The global burden of postpartum haemorrhage. Postpartum haemorrhage (PPH) is the leading cause of maternal death worldwide

were the WHO recommendations updated?

03

What are the updated WHO recommendations?

04

So what’s new?

05

06

Implementing the WHO recommendations

maternal death worldwide.
Postpartum haemorrhage (PPH) is commonly defined as a blood loss of 500 ml or more within 24 hours after birth. It affects about 5% of all women giving birth around the world.
Globally, nearly one quarter of all maternal deaths are associated with PPH. In most low-income countries, it is the main cause of maternal mortality.

The majority of PPH-associated deaths could be avoided by the use of prophylactic uterotonics during the third stage of labour and appropriate treatment.
Improving health care for women during childbirth to prevent and treat PPH is a necessary step towards achievement of the health targets of the Sustainable Development Goals (SDGs).

1. the global burden of postpartum haemorrhage

section 01

99% of all maternal deaths occur in low- and
middle-income countries (LMICs).

02
196 trials (135 559 women) across 53 countries
Any trial comparing a uterotonic vs placebo, no uterotonic or another uterotonic
Single agents (oxytocin, carbetocin, misoprostol, ergometrine) or combination agents (oxytocin plus ergometrine, oxytocin plus misoprostol)

A Cochrane systematic review and network meta-analysis compared uterotonic options with no uterotonic and other uterotonic options.

Gallos et al. Uterotonic agents for preventing postpartum haemorrhage: a network meta‐analysis. Cochrane Database Syst Rev. CD011689.

02
196 trials (135 559 women) across 53 countries
Any trial comparing a uterotonic vs placebo, no treatment or another uterotonic
Single agents (oxytocin, carbetocin, misoprostol, ergometrine) or combination agents (oxytocin plus ergometrine, oxytocin plus misoprostol)

A Cochrane systematic review and network meta-analysis compared all uterotonic options and placebo or no treatment.

In light of this new evidence, the WHO recommendations on uterotonics for PPH prevention have been updated
The WHO PPH recommendations were first published in 2012.
These updated recommendations (2018) supersede the previous recommendations on uterotonics for PPH prevention.

the WHO handbook on guideline development

3. how were the WHO recommendations updated?

section 03

Updating involves:
WHO Steering Group
Guideline Development Group (GDG)
Executive Guideline Steering Group (GSG)
External Review Group
Systematic review team
External partners and observers

& October 2018
The GDG comprised 18 external experts and relevant stakeholders with expertise in research, guideline development, policy and programmes on PPH prevention and treatment.

3. how were the WHO recommendations updated?

section 03

GDG members considered:
Balance between desirable and undesirable effects
Overall quality of supporting evidence
Values and preferences of stakeholders
Resource requirements
Cost-effectiveness
Acceptability
Feasibility
Equity

vs placebo or no treatment

4. What are the updated WHO recommendations?

section 04

Which one?
Choice of uterotonics for PPH prevention
uterotonic options
vs
other uterotonic options

of PPH during the third stage of labour is recommended for all births.

To effectively prevent PPH, only one of the following uterotonics should be used:
Oxytocin
Carbetocin
Misoprostol
Ergometrine/methylergometrine
Oxytocin and ergometrine fixed-dose combination

4. What works: efficacy and safety of uterotonics for PPH prevention

section 04

of PPH during the third stage of labour is recommended for all births.

To effectively prevent PPH, only one of the following uterotonics should be used:
Oxytocin
Carbetocin
Misoprostol
Ergometrine/methylergometrine
Oxytocin and ergometrine fixed-dose combination

4. What works: efficacy and safety of uterotonics for PPH prevention

section 04

Recommendation 1.1
The use of oxytocin (10 IU, IM/IV) is recommended for the prevention of PPH for all births.
Vaginal birth or caesarean section
Skilled health personnel required to administer
At caesarean section: consider dividing doses and avoid a rapid IV bolus

of PPH during the third stage of labour is recommended for all births.

