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Meta-Analysis
. 2021 Mar 11;3(3):CD001337.
doi: 10.1002/14651858.CD001337.pub3.

Umbilical vein injection for management of retained placenta

Nimisha Kumar  1 , Shayesteh Jahanfar  2 , David M Haas  1 , Andrew D Weeks  3
Affiliations
Meta-Analysis

Umbilical vein injection for management of retained placenta

Nimisha Kumar et al. Cochrane Database Syst Rev. .

Abstract

Background: 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.

Objectives: 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.

Search methods: 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.

Selection criteria: 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.

Data collection and analysis: 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.

Main results: 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.

Authors' conclusions: 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.

Trial registration: ClinicalTrials.gov NCT02704780.

PubMed Disclaimer

Conflict of interest statement

NK: my stipend as the Cochrane Fellow of the US Satellite of the Cochrane Pregnancy & Childbirth Group was funded by a grant from the Indiana Clinical and Translational Sciences Institute (CTSI), but is independent from my work on this review.

SJ: none.

DH: none.

AW: is an inventor of the PPH Butterfly, a device to allow minimally invasive uterine compression to treat postpartum haemorrhage, and one of the inventors of the LifeStart Trolley, a bedside neonatal resuscitation trolley. He is also Chief Investigator for the COPE study, funded by the National Institute for Health Research, that compares oxytocin and carboprost for the first line treatment of postpartum haemorrhage (including retained placenta). He was the Chief Investigator for the Release study, the largest of the studies in this review (Weeks 2009). NK and SJ assessed this trial for risk of bias and extracted data from it.

