Featured Review: Uterotonic agents for preventing postpartum haemorrhage

New evidence on the best drugs to prevent postpartum haemorrhage point away from Oxytocin – the standard drug currently used to prevent this condition.

  • Bleeding after birth is the most common reason why mothers die in childbirth worldwide.
  • Includes data from 88,000 women across 140 trials.
  • The review found that ergometrine plus oxytocin, misoprostol plus oxytocin, and carbetocin were more effective drugs for reducing excessive bleeding at childbirth than oxytocin which is the current standard drug used to treat this condition.

Bleeding after birth is the most common reason why mothers die in childbirth worldwide. Although most healthy women can cope well with some bleeding at childbirth, others do not, and this can pose a serious risk to their health and even life. To reduce excessive bleeding at childbirth, the routine administration of a drug to contract the uterus (uterotonic) has become standard practice across the world.

The aim of this research from Cochrane Pregnancy and Childbirth was to identify which drug is most effective in preventing excessive bleeding after childbirth with the least side-effects.

Different drugs given routinely at childbirth have been used for preventing excessive bleeding. They include oxytocin, misoprostol, ergometrine, carbetocin, and combinations of these drugs, each with different effectiveness and side-effects. Side-effects may include: vomiting, high blood pressure and fever. We analysed all the available evidence to compare all of these drugs and calculated a ranking among them, providing robust effectiveness and side-effect profiles for each drug.

This network meta-analysis includes 140 randomised trials with data from 88,947 women.

The authors’ of the review concluded:

Ergometrine plus oxytocin, misoprostol plus oxytocin, and carbetocin were more effective drugs for reducing excessive bleeding at childbirth than oxytocin which is the current standard drug used to treat this condition.

Carbetocin has the least side-effects (less vomiting, high blood pressure and fever) among the top three drug options, but to date studies of carbetocin were small and of poor quality.

There are some ongoing studies that are not yet complete, including two key studies. One is a large study (involving around 30,000 women across 10 different countries) comparing the effectiveness of carbetocin versus oxytocin for preventing PPH among women having a vaginal birth. The other is a UK-based trial (involving more than 6000 women) comparing carbetocin, oxytocin and ergometrine plus oxytocin combination. Both trials are expected to report in 2018 and these results will be incorporated when this review is updated.

University of Birmingham Clinician Scientist Dr Ioannis Gallos, of the Cochrane Pregnancy and Childbirth Group and Review Author, said: "Whilst postpartum haemorrhage is a rare complication, it is the most common reason why mothers die in childbirth worldwide and happens because a woman's womb has not contracted strongly enough after birth or the placenta has been left in the womb and results in excessive bleeding.

"Currently, to reduce excessive bleeding at childbirth, the standard practice across the world is to administer to women during the third stage of labour a drug called oxytocin - a uterotonic which contracts the uterus and stimulates contractions to help push out the placenta.

"However, there are a number of other uterotonics and combinations of these drugs that can be given that may be more effective and result in fewer side effects.

"By analysing data from 140 different clinical trials involving over 88,000 women, we have been able to use evidence to compare all of these drugs and calculate a ranking among them, providing robust effectiveness and side-effect profiles for each drug.

"Our research is important as it has highlighted which drugs may be more effective than oxytocin and we hope that this could impact existing recommendations worldwide."

This Cochrane review is expected to be updated later this year to incorporate the results of some key ongoing studies which will report their findings in coming months, including a large study involving around 30,000 women across 10 different countries comparing the effectiveness of carbetocin versus oxytocin for preventing bleeding in women having a vaginal birth, and a UK-based trial involving more than 6,000 women comparing carbetocin, oxytocin and ergometrine plus oxytocin combination.