• The GDG agreed that the high recurrent costs of haemoglobin testing with haemoglobinometers might reduce the feasibility of this method in some low-resource settings, in which case the WHO haemoglobin colour scale method may be used.
• Other low-technology on-site methods for detecting anaemia need development and/or investigation.

• This recommendation should be considered alongside Recommendation 3 on intermittent iron supplementation.
• In settings where anaemia in pregnant women is a severe public health problem (i.e. where at least 40% of pregnant women have a blood haemoglobin concentration <110 g/L), a daily dose of 60 mg of elemental iron is preferred over a lower dose.
• In the first and third trimesters, the haemoglobin threshold for diagnosing anaemia is 110 g/L; in the second trimester, the threshold is 105 g/L (33).
• If a woman is diagnosed with anaemia during pregnancy, her daily elemental iron should be increased to 120 mg until her haemoglobin concentration rises to normal (110 g/L or higher) (34, 35). Thereafter, she can resume the standard daily antenatal iron dose to prevent recurrence of anaemia.
• Effective communication with pregnant women about diet and healthy eating, including providing information about food sources of vitamins and minerals, and dietary diversity, is an integral part of preventing anaemia and providing quality ANC.
• Effective communication strategies are vital for improving the acceptability of, and adherence to, supplementation schemes.
• Stakeholders may need to consider ways of reminding pregnant women to take their supplements and of assisting them to manage associated side-effects.
• In areas with endemic infections that may cause anaemia through blood loss, increased red cell destruction or decreased red cell production, such as malaria and hookworm, measures to prevent, diagnose and treat these infections should be implemented.
• Oral supplements are available as capsules or tablets (including soluble tablets, and dissolvable and modified-release tablets) (36). Establishment of a quality assurance process is important to guarantee that supplements are manufactured, packaged and stored in a controlled and uncontaminated environment (37).
• A better understanding of the etiology of anaemia (e.g. malaria endemicity, haemoglobinopathies) and the prevalence of risk factors is needed at the country level, to inform context-specific adaptations of this recommendation.
• Standardized definitions of side-effects are needed to facilitate monitoring and evaluation.
• Development and improvement of integrated surveillance systems are needed to link the assessment of anaemia and iron status at the country level to national and global surveillance systems.
• To reach the most vulnerable populations and ensure a timely and continuous supply of supplements, stakeholders may wish to consider task shifting the provision of iron supplementation in community settings with poor access to health care professionals.

• This recommendation should be considered alongside Recommendation 2.
• In general, anaemia prevalence of less than 20% is classified as a mild public health problem (38).
• Before commencing intermittent iron supplementation, accurate measurement of maternal blood haemoglobin concentrations is needed to confirm the absence of anaemia. Therefore, this recommendation may require a strong health system to facilitate accurate haemoglobin measurement and to monitor anaemia status throughout pregnancy.
• If a woman is diagnosed with anaemia (haemoglobin <110 g/L) during ANC, she should be given 120 mg of elemental iron and 400 μg (0.4 mg) of folic acid daily until her haemoglobin concentration rises to normal (110 g/L or higher) (34, 35). Thereafter, she can continue with the standard daily antenatal iron and folic acid dose (or the intermittent regimen if daily iron is not acceptable because of side-effects) to prevent recurrence of anaemia.
• Stakeholders may need to consider ways of reminding pregnant women to take their supplements on an intermittent basis and of assisting them to manage associated side-effects.

Justification

Intravenous iron may increase haemoglobin compared to oral iron and may also decrease the number of women with anaemia postpartum (number needed to treat = 6).

Even though intravenous iron causes fewer gastrointestinal side-effects, it carries a risk of hypersensitivity reaction and perhaps also life-threatening anaphylactic reaction. Properly trained health care workers must monitor treatment for signs of adverse reactions and be prepared and equipped to respond quickly if needed. Although anaphylaxis is a rare event, robust monitoring and surveillance systems should be in place to track safety data as the intervention is scaled up.

The treatment involves moderate costs compared to oral iron preparations and may reduce equity if not made more accessible and affordable to all women.

• Intravenous iron should not be administered before confirmation of iron deficiency. Ferritin of less than 30 mg/mL was typically used in the studies included in the evidence base to identify women who would benefit from intravenous iron. If ferritin testing is not available, a peripheral blood smear demonstrating microcytic hypochromic anaemia typical of iron deficiency, while other causes of anaemia are reasonably excluded, can be an alternative. Alternatively, health workers may consider a treatment test where an improvement of anaemia is demonstrated after 2 weeks of oral iron treatment, if that is feasible.
• Oral iron may not be tolerated because of side-effects, and may be contraindicated or not absorbed (e.g. pre-existing condition leading to poor intestinal absorption).
• Rapid correction of anaemia may be required for women with severe anaemia close to the time of birth to avoid adverse outcomes from postpartum haemorrhage.
• Women need to be monitored during intravenous iron infusion and for at least 30 minutes after infusion for anaphylactic reactions; health systems need to have monitoring systems in place to track safety. Some intravenous preparations (e.g. iron dextran) appear to increase the risk of anaphylactic reactions more than others and should be avoided. The risk of anaphylaxis is estimated to be 9.8 per 10 000 for iron dextran, 1.5 per 10 000 for ferric gluconate, 1.2 per 10 000 for iron sucrose and 0.8 per 10 000 for ferric carboxymaltose.
• Intravenous iron preparations have been approved for treatment of iron-deficiency anaemia but not specifically for iron-deficiency anaemia in pregnancy. Therefore, treatment with intravenous iron should be confined to the second and third trimesters if the benefit is judged to outweigh the potential risk for both mother and fetus. The decision to use intravenous iron therapy should be made with the informed consent of the woman, ensuring that she fully understands the potential benefits and risks.
• Studies mostly used intravenous iron sucrose or ferric carboxymaltose. Iron sucrose was usually given as several 200-mg infusions on alternating days until the calculated iron deficit was reached. Ferric carboxymaltose was usually given as single infusion of 20 mg/kg body weight or up to a maximum of 1000 mg.
• The use of intravenous iron increases costs (related to both medication and infrastructure), and so the frequency of its use will need to be considered in the context of resources available.

Justification

Evidence suggests that perineal massage may increase the chance of keeping the perineum intact and reduces the risk of serious perineal tears, and that warm perineal compresses reduce third-degree and fourth-degree perineal tears. Most women accept these low-cost preventive perineal techniques and highly value the outcomes that they impact. Although the evidence on the effectiveness of these techniques to prevent PPH is uncertain, the GDG considered that these techniques are unlikely to cause harm and, as they reduce the incidence of perineal tears, are likely to reduce excessive bleeding. Consequently, they should be incorporated as part of a holistic approach to PPH prevention.

The evidence on the effect of a hands-on approach (guarding) on reducing perineal tears is uncertain. However, the GDG noted that this technique is unlikely to cause harm, requires minimal resources, may reduce traumatic injury and is embedded in clinical practice. In the absence of evidence of harm, the GDG determined that the existing recommendation on this technique should be maintained.

Evidence on Ritgen’s manoeuvre (using one hand to pull the fetal chin from between the maternal anus and the coccyx, and the other hand placed on the fetal occiput to control speed of birth) is very uncertain; therefore, this technique is not recommended.

• Health workers will need to respect the preferences and choices of the woman in labour and tailor these techniques accordingly. Health workers will also need to provide clear and compassionate communication to ensure women are supported and informed about the available techniques and what they entail. Perineal techniques should be performed gently and always with the woman’s consent, which ideally should be obtained before or in early labour.
• Warm compresses should be used with a temperature that is comfortable to the woman.
• Regular simulation-based training and education can enhance skills and improve outcomes for both mother and baby.

• Although the review evidence on comparative effects of episiotomy policies was presented as selective/restrictive versus routine/liberal use of episiotomy, because of the beneficial effects of selective/restrictive compared with routine/liberal episiotomy policy, the lack of evidence on the effectiveness of episiotomy in general and the need to discourage the excessive use of routine episiotomy across all settings, the GDG felt that it was important to emphasize that routine/liberal use of episiotomy is not recommended, rather than recommending the selective/restrictive use of episiotomy (although this is implied).
• The GDG acknowledged that, at the present time, there is no evidence corroborating the need for any episiotomy in routine care, and an acceptable rate of episiotomy is difficult to determine. The role of episiotomy in obstetric emergencies, such as fetal distress requiring instrumental vaginal birth, remains to be established.
• If an episiotomy is performed, effective local anaesthesia and the woman’s informed consent is essential. The preferred technique is a medio-lateral incision because midline incisions are associated with a higher risk of complex obstetric anal sphincter injury. A continuous suturing technique is preferred to interrupted suturing (39).
• Episiotomies do not warrant the routine use of prophylactic antibiotics, as general infection control measures should be respected at all times (40).

Justification

When used for PPH prevention, oxytocin is associated with a substantial reduction in PPH (≥500 mL), severe PPH (≥1000 mL), blood transfusion and the use of additional uterotonics when compared with placebo or no uterotonic. In the same context, oxytocin makes little or no difference to the risks of experiencing side-effects commonly associated with uterotonics, including nausea, vomiting, abdominal pain, headache, hypertension, shivering, fever and diarrhoea. There is probably no important variability in, or uncertainty about, how much women value the health outcomes associated with oxytocin. Although there is no direct evidence, oxytocin is probably cost-effective because it is inexpensive and is associated with substantial clinical benefits and minimal side-effects. It is widely available in all settings at a low cost and probably increases health equity. The currently available injectable form is feasible to implement in most settings, and is probably acceptable to health personnel as it is given routinely to women after birth for PPH prevention.

• This recommendation applies to women giving birth vaginally or via caesarean section. Skilled health personnel who are trained to administer injectable uterotonics are required.
• The GDG advised that all women are to be provided with information – ideally during antenatal care – on the need for an effective uterotonic to prevent PPH.
• To maximize efficacy, oxytocin is best given immediately (preferably within 1 minute) after the birth of the baby or babies. Administration for prevention of PPH need not impede the delaying of cord clamping.
• The GDG noted that, to effectively prevent PPH and avoid potentially harmful haemodynamic side-effects at caesarean section, there was insufficient evidence from randomized controlled trials to recommend one oxytocin regimen over another. The group agreed that, in view of a number of observational studies suggesting dose-related side-effects (particularly hypotension and tachycardia), and potential effectiveness of oxytocin at doses much lower than 10 international units (IU), consideration needs to be given to dividing the recommended 10-IU dose between a smaller intravenous bolus and an infusion. A rapid intravenous bolus injection must be avoided. The GDG considered the identification of the optimal regimen of intravenous oxytocin at caesarean section to be an important research priority.
• For local adaptation of this recommendation as it applies to caesarean section, health systems need to ensure that adequate human resources exist to implement feasible intravenous oxytocin dosing strategies, without compromising the woman’s safety. Personnel administering oxytocin at caesarean section must be alert to the potential haemodynamic side-effects associated with intravenous oxytocin use, exercise caution in its administration and be prepared to provide effective resuscitation therapy should the need arise.
• Oxytocin is relatively inexpensive and widely available; however, it requires refrigerated transport and storage (2–8 °C). In settings where this cannot be guaranteed, the quality and effectiveness of oxytocin may be adversely affected. In these situations, an effective heat-stable uterotonic should be considered as recommended in Recommendation 11.

Justification

When used for PPH prevention, carbetocin is associated with a substantial reduction in PPH (≥500 mL), severe PPH (≥1000 mL), blood transfusion and the use of additional uterotonics when compared with placebo or no uterotonic. It makes little or no difference to the risks of experiencing side-effects such as nausea, abdominal pain, headache, shivering and fever. There is probably no important variability in, or uncertainty about, how much women value the health outcomes associated with carbetocin. Given the substantial beneficial effects and minimal side-effects, carbetocin would probably be cost-effective in settings where the cost of managing PPH and its complications is substantial. However, its impact on equity would vary across settings as the current unit cost is high. Carbetocin in the current injectable form is acceptable and feasible to implement because its heat-stable formulation does not require cold-chain transport or refrigerated storage.

• This recommendation applies to women giving birth vaginally or via caesarean section. Skilled health personnel who are trained to administer injectable uterotonics are required.
• The GDG advised that all women are to be provided with information – ideally during antenatal care – on the need for an effective uterotonic to prevent PPH.
• By “where cold chain cannot be guaranteed”, the GDG refers to settings in which continuous refrigeration (typically 2–8°C) during storage, transport and handling of temperature-sensitive medicines cannot be consistently maintained because of infrastructure limitations, unreliable electricity supply or lack of temperature-monitoring systems. Many low- and middle-income countries, particularly in rural or remote areas, fall into this category.
• To maximize efficacy, carbetocin is best given immediately (preferably within 1 minute) after the birth of the baby or babies. Administration for the prevention of PPH need not impede the delaying of cord clamping.
• This recommendation applies only to the use of carbetocin for the prevention of PPH. Carbetocin is not currently recommended for other obstetric indications (such as labour induction, labour augmentation or treatment of PPH).
• The GDG noted that both heat-stable and non-heat-stable formulations of carbetocin are available. The heat-stable formulation differs from the non-heat-stable formulation only in its excipients and not in the active pharmaceutical ingredients. Heat-stable carbetocin does not require refrigeration and therefore eliminates the costs associated with refrigerated storage and transport for non-heat-stable uterotonics.
• The evidence underpinning this recommendation included both heat-stable and non-heat-stable formulations of carbetocin because the active pharmaceutical ingredients in these formulations are the same. Therefore, the recommendation applies to both formulations. In settings where reliable cold-chain storage and transport can be consistently maintained, the heat-stable formulation may not offer additional advantages and is not specifically required.
• Previous trials of carbetocin have used both intramuscular and intravenous administration. A WHO multi-country trial of nearly 30 000 women used a regimen of 100 μg intramuscular carbetocin (heat-stable formulation) in a range of high-, middle- and low-income settings.
• Previous trials of carbetocin have all been conducted in hospital settings. While the GDG acknowledged that the effectiveness of carbetocin in preventing PPH in community settings has not been evaluated in trials, the group agreed that there is no reason to expect differential effectiveness between hospital and community settings, provided that carbetocin is administered under similar conditions as other injectable uterotonics.