Figures

1
1
Methodological quality graph: review authors' judgements about each methodological quality item presented as percentages across all included studies.
2
2
Study flow diagram.
3
3
Methodological quality summary: review authors' judgements about each methodological quality item for each included study.
4
4
Funnel plot of comparison: 3 Oxytocin solution versus saline solution, outcome: 3.1 Manual removal of the placenta – by overall risk of bias.
5
5
Funnel plot of comparison: 3 Oxytocin solution versus saline solution, outcome: 3.2 Manual removal of the placenta – by oxytocin dose.
1.1
1.1. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 1: Manual removal of the placenta
1.2
1.2. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 2: Maternal mortality
1.3
1.3. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 3: Blood loss ≥ 1000 mL after entry
1.4
1.4. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 4: Blood transfusion
1.5
1.5. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 5: Infection
1.6
1.6. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 6: Haemoglobin 24–48 hours postpartum
1.7
1.7. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 7: Haemoglobin 40–45 days postpartum
1.8
1.8. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 8: Serious maternal morbidity
1.9
1.9. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 9: Blood loss ≥ 500 mL after entry
1.10
1.10. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 10: Mean blood loss (mL)
1.11
1.11. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 11: Time from injection to placental delivery (minutes)
1.12
1.12. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 12: Surgical evacuation of retained products of conception
1.13
1.13. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 13: Maternal dissatisfaction with third‐stage management
1.14
1.14. Analysis
Comparison 1: Saline solution versus expectant management, Outcome 14: Stay at hospital > 2 days
2.1
2.1. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 1: Manual removal of the placenta
2.2
2.2. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 2: Maternal mortality
2.3
2.3. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 3: Blood loss ≥ 1000 mL after entry
2.4
2.4. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 4: Blood transfusion
2.5
2.5. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 5: Additional therapeutic uterotonics
2.6
2.6. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 6: Infection
2.7
2.7. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 7: Haemoglobin 24–48 hours postpartum
2.8
2.8. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 8: Haemoglobin 40–45 days postpartum
2.9
2.9. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 9: Serious maternal morbidity
2.10
2.10. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 10: Blood loss ≥ 500 mL after entry
2.11
2.11. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 11: Mean blood loss (mL)
2.12
2.12. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 12: Time from injection to placental delivery (minutes)
2.13
2.13. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 13: Surgical evacuation of retained products of conception
2.14
2.14. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 14: Maternal dissatisfaction with third‐stage management
2.15
2.15. Analysis
Comparison 2: Oxytocin solution versus expectant management, Outcome 15: Stay at hospital > 2 days
3.1
3.1. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 1: Manual removal of the placenta – by overall risk of bias
3.2
3.2. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 2: Manual removal of the placenta – by oxytocin dose
3.3
3.3. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 3: Maternal mortality
3.4
3.4. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 4: Severe postpartum haemorrhage (≥ 1000 mL after entry)
3.5
3.5. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 5: Blood transfusion
3.6
3.6. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 6: Additional therapeutic uterotonics
3.7
3.7. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 7: Antibiotic use
3.8
3.8. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 8: Infection
3.9
3.9. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 9: Serious maternal morbidity
3.10
3.10. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 10: Haemoglobin 24–48 hours postpartum
3.11
3.11. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 11: Haemoglobin 40–45 days postpartum
3.12
3.12. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 12: Postpartum haemorrhage (≥ 500 mL after entry)
3.13
3.13. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 13: Mean blood loss (mL)
3.14
3.14. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 14: Time from injection to placental delivery (minutes)
3.15
3.15. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 15: Haemoglobin levels fall
3.16
3.16. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 16: Surgical evacuation of retained products of conception
3.17
3.17. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 17: Hypertension following injection
3.18
3.18. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 18: Shivering following injection
3.19
3.19. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 19: Nausea following injection
3.20
3.20. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 20: Headache following injection
3.21
3.21. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 21: Abdominal pain
3.22
3.22. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 22: Maternal dissatisfaction with third‐stage management
3.23
3.23. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 23: Fever
3.24
3.24. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 24: Length of third stage of labour (minutes)
3.25
3.25. Analysis
Comparison 3: Oxytocin solution versus saline solution, Outcome 25: Stay at hospital > 2 days
4.1
4.1. Analysis
Comparison 4: Oxytocin solution versus plasma expander, Outcome 1: Manual removal of the placenta
4.2
4.2. Analysis
Comparison 4: Oxytocin solution versus plasma expander, Outcome 2: Severe postpartum haemorrhage (> 1000 mL)
5.1
5.1. Analysis
Comparison 5: Oxytocin solution versus ergometrine solution, Outcome 1: Manual removal of the placenta
5.2
5.2. Analysis
Comparison 5: Oxytocin solution versus ergometrine solution, Outcome 2: Time from injection to placental delivery (minutes)
6.1
6.1. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 1: Manual removal of the placenta
6.2
6.2. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 2: Additional therapeutic uterotonics
6.3
6.3. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 3: Mean blood loss (mL)
6.4
6.4. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 4: Vomiting following injection
6.5
6.5. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 5: Shivering following injection
6.6
6.6. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 6: Nausea following injection
6.7
6.7. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 7: Headache following injection
6.8
6.8. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 8: Maternal pain following injection
6.9
6.9. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 9: Abdominal pain
6.10
6.10. Analysis
Comparison 6: Prostaglandin solution versus saline solution, Outcome 10: Fever
7.1
7.1. Analysis
Comparison 7: Prostaglandin solution versus oxytocin solution, Outcome 1: Manual removal of the placenta
7.2
7.2. Analysis
Comparison 7: Prostaglandin solution versus oxytocin solution, Outcome 2: Additional therapeutic uterotonics
7.3
7.3. Analysis
Comparison 7: Prostaglandin solution versus oxytocin solution, Outcome 3: Mean blood loss (mL)
7.4
7.4. Analysis
Comparison 7: Prostaglandin solution versus oxytocin solution, Outcome 4: Time from injection to placental delivery (minutes)
7.5
7.5. Analysis
Comparison 7: Prostaglandin solution versus oxytocin solution, Outcome 5: Shivering following injection
7.6
7.6. Analysis
Comparison 7: Prostaglandin solution versus oxytocin solution, Outcome 6: Fever
7.7
7.7. Analysis
Comparison 7: Prostaglandin solution versus oxytocin solution, Outcome 7: Abdominal pain
8.1
8.1. Analysis
Comparison 8: Prostaglandin solution versus ergometrine solution, Outcome 1: Manual removal of the placenta
8.2
8.2. Analysis
Comparison 8: Prostaglandin solution versus ergometrine solution, Outcome 2: Time from injection to placental delivery (minutes)
9.1
9.1. Analysis
Comparison 9: Carbetocin solution versus oxytocin solution, Outcome 1: Manual removal of the placenta
9.2
9.2. Analysis
Comparison 9: Carbetocin solution versus oxytocin solution, Outcome 2: Blood transfusion
9.3
9.3. Analysis
Comparison 9: Carbetocin solution versus oxytocin solution, Outcome 3: Additional uterotonics
9.4
9.4. Analysis
Comparison 9: Carbetocin solution versus oxytocin solution, Outcome 4: Postpartum haemoglobin concentration (g/dL)
9.5
9.5. Analysis
Comparison 9: Carbetocin solution versus oxytocin solution, Outcome 5: Postpartum haemorrhage (> 500 mL)
9.6
9.6. Analysis
Comparison 9: Carbetocin solution versus oxytocin solution, Outcome 6: Mean blood loss (mL)
9.7
9.7. Analysis
Comparison 9: Carbetocin solution versus oxytocin solution, Outcome 7: Change in haemoglobin concentration (g/dL)
9.8
9.8. Analysis
Comparison 9: Carbetocin solution versus oxytocin solution, Outcome 8: Adherent placenta, piecemeal removal, and uterine curettage
See this image and copyright information in PMC

