Jurnal injeksi vena umbilikan untuk mencegah perdarahan postpartum 1.pdf

Umbilical vein injection for management of retained placenta (Review) Nardin JM, Weeks A, Carroli G

This is a reprint reprint of a Cochrane Cochrane review review,, prepare preparedd and maintain maintained ed by The Cochran Cochranee Collabor Collaboratio ationn and published published in The Cochrane Library 2012, Issue 2 http://www.thecochranelibrary.com

Umbilical vein injection for management of retained placenta (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

T AB LE O F C ON T EN TS

HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . AUTHORS’ CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ACKNOWLEDGEMENTS ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.1. Comparison 1 Saline solution versus expectant management, Outcome 1 Manual removal of the placenta. Analysis 1.2. Comparison 1 Saline solution versus expectant management, Outcome 2 Blood loss. . . . . . . . Analysis 1.3. Comparison 1 Saline solution versus expectant management, Outcome 3 Blood loss = or > 500 ml after entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.4. Comparison 1 Saline solution versus expectant management, Outcome 4 Blood loss = or > 1000 ml after entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.5. Comparison 1 Saline solution versus expectant management, Outcome 5 Blood transfusion. . . . . Analysis 1.6. Comparison 1 Saline solution versus expectant e xpectant management, Outcome 6 Haemoglobin 24-48 hours postpartum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.7. Comparison 1 Saline solution versus expectant management, Outcome 7 Haemoglobin 40-45 days postpartum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.8. Comparison 1 Saline solution versus expectant management, Outcome 8 Maternal mortality. . . . . Analysis 1.9. Comparison 1 Saline solution versus expectant management, Outcome 9 Serious maternal morbidity. morbidity. . Analysis 1.10. Comparison 1 Saline solution versus expectant management, Outcome 10 Surgical evacuation of retained products of conception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 1.11. Comparison 1 Saline solution versus expectant management, Outcome 11 Infection. . . . . . . Analysis 1.12. Comparison 1 Saline solution versus expectant management, Outcome 12 Stay at hospital more than two days. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.1. Comparison 2 Oxytocin solution versus expectant management, Outcome 1 Manual removal of the placenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.2. Comparison 2 Oxytocin solution versus expectant management, Outcome 2 Blood loss. . . . . . . Analysis 2.3. Comparison 2 Oxytocin solution versus expectant management, Outcome 3 Blood loss = or > 500 ml after entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.4. Comparison 2 Oxytocin solution versus expectant management, Outcome 4 Blood loss = or > 1000 ml after entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.5. Comparison 2 Oxytocin solution versus expectant management, Outcome 5 Blood transfusion. . . . Analysis 2.6. Comparison 2 Oxytocin solution versus expectant management, Outcome 6 Haemoglobin 24-48 hours h ours postpartum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.7. Comparison 2 Oxytocin solution versus expectant management, Outcome 7 Haemoglobin 40-45 days postpartum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 2.8. Comparison 2 Oxytocin solution versus expectant management, Outcome 8 Maternal mortality. . . . Analysis 2.9. Comparison 2 Oxytocin solution versus expectant management, Outcome 9 Serious maternal morbidity. morbidity. Analysis 2.10. Comparison 2 Oxytocin solution versus expectant expectant management, Outcome 10 Surgical evacuation evacuation of retained products of conception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Umbilical vein injection for management of retained placenta (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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Analysis 2.11. Comparison 2 Oxytocin solution versus expectant management, Outcome 11 Infection. . . . . . Analysis 2.12. Comparison 2 Oxytocin O xytocin solution versus expectant management, Outcome 12 Stay at hospital more than two days. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.1. Comparison 3 Oxytocin solution versus saline solution, Outcome 1 Manual removal of the placenta - by study quality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.2. Comparison 3 Oxytocin solution versus saline solution, Outcome 2 Manual removal of the placenta - by oxytocin dose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.3. Comparison 3 Oxytocin solution versus saline solution, Outcome 3 Additional therapeutic uterotonics. Analysis 3.4. Comparison 3 Oxytocin solution versus saline solution, Outcome 4 Blood loss. . . . . . . . . . Analysis 3.5. Comparison 3 Oxytocin solution versus saline solution, Outcome 5 Blood loss = or > 500 ml after entry. Analysis 3.6. Comparison 3 Oxytocin solution versus saline solution, Outcome 6 Blood loss = or > 1000 ml after entry. Analysis 3.7. Comparison 3 Oxytocin solution versus saline solution, Outcome 7 Blood transfusion. . . . . . . Analysis 3.8. Comparison Comparison 3 Oxytocin solution versus saline solution, solution, Outcome 8 Haemoglobin 24-48 hours postpartum. Analysis 3.9. Comparison 3 Oxytocin solution versus saline solution, Outcome 9 Haemoglobin 40-45 days postpartum. Analysis 3.10. Comparison 3 Oxytocin solution versus saline solution, Outcome 10 Haemoglobin levels fall. . . . Analysis 3.11. Comparison 3 Oxytocin solution versus saline solution, Outcome 11 Maternal mortality. . . . . . Analysis 3.12. Comparison 3 Oxytocin solution versus saline solution, Outcome 12 Serious maternal morbidity. . . Analysis 3.13. Comparison Comparison 3 Oxytocin solution versus saline solution, Outcome 13 Surgical Surgical evacuation of of retained products of conception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 3.14. Comparison 3 Oxytocin solution versus saline solution, Outcome 14 Nausea following injection. . . Analysis 3.15. Comparison 3 Oxytocin solution versus saline solution, Outcome 15 Infection. . . . . . . . . Analysis 3.16. Comparison 3 Oxytocin solution versus saline solution, Outcome 16 Fever. . . . . . . . . . Analysis 3.17. Comparison 3 Oxytocin solution versus saline solution, Outcome 17 Abdominal pain. . . . . . . Analysis 3.18. Comparison 3 Oxytocin solution versus saline solution, Outcome 18 Stay at hospital more than two days. Analysis 3.19. Comparison 3 Oxytocin solution versus saline solution, Outcome 19 Length of third stage of labour. . Analysis 3.20. Comparison 3 Oxytocin solution versus saline solution, Outcome 20 Headache following injection. . Analysis 3.21. Comparison 3 Oxytocin solution versus saline solution, Outcome 21 Shivering following injection. . Analysis 3.22. Comparison 3 Oxytocin solution versus saline solution, Outcome 22 Hypertension following injection. Analysis 4.1. Comparison 4 Oxytocin solution versus plasma expander, expander, Outcome 1 Manual removal of the placenta. Analysis 4.2. Comparison 4 Oxytocin solution versus plasma expander, expander, Outcome 2 Blood loss > 1000 ml. . . . . Analysis 5.1. Comparison 5 Prostaglandin solution versus saline solution, Outcome 1 Manual removal of the placenta. Analysis 5.2. Comparison 5 Prostaglandin Prostaglandin solution versus saline saline solution, Outcome 2 Additional therapeutic uterotonics. uterotonics. Analysis 5.3. Comparison 5 Prostaglandin solution versus saline solution, Outcome 3 Blood loss. . . . . . . . Analysis 5.4. Comparison 5 Prostaglandin solution versus saline solution, Outcome 4 Abdominal pain. . . . . . Analysis 5.5. Comparison 5 Prostaglandin solution versus saline solution, Outcome 5 Fever. Fever. . . . . . . . . . Analysis 6.1. Comparison Comparison 6 Prostaglandin Prostaglandin solution versus oxytocin solution, Outcome 1 Manual Manual removal of the placenta. Analysis 6.2. Comparison 6 Prostaglandin Prostaglandin solution versus oxytocin solution, Outcome 2 Additional therapeutic the rapeutic uterotonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Analysis 6.3. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 3 Blood loss. . . . . . . Analysis 6.4. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 4 Fever. Fever. . . . . . . . . Analysis 6.5. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 5 Abdominal pain. . . . . Analysis 6.6. Comparison 6 Prostaglandin Prostaglandin solution versus oxytocin solution, Outcome 6 Time from injection to placental delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . WHAT’S WHAT’S NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .


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[Intervention Review]

Umbilical vein injection for management of retained placenta Juan Manuel Nardin1 , Andrew Weeks2 , Guillermo Carroli1 1 Centro

Rosarino de Estudios Perinatales, Rosario, Argentina. 2 Department of Women’s and Children’s Health, The University of Liverpool, Liverpool, UK Contact address: Juan Manuel Nardin,Centro Rosarino de Estudios Perinatales, Moreno 878 piso6, Rosario, SantaFe, 2000, Argentina. [email protected]. [email protected]. Editorial group: Cochrane Pregnancy and Childbirth Group. Publication status and date: Edited (no change to conclusions), published in Issue 2, 2012. Review content assessed as up-to-date: 10 March 2011. Citation: Nardin JM, Weeks A, Carroli G. Umbilical vein injection for management of retained placenta. Cochrane Database of Systematic Reviews 2011, Issue 5. Art. No.: CD001337. DOI: 10.1002/14651858.CD001337.pub2.

Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

ABSTRACT

Background

If a retained placenta is left untreated, there is a high risk of maternal death. However, manual removal of the placenta is an invasive procedure with serious complications of haemorrhage, infection or genital tract trauma. Objectives

To assess the use of umbilical vein injection (UVI) of saline solution alone or with oxytocin in comparison either with expectant management or with an alternative solution or other uterotonic agent for retained placenta. Search methods

We searched the Cochrane Pregnancy and Childbirth Group’s Trials Register (28 February 2011). Selection criteria

Randomized trials comparing UVI of saline or other fluids, with or without oxytocics, either with expectant management or with an alternative solution or other uterotonic agent, in the management of retained placenta. Data collection and analysis

Two review authors assessed the methodological quality of the studies and extracted the data. Main results

We included 15 trials (1704 women). The trials were of variable quality. Compared with expectant management, UVI of saline solution alone did not show any significant difference in the incidence of manual removal of the placenta (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.84 to 1.16). UVI of oxytocin solution compared with expectant management showed no reduction in the need for manual removal (RR 0.87; 95% CI 0.74 to 1.03). Oxytocin solution compared with saline solution alone showed a reduction in manual removal of the placenta, but this was not statistically significant (RR 0.91; 95% CI 0.82 to 1.00). When only high-quality studies were assessed, there was no statistical difference (RR 0.92; 95% CI 0.83 to 1.01). We detected no differences in any of the other outcomes. UVI of oxytocin solution compared with UVI of plasma expander showed no statistically significant difference in the outcomes assessed by the only one small trial included. Prostaglandin solution compared with saline solution alone was associated with a statistically Umbilical vein injection for management of retained placenta (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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significant lower incidence in manual removal of placenta (RR 0.42; 95% CI 0.22 to 0.82) but we observed no difference in the other outcomes evaluated. Prostaglandin plus saline solution showed a statistically significant reduction in manual removal of placenta when compared with oxytocin plus saline solution (RR 0.43; 95% CI 0.25 to 0.75), and we also observed a small reduction in time from injection to placental delivery (mean difference -6.00; 95% CI -8.78 to -3.22). However, there were only two small trials contributing to this meta-analysis. Authors’ conclusions

UVI of oxytocin solution is an inexpensive and simple intervention that could be performed while placental delivery is awaited. However, high-quality randomized trials show that the use of oxytocin has little or no effect. Further research into the optimal timing of manual removal and into UVI of prostaglandins or plasma expander is warranted.