Justification

When used for PPH prevention, misoprostol is associated with a substantial reduction in PPH (≥500 mL), severe PPH (≥1000 mL), blood transfusion and the use of additional uterotonics when compared with placebo or no uterotonic. However, in the same context, misoprostol substantially increases the risks of shivering, fever and diarrhoea, but makes little or no difference to other side-effects. There is probably no important variability in, or uncertainty about, how much women value the health outcomes associated with misoprostol. Overall, the balance of effects favours misoprostol because these side-effects are often self-limiting. Because it is inexpensive and can also be used by lay health workers in community settings, it is associated with moderate savings and is probably cost-effective, especially when implemented in settings with a shortage of skilled health personnel. It probably increases health equity because it can be applied by all health care worker cadres in any birth setting and thus increases coverage. Its acceptability may be limited in settings where providers have concerns regarding potential misuse, or where health care providers need more information on its effectiveness and implementation.

• The GDG noted that evidence on the efficacy of misoprostol was largely derived from trials involving women giving birth vaginally. However, misoprostol has been used for women giving birth via caesarean section in a few trials. The GDG emphasized that there may be a need for the use of alternative routes of administration, such as rectal for women under general anaesthesia for caesarean section, or rectal or sublingual for women under spinal anaesthesia for caesarean section.
• The GDG advised that all women are to be provided with information – ideally during antenatal care – on the need for an effective uterotonic to prevent PPH.
• The GDG noted that previous trials have largely used 600-μg or 400-μg doses of misoprostol. While there is currently no clear evidence to demonstrate that a 600-μg dose provides greater efficacy over a 400-μg dose, there is some evidence that higher doses are likely to have worse side-effects.
• To maximize efficacy, misoprostol is best given immediately (preferably within 1 minute) after the birth of the baby or babies. Administration for the prevention of PPH need not impede the delaying of cord clamping.
• Although different routes of administration (i.e. oral, buccal, sublingual, rectal) have been evaluated in trials of misoprostol for PPH prevention, the recommended route of administration is based on the consideration of a woman’s preferences for oral over rectal administration.
• Providers administering misoprostol need to ensure that women are aware of the possible adverse effects of misoprostol (including shivering, fever and diarrhoea), and must be prepared to manage these if they occur.
• Misoprostol for PPH prevention can be used in both hospital and community settings.

Justification

There is clear evidence in favour of intravenous oxytocin in terms of health outcomes. When compared to intramuscular oxytocin, intravenous oxytocin reduces the risk of PPH, severe PPH, blood transfusion and severe maternal morbidity, with no clear differences in undesirable effects. While it is uncertain whether intravenous administration is more cost-effective, routine intravenous oxytocin use for PPH prevention imposes additional resource requirements, may negatively impact women’s comfort and can increase health inequities. The feasibility of intravenous administration may also vary in different settings. However, in situations where intravenous access is already in place at vaginal birth, the clinical benefits of intravenous administration outweigh these other considerations.

• The GDG acknowledged that either intravenous or intramuscular oxytocin is effective in preventing PPH and both routes of administration are currently recommended by WHO for this indication.
• While noting that the balance of effects favours intravenous oxytocin for important health outcomes, the GDG placed its emphasis on other considerations (including feasibility and impacts on resources, health equity and women’s comfort), as well as studies suggestive of possible safety concerns with a rapid intravenous bolus of oxytocin. In instances where women already have intravenous access (for another medical indication), it is recommended to administer oxytocin intravenously.
• The GDG acknowledged existing WHO recommendations against the routine use of intravenous fluids during labour and childbirth, with emphasis on the widespread and unnecessary use of routine administration of intravenous fluids for all women in labour in many health facilities in low-, middle- and high-income settings that increases cost and has an impact on resource use (42). The GDG emphasized that intravenous access should not be placed routinely for the sole purpose of administering intravenous oxytocin for PPH prevention.
• The GDG noted that the previous trials considered for this question have all administered an oxytocin dose of 10 IU intravenously for PPH prevention during vaginal birth. However, the speed of injection ranged from 1 minute (for bolus injection) to 40 minutes (for infusion) and volume of dilution from 1 mL (for bolus injection) to 1000 mL of saline (for infusion). There is no direct evidence comparing the different regimens for administering intravenous oxytocin during vaginal birth, and there were no safety concerns (such as hypotension or tachycardia) in trials comparing slow intravenous administration of 10 IU oxytocin over 1 minute with 10 IU intramuscular oxytocin (43, 44). However, observational studies in women undergoing caesarean section suggest that rapid intravenous results in harmful haemodynamic effects (44, 45). Therefore, the GDG suggests avoiding a rapid injection, and agreed that the 10-IU oxytocin dose should preferably be diluted and administered slowly (over 1–2 minutes).
• This recommendation reflects available evidence from direct comparison of intravenous versus intramuscular oxytocin during vaginal birth. For women undergoing caesarean section, WHO currently recommends 10 IU for PPH prevention without preference for intravenous or intramuscular route (10).
• This recommendation does not relate to the use of oxytocin for other obstetric indications (such as labour induction).

Justification

When used for PPH prevention, it is uncertain whether ergometrine/methylergometrine reduces the risk of PPH ≥500 mL or PPH ≥1000 mL, though it may slightly reduce mean blood loss when compared with placebo or no uterotonic. However, it is also associated with several side-effects, including nausea, vomiting, hypertension, headache and abdominal pain. There is no evidence of uncertainty regarding how much women value the health outcomes associated with its use. While ergometrine/methylergometrine in the injectable form is widely available and feasible to use, its cost–effectiveness and impact on health equity are not known because of the increased likelihood of side-effects, particularly hypertension, which means that the presence of skilled health personnel is required for its safe use. The GDG placed its emphasis on the danger of the increased risk of hypertension (43 per 1000 births) associated with ergometrine/methylergometrine use, and the potential harm to women with underlying cardiovascular disorders. Based on the balance between effectiveness and side-effect profiles, the GDG determined that the use of ergometrine/methylergometrine is not recommended to prevent PPH. The group also highlighted the importance of expanding access to safer and more effective uterotonics – oxytocin, carbetocin (heat-stable or non-heat-stable) and misoprostol – as preferable alternatives for PPH prevention.

• Ergometrine/methylergometrine was previously included in the 2018 WHO recommendations on uterotonics as a context-specific option for PPH prevention, with the condition that it is used only when hypertensive disorders could be safely excluded. Upon review of updated evidence, the GDG noted that it offers limited clinical benefit and remains associated with a high risk of adverse effects, particularly hypertension. In view of these safety concerns, the GDG concluded that ergometrine/methylergometrine is not recommended for the prevention of PPH in current practice, in favour of uterotonics with a more favourable balance of effectiveness and safety.
• Effective prophylactic uterotonics with better safety profiles and less risk of concerning adverse effects – oxytocin, carbetocin (heat-stable or non-heat-stable formulations) and misoprostol – are available and should be prioritized for procurement by health systems for the prevention of PPH. The GDG emphasized that the prophylactic use of ergometrine cannot be justified, given the absence of clear added benefit over safer alternatives. Countries are encouraged to update national guidelines, essential medicines lists, formularies and procurement lists to reflect this recommendation, while recognizing that ergometrine may still be procured in limited quantities for treatment purposes, in line with WHO recommendations for the treatment of PPH.
• This recommendation applies to women undergoing a vaginal birth or caesarean section.
• The GDG acknowledged that ergometrine and methylergometrine injections (200–500 μg, intramuscularly/intravenously) continue to be widely used in some countries for the prevention of PPH, largely because of historical practice patterns and routine procurement systems. However, the current evidence does not support their continued use for this indication.
• Ergometrine/methylergometrine is associated with a range of undesirable side-effects – most notably hypertension – which may pose significant risks, particularly for women with undiagnosed or pre-existing cardiovascular conditions.
• This recommendation applies only to the use of ergometrine/methylergometrine for prevention of PPH; it does not relate to its use in the treatment of PPH, where it may still be considered as part of second-line management (see Recommendation 25).

Justification

When used for PPH prevention, the fixed-dose combination of oxytocin and ergometrine demonstrated a substantial reduction in PPH (≥500 mL), severe PPH (≥1000 mL), blood transfusion and the use of additional uterotonics when compared with placebo or no uterotonic. However, it probably increases women’s risk of experiencing nausea and vomiting; the impact on other side-effects ranges from substantial benefits to considerable harm. While there is no clear difference in the risk of hypertension when oxytocin plus ergometrine was compared with placebo or no uterotonic, the GDG expressed concern about the potential risk of hypertension associated with the ergometrine component of this combination, especially for women with pre-existing hypertensive disorders. The group agreed that the potential benefits of this combination may outweigh the harms if hypertensive disorders can be safely excluded but acknowledged that such capacity does not exist in many settings. Although there is no direct evidence, oxytocin plus ergometrine combination compared with no PPH prevention might be cost-effective because the desirable effects are substantial. The combination is probably acceptable to health workers given that the individual components are widely used, but perhaps less so to women because of the nausea and vomiting. However, its feasibility may be restricted in settings with limited capacity for storage of heat-sensitive uterotonics, where it is not readily available, and it may reduce health equity where screening or care for hypertensive disorders in pregnancy is not possible.

As the fixed-dose combination includes even a larger dose of ergometrine than when ergometrine is used alone in routine practice, the GDG placed its emphasis on the danger of the increased risk of hypertension associated with the ergometrine component of the combination, especially in populations where capacity to exclude cardiovascular disorders before use is limited or non-existent, and therefore determined that the use of fixed-dose combination of oxytocin and ergometrine (5 IU/500 μg, intramuscularly) is not recommended for PPH prevention.

• The fixed-dose combination of oxytocin and ergometrine (5 IU/500 μg, intramuscularly) (e.g. Syntometrine^®) was previously included as a context-specific option in the 2018 WHO recommendations on uterotonics for the prevention of PPH, with the condition that hypertensive disorders could be safely excluded before use. However, in revisiting the evidence, the GDG decided to revise this recommendation by placing greater emphasis on the safety profile of uterotonics used for prophylaxis. The combination product contains a relatively high dose of ergometrine, which is now not recommended for routine use because of its association with adverse effects – particularly hypertension – and the availability of safer and comparably effective alternatives. In light of these concerns, and to ensure consistency across uterotonic guidance, the GDG recommended against the use of this fixed-dose combination for PPH prevention.
• Effective prophylactic uterotonics with better safety profiles and lower risk of serious adverse effects – such as oxytocin, carbetocin (heat-stable or non-heat-stable formulations) and misoprostol – are available and should be prioritized for procurement by health systems for the prevention of PPH. The GDG emphasized that the routine use of fixed-dose combination of oxytocin and ergometrine cannot be justified in light of its side-effect profile and the availability of safer alternatives. Countries are encouraged to update national guidelines, essential medicines lists, formularies and procurement lists accordingly, while recognizing that limited quantities of this combination may still be procured for treatment purposes, where clinically appropriate and aligned with WHO recommendations for the treatment of PPH.
• This recommendation applies to women giving birth vaginally or via caesarean section. The GDG highlighted that there is an added anaesthetic and surgical risk from nausea and vomiting for women having a caesarean birth, especially if under general anaesthesia, which further supports the recommendation against the prophylactic use of the fixed-dose combination.
• Most trials that evaluated the efficacy of this fixed-dose combination have used the synthetic, fixed-dose combination of oxytocin and ergometrine (5 IU/500 μg, intramuscularly), which informed the dose specified in this recommendation.
• This recommendation applies only to the use of fixed-dose combination of oxytocin and ergometrine for the prevention of PPH; it does not relate to its use in the treatment of PPH, where it may still be considered as part of second-line management (see Recommendation 25).

Justification

When used for PPH prevention, injectable prostaglandins (carboprost and sulprostone) are not beneficial for substantive priority outcomes (PPH ≥500 mL, severe PPH ≥1000 mL, and blood transfusion) except the use of additional uterotonics, for which they show a 69% risk reduction compared with placebo or no uterotonic. However, they are associated with increased risk of vomiting and diarrhoea. Injectable prostaglandins are currently not available in all settings; where they are available, the unit cost is high. While there is no direct evidence on cost analysis regarding these uterotonics compared to no uterotonics, they are probably not cost-effective because of lack of benefits for most priority outcomes and substantial side-effects. As they are not widely available and not routinely used for obstetric indications, their acceptability is not known and the feasibility of implementation in clinical practice would vary according to local availability. The potential costs of these uterotonics may prohibit access for women in disadvantaged regions and thus would probably reduce equity.