Update of

References

References to studies included in this review

Bider 1996 {published data only}
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Harara 2011 {published data only}
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Huber 1991 {published data only}
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Kristiansen 1987 {published data only}
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Lim 2011 {published data only}
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Makkonen 1995 {published data only}
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Nazeer 2016 {published data only}
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Rajab 2014 {published data only}
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Rogers 2007 {published data only}
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Salem 2019 {published data only}
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Samanta 2013 {published data only}
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References to studies excluded from this review

Alalaf 2020 {published data only}
    1. Alalaf SK, Al Tawil NG, Jawad AK, Mahmoud MB, Muhamad BQ, Abdul Rahman KH, et al. Umbilical vein injection of 400 versus 800 mug misoprostol for the treatment of retained placenta: a multicenter, randomized double-blind controlled trial. Journal of Obstetrics and Gynaecology Research 2020;46(5):727-35. [CENTRAL: CN-02096263] [EMBASE: 2004388827] [PMID: ] - PubMed
    1. NCT02704780. Umbilical vein injection of 800µg misoprostol versus 400 µg misoprostol in the treatment of retained placenta: a multicenter, randomized double blind controlled trial. clinicaltrials.gov/ct2/show/NCT02704780 (first received 10 March 2016).
Das 2008 {published data only}
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Elfayomy 2015 {published data only}
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Habek 2001 {published data only}
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Habek 2007 {published data only}
    1. Habek D, Franicevic D. Intraumbilical injection of uterotonics for retained placenta. International Journal of Gynecology & Obstetrics 2007;99(2):105-9. - PubMed
Maher 2017 {published data only}
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References to studies awaiting assessment

IRCT2015102824754N1 {published data only}
    1. IRCT2015102824754N1. Clinical trial of the effects of misoprostol injection compared with oxytocin injection in the umbilical vein in treatment of placenta retaining after delivery. www.irct.ir/trial/20829 (first received 10 May 2016). 16489737.
    1. IRCT2015102824754N1. The effect of misoprostol and oxytocin in the treatment of placenta retaining. www.who.int/trialsearch/Trial2.aspx?TrialID=IRCT2015102824754N1 [CENTRAL: CN-01882321] 16489738.

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References to other published versions of this review

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