Key messages

• Most medications (uterotonics) to prevent excessive blood loss after childbirth (postpartum haemorrhage (PPH)) are more effective than no treatment.

• Ergometrine plus oxytocin, and misoprostol plus oxytocin are most effective compared with oxytocin (standard treatment).

• All uterotonics, except for carbetocin, are associated with an increased risk of unwanted effects compared with oxytocin.

What is postpartum haemorrhage, and how is it treated?

Postpartum haemorrhage (PPH) is excessive blood loss, of more than 500 mL, in the first 24 hours after childbirth. It is the most common reason mothers die in childbirth worldwide. Treatments, such as blood transfusion or hysterectomy, are a burden on women's health and health services. To reduce the risk of PPH, clinicians often give medication to make the uterus (womb) contract - a uterotonic. Uterotonics include oxytocin, misoprostol, ergometrine, carbetocin, injectable prostaglandins and combinations of these medications. They may cause unwanted effects, including nausea, vomiting, diarrhoea and fever. Oxytocin is currently recommended as the standard medication to reduce the risk of PPH.

What did we want to find out?

We aimed to find out which uterotonic is most effective in preventing PPH and has the fewest unwanted effects. We were interested in how well they prevented blood loss (more than 500 mL and more than 1000 mL); whether additional uterotonics or a blood transfusion were needed; and unwanted effects.

What did we do?

We collected and analysed all the relevant, trustworthy studies that investigated uterotonics to prevent PPH.

What did we find?

We found 122 studies involving 121,931 women, in 48 countries. Most women gave birth normally (vaginally), in hospital.

All uterotonics are more effective in preventing blood loss than placebo (sham medicine) or no treatment. We are not sure about injectable prostaglandins and ergometrine because we did not find much evidence about them. The two most effective uterotonics were ergometrine plus oxytocin, and misoprostol plus oxytocin.

Blood loss of 500 mL or more
Based on our results, for vaginal birth, 83 women in 1000 given oxytocin would experience blood loss of 500 mL or more.

Compared with oxytocin:

• ergometrine plus oxytocin reduces the likelihood of blood loss of 500 mL or more. Of 1000 women having a vaginal birth, 63 given ergometrine plus oxytocin would experience blood loss of 500 mL or more;

• misoprostol plus oxytocin probably reduces the likelihood of blood loss of 500 mL or more. Of 1000 women having a vaginal birth, 58 given misoprostol plus oxytocin would experience blood loss of 500 mL or more;

• carbetocin makes little or no difference; injectable prostaglandins and ergometrine probably make little or no difference. We are uncertain about the effects of misoprostol.

Blood loss of 1000 mL or more
Based on our results, for vaginal birth, 24 women in 1000 given oxytocin would experience blood loss of 1000 mL or more.

Compared with oxytocin:

• carbetocin and injectable prostaglandins probably, and misoprostol plus oxytocin may make little to no difference;

• misoprostol may be less effective than oxytocin; 30 of 1000 women having a vaginal birth given misoprostol may experience blood loss of 1000 mL or more;

• we are uncertain about the effects of ergometrine, and ergometrine plus oxytocin.

Other results
Compared with oxytocin:

• misoprostol plus oxytocin probably reduces the need for additional uterotonics and the need for blood transfusion;

• carbetocin probably makes little or no difference to the need for blood transfusion;

• we are less sure about the other medications.

Unwanted effects
Compared with oxytocin:

• misoprostol probably increases the likelihood of diarrhoea and may increase the likelihood of nausea, vomiting and fever;

• injectable prostaglandins may increase the likelihood of diarrhoea;

• ergometrine probably increases the likelihood of nausea and vomiting, and may increase the likelihood of high blood pressure, headache and diarrhoea;

• ergometrine plus oxytocin may increase the likelihood of nausea, vomiting and diarrhoea;

• misoprostol plus oxytocin probably increases the likelihood of nausea, vomiting and diarrhoea, and may increase the likelihood of fever;

• carbetocin was associated with few unwanted effects.

We found similar results whether women gave birth normally or by caesarean section, in hospital or in the community, were at high or low risk for PPH, received a high or low dose of misoprostol, and whether they received one single large injection or an infusion (drip) of oxytocin, or both.

What are the limitations of the evidence?

We found little information about home births or about women giving birth by caesarean section, or who had other illnesses and who were at high risk of having PPH. We did not differentiate between the different doses and methods of giving the different uterotonics. Not all the studies provided information about unwanted effects, and they used different methods to measure blood loss.

How up to date is the evidence?

This evidence is up to date until 5 February 2024.