• Trials of systemic injectable prostaglandins for the prevention of PPH have used carboprost or sulprostone.
• Local administration of injectable prostaglandins, such as intrauterine injections during caesarean section, was not considered.
• This recommendation applies only to the use of injectable prostaglandins for the prevention of PPH; it does not relate to its use in the treatment of PPH, where it may still be considered as part of second-line management (see Recommendation 25).

Justification

When used for PPH prevention, oxytocin, carbetocin, misoprostol and the fixed-dose combination of oxytocin and ergometrine demonstrated variable clinical benefits and side-effects, ranging from minor to significant, when compared with one another. As oxytocin is the most widely used and most frequently investigated of all these uterotonics, different uterotonic options have been compared with oxytocin as the reference agent across all important considerations to determine the most efficacious uterotonic option with the best safety profile, which is also cost-effective, acceptable to stakeholders, feasible to implement and likely to increase health equity.

Carbetocin has similar desirable effects compared with oxytocin, although it is likely to be superior to oxytocin in reducing the need for additional uterotonics for PPH treatment (32 fewer per 1000 women). The mean change in haemoglobin level (before versus after birth) may be smaller among women receiving carbetocin. There is no clear difference between carbetocin and oxytocin in terms of undesirable effects. While the balance of effects probably favours carbetocin, especially in contexts where the subsidized supply cost of carbetocin is comparable to that of oxytocin, the non-subsidized supply cost is approximately 19 times more than oxytocin. It is uncertain whether the additional benefits justify the additional cost of routinely implementing carbetocin in settings where its cost is not comparable to that of other uterotonics.

Misoprostol has similar desirable effects to oxytocin, but it is less effective for reducing severe PPH (≥1000 mL) (11 more per 1000 women). Misoprostol causes more undesirable effects than oxytocin (including nausea, vomiting, fever and diarrhoea). While misoprostol is cheaper, heat-stable, can be used orally and is probably acceptable and feasible to use, the lower effectiveness for severe PPH and greater undesirable effects may increase costs (these costs may vary according to the setting, depending on factors such as bed costs and the approach to managing these side-effects). Misoprostol has the advantage that it can be task-shifted to lay and community health workers because it requires minimal training and no additional supplies for implementation.

There is no clear evidence of any difference in desirable effects between ergometrine/methylergometrine and oxytocin when used for PPH prevention. However, women are more likely to experience nausea (73 more per 1000 women), vomiting (25 more per 1000), headache (41 more per 1000), hypertension (442 more per 1000) and diarrhoea (5 more per 1000) with ergometrine/methylergometrine. The costs associated with managing these undesirable effects, as well as the need to screen for hypertension, implies that oxytocin is probably more cost-effective. Ergometrine/methylergometrine may have negative effects on health equity in settings with high rates of – or lack of screening for – hypertensive disorders.

The fixed-dose combination of oxytocin and ergometrine is similar to oxytocin in terms of preventing severe PPH (≥1000 mL), although it is more effective in preventing PPH (≥ 500 mL) (28 fewer per 1000) and possibly superior to oxytocin in reducing blood transfusion (6 fewer per 1000) and the use of additional uterotonics (40 fewer per 1000). However, it has more undesirable effects than oxytocin, including nausea (49 more per 1000 women) and vomiting (43 more per 1000). The costs related to managing associated undesirable effects, and the need to screen for women with hypertensive disorders because of concern regarding the ergometrine component, imply that oxytocin is probably more cost-effective. Compared with oxytocin alone, the fixed-dose combination of oxytocin and ergometrine may have a negative impact on health equity, particularly in settings with limited capacity and capability to routinely screen for hypertensive disorders of pregnancy.

The combination of oxytocin and misoprostol is probably superior to oxytocin alone in terms of blood transfusion (13 fewer per 1000), need for additional uterotonics for PPH treatment (55 fewer per 1000) and blood loss (60 mL less on average). The combination may possibly prevent more PPH (≥500 mL) (35 fewer per 1000) and result in a smaller mean change in haemoglobin level (before versus after birth) compared with oxytocin. However, this combination is associated with more undesirable effects than oxytocin, including nausea (56 more per 1000), vomiting (25 more per 1000), diarrhoea (2 more per 1000) and fever (68 more per 1000). Consequently, the cost–effectiveness of the combination may vary in different settings – costs may be reduced due to improved desirable outcomes, but costs may increase for the management of undesirable effects. The feasibility of the oxytocin plus misoprostol combination is limited because of the complexity of using two separate medications through different routes of administration.

Oxytocin is the most extensively studied uterotonic and demonstrates a strong overall balance of efficacy, safety, feasibility, acceptability and cost–effectiveness across diverse settings. While alternatives like carbetocin and misoprostol have some benefits in specific contexts, they also present trade-offs related to cost (carbetocin), side-effects or lower efficacy (misoprostol). Uterotonics containing ergometrine or combinations involving oxytocin and misoprostol or ergometrine present higher risks of adverse effects and implementation challenges. Based on these trade-offs, the GDG identified oxytocin as the preferred uterotonic when multiple options are available.

• This recommendation applies to women giving birth vaginally or via caesarean section. Skilled health personnel who are trained to administer injectable uterotonics are required.
• All remarks for Recommendation 7.1 apply to this recommendation.
• While the GDG acknowledged that there is evidence that fixed-dose combination of oxytocin and ergometrine and combination of oxytocin and misoprostol may be more effective than oxytocin alone for some priority outcomes, there are concerns that these combinations also increase important side-effects for women. The fixed-dose combination of oxytocin and ergometrine is not widely available and there is no fixed-dose combination of oxytocin and misoprostol, so the two agents have to be administered through separate routes (parenteral and oral). Hence, the GDG considered the applications of these combinations less feasible when used routinely in clinical settings compared with using oxytocin or misoprostol alone as a single agent. This is consistent with the GDG position not to recommend the prophylactic use of fixed-dose combination of oxytocin and ergometrine because of concerns about safety. However, if the health worker and the woman regard the additional benefits of a combination of oxytocin and misoprostol (over either of these agents alone) as important in improving overall maternal outcomes, the use of this combination could be considered.

Justification

Both carbetocin and misoprostol are effective uterotonics for the prevention of PPH, offering substantial reductions in blood loss, severe PPH, blood transfusion and the need for additional uterotonics when compared with placebo or no uterotonic.

Carbetocin is associated with minimal side-effects and has a favourable balance of benefits and harms compared with oxytocin. Its heat-stable formulation does not require cold-chain transport or refrigeration, making it well suited for settings where maintaining the cold chain for oxytocin is not feasible. While its unit cost may limit its accessibility in some settings, it is likely to be cost-effective in contexts where the cost is comparable to that of oxytocin, where the cost associated with managing PPH and its complications is high or where the quality of oxytocin available for use is substandard. Its acceptability and feasibility are high in facilities with adequate capacity to deliver injectable uterotonics, similar to oxytocin. Misoprostol, while also effective for PPH prevention, is associated with increased risks of side-effects, such as shivering, fever and diarrhoea. However, these are typically self-limiting.

Misoprostol is inexpensive, does not require refrigeration and can be administered orally, making it particularly feasible for use in low-resource settings, including by lay health workers at the community level because it requires minimal training and no additional supplies for implementation. It is likely to be cost-effective and likely to increase equity, especially where skilled health personnel are limited and access to oxytocin or heat-stable carbetocin is not assured. However, its use may be constrained in settings where concerns about misuse persist.

Taking these factors into account, the GDG recommended heat-stable carbetocin as the first-line choice in settings where the oxytocin cold-chain requirements cannot be consistently met, and misoprostol as an appropriate alternative where heat-stable carbetocin is not available.

• This recommendation applies to women giving birth vaginally or via caesarean section. Heat-stable carbetocin must be administered by skilled health personnel trained in the use of injectable uterotonics, while misoprostol can be administered by skilled, community or lay health workers.
• In the 2018 WHO recommendations on uterotonics for the prevention of PPH, additional injectable uterotonic options – ergometrine/methylergometrine and the fixed-dose combination of oxytocin and ergometrine – were included for use in settings where oxytocin is unavailable (or its quality cannot be guaranteed). In this updated recommendation, the GDG placed greater emphasis on the safety profile of uterotonics and the availability of safer and comparably or more effective alternatives. Consequently, these previously recommended options are no longer included; only heat-stable carbetocin or misoprostol is now recommended in settings where the oxytocin cold chain cannot be reliably maintained.
• “Where oxytocin cold chain cannot be consistently maintained” refers to settings where continuous refrigeration (typically 2–8 °C) during storage, transport and handling of oxytocin cannot be reliably ensured because of infrastructure limitations, unstable electricity supply or lack of temperature-monitoring systems. Many low- and middle-income countries, particularly their rural and remote areas, fall into this category.
• Both heat-stable carbetocin and misoprostol are most effective when administered immediately after the birth of the baby or babies, preferably within 1 minute. Administration for PPH prevention does not preclude delayed cord clamping.
• This recommendation applies only to the use of heat-stable carbetocin for the prevention of PPH. The heat-stable and non-heat-stable formulations of carbetocin are not currently recommended for other obstetric indications (such as labour induction, labour augmentation or treatment of PPH).
• The heat-stable formulation differs from the non-heat-stable formulation only in its excipients⁶ , and not the active pharmaceutical ingredients (46). It does not require refrigeration; therefore, it eliminates the costs and logistic constraints associated with cold-chain storage and transport for non-heat-stable uterotonics.
• Clinical trials of carbetocin have used both intramuscular and intravenous routes of administration, including a WHO multi-country trial of nearly 30 000 women that used a regimen of 100 μg intramuscular heat-stable carbetocin in a range of high-, middle- and low-income settings. Thus, the available evidence supports the recommendation of either intramuscular or intravenous route of administration for heat-stable carbetocin, depending on the clinical setting and available expertise.
• Although existing trials of carbetocin have been conducted exclusively in hospital settings, the GDG agreed that there are no biological or pharmacological reasons to expect different effectiveness in community settings, provided carbetocin is administered under conditions similar to other injectable uterotonics.

Justification

Misoprostol is effective in reducing the risk of PPH (≥500 mL), severe PPH (≥1000 mL), blood transfusion and the need for additional uterotonics when compared with placebo or no uterotonic. In the context of community-level births where skilled health personnel are not available to administer injectable uterotonics, no uterotonic prophylaxis is often the default alternative. While misoprostol increases the risk of side-effects such as shivering, fever and diarrhoea, these are typically self-limiting and often do not require clinical intervention. Given its oral route of administration, stability at room temperature and low cost, misoprostol is particularly suitable for use in settings where injectable uterotonics cannot be administered because of the absence of skilled health personnel. Evidence supports its safe and effective use by trained community health workers and lay health workers. This task-sharing approach is likely to improve coverage and equity of PPH prevention interventions in remote or resource-limited areas. Although concerns about misuse or need for additional provider training may affect acceptability in some contexts, these can be addressed through appropriate training, supervision and community engagement.

• The remarks for Recommendation 7.3 apply to this recommendation.
• Skilled health personnel who provide care during childbirth are defined by the 2018 joint statement by WHO, the United Nations Population Fund, the United Nations Children’s Fund (UNICEF), the ICM, the International Council of Nurses (ICN), FIGO and the International Pediatric Association (IPA) as competent maternal and newborn health (MNH) professionals who hold identified MNH competencies; are educated, trained and regulated to national and international standards; and are supported within an enabling environment in the health system (47).
• The GDG acknowledged that there are settings where skilled health personnel may not be present, or where they may not have been trained to administer injectable uterotonics appropriately. In these settings, oral misoprostol would be the preferred uterotonic.
• Community and lay health workers should receive appropriate training and supervision to safely administer misoprostol for PPH prevention, including education on correct dosing, timing, potential side-effects and referral procedures in the event of complications.
• The availability of misoprostol at the community level should be supported by consistent supply chain management and integration into national essential medicines lists and procurement plans.
• Engagement with women, families and community leaders is important to promote awareness, acceptability and trust in community-based PPH prevention efforts involving misoprostol.
• Where feasible, implementation of misoprostol by lay health workers should be accompanied by mechanisms for monitoring and evaluation to assess safety, coverage and effectiveness.

Justification

There is insufficient trial evidence to assess the benefits and possible harms of advance misoprostol distribution for PPH prevention. However, misoprostol is an effective uterotonic agent for PPH prevention and is recommended by WHO in settings where oxytocin is unavailable, its cold chain cannot be consistently maintained or skilled health personnel are not present to administer it. Observational studies and evaluations of advance misoprostol distribution programmes in several countries indicate that this strategy can increase coverage of uterotonic use for PPH prevention in remote and hard-to-reach areas where no skilled health personnel can attend birth, with very few reports of incorrect use of misoprostol or adverse events. As this strategy is specifically aimed at preventing PPH in women in more remote or underserved areas who would otherwise not receive any uterotonic during birth, it is likely to increase health equity and improve health outcomes. These programmes are probably acceptable to women and providers. While the cost–effectiveness of this strategy is not known, it is likely to confer cost savings.