P LA IN L AN GU AG E S UM MA RY

Umbilical vein injection for management of retained placenta

The placenta provides nourishment for the baby in the womb (uterus) through the umbilical cord. It is usually delivered shortly after the baby. If the placenta remains in the womb (retained placenta), women have an increased risk of bleeding heavily (haemorrhage), infection and very occasionally death. Manual removal of the placenta involves an operation to remove the placenta, but it can have adverse effects. The injection of oxytocin solution into the umbilical cord after the cord is cut is an inexpensive and simple intervention that could be performed while placental delivery is awaited. There was some evidence from the review of 15 trials, involving 1704 women, that an injection of oxytocin into the umbilical vein could reduce the need for manual removal of retained placenta after childbirth. However, high-quality randomized trials show that the use of oxytocin has little or no effect. Around half of the retained placentas will come out spontaneously if left; the optimal timing of manual removal is not known.

BACKGR OUND

Normally the uterine contractions that occur immediately after the delivery of the baby result in the spontaneous detachment of the placenta from the uterine wall and subsequent delivery. The term ’retained placenta’ is used when the placenta has not been delivered within one hour after the birth of the baby ( WHO 1990). Retained placenta is a potentially life-threatening complication of the third stage of labour. If untreated, as may happen after home births in developing countries, there is a high risk of maternal death from haemorrhage or infection. The current standard management of retained placenta, by manual removal, aims to prevent these problems, but it is unsatisfactory. Manual removal involves the clinician passing a hand through the vagina into the cavity of uterus, and usually requires general or regional anaesthesia in hospital. It is an invasive procedure with its own serious complications of haemorrhage, infection or genital tract trauma. Any management simple and safe enough to be performed at the place of delivery which reduces the need for manual removal of placenta could be of major benefit to women worldwide. The umbilical vein injection (UVI) of saline solution or any other fluid alone or

plus an uterotonic drug (to induce uterine contractions) seems a promising intervention. Uterotonic drugs are those that increase the uterine tone and/or contractility and include ergot alkaloids, oxytocin and prostaglandins. Injection of the solution into the umbilical vein in the cord after delivery of the baby is an inexpensive and simple intervention. UVI for the management of retained placenta was first described by Mojon and Asdrubali in 1826 (Koerting 1926). In the early twentieth century, various authors reported the use of UVI of saline solution with volumes that have varied widely between 200 mland400ml(Gabaston 1914; Jarcho 1928). Subsequent studies have concentrated on smaller volumes of UVI of saline solution plus oxytocin, although most of these were uncontrolled (Golan 1983; Golan 1984; Hauksson 1986; Heinonen 1985; Neri 1966). The hypothesized beneficial effectof the UVI is that it may reduce the need for manual removal of the placenta (Carroli 1991). The aim of this review was to evaluate the available evidence about the possible benefits and risks of the use of UVI versus expectant management for retained placenta. We also evaluated benefits and


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risks of the use of umbilical injection with different fluids and uterotonic drugs.

OBJECTI VES

To determine the possible benefits and risks of the use of UVI for retained placenta. We considered UVI as an intervention for retainedplacentawhenthelatterremainedundelivered15minutes or more after the delivery of the baby. Also, to assess the effects of alternative fluids and uterotonic drugs.

METHODS

Criteria for considering studies for this review

Types of studies

Any adequately randomized controlled trial comparing UVI of saline solution or other fluids, with or without uterotonic drugs, either with expectant management or with an alternative solution or other uterotonic agent, in themanagement of retained placenta. Types of participants

All women having a vaginal delivery with a retained placenta. For this review, we consider trials including women in whom the placenta was not delivered spontaneously at least 15 minutes after delivery of the baby. Types of interventions

1. UVI of saline solution versus expectant management. 2. UVI of oxytocin plus saline solution versus expectant management. 3. UVI of oxytocin plus saline solution versus UVI of saline solution. 4. UVI of oxytocin plus saline solution versus UVI of plasma expander. 5. UVI of prostaglandin plus saline solution versus UVI of saline solution. 6. UVI of prostaglandin plus saline solution versus UVI of oxytocin plus saline solution. Types of outcome measures

Primary outcomes

1. Manual removal of the placenta. 2. Maternal mortality. 3. Severe postpartum haemorrhage (PPH) (defined as clinically estimated blood loss greater than or equal to 1000 ml). 4. Blood transfusion. 5. Addition of therapeutic uterotonics. Secondary outcomes

1. Serious maternal morbidity (hysterectomy, admission to intensive care, renal or respiratory failure, and other additional surgical procedures to treat PPH other than manual removal of placenta, related to the randomized interventions). 2. PPH (defined as clinically estimated or measured blood loss greater than or equal to 500 ml). 3. Maternal postpartum anaemia (defined by the haemoglobin concentration according to local standards). 4. Mean blood loss (ml). 5. Mean time from injection to placental removal (minutes). 6. Perinatal fall in haemoglobin levels (defined as decrease in previous haemoglobin concentration levels by at least 10%). 7. Iron tablets during the puerperium. 8. Subsequent surgical evacuation of retained products of conception. 9. Diastolic blood pressure greater than 100 mmHg between injection and discharge from the labour ward. 10. Vomiting between injection and discharge from the labour ward. 11. Shivering between injection and discharge from the labour ward. 12. Nausea between injection and discharge from the labour ward. 13. Headache between injection and discharge from the labour ward. 14. Maternal pain between injection and discharge from the labour ward. 15. Maternal dissatisfaction with third stage management. 16. Secondary PPH (after 24 hours and before six weeks). 17. Bleeding needing readmission. 18. Need for treatment with antibiotics. 19. Maternal fatigue. 20. Breastfeeding at discharge from hospital.

