What is the issue?
The placenta provides nourishment for the baby in the womb (uterus) through the umbilical cord. It usually comes out shortly after the baby. If the placenta remains in the womb (a 'retained placenta'), women have an increased risk of bleeding heavily (haemorrhage), infection, and very occasionally death. Manual removal of the placenta involves a doctor passing their hand through the vagina into the womb to remove the placenta. However, it requires an anaesthetic and can have side effects. Use of medicines injected into the placenta through blood vessels (veins) in the umbilical cord is an attractive alternative to remove the placenta.
Why is this important?
The injection of oxytocin (a hormone released from the brain into the blood during labour) solution into the umbilical cord after the cord is cut is a cheap and simple intervention that could be performed to deliver the placenta. It is especially attractive for low-income countries where there is not easy access to doctors or an operating theatre.
What evidence did we find?
We searched for evidence in June 2020 and combined the data from 24 trials involving 2348 women.
Injection of a saline (salt) solution made little or no difference in the need for manual removal of placenta in comparison to waiting for spontaneous delivery. There is some evidence that injecting an oxytocin solution into the umbilical vein may be beneficial, but many of the studies are at high risk of bias, the results are inconsistent, and the benefits are seen only in a few outcomes. Small studies suggest there may be some effect of an injection of a prostaglandin (that stimulate contractions of the womb; misoprostol or carboprost) when compared to oxytocin solution. One study comparing a carbetocin (which is similar to oxytocin) solution to oxytocin did not show any difference in the need for manual removal.
What does this mean?
The use of umbilical vein injections for retained placenta may or may not have a benefit for women with retained placenta. An umbilical vein injection of prostaglandin shows promise and requires more research.
UVI of oxytocin solution is an inexpensive and simple intervention that can be performed when placental delivery is delayed. This review identified low-certainty evidence that oxytocin solution may slightly reduce the need for manual removal. However, there are little or no differences for other outcomes. Small studies examining injection of prostaglandin (such as dissolved misoprostol) into the umbilical vein show promise and deserve to be studied further.
Retained placenta is a common complication of pregnancy affecting 1% to 6% of all births. If a retained placenta is left untreated, spontaneous delivery of the placenta may occur, but there is a high risk of bleeding and infection. Manual removal of the placenta (MROP) in an operating theatre under anaesthetic is the usual treatment, but is invasive and may have complications. An effective non-surgical alternative for retained placenta would potentially reduce the physical and psychological trauma of the procedure, and costs. It could also be lifesaving by providing a therapy for settings without easy access to modern operating theatres or anaesthetics. Injection of uterotonics into the uterus via the umbilical vein and placenta is an attractive low-cost option for this. This is an update of a review last published in 2011.
To assess the use of umbilical vein injection (UVI) of saline solution with or without uterotonics compared to either expectant management or with an alternative solution or other uterotonic agent for retained placenta.
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (14 June 2020), and reference lists of retrieved studies.
Randomised controlled trials (RCTs) comparing UVI of saline or other fluids (with or without uterotonics), either with expectant management or with an alternative solution or other uterotonic agent, in the management of retained placenta. We considered quasi-randomised, cluster-randomised, and trials reported only in abstract form.
Two review authors independently assessed trials for inclusion and risk of bias, extracted data, and checked them for accuracy. We assessed the certainty of the evidence using the GRADE approach. We calculated pooled risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs), and presented results using 'Summary of findings' tables.
We included 24 trials (n = 2348). All included trials were RCTs, one was quasi-randomised, and none were cluster-randomised. Risk of bias was variable across the included studies. We assessed certainty of evidence for four comparisons: saline versus expectant management, oxytocin versus expectant management, oxytocin versus saline, and oxytocin versus plasma expander. Evidence was moderate to very-low certainty and downgraded for risk of bias of included studies, imprecision, and inconsistency of effect estimates.
Saline solution versus expectant management
There is probably little or no difference in the incidence of MROP between saline and expectant management (RR 0.93, 95% CI 0.80 to 1.10; 5 studies, n = 445; moderate-certainty evidence). Evidence for the following remaining primary outcomes was very-low certainty: severe postpartum haemorrhage 1000 mL or greater, blood transfusion, and infection. There were no events reported for maternal mortality or postpartum anaemia (24 to 48 hours postnatal). No studies reported addition of therapeutic uterotonics.
Oxytocin solution versus expectant management
UVI of oxytocin solution might slightly reduce in the need for manual removal compared with expectant management (mean RR 0.73, 95% CI 0.56 to 0.95; 7 studies, n = 546; low-certainty evidence). There may be little to no difference between the incidence of blood transfusion between groups (RR 0.81, 95% CI 0.47 to 1.38; 4 studies, n = 339; low-certainty evidence). There were no maternal deaths reported (2 studies, n = 93). Evidence for severe postpartum haemorrhage of 1000 mL or greater, additional uterotonics, and infection was very-low certainty. There were no events for postpartum anaemia (24 to 48 hours postnatal).
Oxytocin solution versus saline solution
UVI of oxytocin solution may reduce the use of MROP compared with saline solution, but there was high heterogeneity (RR 0.82, 95% CI 0.69 to 0.97; 14 studies, n = 1370; I² = 54%; low-certainty evidence). There were no differences between subgroups according to risk of bias or oxytocin dose for the outcome MROP. There may be little to no difference between groups in severe postpartum haemorrhage of 1000 mL or greater, blood transfusion, use of additional therapeutic uterotonics, and antibiotic use. There were no events for postpartum anaemia (24 to 48 hours postnatal) (very low-certainty evidence) and there was only one event for maternal mortality (low-certainty evidence).
Oxytocin solution versus plasma expander
One small study reported UVI of oxytocin compared with plasma expander (n = 109). The evidence was very unclear about any effect on MROP or blood transfusion between the two groups (very low-certainty evidence). No other primary outcomes were reported.
For other comparisons there were little to no differences for most outcomes examined. However, there was some evidence to suggest that there may be a reduction in MROP with prostaglandins in comparison to oxytocin (4 studies, n = 173) and ergometrine (1 study, n = 52), although further large-scale studies are needed to confirm these findings.