• Antenatal distribution of misoprostol to pregnant women should not replace standard policies for scaling up effective uterotonic use, but it should be considered as a strategy for increasing coverage of uterotonic use in settings where a large proportion of women still give birth outside health facilities and where it is highly likely that skilled health personnel will not be present at the time of birth.
• While acknowledging that there is currently no clear evidence of harm with a strategy of antenatal misoprostol distribution, the GDG agreed that to address potential safety concerns, such programmes should only be implemented with appropriate monitoring and evaluation. These should consider:

  –

  whether women are trained appropriately in the use of misoprostol;

  –

  monitoring the distribution, use and potential misuse of misoprostol;

  –

  the effect of the programme on the use of health services and health outcomes – this should include (but is not limited to) the rate of ANC attendance and facility-based childbirth, maternal and perinatal mortality, and severe maternal morbidity and potential complications from inappropriate use (such as uterine rupture); and

  –

  whether appropriate supervisory systems of health personnel involved in the distribution of misoprostol are in place.

• Within an antenatal distribution programme, misoprostol ideally should be provided to women during an ANC visit in the third trimester of pregnancy (typically as part of a safe delivery kit). It should be accompanied by clear, culturally appropriate instructions on its purpose, correct dose (400 or 600 μg for oral administration) and timing of use, possible side-effects and remedies for these, prompt recognition of danger signs and how to access health services, while emphasizing the importance of giving birth in a health facility.
• In settings where a strategy of antenatal distribution of misoprostol will be initiated, prospective research that evaluates the impact of introducing these programmes on maternal health outcomes and health service use should be considered a priority.

Justification

When used for PPH prevention at vaginal birth, tranexamic acid (TXA) demonstrated no clinical benefits over and above standard prophylactic measures in terms of PPH reduction compared to no TXA.

While there is no clear evidence of increased risk of maternal or newborn harms, or serious life-threatening adverse events with TXA, the GDG agreed that a modest increase in potentially fatal and non-fatal thromboembolic events with the use of TXA cannot be confidently ruled out, and that this risk outweighs the theoretical benefit of TXA for reducing postpartum blood loss at childbirth when the baseline risk of thromboembolism is increased.

Evidence suggests that there may be important variability in, or uncertainty about, the degree to which women value the health outcomes that could be impacted by TXA.

Although resource requirements would vary according to setting, routine application of TXA for all vaginal births is likely to be associated with a moderate increase in health system costs (i.e. human resources and procurement of quality-assured TXA). The cost–effectiveness of TXA for PPH prevention at vaginal birth is uncertain because of invalid and non-generalizable assumptions applied in available health economic evaluation evidence. However, the GDG considered TXA for PPH prevention unlikely to be cost-effective given the lack of clinical benefits for priority outcomes.

TXA is not yet widely available for the recommended PPH treatment indication. Consequently, the GDG noted that the additional health system costs implied by introducing TXA as an additional prophylactic measure for the entire obstetric population could further limit access for disadvantaged women (who may be more likely to need TXA for PPH treatment); thus, using TXA for PPH prevention would probably reduce equity.

Despite evidence suggesting that introduction of TXA for PPH prevention may be acceptable and feasible, the GDG placed its emphasis on the small yet important risk of serious adverse events of TXA when routinely applied at the population level, against the background of a lack on compelling evidence of superior clinical benefits for priority woman-centred outcomes over and above existing PPH prevention strategies, and therefore recommended against the use of TXA for the purpose of preventing PPH during vaginal birth.

• The GDG recognizes that this recommendation applies at the population level to all vaginal births and depends on the capacity to accurately assess blood loss and diagnose PPH. Future research may identify specific subpopulations that may benefit from prophylactic use of TXA before the onset of significant bleeding.
• TXA remains recommended for treatment of PPH (Recommendation 27) and as part of the treatment bundle (Recommendation 29), where the balance of benefits and potential risks is well established and clearly favours its use.
• TXA is an antifibrinolytic – not a uterotonic – and should never be used as a substitute for first-line prophylactic uterotonics (oxytocin, carbetocin or misoprostol) when preventing PPH at vaginal birth. Its mechanism does not promote uterine contraction and, as shown by the evidence, it provides no added preventive benefit.

Justification

In the context of caesarean birth, the use of TXA for PPH prevention does not confer any additional benefit in reducing postpartum blood loss compared to standard prophylactic measures.

Although no clear increase in maternal or newborn life-threatening adverse events was observed, the GDG noted that a small but clinically important increase in thromboembolic risk associated with TXA use cannot be ruled out, which is particularly relevant during caesarean birth when baseline thrombotic risk is elevated.

The degree to which women value the potential outcomes associated with TXA use remains uncertain and may vary across populations.

Introducing TXA as a routine preventive measure for all caesarean births would likely entail moderate increases in health system costs, including procurement and training needs. The cost–effectiveness of this intervention remains unclear because existing economic evaluations are limited in quality and generalizability. Therefore, the GDG judged TXA to be an unlikely cost-effective option for this indication, given the lack of measurable benefit in key maternal outcomes.

Moreover, TXA is not yet broadly available for its role in PPH treatment. Scaling up its use for prevention across all caesarean births could place additional pressure on supply chains and divert access from women who may benefit most from PPH treatment, potentially worsening equity.

While the use of TXA for caesarean section may be technically feasible and acceptable in many health systems, the GDG placed its emphasis on the potential for rare but serious adverse events, and the lack of meaningful clinical benefit over current prevention strategies, in making this recommendation against TXA use for prophylaxis at caesarean birth.

• The GDG recognizes that this recommendation applies at the population level to all caesarean births and depends on the capacity to accurately assess blood loss and diagnose PPH. Future research may identify specific subpopulations that may benefit from prophylactic use of TXA before the onset of significant bleeding.
• For caesarean sections, PPH prophylaxis typically means administering TXA before the incision (pre-incision). However, some studies administered TXA after cord clamping to avoid fetal exposure, which could address some bleeding, aligning more with treatment than true prophylaxis.
• Clinical judgement should be used because individual woman needs and circumstances can vary. For certain high-risk women, benefits may outweigh the harms, and clinicians could consider using TXA to control bleeding even before the diagnostic criteria of PPH are met.
• Further, the GDG noted the increasing frequency of published reports on fatal and non-fatal medication errors regarding intrathecal administration of TXA. These reports seem to be concentrated in certain contexts where procured TXA is manufactured in ampoules that appear similar to bupivacaine ampoules. Consequently, care should be taken to ensure that TXA and bupivacaine are stored separately in the operating theatre. Additionally, TXA manufacturers are encouraged to improve product labelling and packaging to ensure they are easily distinguishable from bupivacaine (48).
• TXA remains recommended for treatment of PPH (Recommendation 27) and as part of the treatment bundle (Recommendation 29).
• TXA is not a uterotonic and should not be used as a substitute for uterotonics recommended for PPH prevention during caesarean birth (such as oxytocin).
• Where TXA is currently included in national guidelines or facility protocols for prophylaxis at caesarean birth, these policies should be reviewed in light of this recommendation. National programmes are encouraged to ensure that TXA is reserved for evidence-based indications to support safe, effective and equitable PPH care.

• This recommendation is based on a large randomized controlled trial in which oxytocin 10 IU was used for the prevention of PPH in all participants. Based on this evidence, controlled cord traction (CCT) was regarded as safe when applied by skilled birth attendants because it provides small beneficial effects on blood loss (average reduction of 11 mL on blood loss) and on the duration of the third stage of labour (average reduction of 6 minutes). The decision to implement CCT in the context of a prophylactic uterotonic drug should be discussed by the care provider and the woman herself before or early in labour.
• CCT should only be performed by skilled birth attendants who are trained in its correct technique. Incorrect use of CCT can increase the risk of uterine inversion or retained placenta.
• This recommendation does not apply in settings where skilled health personnel are not available or not trained to perform CCT safely.
• There is insufficient evidence to determine the benefit or risk of CCT when used in conjunction with misoprostol.
• CCT is the first intervention to treat the retained placenta; therefore, the teaching of CCT in medical and midwifery curricula is essential.
• The benefits of CCT may be more relevant in high-volume facilities where even small time savings in third-stage management may contribute to workflow efficiency.

• This recommendation is based on a large randomized controlled trial in which oxytocin 10 IU was used for the prevention of PPH in all participants. Based on this evidence, CCT was regarded as safe when applied by skilled birth attendants because it provides small beneficial effects on blood loss (average reduction of 11 mL on blood loss) and on the duration of the third stage of labour (average reduction of 6 minutes). The decision to implement CCT in the context of a prophylactic uterotonic drug should be discussed by the care provider and the woman herself before or early in labour.
• CCT should only be performed by personnel trained in its correct and safe use. When improperly performed, CCT carries a risk of complications, such as uterine inversion or retained placenta.
• In the absence of skilled birth attendants, expectant management of the third stage of labour is preferred, along with administration of a prophylactic uterotonic.
• There is insufficient evidence to determine the benefit or risk of CCT when used in conjunction with misoprostol.
• CCT is the first intervention to treat the retained placenta; therefore, the teaching of CCT in medical and midwifery curricula is essential.
• Based on the most recent evidence, the understanding of the contribution of each component of the active management of the third stage of labour package has evolved. The GDG considered that this package has a primary intervention: the use of an uterotonic. In the context of oxytocin use, CCT may add a small benefit, while uterine massage may add no benefit for the prevention of PPH. Early cord clamping is generally contraindicated.

• Cord traction at caesarean section refers to the gentle and steady pulling on the umbilical cord to assist removal of the placenta and membranes, after uterine incision and delivery of the baby.
• Cord traction in this context is preferred over manual removal of the placenta because it is associated with a lower risk of postoperative infection, particularly endometritis.
• Manual removal of the placenta may be necessary if the placenta does not separate spontaneously within a reasonable time or if cord traction is ineffective or unsafe.
• Cord traction should be performed under direct visualization of the uterine cavity and with concurrent uterotonic administration to promote uterine contraction and minimize blood loss.
• Proper training in technique and infection prevention, and readiness to manage complications (e.g. retained placenta or uterine atony), is essential for safe implementation.

• The evidence base for recommendation for the timing of cord clamping includes both vaginal and caesarean births. The GDG considers this recommendation to be equally important for caesarean sections.
• Delayed cord clamping (for 1–3 minutes) should be performed during the provision of essential newborn care. For essential newborn care and resuscitation, please refer to the WHO Guidelines on neonatal resuscitation (49).
• The recommendations for the timing of cord clamping apply equally to preterm and term births. The GDG considers the benefits of delayed clamping for infants born preterm to be particularly important (50).
• Some health professionals working in areas of high HIV prevalence have expressed concern regarding delayed cord clamping as part of management of the third stage of labour. These professionals are concerned that during placental separation, a partially detached placenta could be exposed to maternal blood and this could lead to a micro-transfusion of maternal blood to the baby. It has been demonstrated that the potential for mother-to-child transmission of HIV can take place at three different points in time: micro-transfusions of maternal blood to the fetus during pregnancy (intrauterine HIV transmission); exposure to maternal blood and vaginal secretions when the fetus passes through the birth canal in vaginal births (intrapartum transmission); and during breastfeeding (postnatal infection). For this reason, the main intervention to reduce mother-to-child transmission is the reduction of maternal viral load through the use of antiretroviral drugs during pregnancy, childbirth and the postnatal period. There is no evidence that delaying cord clamping increases the possibility of HIV transmission from the mother to the newborn. Maternal blood percolates through the placental intervillous space throughout pregnancy with a relatively low risk of maternal fetal transmission before birth. It is highly unlikely that separation of the placenta increases exposure to maternal blood, and it is highly unlikely that it disrupts the fetal placental circulation (i.e. it is unlikely that during placental separation the newborn circulation is exposed to maternal blood). Thus, the proven benefits of a 1–3 minute delay at least in clamping the cord outweigh the theoretical, and unproven harms. Late cord clamping is recommended even among women living with HIV or women with unknown HIV status.

• The understanding of the contribution of each component of the active management of the third stage of labour package has evolved in light of established evidence. The GDG reaffirmed that the primary intervention within this package is the use of a uterotonic. When oxytocin is administered, controlled cord traction may offer a small additional benefit, while uterine massage appears to offer no added value in preventing PPH. Early cord clamping remains generally contraindicated.

• Sustained uterine massage refers to the continuous, repetitive manual stimulation of the uterine fundus after birth to encourage uterine contraction.
• There is a lack of evidence regarding the role of uterine massage for PPH prevention when no uterotonic drugs are used, or if a uterotonic drug other than oxytocin is used (e.g. carbetocin or misoprostol). In such cases, close and ongoing monitoring of uterine tone and the woman’s overall clinical status is essential, and any decision to perform uterine massage should be guided by clinical judgement rather than applied routinely.
• Although the GDG acknowledged that one small study reported that sustained uterine massage and clot expulsion were associated with a reduction in the use of additional uterotonics, there is lack of robust evidence supporting other benefits. However, the GDG considered that routine and frequent uterine tone assessment remains a crucial part of immediate postpartum care, particularly for the optimization of early PPH diagnosis.
• Intermittent uterine tone assessment (e.g. periodic palpation) remains important as part of routine postpartum monitoring to detect uterine atony and guide further action if needed (see Recommendation 23).