To effectively prevent PPH, only one of the following uterotonics should be used:
Oxytocin
Carbetocin
Misoprostol
Ergometrine/methylergometrine
Oxytocin and ergometrine fixed-dose combination

4. What works: efficacy and safety of uterotonics for PPH prevention

section 04

Recommendation 1.2
The use of carbetocin (100 µg, IM/IV) is recommended for the prevention of PPH for all births in contexts where its cost is comparable to other effective uterotonics.
Vaginal birth or caesarean section
Skilled health personnel required to administer
For PPH prevention only

of PPH during the third stage of labour is recommended for all births.

To effectively prevent PPH, only one of the following uterotonics should be used:
Oxytocin
Carbetocin
Misoprostol
Ergometrine/methylergometrine
Oxytocin and ergometrine fixed-dose combination

4. What works: efficacy and safety of uterotonics for PPH prevention

section 04

Recommendation 1.3
The use of misoprostol (either 400 µg or 600 µg PO) is recommended for the prevention of PPH for all births.
Alternative routes may be needed at caesarean section, but oral route is preferred by women
No clear evidence of which dose is superior, but higher doses have more side effects
Inform women of possible adverse effects
Can be used in hospital or community

of PPH during the third stage of labour is recommended for all births.

To effectively prevent PPH, only one of the following uterotonics should be used:
Oxytocin
Carbetocin
Misoprostol
Ergometrine/methylergometrine
Oxytocin and ergometrine fixed-dose combination

4. What works: efficacy and safety of uterotonics for PPH prevention

section 04

Recommendation 1.4
The use of ergometrine (200 µg, IM/IV) is recommended for the prevention of PPH in contexts where hypertensive disorders can be safely excluded prior to its use
Vaginal birth or caesarean section
Skilled health personnel are required
Inform women of possible side effects - other options may have better side effect profile

of PPH during the third stage of labour is recommended for all births.

To effectively prevent PPH, only one of the following uterotonics should be used:
Oxytocin
Carbetocin
Misoprostol
Ergometrine/methylergometrine
Oxytocin and ergometrine fixed-dose combination

4. What works: efficacy and safety of uterotonics for PPH prevention

section 04

Recommendation 1.5
The use of oxytocin and ergometrine fixed-dose combination (5 IU/500 µg IM) is recommended for the prevention of PPH in contexts where hypertensive disorders can be safely excluded prior to its use.
Vaginal birth or caesarean section
Skilled health personnel are required

of PPH during the third stage of labour is recommended for all births.

To effectively prevent PPH, only one of the following uterotonics should be used:
Oxytocin
Carbetocin
Misoprostol
Ergometrine/methylergometrine
Oxytocin and ergometrine fixed-dose combination
Injectable prostaglandins

4. What works: efficacy and safety of uterotonics for PPH prevention

section 04

Recommendation 1.6
Injectable prostaglandins (carboprost or sulprostone) are not recommended for the prevention of PPH

a uterotonic of choice

section 04

Comparing uterotonics through oxytocin as a common comparator
Oxytocin is current standard of care
Largest number of trials in the network meta-analysis
The natural sequence for introducing a new uterotonic option is to evaluate efficacy with the “gold standard” option

section 04

Oxytocin

criteria were considered by the GDG for each uterotonic option

is the reference comparator

compared to oxytocin

Similar desirable effects, and carbetocin likely superior in reducing PPH (≥  500 ml) (41 fewer events per 1000 women), use of additional uterotonics (74 fewer per 1000) and blood loss after birth (81 ml less on average).
No clear difference in undesirable effects
While balance of effects probably favours carbetocin, the supply cost of carbetocin is approximately 20 times more than oxytocin
Uncertain whether the additional benefits justify the additional cost of routinely implementing carbetocin at the current unit price
Acceptability among stakeholders and impact on health equity would vary across settings compared with oxytocin.

compared to oxytocin

Misoprostol has similar desirable effects to oxytocin, but it is less effective for reducing severe PPH (≥  1000 ml) (7 more events per 1000 women).
Causes more undesirable effects (including nausea, vomiting, shivering, fever and diarrhoea).
Misoprostol is cheaper, heat-stable, can be used orally, and is probably acceptable and feasible to use.
Lower effectiveness for severe PPH and greater undesirable effects may increase costs (these costs may vary according to the setting).
Can be task-shifted to lay health workers and community health workers.