Search methods for identification of studies

Electronic searches

We evaluated the following maternal outcomes. We chose five We searched the Cochrane Pregnancy and Childbirth Group’s primary outcomes as being the most representative of the clinically Trials Register by contacting the Trials Search Co-ordinator (28 important measures of ineffectiveness and complications. February 2011). Umbilical vein injection for management of retained placenta (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

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The Cochrane Pregnancy and Childbirth Group’s Trials Register is maintained by the Trials Search Co-ordinator and contains trials identified from: 1. quarterly searches of the Cochrane Central Register of Controlled Trials (CENTRAL); 2. weekly searches of MEDLINE; 3. weekly searches of EMBASE; 4. handsearches of 30 journals and the proceedings of major conferences; 5. weekly current awareness alerts for a further 44 journals plus monthly BioMed Central email alerts. Details of the search strategies for CENTRAL, MEDLINEand EMBASE, the list of handsearched journals and conference proceedings, and the list of journals reviewed via the current awareness service can be found in the ‘Specialized Register’ section within the editorial information about the Cochrane Pregnancy and Childbirth Group. Trials identified through the searching activities described above are each assigned to a review topic (or topics). The Trials Search Co-ordinator searches the register for each review using the topic list rather than keywords. We did not apply any language restrictions.

Data collection and analysis

Selection of studies

(1) Sequence generation (checking for possible selection bias)

We described for each included study the method used to generate the allocation sequence in sufficient detail to allow an assessment of whether it should produce comparable groups. We assessed the method as: • low risk of bias (any truly random process, e.g. random number table; computer random number generator), • high risk of bias (any non-random process, e.g. odd or even date of birth; hospital or clinic record number) or, • unclear risk of bias. (2) Allocation concealment (checking for possible selection bias)

We described for each included study the method used to conceal the allocation sequence in sufficient detail and determine whether intervention allocation could have been foreseen in advance of, or during recruitment, or changed after assignment. We assessed the methods as: • low risk of bias (e.g. telephone or central randomisation; consecutively numbered sealed opaque envelopes); • high risk of bias (open random allocation; unsealed or nonopaque envelopes, alternation; date of birth); • unclear risk of bias, (3) Blinding (checking for possible performance bias)

We described for each included study the methods used, if any, to blind study participants and personnel from knowledge of which intervention a participant received. We judged studies at low risk of bias if they were blinded, or if we judge that the lack of blinding could not have affected the results. We assessed blinding separately for different outcomes or classes of outcomes. We assessed the methods as: Data extraction and management • low, high or unclear risk of bias participants; We designed a form to extract data. For eligible studies, two review • low, high or unclear risk of bias for personnel; authors (JM Nardin, A Weeks) extracted the data using the agreed • low, high or unclear risk of bias for outcome assessors. form.We resolved discrepancies through discussion or, if required, consulting a thirdperson (G Carroli).We entered data into Review (4) Incomplete outcome data (checking for possible attrition Manager software (RevMan 2008) and checked for accuracy. When information regarding any of the above was unclear, we bias through withdrawals, dropouts, protocol deviations) attempted to contact authors of the original reports to provide We assessed for each included study, and for each outcome or class further details. of outcomes, the completeness of data including attrition and exclusions from the analysis. We stated whether attrition and exclusions were reported, the numbers included in the analysis at each Assessment of risk of bias in included studies stage (compared with the total randomized participants), reasons Two review authors (JM Nardin,A Weeks) independently assessed for attritionor exclusionwherereported,andwhethermissingdata riskofbiasforeachstudyusingthecriteriaoutlinedinthe Cochrane were balanced across groups or were related to outcomes. Where Handbook for Systematic Reviews of Interventions (Higgins 2008). sufficient information was reported, or was supplied by the trial We resolved any disagreement by discussion or by involvinga third authors, we re-included missing data in the analyses. We assessed assessor. methods as: Two review authors (JM Nardin,A Weeks) independently assessed for inclusion all the potential studies identified as a result of the search strategy. We resolved any disagreement through discussion or, if required, by consulting a third person (G Carroli).


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low risk of bias (e.g. no missing outcome data; missing outcome data balanced across groups); • high risk of bias (e.g. numbers or reasons for missing data imbalanced across groups; ‘as treated’ analysis done with substantial departure of intervention received from that assigned at randomization) • unclear risk of bias. •

Continuous data

For continuous data, we used themean difference if outcomes were measured inthe same waybetween trials. We used the standardized mean difference to combine trials that measure the same outcome, but use different methods.

Unit of analysis issues (5) Selective reporting bias

We described for each included study how we investigated the possibility of selective outcome reporting bias and what we found. We assessed the methods as: • low risk of bias (where it is clear that all of th e study’s prespecified outcomes and all expected outcomes of interest to the review have been reported); • high risk of bias (where not all the study’s pre-specified outcomes have been reported; one or more reported primary outcomes were not pre-specified; outcomes of interest are reported incompletely and so cannot be used; study fails to include results of a key outcome that would have been expected to have been reported); • unclear risk of bias.

(6) Other sources of bias

We described for each included study any important concerns we have about other possible sources of bias. We assessed whether each study was free of other problems that could put it at risk of bias: • low risk of other bias; • high risk of other bias; • unclear whether there is risk of other bias.

(7) Overall risk of bias

Cluster-randomized trials

The search included cluster-randomized trials along with individually randomized trials. Their sample sizes would have been adjusted according to the methods described in the Handbook (Higgins 2008) using an estimate of theintracluster correlation coefficient (ICC) derived from the trial (if possible), or from another source. However, we found no cluster randomized trials with this search strategy.

Dealing with missing data

For included studies, we noted levels of attrition. We explored the impact of including studies with high levels of missing data in the overall assessment of treatment effect by using sensitivity analysis. For all outcomes we carried out analyses, as far as possible, on an intention-to-treat basis, i.e. we attempted to include all participants randomized to each group in the analyses. The denominator for each outcome in each trial was the number randomized minus any participants whose outcomes are known to be missing.