• Visual estimation of postpartum blood loss is frequently inaccurate, meaning that PPH often goes unrecognized or is identified when it is too late to provide a life-saving intervention. Objective methods of quantifying blood loss, which are superior to visual estimation, are more likely to detect PPH. For women who have had a vaginal birth, most of the available evidence on postpartum blood loss measurement comes from the use of a calibrated drape.
• Blood loss measurement is particularly critical in the first few hours after birth. Women should also be regularly monitored for early warning signs of excessive blood loss (e.g. tachycardia or hypotension).
• To be effective, measurement of postpartum blood loss must be linked with a standardized treatment approach or protocol, and vice versa. Detecting PPH, in the absence of prompt initiation of treatment, is unlikely to improve a woman’s health outcomes.
• The available studies have been conducted in women giving birth vaginally. However, the measurement of blood loss in women undergoing a caesarean section is also clinically important.
• The process for postpartum blood loss measurement should ensure that a woman’s customary or cultural requirements, including choice of birth position, are respected and maintained.
• Birth-related bleeding risks and the signs and symptoms of excessive blood loss should be discussed with women across the birth continuum (including antenatally) to foster shared decision-making.
• The GDG acknowledged that alternatives to calibrated drapes, such as blood collection trays and jars, are increasingly being promoted in some settings for measuring postpartum blood loss. However, current evidence does not support the diagnostic accuracy of these alternatives. By contrast, calibrated blood collection drapes have been shown to provide more accurate quantification of postpartum blood loss compared to visual estimation (54). Countries or programmes considering the scale-up of postpartum blood loss measurement should ensure that any chosen device is evidence-based and fit for purpose, so that the intended impact of timely PPH detection and treatment is not undermined by the use of less reliable tools.
• There should be consideration and investments made into the development and use of sustainable and climate-friendly drapes.

Justification

This recommendation is based on a meta-analysis of individual participant data including over 300 000 women from 12 datasets across 23 countries (28), offering moderate-certainty, individual-level evidence with global representativeness. The findings show that a threshold of ≥300 mL blood loss combined with any abnormal haemodynamic sign offers a good balance between sensitivity and specificity in identifying women at increased risk of severe adverse outcomes from postpartum bleeding, outperforming the conventional ≥500 mL threshold, in both accuracy and clinical utility. These diagnostic criteria may support earlier identification at lower thresholds, allowing prompt initiation of the first-response treatment bundle, which has been proven to prevent progression to severe morbidity or death from PPH (55). The first-response treatment bundle is generally low risk, and affordable, and becoming widely available and feasible in most facility settings.

Prioritizing sensitivity in this context helps ensure that fewer women with life-threatening postpartum bleeding are missed, which is especially crucial in low-resource settings. While a lower blood loss threshold increases the number of women identified and treated, and thus raises concerns about overtreatment, this is outweighed by the benefits of preventing severe adverse outcomes, especially because first-response interventions are safe and well tolerated. Women and health workers are also more likely to prioritize sensitivity over specificity, underscoring the value of preventing missed cases over the risk of modest overtreatment, given the potential, severe consequences of PPH if it is not identified and treated in a timely manner.

The evidence supports the use of a threshold of ≥300 mL objectively measured blood loss with any abnormal haemodynamic signs as an add-on test to overcome the shortcomings of the conventional threshold of ≥500 mL across health care settings, with particular benefit in low-resource countries. Economic modelling and health system data suggest that earlier intervention may be cost-effective; increased identification may require more commodities for first-line treatment but this will reduce the need for costly, resource-intensive care such as blood or blood product transfusion or surgery.

Implementation of these diagnostic criteria is feasible, cost-effective and likely to increase equity by reducing severe PPH outcomes, particularly in low-resource settings. However, the findings are applicable across diverse settings, modes of birth (with some limitations for caesarean section) and health system contexts, and thus applicable for global use.

Evidence on the time horizon for this diagnostic criteria indicates that most bleeding events meeting the threshold occur within the first 1–2 hours after birth (52). However, the 24-hour period remains relevant because it aligns with historical definitions and captures most acute maternal complications after birth.

• This recommendation provides a therapeutic definition of PPH, that is, a diagnostic threshold designed to guide the decision to initiate treatment rather than to define the condition solely for classification purposes. The objective is to support timely clinical action by identifying women at increased risk of adverse outcomes from postpartum bleeding. This approach prioritizes early intervention and the woman’s safety by aligning diagnosis with immediate treatment needs.
• The recommendation on the time horizon for this definition was informed by evidence showing that most postpartum bleeding events meeting the diagnostic criteria occur within the first 2 hours after birth. However, as life-threatening bleeding can still occur beyond this immediate postpartum period, continued monitoring for clinical signs of concealed or revealed blood loss is essential throughout the first 24 hours postpartum. The GDG acknowledged that the 24-hour time horizon is largely historical and conventional but noted that it also reflects evidence indicating that most acute maternal morbidity and mortality after birth occur within this window, underscoring the need for vigilant observation during this critical period, both inside and outside the labour ward, for optimal maternal care and outcomes.
• Abnormal haemodynamic signs in the context of these diagnostic criteria include any of the following: pulse rate >100 bpm, systolic BP <100 mmHg, diastolic BP <60 mmHg, or shock index >1 (calculated as pulse rate divided by systolic BP, which is >1 when pulse rate is higher than the systolic BP).
• These diagnostic criteria should be linked to the first-response treatment bundle because diagnosing PPH in the absence of timely treatment is unlikely to improve outcomes. The criteria are recommended as the basis for first-response PPH treatment and referral decisions (where needed), not as an absolute trigger for initiating advanced therapies or surgical interventions. Clinical judgement should guide the escalation of care.
• Although this recommendation offers diagnostic criteria for identifying women at risk of adverse outcomes from postpartum bleeding and initiating treatment, it is recognized that health system readiness for postpartum monitoring and treatment initiation (e.g. availability of staff, equipment) varies across different settings. Implementers may choose different thresholds for initiating treatment considering the realities of their local contexts (i.e. earlier intervention and faster escalation if referrals are difficult and time-consuming).
• Wider adoption of these diagnostic criteria may increase demand for basic monitoring equipment (e.g. calibrated drapes, BP devices), and may require additional staff training and resources for objective blood loss measurement and haemodynamic monitoring. However, this investment is offset by reduced demand for expensive, complex interventions for severe PPH that are not available in many settings.
• The diagnostic criteria can be applicable in the context of home-based or community-based births. Adaptations in care may be needed to obtain access to innovative tools for objective quantification of blood loss and monitoring of abnormal haemodynamic signs.
• The risks of bleeding and the signs and symptoms of excessive blood loss should be discussed with women across the birth continuum (including antenatally) to foster shared decision-making and support women in identifying warning signs and promptly seeking care.
• Implementation of the diagnostic test strategy may increase reported rates of PPH, particularly in settings simultaneously introducing objective assessment of blood loss. This should not be interpreted as a decline in care quality but as improved detection and prevention of severe maternal complications.
• The GDG acknowledged that the evidence base overwhelmingly represents facility-based vaginal births, with only one large study of caesarean births included, thus limiting the overall confidence in the generalizability of these criteria to the caesarean birth population. The group agreed that quantitative assessment of intraoperative blood loss can be challenging and changes to clinical signs may be anaesthesia-induced rather than indicative of haemodynamic instability. Nonetheless, the GDG noted that nearly all the components of the first-response treatment bundle that the new diagnostic criteria would trigger are already part of routine care for caesarean birth – uterine massage, oxytocic drugs, intravenous fluids and identification of the source(s) of bleeding – which are often implemented before detection of significant blood loss. The group further emphasized that although the pattern of blood loss may differ according to mode of birth, the physiological impact of a given volume of blood loss, and the associated risk of adverse outcomes, are not expected to differ between vaginal and caesarean births. Consequently, in making this recommendation, the GDG placed its emphasis on the clinical importance of standardized and consistent diagnostic criteria to identify PPH and initiate timely treatment for all births, while recognizing the need for additional research data for the caesarean section population. The GDG also cautioned that the relatively higher blood loss patterns that are associated with caesarean sections should not be normalized or considered acceptable because this may contribute to dangerous delays in intervention, particularly in view of the disproportionately high burden of PPH-related mortality associated with caesarean birth.

• This recommendation emphasizes the importance of early detection of uterine atony, which is the most common cause of PPH. Immediately after the birth of the baby or babies and placenta, regular abdominal palpation to assess uterine firmness and ensure that the fundus is well contracted and centrally located should be initiated. The first hour after birth is particularly important; close regular assessment during this time, ideally every 15 minutes, is essential. Continued assessments should follow local protocols but typically extend through the first 1–2 hours postpartum, with reduced frequency thereafter if no abnormalities are detected. Finding of a soft or boggy uterus at any time should prompt further examination and clinical response to prevent severe blood loss and clinical deterioration.
• The frequency and duration of assessment may be adapted based on clinical judgement, local protocols and individual risk factors.
• Although uterine massage is not recommended as a routine prophylactic intervention, it remains a first-line response in cases where uterine atony is identified during uterine tonus assessment. This distinction should be clearly understood in clinical practice.
• The implementation of this recommendation is especially critical in settings where quantitative blood loss measurement is not yet accessible because changes in uterine tone can be an early and important clinical marker of ongoing bleeding.

• The GDG recommended intravenous oxytocin as the first-line uterotonic drug for the treatment of PPH, including when women have already received this drug for the prophylaxis of PPH. Repeated dosing is considered safe and effective when PPH develops despite prophylactic use.
• The GDG recognized that intravenous oxytocin may not be available in all settings. Health care decision-makers are encouraged to prioritize the procurement and distribution of quality-assured oxytocin.
• For the treatment of PPH, 10 IU oxytocin is commonly administered intravenously as the initial dose. Rapid intravenous injection should be avoided to reduce the risk of hypotension and other adverse effects. The dose should preferably be diluted and administered slowly over 1–2 minutes as a bolus or diluted in a small volume of crystalloids and infused over 5–10 minutes. A maintenance infusion of oxytocin (10–20 IU diluted in crystalloids) may be required over the subsequent 4 hours to sustain uterine contraction and prevent recurrence of bleeding after initial control of PPH. The infusion should be titrated based on uterine response and clinical condition. Ongoing monitoring of blood loss, uterine tone and haemodynamic status throughout this period is essential to ensure treatment effectiveness and to enable timely escalation if bleeding continues or the woman’s condition deteriorates.
• The GDG acknowledged that there is limited evidence from studies on the best oxytocin regimen for the treatment of PPH and noted that variations in oxytocin regimen exist both in the initial and maintenance doses and the amount of fluids used for dilution. The regimen provided here reflects consensus and successful implementation in a large-scale PPH trial, which demonstrated its feasibility and favourable outcomes in four low- and middle-income countries.

• In settings where intravenous oxytocin is unavailable to women who have received prophylactic intramuscular oxytocin during the third stage of labour, the GDG considered misoprostol to be a valid alternative for the treatment of PPH.
• If PPH prophylaxis with misoprostol has been administered and if injectable uterotonics are unavailable, there is insufficient evidence to guide additional misoprostol dosing. Providers should weigh the potential for toxicity when considering repeated doses.

• There is no added benefit to offering misoprostol simultaneously to women receiving oxytocin for the treatment of PPH (i.e. adjunct misoprostol).
• The GDG noted that the two largest trials of misoprostol for the treatment of PPH reported the use of a 800-μg dose administered sublingually (56, 57). Most of the GDG members agreed that 800 μg is an acceptable sublingual misoprostol dose for the treatment of PPH, although some members of the GDG expressed concern related to the risk of hyperpyrexia associated with this dosage.
• If intravenous oxytocin has been used for the treatment of PPH and the bleeding does not stop, there is paucity of data to recommend preferences for second-line uterotonic drug treatment. Decisions in such situations must be guided by the experience of the provider, the availability of the drugs and by the known contraindications.
• In situations in which intramuscular oxytocin can be administered and there is no possibility of intravenous treatment with ergot alkaloids/injectable prostaglandins, there is a paucity of data to recommend a preference for intramuscular oxytocin over misoprostol or other uterotonics. Decisions in such situations must be guided by the experience of the provider, the availability of the drugs and by the known contraindications.
• Carbetocin (heat-stable and non-heat-stable formulations), although recommended for PPH prevention, has not been adequately studied for repeated dosing for PPH treatment, when carbetocin has been used for PPH prophylaxis. Therefore, the use of carbetocin (heat-stable and non-heat-stable formulations) in this context should be discouraged until robust evidence on safety and efficacy for PPH treatment becomes available.
• While there is no evidence to suggest that carbetocin is less safe or less effective than the injectable uterotonics recommended here for PPH treatment, its use in this context has not been adequately studied. In contrast, ergometrine and the fixed-dose oxytocin and ergometrine combination have a longer history of clinical use for both the prevention and treatment of PPH, and their safety concerns are known and can be mitigated in clinical practice.

