appreciable benefit and appreciable harm.Although the trial presented data both for primary and secondary outcomes, it seemed to be underpowered to detect differences in the primary outcomes that are the ones more relevant for making judgments about the potential applicability of the intervention in other settings (especially severe PPH).Therefore, taking into account the extreme setting where the intervention was implemented, the limited role of the CHO in the trial and the lack of power for detecting effects on primary (relevant) outcomes, the applicability of the evidence found seems to be rather limited.Further well-executed and adequately-powered randomised controlled trials assessing the effects of using oxytocin in pre-filled injection devices or other new delivery systems (spray-dried ultrafine formulation of oxytocin) on severe PPH are urgently needed. Likewise, other important outcomes like possible adverse events and acceptability of the intervention by mothers and other community stakeholders should also be assessed.

Background: Advance community distribution of misoprostol for preventing or treating postpartum haemorrhage (PPH) has become an attractive strategy to expand uterotonic coverage to places where conventional uterotonic use is not feasible. However, the value and safety of this strategy remain contentious., Objectives: To assess the effectiveness and safety of a strategy of advance misoprostol distribution for PPH prevention and treatment in non-facility births., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (5 October 2011). We did not apply any language restrictions., Selection Criteria: Randomised or quasi-randomised controlled trials of advance misoprostol distribution to lay health workers or pregnant women compared with usual care for PPH prevention or treatment in non-facility births. We excluded studies without any form of random design., Data Collection and Analysis: Two review authors independently assessed trial eligibility for inclusion., Main Results: The search strategies identified three studies. None of the studies met the inclusion criteria., Authors' Conclusions: There is no evidence from randomised or quasi-randomised trials on the benefits or risks of a strategy of advance misoprostol distribution for PPH prevention or treatment in non-facility births. In view of the increasing interest to scale up this strategy, there is an urgent need for large and well-designed randomised trials to evaluate its comparative benefits and risks.

Background: There is a general agreement that oxytocin given either through the intramuscular or intravenous route is effective in reducing postpartum blood loss. However, it is unclear whether the subtle differences between the mode of action of these routes have any effect on maternal and infant outcomes., Objectives: To determine the comparative effectiveness and safety of oxytocin administered intramuscularly or intravenously for prophylactic management of the third stage of labour after vaginal birth., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 December 2011)., Selection Criteria: Randomised trials comparing intramuscular with intravenous oxytocin for prophylactic management of the third stage of labour after vaginal birth. We excluded quasi-randomised trials., Data Collection and Analysis: Two review authors planned to independently assess trials for inclusion, assess risk of bias and extract data., Main Results: The search strategies identified no trials for consideration but we identified one ongoing study., Authors' Conclusions: There is no evidence from randomised trials to evaluate the comparative benefits and risks of intramuscular and intravenous oxytocin when given to prevent excessive blood loss after vaginal birth. Randomised trials with adequate design and sample sizes are needed to assess whether the route of prophylactic oxytocin after vaginal birth affects maternal or infant outcomes. Such trials should be large enough to detect clinically important differences in major side effects reported in observational studies and also to consider the acceptability of the intervention to mothers and providers as important outcomes.

Postpartum haemorrhage (PPH) is an important cause of maternal mortality. We conducted a systematic review of the prevalence of PPH with the objective of evaluating its magnitude both globally and in different regions and settings: global figures, as well as regional, country and provincial variations, are likely to exist but are currently unknown. We used prespecified criteria to select databases, recorded the database characteristics and assessed their methodological quality. After establishing PPH (>or=500 mL blood loss) and severe PPH (SSPH) (>or=1000 mL blood loss) as main outcomes, we found 120 datasets (involving a total of 3,815,034 women) that reported PPH and 70 datasets (505,379 women) that reported SPPH in the primary analysis. The prevalence of PPH and SPPH is approximately 6% and 1.86% of all deliveries, respectively, with a wide variation across regions of the world. The figures we obtained give a rough estimate of the prevalence of PPH and suggest the existence of some variations. For a reliable picture of PPH worldwide - its magnitude, distribution and consequences - a global survey tackling this condition is necessary.