Assessment of heterogeneity

We made explicit judgements about whether studies are at high risk We applied tests of heterogeneity between trials, if appropriate, usof bias, according to the criteria given in the Handbook (Higgins ing I² statistic. If we identified high levels of heterogeneity among 2008). With reference to (1) to (6) above, we assessed the likely the trials (I² exceeding 50%), we performed prespecified sensitivmagnitude and direction of the bias and whether we consider it is ity analyses according to the methodological quality of the studies. likelytoimpactonthefindings.Weexploredtheimpactofthelevel We used a random-effect meta-analysis as an overall summary if of bias through undertaking sensitivity analyses - see Sensitivity this was considered appropriate. analysis. Assessment of reporting biases Measures of treatment effect

Dichotomous data

For dichotomous data, we presented results as summary risk ratio with 95% confidence intervals.

Where we suspected reporting bias (see ‘Selective reporting bias’ above), we attempted to contact study authors asking them to provide missing outcome data. Where this was not possible, and the missing data were thought to introduce serious bias, we explored the impact of including such studies in the overall assessment of results by a sensitivity analysis .


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Data synthesis

We carried out statistical analysis using the Review Manager software (RevMan 2008). We used fixed-effect meta-analysis for combining data where trials were examining the same intervention, and the trials’ populations and methods were judged sufficiently similar. Where we suspect clinical or methodological heterogeneity between studies sufficient to suggest that treatment effects may differ between trials, we used random-effects meta-analysis. If we identified substantial heterogeneity in a fixed-effect metaanalysis, we have noted this and repeated the analysis using a random-effects method.

Subgroup analysis and investigation of heterogeneity

We did not plan to perform subgroup analyses in advance. We performed analyses by study size and dosage post hoc, but due to

the risk of spurious results, have not presented these in the review. Sensitivity analysis

We carried out sensitivity analyses to explore the effect of trial quality (Figure 1). This involved analyses based on each trial’s risk of bias rating (adequate/inadequate/unclear) for allocation, incomplete outcome data, and blinding (Figure 2). We excluded studies of poor quality in the analysis (those rated as inadequate or unclear) in order to assess for any substantive difference to the overall result. We considered only studies which were rated as ’adequate’ for allocation concealment and ’adequate’ for blinding (due to the nature of the intervention, blinding was considered critical), ’high quality’ (except if the study was rated as ’inadequate’ or ’unclear’ for incomplete outcome data) and selected for the report of the sensitivity analysis. We also analyzed data according to study size and dosage.

Figure 1. Forest plot of comparison: 3 OXYTOCIN SOLUTION vs. SALINE SOLUTION, outcome: 3.1 Manual removal of the placenta.


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Figure 2. Methodological quality graph: review authors’ judgements about each methodological quality item presented as percentages across all included studies.

RESULTS Description of studies

See: Characteristicsofincludedstudies; Characteristicsof excluded studies; Characteristics of studies awaiting classification. For a detailed description of studies see table of Characteristics of included studies and Figure 2. The following text summarizes the main characteristics. The search strategy identified 18 relevant studies that we assessed for inclusion. Of these, 15 (1704 women) fulfilled the selection criteria and were included in the meta-analyses. We incorporated threeofthem(659women)inthisupdatesincethelastpublication of this review. Five trials were published in the late 1980s, six in the 1990s, two since 2000 and two studies are still unpublished. Twelve studies are small and three are relatively large. The largest trial includes 577 women. We have categorized included trials into six subgroups according to the type of fluids or drugs being compared (see below). Interventions

The agents and uterotonic drugs used in these trials include: saline solution alone, plasma expander alone, oxytocin plus saline solution and prostaglandin plus saline solution injected into the umbilical vein. Saline solution alone versus expectant management was compared in four trials including 403 women. Oxytocin plus saline solution

was compared to expectant management in five trials with 444 women. Oxytocin plus saline solution versus saline solution alone was compared in 12 trials including 1276 women. Oxytocin plus saline solution versus plasma expander was compared in only one trial with 109 women. Prostaglandin plus saline solution versus salinesolutionalone was compared in twosmalltrials (51women). Prostaglandin plus saline solution versus oxytocin plus saline solution was compared in the same two small studies (62 women). The volume injected into the umbilical vein was mostly 20 ml (10 studies) whereas four trials used a higher dose (30 ml) and only trial used a lower dose (10 ml). Seven studies used 10 IU of oxytocin, two studies used 20 IU, two used 30 IU, three trials used 50 IUandonlyoneusedadoseof100IUofoxytocin( Wilken-Jensen 1989). Prostaglandin doses used were 20 mg of F2 α in one study (Bider 1996) and 800 mcg of E1 analog (misoprostol) in another study (Rogers 2007). Plasma expander (Dextran 70) 20 ml was administered in one trial (Makkonen 1995). Time to trial entry

The time to trial entry after delivery of the baby was 15 minutes in two studies; 20 minutes in five studies; 30 minutes in other six; 45 minutes in one study; and 60 minutes in another study. Limit time for manual removal of the placenta

The limit time for manual removal of the placenta was 15 minutes in four trials, 30 minutes in six trials and 40 to 45 minutes in two trials. In one trial, timing of the procedure was left to the


7

judgement of attending clinicians and in two trials it was not prespecified. Included studies

See Characteristics of included studies. Excluded studies

See Characteristics of excluded studies.