• Uterine massage as a therapeutic measure is defined as the rubbing of the uterus achieved through the manual massaging of the abdomen. This is typically sustained until the bleeding stops or the uterus contracts. The GDG emphasized that uterine massage should be started once PPH has been diagnosed, as part of the first-response treatment bundle, which includes administration of uterotonics, tranexamic acid, intravenous fluids and examination of the genital tract and escalation of care.
• The initial rubbing of the uterus and expression of blood clots are not regarded as therapeutic uterine massage.
• Uterine massage may be repeated or continued intermittently, based on the clinical response, particularly if bleeding persists despite administration of uterotonics.
• The GDG noted that the application of this intervention requires training and that maternal discomfort and complications associated with these procedures have been reported.
• When formulating this recommendation, the low cost and safety of uterine massage were considered.
• This recommendation is specific to the treatment of PPH and not intended for routine or sustained use as a preventive measure in women who have already received prophylactic uterotonics (see Recommendation 20 on uterine massage for PPH prevention).

• Based on the dosing regimen used in the WOMAN trial (58), the GDG supports the administration of TXA at a fixed dose of 1 g (100 mg/mL) intravenously at 1 mL per minute (i.e. administered over 10 minutes), with a second dose of 1 g intravenously if bleeding continues after 30 minutes or if bleeding restarts within 24 hours of completing the first dose.
• The GDG acknowledged that while the WOMAN trial used clinically diagnosed PPH based on estimated blood loss or signs of haemodynamic instability, the diagnosis of PPH should no longer rely solely on clinical estimation. Therefore, this recommendation has been aligned with the updated WHO guidance on objective blood loss assessment and diagnostic criteria for PPH, which include ≥300 mL blood loss with abnormal haemodynamic signs or ≥500 mL blood loss, whichever occurs first.
• Based on evidence from the WOMAN trial, the reference point for the start of the 3-hour window for starting TXA administration is time of birth. If time of birth is unknown, the best estimate of time of birth should be used as the reference point. Because most deaths due to PPH occur within the first 2–3 hours after birth, it is critical that TXA is given as soon as possible to achieve clinical benefits.
• Analysis of the effects of timing of administration in the WOMAN trial, as well as a meta-analysis of the individual participant data of 40 138 bleeding patients (including WOMAN trial participants), indicates that TXA administration beyond 3 hours does not confer any clinical benefit. Furthermore, the point estimates of effect of TXA use beyond 3 hours on death due to trauma or after PPH were both in the direction of harm, albeit not statistically significant for women with PPH. In view of this evidence, the GDG does not support the use of TXA more than 3 hours after birth.
• Administration of TXA should be considered as part of the first-response treatment bundle (massage, administration of oxytocin, TXA, intravenous fluids, examination of the genital tract and escalation of care, to ensure timely and coordinated care) (see Recommendation 29). Other standard care in the context of this recommendation includes non-surgical temporizing measures in the management of PPH (e.g. bimanual compression, intrauterine balloon tamponade, non-pneumatic anti-shock garment, external aortic compression) and surgical interventions (e.g. brace sutures, arterial ligation or hysterectomy) in accordance with WHO guidelines or adapted local PPH treatment protocols.
• TXA should be used in all cases of PPH, regardless of whether the bleeding is due to genital tract trauma or other causes. Therefore, administration does not require the confirmation of the source of bleeding.
• The use of TXA should be avoided in women with a clear contraindication to antifibrinolytic therapy (including TXA) (e.g. a known thromboembolic event during pregnancy).
• This recommendation applies only to intravenous use. The evaluation of benefits and potential harms of other routes of TXA administration (e.g. intramuscular regimen) is a research priority.
• Regardless of the level of health system resources, TXA should be recognized as a life-saving intervention and be made readily available for the management of PPH in settings where emergency obstetric care is provided.

• This recommendation is based on indirect evidence from studies primarily involving trauma and critically ill patients, where isotonic crystalloids (e.g. Ringer’s lactate or normal saline) were associated with similar or better outcomes compared to colloids, without the increased cost or risk of adverse events, such as anaphylaxis.
• The physiological rationale and safety profile of crystalloids support their use as the preferred first-line fluid resuscitation strategy in women with PPH. Colloids have not been shown to provide a significant clinical advantage and may pose greater risk in resource-poor settings.
• Crystalloids are widely available, inexpensive and simple to use, making them the most practical and scalable choice for volume replacement in both high-resource and low-resource settings. In contrast, colloids are more expensive, may require stricter storage conditions and are not universally accessible.
• The goal of fluid resuscitation in PPH is to stabilize circulation and maintain perfusion while definitive treatment of bleeding is underway. Isotonic crystalloids are effective for this purpose and should be administered alongside other components of the PPH treatment bundle (e.g. uterotonics, tranexamic acid, uterine massage and examination of the genital tract to identify the source of bleeding).
• Caution is needed to avoid fluid overload during resuscitation, particularly in women with pre-eclampsia or cardiac conditions. Clinical judgement and ongoing monitoring of haemodynamic status should guide the volume and rate of fluid administration.

• All interventions included in the PPH treatment bundle are individually recommended for PPH treatment (see Recommendations 24–28).
• The examination of the genital tract involves a thorough inspection of the birth canal and surrounding areas to identify any sources of bleeding. This examination typically includes checking for lacerations, tears or haematomas in the vagina, perineum and cervix, assessment of the uterus to ensure it is contracting properly, and examination of the placenta and membranes to ensure there are no retained placental fragments.
• In the context of this recommendation, the GDG emphasizes the need for a consistent use and interpretation of the term bundle as a clinical care bundle for the treatment of PPH. This should not be misconstrued with the use of this term in other contexts.
• To ensure the maximal success of the PPH treatment bundle, early detection of PPH is a key and indissociable component of the first-response intervention. The available evidence on postpartum blood loss measurement is largely from trials that used calibrated drapes for women who had a vaginal birth (see Recommendation 21).
• Clinical judgement is important to guide PPH treatment decision-making. In a large trial, the treatment care bundle was initiated when measured blood loss was 500 mL or greater, or when measured blood loss was 300 mL or greater with early warning signs of excessive blood loss (see Recommendation 22 and corresponding remarks).
• The trial underlying this recommendation included multiple implementation and health system strengthening strategies, which helped to achieve high coverage in the consistent use of the treatment bundle (55). These included ensuring availability of required human resources, strengthened by dedicated research staff, regular health care facility-level audit and feedback, designated facility champions to oversee change, restocking of PPH trolleys or carry cases so that all necessary medicines and equipment were readily available in one place, and training for health workers.
• The PPH treatment bundle requires standardized and timely use of all included interventions. All bundle treatment interventions should ideally be initiated within the first 15 minutes after a diagnosis of PPH. However, health system readiness (e.g. availability of staff, equipment) varies across different settings. In the event that not all bundle interventions are available, available components should be initiated in a timely and standardized manner.
• In cases of refractory postpartum bleeding – where a woman has received all interventions within the PPH treatment bundle yet continues to bleed – prompt escalation to a higher-level health care facility or a senior clinical provider capable of providing further management is critical.
• The GDG acknowledges that the evidence supporting the treatment bundle is largely from trials on vaginal births, and does not have any clear evidence to refute that the findings would be different for a caesarean section. The individual PPH treatment interventions included in the PPH treatment bundle are also recommended by WHO for women undergoing a caesarean section. However, the group acknowledged that additional research is required to confidently recommend bundle care for caesarean section births.
• National, regional, subregional and district-level health systems must be strengthened so that sufficient resources are available, ensuring the sustainability of treatment bundle implementation. Adequate numbers of staff and availability of commodities are essential to achieve the benefits of treatment bundles.
• The supporting evidence has largely been generated from studies conducted in secondary-level health care facilities. However, prompt recognition and treatment of PPH for women who give birth in primary care settings, in the community or at home are equally relevant. Appropriate resources and health worker training integrated with setting-specific implementation strategies are necessary to facilitate this.
• Engagement with women and their communities is paramount to promote women’s human rights and agency in their health, and foster their participation in shared decision-making around PPH treatment.

Justification

The evidence on the benefits of administering uterotonics for retained placenta in the absence of PPH is very uncertain. The effect of intravenous oxytocin – commonly regarded as standard practice – has not been established. There is limited evidence available to assess uterotonics other than intravenous oxytocin (e.g. prostaglandin E2 analogue (sulprostone), misoprostol, carbetocin). Available evidence suggests that these agents may have minimal or no clinical benefit in this context, and there is some low-certainty evidence of small undesirable effects.

Uterotonics are already recommended for PPH prevention in all women and as a core component of the first-response treatment bundle for women who are actively bleeding. However, in the absence of PPH or other complications, the GDG determined that the balance of effects does not favour the routine use of uterotonics for the retained placenta. There is no compelling evidence of improved outcomes, and their use may delay definitive management, such as manual removal of the placenta, and hinder effective clinical assessment or removal because of increased uterine tone.

The historical safety concerns related to agents such as ergometrine and prostaglandin E2 analogues (e.g. sulprostone or dinoprostone) remain relevant, particularly in settings where contraindications may not be easily ruled out. Until more robust evidence becomes available, the current evidence does not support the routine use of uterotonics solely to treat the retained placenta in the absence of active bleeding.

• The first-response treatment bundle for PPH includes rapid institution of uterine massage, administration of a uterotonic agent and tranexamic acid, intravenous fluids, examination of the genital tract and escalation of care as needed. The bundle should be applied to all women diagnosed with PPH, regardless of cause (including those with a retained placenta) (see Recommendation 29).
• The GDG found very limited evidence to support recommending routine use of uterotonics for the treatment of the retained placenta in the absence of PPH. Recommendation 30 was reached by consensus.
• Ergometrine and prostaglandin E2 alpha (dinoprostone or sulprostone) should be avoided in the presence of the retained placenta. Ergometrine may cause tetanic uterine contractions, which may delay the expulsion of the placenta and may increase a woman’s risk of adverse events, particularly cardiac events.
• If the placenta is not expelled spontaneously within 15 minutes after birth and PPH has not been diagnosed, health care workers should take steps to remove the placenta. These include controlled cord traction (CCT), mobilizing, squatting or emptying the bladder before manual removal of the placenta becomes clinically indicated. While undertaking these steps, health workers should monitor the woman for blood loss or other signs and symptoms consistent with PPH.
• If the placenta remains undelivered after 30 minutes and no PPH has been diagnosed, preparations for manual removal should be initiated. Delaying removal beyond 30 minutes has been associated in some studies with increased blood loss and higher rates of severe PPH; however, a longer wait time may also allow for more cases of spontaneous placental expulsion.
• In clinical practice, uterotonics are usually used immediately after manual removal of the placenta to support contraction of the uterus and reduce bleeding.

Justification

The evidence on the desirable and undesirable effects of using prophylactic antibiotics during manual removal of a retained placenta is limited. Specifically, the evidence on reducing the risk of postpartum endometritis is very uncertain.

Although the evidence is limited, the GDG placed its emphasis on the important concerns regarding the risk of infection after manual removal of the placenta and intrauterine exploration procedures. The group also considered indirect evidence from studies on prophylactic antibiotics in other obstetric contexts, such as caesarean section and abortion care, as well as observational studies involving intrauterine manipulation, which suggest potential benefit in reducing infectious morbidity.

• For the purpose of administering prophylactic antibiotics, manual removal is intended as any form of uterine manipulation, either manual or instrumentation within the uterine cavity for removing the placenta or exploring the cavity for any residual fragments.
• Current practice suggests that ampicillin or first-generation cephalosporins may be administered when manual removal of the placenta is performed. Alternatively, a single dose of intravenous amoxicillin (1 g) and clavulanic acid (200 mg) could be used, like the regimen used for operative vaginal birth. All regimens have a broad spectrum of activities and are widely available. When the recommended antibiotic classes are not available, other classes of antibiotics may also be used. The choice of such an antibiotic class should be informed by the local bacteriological patterns of infectious morbidity, the availability of such antibiotic class, the woman’s allergy history, the clinician’s experience with that class of antibiotics and cost.
• Infection prevention during and after manual removal of the placenta should not rely on antibiotics alone. Adherence to standard infection prevention and control practices, including hand hygiene and aseptic technique, remains essential. Prevention or prompt management of conditions such as anaemia may further reduce infection risk and support recovery.

Justification

Evidence from trials that compared both umbilical vein injection of oxytocin versus expectant management, and umbilical vein injection of oxytocin versus umbilical vein injection of saline, suggest that this intervention may lead to a reduction in manual removal of the placenta. However, the effect of this intervention on other priority outcomes (including infections, maternal satisfaction and length of hospitalization) is unclear. While the cost–effectiveness is not known, additional costs in supplies required to implement this intervention are probably negligible. When compared with injection of other solutions and uterotonics, no other umbilical vein injection regimen was shown to be clearly better than umbilical vein injection of oxytocin.

• The GDG acknowledged the potential of umbilical vein injection of oxytocin solution in the treatment of the retained placenta but considered the evidence of benefit in terms of manual removal of the placenta without impact on other priority outcomes insufficient to make a recommendation for routine clinical practice. The group agreed that high-quality randomized trials comparing umbilical vein injection of uterotonics with expectant management of women with a retained placenta are needed, with the aim of demonstrating its impact on severe postpartum haemorrhage-related morbidity in addition to a reduction in manual removal of the placenta.
• When used in a research context, it is safer to consider the use of this intervention in situations in which a retained placenta occurs in the absence of abnormal bleeding.
• There are three types of retained placenta; umbilical vein injection of oxytocin is likely to be only effective in treating placenta adherens, the most common type of retained placenta, which occurs because of failed contraction of the retroplacental myometrium. To date, studies have not distinguished the subtypes before treatment; this may have contributed to the results showing lack of efficacy of treatment with umbilical vein injection for the retained placenta.

