The results of a trial in the UK, Pakistan, and Uganda are published in an article Online First and in an upcoming edition of The Lancet. It reports that umbilical oxytocin has no effect on the need for manual removal for women with retained placenta. Until now, meta-analysis had suggested that umbilical injection of oxytocin could increase placental expulsion without the need for a surgeon or anaesthetic. However the general need for manual removal is greater in the UK and other high-income settings than in low-income countries such as Pakistan and Uganda. The study is the work of Dr Andrew D Weeks, University of Liverpool and Liverpool Women’s Hospital, UK, and team.

Records show that retained placenta complicates 0.1 to 2.0 percent of deliveries. Since the 1920s, the rate has increased in Europe. It is now nearly ten times that of resource-poor settings. It is believed that this might be due to higher induction rates, as well as a greater availability of facilities for the procedure. Without prompt treatment, women are at high risk of haemorrhage. Presently, treatment is by manual removal of placenta. This requires an operating room, a surgeon, and an anaesthetist. Such facilities are often unavailable to women in low-resource settings. As a result, this condition has a case fatality rate of almost 10 percent in rural communities. An efficient, low cost, low technology treatment is urgently needed.

Large amounts of the oxytocin hormone are released after distension of the cervix and vagina during labour. Injecting oxytocin into the placenta via umbilical vein is a low-cost solution. However, in order to reach the placental bed, at least 30 mL of solution needs to be injected through an umbilical vein catheter. This technique has not been used in any previous study. The Release Study aimed to assess this technique of umbilical vein oxytocin as a treatment for retained placenta.

Women who were not bleeding or in shock, and with a placenta retained for more than thirty minutes, were recruited in this randomised controlled trial from thirteen sites in the UK, Uganda, and Pakistan. A total of 577 women were assigned to 30 mL saline containing either 50 IU oxytocin (n=292) or 5 mL water (n=285), which was injected into the placenta through an umbilical vein catheter. The primary outcome was the need for manual removal of the placenta.

The researchers detected no difference between the groups in the need for manual removal of placenta: oxytocin 179/292 was 61.3 percent compared to placebo 177/285 which was 62.1 percent. When combining the groups, the authors showed that the need for manual removal was higher in the UK than in Uganda or Pakistan:

• UK 250/361 was 69 percent
• Uganda 90/190 was 47 percent
• Pakistan 16/26 was 62 percent

Adverse events did not differ between the two groups.

The authors remark: “These findings accord with a review in which rates of retained placenta in the UK are seen to be rising with time and seem to be greater in high-resource settings than in low-resource settings. The reasons for this result are not clear, but it could represent the amount of exertion that is put into removal of the placenta by the attendants. In settings in which there are long waits for theatre and in which women are tolerant of pain, there can be many attempts at placental delivery with prolonged cord traction, grasping of vaginal portions of the placenta, and uterine massage. In the UK, by contrast, operating theatres with regional anaesthesia are easily accessible and so the woman does not need to undergo the discomfort of repeated attempts at placental delivery.”

They write in closing: “Findings from the Release Study have shown that umbilical vein oxytocin had no significant effect on the need for manual removal of the placenta or any other clinical outcome.”

In an associated note, Dr Bissallah Ekele, University of Abuja, Abuja, Nigeria, and Dr Imran Morhason-Bello, University College Hospital, Ibadan, Nigeria, comment: “The benefit of intra-umbilical oxytocin injection over manual removal of the placenta in terms of avoidable anaesthetic risks, lower chances of genital tract trauma, infection, uterine synaechia, and infertility might have informed its inclusion in the 2007 guidelines from the UK’s National Institute for Health and Clinical Excellence for the treatment of retained placenta. But with the strength of the evidence from Release, the guidelines might be revisited. WHO might also reconsider their recommendation that intraumbilical vein injection of oxytocin with saline may be offered for the management of retained placenta, especially because the evidence was classified as weak. We do agree that the optimum period before manually removing the placenta remains to be determined.”

“Umbilical vein oxytocin for the treatment of retained placenta (Release Study): a double-blind, randomised controlled trial”
Andrew D Weeks, Godfrey Alia, Gillian Vernon, Annette Namayanja, Radhika Gosakan, Tayyaba Majeed, Anna Hart, Hussain Jafri, Juan Nardin, Guillermo Carroli, Fiona Fairlie, Yasmin Raashid, Florence Mirembe, Zarko Alfirevic
DOI: 10.1016/S0140-6736(09)61752-9
The Lancet

Written by Stephanie Brunner (B.A.)