Risk of bias in included studies

Selection bias at entry to the trial

Four trials describe clearly the random method generation and concealment of allocation, making selection bias at entry to the trials unlikely (Carroli 1998; Frappell 1988; Rogers 2007; Weeks 2009). In another four trials, concealment of allocation (coded by the pharmacist) was sound; the possibility of selection bias is unlikely but none of them describe the random generation method (Hansen 1987; Huber 1991; Selinger 1986; Wilken-Jensen1989). Calderale1994, although described as double blind with a placebo administered, does not clearly state the allocation concealment. Gazvani 1998 describes clearly the random generation and the concealment of allocation by sealed envelopes. Thiery 1987 describes only the concealment allocation method which is by sealed envelopes. Finally, three trials did not describe the random generation nor the allocation concealment method and, consequently, are open to selection bias at entry (Bider 1996; Kristiansen 1987; Makkonen 1995). In Sivalingam 2001, the method of randomization is described as ’use of box containing equal number of envelopes’that were taken randomly; however, no attempt to conceal the randomization sequence is described and, therefore, this study could be prone to selection bias. Selection bias after entry to the trial

No withdrawals were stated to have occurred from 10 trials (Calderale 1994; Gazvani 1998; Hansen 1987; Kristiansen 1987; Makkonen 1995; Rogers 2007; Selinger 1986; Sivalingam 2001; Thiery 1987; Weeks 2009), so the likelihood of selection bias after entry to these trials is low. In Huber 1991, 4.5% of the women were excluded from the analyses for violations of the treatment protocol, and in Carroli 1998, 1.7% of the participants were lost to follow-up, giving these two trials a very low risk of selection bias after entry. In the remaining trials, the withdrawals were as follows: Bider 1996,8%; Frappell 1988, 18%; and Wilken-Jensen 1989, 7.5%, without any explanation about the reason for the exclusions leaving open the potential for serious selection bias after entry into the trials.

Blinding

Bider 1996 and Makkonen 1995 are likely to suffer assessment bias because they did not describe the masking procedure between both arms of the trial. Inan effort todiminish the bias, a time limit of 40 minutes and 30 minutes, respectively, for manual removal of placenta was established, but they did not measure compliance with the protocol. Calderale 1994 is not prone to assessment bias because both arms are indistinguishable and a limit time for manual removal of the placenta was established. There is limited details in the report of blinding except to state that a ’double-blind methodology’ was used. Carroli 1998 is unlikely to suffer assessment bias between both injection arms of the trial because the physicians were not aware of the treatment given and a time limit of 30 minutes was established for manual removal the placenta; to assess compliance with the protocol, the time that had elapsed from entry to the trial to manual removal of the placenta was measured. Frappell 1988 and Wilken-Jensen 1989 are potentially free of assessment bias because, in both arms of the trials, the treatments given to the women were indistinguishable to the physician and also because they established a time limits of 15 minutes and 40 minutes respectively, for manual removal of placenta but they did not describe any method to control for protocol compliance. Gazvani 1998 could suffer assessment bias because the observer wasawareofthetreatmentgiventoeachpatientbutatimelimitfor manual removal of the placenta was established to try to minimize the bias. Hansen 1987 is likely to be free of assessment bias because the physicians were notaware of thetreatment givento the women but they did not set a limit time for manual removal of the placenta. Huber 1991 is not prone to assessment bias in the comparison between the two injection arms of the trial, but is prone to bias in the comparison to the expectant management arm because the treatment given was known by the physician and a limit time for manual removalof theplacentawas notestablished inthe protocol; furthermore, timing was determined by the clinical judgement of the obstetrician. Kristiansen1987 isproneto assessment bias becausethe physicians were aware of the treatment given and there was not an established limit time for manual removal of placenta. Rogers 2007 is prone to assessment bias because the physicians were aware of the treatment given as solutions were not similar in colour but the established time limit of 30 minutes for manual removal of the placenta could minimize the bias. Selinger 1986 is potentially free of assessment bias because both arms of the trial were indistinguishable and also they did establish a time limit of 20 minutes for manual removal of the placenta, although they described three women delivering the placenta spontaneously at 30, 55 and 80 minutes after entry to the trial. Sivalingam 2001 is unlikely to suffer from assessment bias as solutions, similar in colour and consistency, were prepared by a mid-


8

wife, which kept the physician unaware of the content of the syringe. A limit time of 30 minutes for manual removal of the placenta was also established. Thiery 1987 is prone to assessment bias because the physicians were aware of the treatment given. To alleviate this problem a time limit of 15 minutes was set up for manual removal of the placenta but the researchers did not describe any effort to measure compliance with the protocol. Weeks 2009 is unlikely to suffer assessment bias between both injection arms of the trial because the physicians were not aware of

the treatment given and a time limit of 30 minutes was established for manual removal of the placenta. In summary, according to the criteria applied for the sensitivity analysis,eighttrialsweremethodologicallysound( Calderale 1994; Carroli 1998; Frappell 1988; Hansen 1987; Huber 1991; Selinger 1986; Sivalingam2001; Weeks 2009)andseventrialswereofpoor methodological quality or there was insufficient information for inclusion into the high-quality group ( Bider 1996; Gazvani 1998; Kristiansen 1987; Makkonen 1995; Rogers 2007; Thiery 1987; Wilken-Jensen 1989) (Figure 3).


9

Figure 3. Methodological quality summary: review authors’ judgements about each methodological quality item for each included study.


10

Effects of interventions

bin, blood transfusion, curettage, infection and hospital stay (for treatment effects and 95% CI see ’data and analyses’ tables).

Overall, we have included 15 trials with a total of 1704 women. We carried out a total of 25 meta-analyses (more than one trial analysed), while theother 36 reported results correspond to singletrial analyses.