• Bimanual uterine compression is a simple, immediate, low-technology intervention that can be used by trained health personnel at all levels of the health system, including in settings with limited resources. This manoeuvre involves placing one hand inside the vagina to elevate and compress the uterus against the posterior wall of the abdomen, while the other hand applies firm pressure externally on the fundus. The goal is to mechanically compress the uterus to promote contraction and reduce bleeding.
• It is intended as a temporizing measure, not a definitive treatment, to stabilize the woman while preparing or arranging for additional interventions, such as uterotonics, balloon tamponade or surgical interventions.
• The GDG noted that the application of this intervention requires training in the proper technique and regular emergency drills to improve the correct and timely use of bimanual uterine compression in clinical practice.
• The procedure can be physically demanding for the health care provider and uncomfortable for the woman; complications associated with this procedure have been reported. Therefore, effective communication and use of pain relief, when feasible, are important. A less invasive, new device that could replicate bimanual compression is awaiting further evaluation (59).

• External aortic compression is a non-invasive manoeuvre used to reduce blood flow to the uterus by applying firm downward pressure over the abdominal aorta, just above the umbilicus and slightly to the left of the midline.
• External aortic compression has long been recommended as a potential life-saving technique; mechanical compression of the aorta, if successful, slows down blood loss. The GDG placed a high value on this procedure as a temporizing measure in the treatment of PPH.
• The effectiveness of aortic compression can be assessed by a reduction in bleeding and diminished or absent femoral pulse. The GDG noted that the manoeuvre should be performed by trained personnel and monitored carefully.
• External aortic compression can be physically demanding to sustain and may cause maternal discomfort.

• The GDG noted that the application of this intervention requires training and that maternal discomfort and complications associated with this procedure have been reported.
• Based on the evidence available, the GDG recommended NASG as a temporizing measure until appropriate care is available. Temporizing may be required while awaiting transfer to a higher level of care, during the transfer and even while awaiting for blood transfusion or surgery within the facilities.

Uterine balloon tamponade is recommended for the treatment of PPH due to uterine atony after vaginal birth in women who do not respond to standard first-line treatment, provided the following conditions are met:

• Immediate recourse to surgical intervention and access to blood products is possible, if needed.
• A primary postpartum haemorrhage first-line treatment protocol (including the use of uterotonics, tranexamic acid, intravenous fluids) is available and routinely implemented.
• Other causes of postpartum haemorrhage (retained placental tissue, trauma) can be reasonably excluded.
• The procedure is performed by health personnel who are trained and skilled in the management of postpartum haemorrhage, including the use of uterine balloon tamponade.
• Maternal condition can be regularly and adequately monitored for prompt identification of any signs of deterioration.

(Context-specific recommendation)

Justification

While there is insufficient evidence from randomized trials conducted in low-resource settings to assess the benefits and potential harms of uterine balloon tamponade when used for PPH treatment, several observational studies suggest a substantial reduction in the risk of maternal morbidity after uterine balloon tamponade use. It is unclear whether this disparity in findings reflects study design, balloon type or access to other essential components of PPH care.

The impact of uterine balloon tamponade for PPH treatment on health equity and cost is likely to vary according to uterine balloon tamponade designs (low-cost improvised or purpose-designed devices versus expensive purpose-designed devices). In contexts where standard PPH treatment protocols are available and implemented, uterine balloon tamponade use for PPH treatment is probably feasible and acceptable to women and providers.

• The GDG acknowledged that the conditions listed above may not be operationalized in a standard and consistent manner across settings. It is uncertain which preconditions are the most important to obtain clinical benefits from uterine balloon tamponade, and this would benefit from further research. In setting these preconditions, the panel’s emphasis was on minimizing harm to the woman, which could result from failure to or delay in implementing other temporizing and more invasive PPH treatment, incorrect patient selection for application of uterine balloon tamponade, poor monitoring or lack of other essential components for quality PPH care.
• In settings where these conditions cannot be met, the GDG agreed that additional rigorous research evidence is needed to determine if the clinical benefits outweigh the potential harms of uterine balloon tamponade in such settings.
• There is currently insufficient evidence to determine the comparative effectiveness and safety of improvised devices or purpose-designed devices. Evidence for this recommendation came from trials that used improvised devices for which there were reported concerns or problems in placement, including delays in inserting the device.

Justification

There is currently insufficient evidence to warrant recommending uterine packing, either with plain gauze or gauze impregnated with haemostatic agent(s).

Given the lack of rigorous evidence of demonstrable benefit of this intervention, the GDG placed its emphasis on long-standing concerns about the potential for harm, particularly in low-resource settings with limited capacity to rapidly escalate interventions in the event of concealed haemorrhage, uterine trauma, infection or other complications.

• On reviewing the available evidence, the GDG agreed that there is currently insufficient evidence to support the use of any form of uterine packing, whether with plain gauze or gauze impregnated with haemostatic agents, for the treatment of PPH.
• Uterine packing may delay escalation to other definitive interventions for PPH that have demonstrable evidence of benefit, thereby increasing the risk of adverse outcomes.
• The GDG recognizes that uterine packing may be useful as a temporizing measure when all medical treatment has failed in contexts where no other interventions for treating PPH are available. Priority should be placed on urgently transferring the woman to higher-level care where definitive life-saving interventions can be administered.
• Well-designed, prospective controlled studies are needed to assess the safety, effectiveness and potential added value of uterine packing, whether with plain gauze or gauze impregnated with haemostatic agents, when used in addition to or as a substitute for currently recommended non-surgical interventions for refractory PPH. Comparative research evaluating uterine packing against recommended interventions, such as uterine balloon tamponade or other conservative options, would be particularly valuable.

• Uterine artery embolization is a highly specialized procedure that requires the availability of interventional radiology services, including trained personnel, appropriate imaging equipment and around-the-clock access. This limits its use to well-resourced, typically tertiary care facilities.
• The GDG noted that timely access is critical to the success of uterine artery embolization; delays in performing the procedure may reduce its effectiveness or increase the risk of adverse outcomes. Therefore, when uterine artery embolization is being considered, parallel preparations for surgical alternatives should not be delayed.
• Where the procedure is available, it may offer fertility-preserving advantages compared to hysterectomy. The GDG recognized this as an important consideration for some women, especially those who desire future pregnancies.
• The procedure is not a replacement for prompt initial treatment, including the PPH first-response bundle. It should be reserved for use after failure of medical and mechanical interventions or when surgical options carry a high risk.
• The GDG noted that uterine artery embolization requires significant resources, in terms of the cost of the treatment, the facilities and the training of health care workers. Health systems considering uterine artery embolization as part of their PPH treatment strategy should invest in protocols to ensure timely referral and coordinated care between obstetrics, anaesthesia and interventional radiology teams.

• The GDG noted that the application of these interventions requires training and that maternal discomfort and complications associated with these procedures have been reported.
• The GDG noted that conservative surgical approaches should be tried first. If these do not work, they should be followed by more invasive procedures. Compression sutures, for example, may be attempted as a first intervention; if these fail, then uterine, utero-ovarian and hypogastric vessel ligation may be tried. If life-threatening bleeding continues even after ligation, then a subtotal (otherwise known as supracervical) or total hysterectomy should be performed.
• The GDG acknowledged that the level of health care provider skills will have a role in the selection and sequence of the surgical interventions.

Justification

Evidence from trials that compared cell salvage versus no cell salvage or usual care for the treatment of PPH suggest that this intervention may lead to a reduction in average blood loss and higher postnatal haemoglobin. However, the effects of this intervention on other priority outcomes (particularly blood transfusion) are generally unclear.

Cell salvage is currently associated with large costs (including training and staffing requirements); cost-effectiveness evidence does not favour the use of cell salvage. However, allogenic blood transfusion is also associated with moderate-to-large costs and may not be readily available in some settings. Innovations that reduce the cost of intraoperative cell salvage may change the cost–effectiveness assessment of this intervention. Allogenic blood transfusion may be refused by women for religious or cultural reasons. The evidence from the available trials excluded women who refuse allogenic blood transfusion. Thus, the effects of cell salvage for this subgroup of women are not known.

• The GDG acknowledged the potential of cell salvage in the treatment of PPH among women having caesarean births but considered the evidence on desirable effects insufficient to make a recommendation for routine clinical practice.
• The group agreed that rigorous research studies comparing cell salvage with no cell salvage, especially in women who are at high risk of PPH and likely to need blood transfusion intraoperatively, are needed. The aim of such studies would be to demonstrate the impact of cell salvage on blood transfusion related to PPH, in addition to improvements on other important outcomes, such as improved well-being and satisfaction. Given the challenges with designing large high-quality randomized trials on this topic, the GDG highlighted the added value of high-quality controlled non-randomized studies, especially those investigating the adverse effects of the intervention.
• To date, studies have used broad criteria for classifying women at risk of PPH, but it was unclear if these women were also at a higher risk for requiring a blood transfusion. If lower-risk women were included, this may have contributed to the results showing lack of efficacy of treatment with cell salvage. Additional research focusing on women at high risk for requiring blood transfusion (e.g. women with placenta accreta) is particularly needed.
• When cell salvage is used in a research context, it is important to monitor for adverse events from autotransfusion and evidence of fetomaternal haemorrhage to adjust the need for anti-D prophylaxis.

Justification

There is no direct evidence available to recommend any criteria or protocol for the transfusion of blood products over another in the context of PPH, obstetric haemorrhage or acute blood loss. Indirect evidence from general surgical and medical populations suggests that instituting restrictive criteria for initiating blood transfusion may reduce the use of blood products and costs compared with usual care, without adversely impacting clinical outcomes. However, it is unclear to what extent these findings can be extrapolated to obstetric populations. In the setting of rapid and massive ongoing PPH, restrictive haemoglobin-based transfusion is often not practical and measurement of haemoglobin may be unreliable. Use of restrictive criteria for initiating blood transfusions might help to ensure evidence-driven allocation of transfusion, which could help conserve scarce resources and improve equity. While there is no evidence on acceptability of health workers and women and their families on using specific criteria for transfusion of blood products, women and their families are more likely to accept criteria that limit receiving any blood transfusion product, and thus may be more favourable to restrictive criteria for transfusion of blood products. Restrictive criteria could improve availability of blood products and are likely to be feasible to implement. However, this would require access to laboratory equipment for closer monitoring of haematological parameters.

Remarks

Transfusion protocols, algorithms and processes:

• Given that no specific transfusion criterion or protocol has been proven to be more effective than another, each hospital will need to address its specific resources and make modifications specific to its unique setting. While acknowledging the lack of firm criteria for initiating transfusion, the GDG emphasizes the importance of judicious use of blood products and suggests that health facilities should favour policies that promote their equitable use.
• Local management algorithms taking a multidisciplinary approach should be established and made available to health workers.
• A massive transfusion protocol should be available in health facilities with adequate blood banking capabilities. Massive transfusion has been variously defined but generally includes transfusion of four units of packed red blood cells (RBCs) within 1 hour when ongoing need for more blood is anticipated, transfusion of 10 or more units of packed RBCs within 24 hours, replacement of more than 50% of the total blood volume of the woman by blood products within 3 hours, or replacement of a total blood volume. Protocols should be established in agreement with local haematology departments.
• All transfusions should be done according to the clinical picture, particularly if vital signs are unstable and blood loss is significant (≥1000 mL) and ongoing. It is important to note that blood loss can be underestimated or concealed.
• The transfusion of individual blood components is preferred to whole blood alone. In settings where only whole blood is available, it should be considered, provided blood is crossmatched or low-titre type O blood is available.
• Health workers should be familiar with the procurement processes, logistic channels and potential limitations of blood product availability within their health service or network of care.
• It is essential to develop strategies and protocols to manage situations where women decline blood products because of religious beliefs, such as those of Jehovah’s Witnesses, or other personal reasons.

Screening and testing:

• To ensure rapid intervention should transfusion of blood products be indicated, blood groups, phenotypes and irregular antibody screening results must be verified on admission of a woman to the labour ward.

Monitoring of haematological response:

• In women with acute haemorrhage, haemoglobin levels may remain normal, making clinical evaluation crucial for timely decision-making. Point-of-care haemoglobin measurements in such cases could be falsely reassuring; therefore, they should be interpreted cautiously. Single haemoglobin or haematocrit measurements can be misleading and may delay the initiation of red cell transfusion; however, serial measurements are valuable for monitoring ongoing treatment.
• The decision to transfuse should not be based on haemoglobin levels alone, but also on the woman’s clinical needs. The following factors must be considered: morbid status, obstetric history, stage of pregnancy, evidence of organ hypoperfusion or failure, and presence of infection (e.g. pneumonia, malaria).