/ methylergometrine compared to oxytocin

No clear evidence of difference in desirable effects.
However, women are more likely to experience nausea, vomiting, headache, hypertension and diarrhoea with ergometrine.
Costs associated with managing undesirable effects, as well as the need to screen for high blood pressure, implies that oxytocin is probably more cost-effective.
Ergometrine may have negative effects on health equity in settings with high rates of – or lack of screening for – hypertensive disorders.

plus ergometrine compared to oxytocin

Similar to oxytocin in terms of desirable outcomes, though it is possibly more effective in preventing PPH (≥  500 ml) (44 fewer events per 1000 women).
More undesirable effects than oxytocin, including nausea, vomiting and diarrhoea.
Balance of effects clearly favours oxytocin.
Costs related to undesirable effects, as well as the need to screen for women with hypertensive disorders, imply that oxytocin is probably more cost-effective.
May have a negative impact on health equity, particularly in settings with limited capacity and capability to routinely screening for hypertensive disorders of pregnancy.

plus oxytocin compared to oxytocin

Probably superior to oxytocin for blood transfusion (11 fewer events per 1000 women), additional uterotonic use (58 fewer per 1000) and blood loss (88 ml less on average). May possibly prevent more PPH (≥  500 ml) (44 fewer per 1000) and result in a smaller mean change in haemoglobin level (before versus after birth).
Associated with more undesirable effects including nausea, vomiting, diarrhoea, shivering and fever.
Balance of effects favours oxytocin.
Cost-effectiveness may vary in different settings.
Feasibility is limited due to the complexity of using two separate medications through different routes of administration.

(10 IU, IM/IV) is the recommended uterotonic agent for the prevention of PPH for all births.

Vaginal birth or caesarean section
Skilled health personnel are required

4. Which one: Choice of uterotonics for PPH prevention

section 04

Combination of misoprostol and oxytocin may be more effective than oxytocin alone for some priority outcomes, however:
increases side effects
not available as a fixed dose combination
requires parenteral and oral administration

section 04

cannot be guaranteed), the use of other injectable uterotonics (carbetocin, or if appropriate ergometrine/methylergometrine or oxytocin and ergometrine fixed-dose combination) or oral misoprostol is recommended.

Vaginal birth or caesarean section
Skilled health personnel are required

4. Which one: Choice of uterotonics for PPH prevention

section 04

to administer injectable uterotonics, the administration of misoprostol (either 400 µg or 600 µg PO) by community health care workers and lay health workers is recommended for the prevention of PPH.

If skilled health personnel are not present or have not been trained to administer injectable uterotonics, oral misoprostol is preferred

4. Which one: Choice of uterotonics for PPH prevention

section 04

recommendation

IV or IM)
Oxytocin is not available, or its quality cannot be guaranteed

Misoprostol
(400 µg or 600 µg PO)

Are skilled health personnel who can administer injectable uterotonics available?

Trained community health workers and lay health workers can administer misoprostol
(400 µg or 600 µg PO)

No

No

Yes

Is oxytocin of sufficient quality?

No

Heat-stable carbetocin (100 µg, IM/IV), in contexts where its cost is comparable to other effective uterotonics.

Ergometrine / methylergometrine (200 µg, IM/IV), in contexts where hypertensive disorders can be safely excluded prior to its use.

Fixed-dose combination of oxytocin and ergometrine, in contexts where hypertensive disorders can be safely excluded prior to its use.

OR

OR

OR

Yes

Yes

section 06

job aids

6. implementing the updated WHO recommendations

Equip health facilities
Ensure necessary supplies, equipment and staff to use uterotonics safely

Support behaviour change
Obtain technical support for implementation, engage stakeholders and partners, and provide training

section 06

updated WHO recommendations

Cold-chain transport & storage
For heat-sensitive uterotonics (oxytocin, ergometrine)

Effective communication
Ensure women are informed of risks, benefits and alternatives

section 06