3. Oxytocin solution versus saline

Twelve trials were included in this comparison. Oxytocin solution compared with salinealone showeda reduction in manual removal 1. Saline versus expectant management ofthe placenta,but this wasnot statisticallysignificant andthe data Four trials were included in this comparison. Umbilical vein injec- had some heterogeneity (RR 0.91; 95% CI 0.82 to 1.00, number tion (UVI) of saline compared with expectant management does needed to treat (NNT): 18; 95% CI 9 to 948; I² = 45%, P = 0.05). not show any significant difference in manual removal of the pla- The NNT and its 95% confidence interval for this outcome was centa (risk ratio (RR) 0.99; 95% confidence interval (CI) 0.84 to 18 (95% CI 9.00 to 948). Exploration of the data revealed that 1.16), blood loss, haemoglobin concentration, blood transfusion, none of the three biggest studies (which together contributed over curettage, infection and hospital stay (for treatment effects and 70% of the data (911/1276)) found any difference in outcome either individually or combined (RR 0.98; 95% CI 0.88 to 1.09). 95% CI see ’data and analyses’ tables). When small but high-quality studies were added there remained no statistically significant difference (RR 0.92; 95% CI 0.83 to 1.01) (Figure 1) and we found no publication bias for this analysis 2. Oxytocin solution versus expectant management when the funnel plot was produced (Figure 4). Dosage appeared Five trialswere included in this comparison. UVIof oxytocin solu- to have no effect as the four studies that used 30 units of oxytocin tioncomparedwithexpectantmanagement showed no statistically or more (Rogers 2007; Sivalingam 2001; Weeks 2009; Wilkensignificant difference in manual removal of the placenta (RR 0.87; Jensen 1989) together showed no significant difference (RR 0.97; 95% CI 0.74 to 1.03) and no difference in blood loss, haemoglo- 95% CI 0.86 to 1.09).


11

Figure 4. Funnel plot of comparison: 3 Oxytocin solution versus saline solution, outcome: 3.1 Manual removal of the placenta.

No statistical differences were found for any of the other evaluated outcomes including maternal mortality, serious maternal morbidity, addition of therapeutic uterotonics, blood loss, postpartum haemorrhage, haemoglobin fall, blood transfusion, curettage, infection, hospital stay, fever, abdominal pain and length of third stage of labour (for treatment effects and 95% CI see ’data and analyses’ tables).

uterotonics (for treatment effects and 95% CI see ’data and analyses’ tables). 6. Prostaglandin solution versus oxytocin solution

Again, only two small trials contributed to these results. UVI of prostaglandin solution versus UVI of oxytocin solution showed a significant difference in manual removal of placenta favourable to 4. Oxytocin solution versus plasma expander the prostaglandin group (RR 0.43; 95% CI 0.25 to 0.75) and a Only one trial contributed to this comparison. UVI of oxytocin slight decrease of statistical significance in time from injection to solution compared with UVI of plasma expander showed a higher, placental delivery (mean difference -6.00; 95% CI -8.78 to -3.22) but not statistically significant, incidence of manual removal of but no statistical differences in blood loss, fever, abdominal pain placenta (RR 1.34; 95% CI 0.97 to 1.85) and no difference in and oxytocin augmentation (for treatment effects and 95% CI see blood loss (for treatment effectsand 95% CI see ’data and analyses’ ’data and analyses’ tables). tables). 5. Prostaglandin solution versus saline

There were two small studies included in this comparison. UVI of prostaglandin solution compared with UVI of saline alone showed a lower incidence of statistical significance in manual removal of placenta (RR 0.42; 95% CI 0.22 to 0.82) but no difference in blood loss, fever, abdominal pain, and addition of therapeutic

DISCUSS ION Saline versus expectant management

One question is whether UVI of saline compared with expectant management reduces the need for manual removal of the placenta.


12

Although this is based in the only four available randomized controlled trials with a small overall sample size, the answer extracted from this systematic review is that there seem to be no advantages in using this intervention to reduce the above-mentioned main outcome.Therewasasimilarlackofeffectonsecondaryendpoints such as blood loss, blood transfusion curettage, hospital stay or any difference in postpartum haemoglobin level.

Oxytocin solution versus plasma expander

UVI of oxytocin solution compared with UVI of plasma expander showed higher, but not statistically significant, incidence of manual removal of placenta and did not show any difference in blood loss but, as it was shown, there is only one trial available to date and considering the poor methodological quality and the small size of it, these results should be interpreted cautiously.

Oxytocin solution versus expectant management

Prostaglandin solution versus saline

In this comparison, UVI of oxytocin solution showed a 13% risk reduction in the incidence of manual removal of placenta, but this benefit is not statistically significant with confidence intervals compatible with a risk reduction of 26% and a marginal risk of increase of 3%. There was no advantage with regards to secondary endpoints such as blood loss, haemoglobin, blood transfusion, curettage, infection and hospital stay.

The use of UVI of prostaglandin solution compared with UVI of saline aloneshowed a statistically significant riskreductionin manual removal of placenta but did not show any difference in blood loss, fever, abdominal pain, and addition of therapeutic uterotonics. The results of this comparison should be taken cautiously as there were only two small trials with 51 women in total and both studies were considered of low methodological quality due to the lack of proper blinding and therefore, prone to bias.

Oxytocin solution versus saline

This is the comparison in which most studies have been done and contributes the largest sample size of all the comparisons included in this systematic review. Overall the results are complex as they show the need for manual removal to be of borderline statistical significance of beneficial effect to the oxytocin solution group and of borderline heterogeneity. When subgroup analysis by quality of studies was performed, the high-quality group showed low heterogeneity and confidence intervals compatible with anything between a risk reduction of 17% and a marginal risk increase of 1% (Figure 1). Post-hoc exploration by oxytocin dose and by funnel plot does not reveal any alternative source of heterogeneity. Dealingwith this data will, therefore,be controversial, especially as two of the authors of this review (A Weeks and G Carroli) are first authors for the two largest studies. Overall, it appears unlikely that there is a major effect of umbilical oxytocin injection on main outcomes. However, with a number needed to treat of 18 (95% confidence interval 9.00 to 948), it could be argued that with no harmful effects found with its administration, and as an inexpensive and simple intervention that could be performed while placental delivery is awaited, it would still have a role in the management of retained placenta. If the intervention is performed within 15 to 30 minutes after delivery of the baby, it may slightly reduce the need for further interventions for retained placenta. This small potential beneficial effect could still be important in settings where resources are scarce and there is no immediate availability of facilities for manual removal. It should be noted that we found no differences in length of third stage of labour, blood loss, postpartum haemorrhage, haemoglobin, blood transfusion, curettage, infection, hospital stay, fever, abdominal pain and addition of therapeutic uterotonics.