Transfusion of blood products

Red blood cells:

• If available, transfusion of red blood cells (RBCs) should be considered. Fully crossmatched RBCs should be used preferentially. When the ABO and rhesus group is known but crossmatching is not possible, ABO and rhesus-compatible uncrossmatched blood should be used. In an emergency scenario when crossmatching is not possible, O-negative RhD-negative blood should be used. The therapeutic goal is often set as haemoglobin >70 g/L.
• Type-specific or type O RhD-negative blood should be readily available and accessible in health facilities providing childbirth services. Transfusion protocols are recommended to enable the timely release of emergency blood products.

Fibrinogen:

• If available, transfusion of fibrinogen can be considered. The therapeutic goal is ≥2 g/L. If fibrinogen is <2 g/L, administer cryoprecipitate to achieve a target fibrinogen level of ≥2 g/L. This typically requires 3–4 g of fibrinogen, corresponding to approximately 8–10 units of cryoprecipitate, depending on the fibrinogen content per unit. If available, pathogen-reduced cryoprecipitate should be chosen.
• The effectiveness of recombinant factor VIIa and prothrombin complex concentrate remain uncertain.

Fresh frozen plasma:

• If available, transfusion of fresh frozen plasma (FFP) should be considered. Transfusion of FFP should not be done for acute haemorrhage before haemostatic results are known and four units of RBCs have been transfused. AB plasma should be used if the ABO type is not known. If lab results are delayed, FFP can be administered at a ratio of 1 unit of FFP to 2 units of RBCs. The therapeutic goal is prothrombin time/activated partial thromboplastin time <1.5 and international normalized ratio ≤1.5.

Platelets:

• If available, transfusion of platelets should be considered when the patient shows clinical signs of microvascular bleeding and if concentrations fall below 50 × 109/L. The standard dose is 5–10 mL/kg.

Massive PPH:

In the management of massive PPH, haemostatic therapy should follow a stepwise approach:

1. Early TXA administration (1 g intravenously over 10 minutes).
2. If available, prioritization of fibrinogen replacement (fibrinogen concentrate or cryoprecipitate) over FFP when a coagulopathy is detected or highly suspected (e.g. amniotic fluid embolism, clinical symptoms).
3. FFP should be considered in cases of documented coagulation factor deficiency, guided by laboratory testing instead of empirical method ratios. For massive blood loss (needing to transfuse four units of RBCs) empirical ratios, for example, 1 unit of FFP to 2 units of RBCs could be used to lessen the development of dilutional coagulopathy.
4. If available, transfusion of platelets could be considered when the woman shows clinical signs of microvascular bleeding and if concentrations fall below 50 × 109 platelets/L. The standard dose is 5–10 mL/kg.

• This recommendation is applicable to all postpartum women, irrespective of their lactation status.
• For ease of implementation and continuity of care, postpartum supplementation should begin as early as possible after birth; the iron supplementation regimen (e.g. dose and whether consumed daily or weekly) should follow that used during pregnancy (3); alternatively, it should start with that planned for menstruating women (61).
• Women should receive counselling on why and how to take iron and folic acid supplements. They should be informed of the common side-effects and be advised on how to manage them (e.g. take with meals or at bedtime) (60).
• Once menses have returned, women should receive supplementation in accordance with the country’s policy or WHO guidance on iron and folic acid supplementation for menstruating women (61).
• In cases in which a woman is diagnosed with anaemia (62), she should be treated in accordance with the country’s policy or the WHO recommendation of daily iron (120 mg of elemental iron plus 400 μg folic acid) supplements until haemoglobin concentrations rise to normal (60, 63).
• In malaria endemic areas, provision of iron and folic acid supplements should be implemented in conjunction with measures to prevent, diagnose and treat malaria (64, 65). In areas using sulfadoxine–pyrimethamine, high doses of folic acid should be avoided because they may interfere with the efficacy of this antimalarial drug (66, 67).
• An iron and folic acid supplementation programme should ideally form part of an integrated programme for postnatal care (68) that promotes exclusive breastfeeding in the first 6 months and continued breastfeeding, screening of all women for anaemia at postpartum visits, use of complementary measures to control and prevent anaemia, and a referral system to manage cases of severe anaemia. Particular attention should be given to identifying potential barriers to equitable access to health care, including postnatal care, suffered by population groups most vulnerable to iron deficiency and iron-deficiency anaemia, such as women in rural areas, women in low-income groups, women from racial or ethnic groups discriminated against, or women in settings where prevailing gender norms greatly disempower them over their body and health. Country programmes should be culturally appropriate to the target populations, so that the intervention is accepted, adopted and sustained.
• Oral supplements are available in capsules or tablets (soluble, dissolvable and modified-release tablets) (69). A strong quality assurance process is important to guarantee that supplements are manufactured, packaged and stored in a controlled and uncontaminated environment (37). Distributers and women should monitor the expiration dates of the supplements to ensure that they are not provided or taken after their expiration date.
• Iron supplements are prepared using several iron compounds, primarily containing ferrous compounds (e.g. fumarate, gluconate, sulfate) that are better absorbed then ferric iron (70). The WHO Essential Medicines List specifies that iron supplements should contain a ferrous salt (71).
• In all settings, breastfeeding mothers should be encouraged to receive adequate nutrition, which is best achieved through consumption of a healthy, balanced diet (one that includes meat, fish, poultry and legumes when available and culturally appropriate), and to refer to guidelines on healthy eating during breastfeeding (72).
• An efficient system for the routine collection of relevant data, including therapeutic adherence and measures of programme performance, is critical to ensure that supplementation programmes are effective and sustained. Monitoring is key to identifying barriers that might be maintaining unequal access to postnatal care, including iron and folic acid supplementation, thus preserving health inequities. Sustained implementation and scale-up greatly benefit from appropriate monitoring mechanisms.

Justification

Although the evidence on the impact on key outcomes is limited or very uncertain, low-certainty evidence suggests that intravenous iron may improve haemoglobin concentrations more rapidly than oral iron at all measured timepoints, that is, within the first week, between 8 and 28 days, and beyond 28 days. Evidence also indicates that intravenous iron probably reduces postpartum fatigue during the first month, which may have meaningful clinical benefits by improving functional capacity, maternal well-being and the ability to care for the newborn child.

Intravenous iron therapy is also associated with fewer gastrointestinal side-effects (such as constipation and nausea) compared to oral iron, which may improve adherence. However, there is a small risk of hypersensitivity reactions, including rare cases of life-threatening anaphylaxis.

While the intervention may not be universally feasible because of cost and the need for more resources compared to oral iron, it is likely to be beneficial for targeted use, appropriate in cases where oral iron cannot be used or is not tolerated, or where clinical judgement indicates that rapid correction of anaemia is needed.

The available evidence suggests that acceptability and uptake of intravenous iron therapy may be influenced by factors such as knowledge of anaemia symptoms, decision-making autonomy, and provider experience and training. Health system barriers such as limited availability of intravenous iron, inadequate staffing and absence of standardized protocols may also affect implementation in some settings.

• Intravenous iron should only be used in women who are likely to be deficient in iron because of pre-existing iron deficiency or acute blood loss from PPH. Iron-deficiency anaemia is usually diagnosed by a low ferritin test. This test is sensitive to inflammation, which will be increased after birth. Therefore, it is not suitable to diagnose iron-deficiency anaemia in the postpartum period; clinicians will have to rely on the severity of PPH and, in case of women with pre-existing anaemia, on a peripheral blood smear demonstrating microcytic hypochromic anaemia typical of iron deficiency while other causes of anaemia are reasonably excluded. Alternatively, health workers may consider a treatment test where an improvement of anaemia is demonstrated after 2 weeks of oral iron treatment.
• Severe anaemia postpartum is defined as a haemoglobin of 80 g/L or less where women are likely to suffer severe or debilitating symptoms of acute anaemia. Intravenous iron in this context may reduce the need for blood transfusion for some women; however, blood transfusion should still be considered as a treatment option where clinically indicated.
• Intravenous iron preparations have been approved for treatment of iron-deficiency anaemia but not specifically in lactating women. Treatment should be confined to women for whom the benefit is judged to outweigh the potential risk for both mother and neonate. The decision to use intravenous iron therapy should be made with the woman’s informed consent, ensuring that she understands the benefits and potential risks. Health workers should clearly explain the rationale for choosing intravenous over oral iron, including how the woman’s symptoms, level of anaemia and ability to tolerate oral iron informed the decision to initiate intravenous iron therapy.
• Some intravenous preparations (e.g. iron dextran) appear to increase the risk of anaphylactic reactions more than others and should be avoided. The risk of anaphylaxis is estimated to be 9.8 per 10 000 for iron dextran, 1.2 per 10 000 for iron sucrose and 0.8 per 10 000 for ferric carboxymaltose. Monitoring for anaphylaxis should occur during the time it takes to infuse the medicine and 30 minutes after the infusion. The available studies mostly used intravenous iron sucrose or ferric carboxymaltose. Iron sucrose was usually given as several 200-mg infusions on alternating days until the calculated iron deficit was reached. Ferric carboxymaltose was usually given as a single infusion of 20 mg/kg body weight or up to a maximum of 1000 mg.
• To safely implement this recommendation, health facilities should ensure availability of resuscitation equipment and staff trained to recognize and manage hypersensitivity or anaphylactic reactions, including Fishbane reactions. A protocol for intravenous iron administration and monitoring should be in place.
• As intravenous iron use expands postpartum, national programmes should ensure that systems are in place to monitor for and report adverse events, especially rare outcomes like anaphylaxis, to support ongoing safety assessment.
• The GDG noted that the availability and cost of intravenous iron may vary across settings. Policy-makers should take steps to ensure equitable access where its use is clinically indicated, especially in facilities managing women with severe PPH or anaemia.

• The GDG acknowledged that the implementation of formal protocols is a complex process that will require the local adaptation of general guidelines.
• Formal protocols should define clear roles and responsibilities within the PPH care team and include timelines for intervention, escalation procedures and referral pathways.
• Protocols should be simple, action-oriented and easy to implement in the clinical environment, especially in settings with high workloads or limited staffing.
• Protocols should be integrated into routine training, clinical supervision and continuous quality improvement activities to ensure consistent use and adherence.
• The GDG emphasized that protocols should be evidence-based and regularly updated in line with evolving recommendations and local audit findings.
• Facilities should monitor implementation of PPH protocols through routine audits and feedback loops to ensure that they are being followed and remain relevant to clinical realities.
• Protocols should also support respectful maternity care by incorporating practices that preserve dignity, informed decision-making and communication with women and their families during emergencies.

• The GDG acknowledged that the implementation of formal protocols is a complex process that will require the local adaptation of general guidelines.
• Transport for referrals from community and between facilities should be included in the protocols, together with provision of health workers who can provide ongoing care for women with PPH during the transfer. Transport should be arranged by the health facility, where possible, avoiding out-of-pocket expenses.
• Referral protocols should clearly define when escalation is needed, who initiates the referral, what stabilization measures must be provided before transfer, and what communication should take place between referring and receiving facilities.
• Protocols should be aligned with local health system capacities and include realistic timelines and contingency plans in case of delays or service unavailability.
• To ensure continuity of care, referral protocols should include mechanisms for documentation and handover, including clinical information, treatment provided and any complications encountered.
• Referral systems should be integrated into emergency preparedness planning and supported by training and regular simulation exercises involving both sending and receiving teams.
• Community-level awareness of referral pathways and emergency transport availability should be promoted so that women and families understand when and how to seek higher-level care.
• Facilities should monitor and audit the timeliness and outcomes of referrals to identify bottlenecks, improve coordination and strengthen the quality and responsiveness of the referral system.
• Where feasible, protocols should consider the use of telecommunication tools (e.g. phone applications such as WhatsApp, mobile phones, radios) to coordinate emergency referrals and provide remote support during transfer.

• The GDG placed a high value on the costs of simulation programmes and acknowledged that there are different types of simulation programmes. Some programmes are high-tech, computerized and costly while others are less expensive and more likely to be affordable in low- and middle-income countries.
• The GDG identified improvement in communication between health care providers and women and their family members as an important priority in the training of health care providers in PPH management. Simulation-based programmes should incorporate communication, leadership and respectful maternity care as core components.
• The target audiences for training include community health workers, traditional birth attendants, nurses, midwives, doctors and emergency medical technicians or paramedics. Local adaptation of training curricula should align with the scope of practice of each cadre and reflect common causes and treatments of PPH in that context.
• Simulation-based training is especially valuable for improving team coordination in time-critical emergencies such as PPH. Regular, team-based drills that mirror real-life scenarios can enhance the clarity of roles, build confidence and reduce delays in implementing appropriate interventions.
• Integrating simulation exercises into routine quality improvement efforts, such as maternal death reviews or clinical audit processes, can enhance their relevance and sustainability, and help translate learning into better preparedness and outcomes.

• The GDG recommended monitoring the use of prophylactic uterotonics as a key process indicator to support programme evaluation and improvement. This indicator is calculated as the number of women receiving prophylactic uterotonic drugs after birth divided by all women giving birth.
• Health programmes are encouraged to integrate this indicator into existing data collection and monitoring systems. Regular analysis can support targeted efforts to improve coverage and quality of PPH prevention.
• The GDG developed a set of key input, output and outcome indicators for monitoring the implementation of PPH interventions. Users of these guidelines are referred to Section 6.3 for the full list of indicators.