Umbilical vein injection for management of retained placenta.

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.

[1]  C. Ananth,et al.  Pharmacologic Intervention for the Management of Retained Placenta:A Systematic Review and Meta-Analysis of Randomized Trials. , 2020, American journal of obstetrics and gynecology.

[2]  S. Alalaf,et al.  Umbilical vein injection of 400 versus 800 μg misoprostol for the treatment of retained placenta: A multicenter, randomized double‐blind controlled trial , 2020, The journal of obstetrics and gynaecology research.

[3]  M. Badr,et al.  Intra-umbilical vein injection of carbetocin versus oxytocin in the management of retained placenta. , 2019, Sexual & reproductive healthcare : official journal of the Swedish Association of Midwives.

[4]  Juan C. Amaya-Restrepo,et al.  Systematic review of prostaglandin analogues for retained placenta , 2018, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[5]  M. Ghasemi,et al.  Umbilical Vein Injection of Misoprostol Versus Oxytocin for Managing Retained Placenta After Parturition: A Randomized Clinical Trial , 2017 .

[6]  M. Maher,et al.  Different routes and forms of uterotonics for treatment of retained placenta: a randomized clinical trial* , 2017, The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians.

[7]  M. Rehman,et al.  Umbilical Vein Injection of Misoprostol Vs Syntocinon in normal saline for the Treatment of Retained Placenta : Randomized Control Trial , 2017 .

[8]  A. Weeks,et al.  Retained placenta: will medical treatment ever be possible? , 2016, Acta obstetricia et gynecologica Scandinavica.

[9]  A. Elfayomy Carbetocin versus intra‐umbilical oxytocin in the management of retained placenta: A randomized clinical study , 2015, The journal of obstetrics and gynaecology research.

[10]  M. Showell,et al.  Pharmacologic Intervention for Retained Placenta: A Systematic Review and Meta-analysis , 2015, Obstetrics and gynecology.

[11]  S. Alalaf,et al.  Umbilical vein injection of misoprostol versus normal saline for the treatment of retained placenta: intrapartum placebo-controlled trial , 2014, BMC Pregnancy and Childbirth.

[12]  P. Pal,et al.  Efficacy of intra‐umbilical oxytocin in the management of retained placenta: A randomized controlled trial , 2013, The journal of obstetrics and gynaecology research.

[13]  Gerald Gartlehner,et al.  [GRADE guidelines: 1. Introduction - GRADE evidence profiles and summary of findings tables]. , 2012, Zeitschrift fur Evidenz, Fortbildung und Qualitat im Gesundheitswesen.

[14]  M. Alberry,et al.  Intraumbilical injection of three different uterotonics in the management of retained placenta , 2011, Archives of Disease in Childhood: Fetal and Neonatal Edition.

[15]  A. Weeks,et al.  The retained placenta: Historical and geographical rate variations , 2011, Journal of obstetrics and gynaecology : the journal of the Institute of Obstetrics and Gynaecology.

[16]  A. Weeks,et al.  Umbilical vein injection for management of retained placenta. , 2011, Cochrane Database of Systematic Reviews.

[17]  P. S. Lim,et al.  Umbilical vein oxytocin in the management of retained placenta: an alternative to manual removal of placenta? , 2011, Archives of Gynecology and Obstetrics.

[18]  Z. Alfirevic,et al.  Umbilical vein oxytocin for the treatment of retained placenta (Release Study): a double-blind, randomised controlled trial , 2010, The Lancet.

[19]  A. Duttaroy Transport of fatty acids across the human placenta: a review. , 2009, Progress in lipid research.

[20]  A. Weeks The retained placenta. , 2008, Best practice & research. Clinical obstetrics & gynaecology.

[21]  D. Habek,et al.  Intraumbilical injection of uterotonics for retained placenta , 2007, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[22]  P. Yuen,et al.  Avoiding manual removal of placenta: evaluation of intra‐umbilical injection of uterotonics using the Pipingas technique for management of adherent placenta , 2007, Acta obstetricia et gynecologica Scandinavica.

[23]  Z. Alfirevic,et al.  The Release Trial: a randomised controlled trial of umbilical vein oxytocin versus placebo for the treatment of retained placenta , 2005, BJOG : an international journal of obstetrics and gynaecology.

[24]  D. Habek,et al.  Treatment of a retained placenta with intraumbilical oxytocin injection. , 2006, Zentralblatt für Gynäkologie.

[25]  N. Sivalingam,et al.  Is there a place for intra-umbilical oxytocin for the management of retained placenta? , 2001, The Medical journal of Malaysia.

[26]  G. Carroli,et al.  Umbilical vein injection for management of retained placenta. , 2000, The Cochrane database of systematic reviews.

[27]  A. Grant,et al.  Intra‐umbilical vein injection and retained placenta: evidence from a collaborative large randomised controlled trial , 1998, British journal of obstetrics and gynaecology.

[28]  A. Drakeley,et al.  Intraumbilical Oxytocin for the Management of Retained Placenta: A Randomized Controlled Trial , 1998, Obstetrics and gynecology.

[29]  D. Mattison,et al.  Human placental transport of oxytocin. , 1996, The Journal of maternal-fetal medicine.

[30]  M. Goldenberg,et al.  Intraumbilical vein injection of prostaglandin F2α in retained placenta , 1996 .

[31]  S. Saarikoski,et al.  Intraumbilical oxytocin for management of retained placenta , 1995, International journal of gynaecology and obstetrics: the official organ of the International Federation of Gynaecology and Obstetrics.

[32]  A. Pipingas,et al.  Umbilical vessel oxytocin administration for retained placenta: in vitro study of various infusion techniques. , 1993, American journal of obstetrics and gynecology.

[33]  G. Kleiverda,et al.  Umbilical vein administration of oxytocin for the management of retained placenta: is it effective? , 1991, American journal of obstetrics and gynecology.

[34]  G. Carroli Management of retained placenta by umbilical vein injection , 1991, British journal of obstetrics and gynaecology.

[35]  C. Begley,et al.  A comparison of 'active' and 'physiological' management of the third stage of labour. , 1990, Midwifery.

[36]  C. Wilken-jensen,et al.  Removing a retained placenta by oxytocin--a controlled study. , 1989, American journal of obstetrics and gynecology.

[37]  J. Pearce,et al.  Intra-umbilical vein oxytocin in the management of retained placenta: a random, prospective, double blind, placebo controlled study , 1988 .

[38]  B. Møller,et al.  The effect of oxytocin injection into the umbilical vein for the management of the retained placenta. , 1987, American journal of obstetrics and gynecology.

[39]  A. Hauksson Oxytocin injection into the umbilical vein in women with retained placenta: a questionable method. , 1986, American journal of obstetrics and gynecology.

[40]  D. James,et al.  Intra-umbilical vein oxytocin in the management of retained placenta. A double blind placebo controlled study , 1986 .

[41]  P. Heinonen,et al.  Pharmacologic management and controlled cord traction in the third stage of labour. , 1985, Annales chirurgiae et gynaecologiae. Supplementum.

[42]  A. Golan,et al.  Reply to Liner , 1984 .

[43]  R. Liner Management of retained placenta. , 1984, American Journal of Obstetrics and Gynecology.

[44]  A. Golan,et al.  A new method for the management of the retained placenta. , 1983, American journal of obstetrics and gynecology.