Prostaglandin solution versus oxytocin solution

The UVI of prostaglandin solution compared with UVI oxytocin solution showed again a significant difference in manual removal of placenta as well as fortime to placentaldelivery favourable to the first group. No other differences reached statistical significance. However, as for the previous comparison, these results should be interpreted guardedly as only two small unblinded trials were included in the meta-analysis.

A U TH O RS ’ C O NC L US I ON S Implications for practice

Given that the meta-analysis of all the main three comparisons showed no major effect, it would not be appropriate to suggest widespread implementation of intra-umbilical oxytocin injection for the treatment of retained placenta. Furthermore, if there is an effect, it does not appear to be large; the number of cases that need to be treated to prevent one manual removal is unlikely to be less than nine and could be high as 948. However, those who currently use the technique can be reassured that there is no evidence of harm, and they may therefore, wish to continue using it. Indeed, with many retained placenta delivering spontaneously with no intervention at all, there may be a benefit to just waiting for a further 30 minutes to allow time for this spontaneous expulsion. However, the risk of bleeding increases with the length of the third stage and so facilities for manual removal and blood transfusion should be readily available.


13

Implications for research

ACKNOWLED GEMEN TS

There is little evidence of the optimal time to wait prior to manual removal of placenta, and a study of immediate versus delayed As part of the pre-publication editorial process, this review has manual removal would help to evaluate the risks and benefits of been commented on by three peers (an editor and two referees this strategy. There is also some evidence that the UVI of plasma who are external to the editorial team) and the Group’s Statistical expander or prostaglandins are beneficial, and so further research Adviser. in this area is justified. The evidence extracted from this review does not support further research on the use of UVI of saline solution alone in comparison to expectant management.

To the Cochrane Pregnancy and Childbirth Group team for their constant support.

REFERENCES

References to studies included in this review Bider 1996 {published data only}

Bider D, Dulitzky M, Goldenberg M, Lipitz S, Mashiach S. Intraumbilical vein injection of prostaglandin F2alpha in retained placenta. European Journal of Obstetrics & Gynecology and Reproductive Biology 1996;64:59–61. Calderale 1994 {published data only}

Calderale L, Dalle NF, Franzoi R, Vitalini R. Is intraumbilical vein administration with oxytocin useful in the treatment of retained placenta? [É utile la somministrazione di ossitocina nella vena ombelicale per il trattamento della placenta ritenuta?]. Giornale Italiano di Ostetricia e Ginecologia 1994;16(5):283–6. Carroli 1998 {published data only}

Carroli G, Belizan JM, Grant A, Gonzalez L, Campodonico L, Bergel E. Intra-umbilical vein injection and retained placenta: evidence from a collaborative large randomised controlled trial. Grupo Argentino de Estudio de Placenta Retenida. British Journal of Obstetrics and Gynaecology 1998; 105(2):179–85. Frappell 1988 {published data only}

Frappell JM, Pearce JM, McParland P. Intra-umbilical vein oxytocin in the management of retained placenta: a random, prospective, double blind, placebo controlled study. Journal of Obstetrics and Gynaecology 1988; 8:322–4. Gazvani 1998 {published data only}

Gazvani MR, Luckas MJM, Drakeley AJ, Emery SJ, Alfirevic Z, Walkinshaw SA. Intraumbilical oxytocin for the management of retained placenta: a randomized controlled trial. Obstetrics & Gynecology 1998; 91:203–7. Hansen 1987 {published data only}

Hansen P, Jorgensen L, Dueholm M, Hansen S. Intraumbilical oxytocin in the treatment of retained placenta. Ugeskrift for Laeger 1987;149:3318–9. Huber 1991 {published data only}

Huber MGP, Wildschut HIJ, Boer K, Kleiverda G, Hoek FJ. Umbilical vein administration of oxytocin for the management of retained placenta: is it effective?. American Journal of Obstetrics and Gynecology 1991;164:1216–9.

Kristiansen 1987 {published data only}

Kristiansen FV, Frost L, Kaspersen P, Moller BR. The effect of oxytocin injection into the umbilical vein for the management of retained placenta. American Journal of Obstetrics and Gynecology 1987;156:979–80. Makkonen 1995 {published data only}

Makkonen M, Suoino S, Saarikoski S. Intraumbilical oxytocin for management of retained placenta. International Journal of Gynecology & Obstetrics 1995; 48:169–72. Rogers 2007 {published data only}

Rogers MS, Yuen PM, Wong S. Avoiding manual removal of placenta: evaluation of intra-umbilical injection of uterotonics using the Pipingas technique for the management of adherent placenta. Acta Obstetricia et Gynecologica 2007; 86:48–54. Selinger 1986 {published data only}

Selinger M, Mackenzie IZ, Dunlop P, James D. Intraumbilical vein oxytocin in the management of retained placenta. A double blind placebo controlled study. Journal of Obstetrics and Gynaecology 1986;7:115–7. Sivalingam 2001 {published data only}

Sivalingam N, Surinder S. Is there a place for intra-umbilical oxytocin for the management of retained placenta?. Medical Journal of Malaysia 2001;56(4):451–9. Thiery 1987 {unpublished data only}

Thiery M. Management of retained placenta with oxytocin injection into the umbilical vein. Personal communication 1987. Weeks 2009 {published and unpublished data}

Weeks A, Mirembe F, Alfirevic Z. The release trial: a randomised controlled trial of umbilical vein oxytocin versus placebo for the treatment of retained placenta. BJOG: an international journal of obstetrics and gynaecology 2005;115 (10):1458. Weeks AD, Alia G, Vernon G, Namavanja A, Gosakan R, Majeed T, et al.The release trial: a multi-centre double blind trial of umbilical oxytocin to treat retained placenta. BJOG:


14

an international journal of obstetrics and gynaecology 2008; 115(s1):32.

Weeks AD, Alia G, Vernon G, Namayanja A, Gosakan R, Majeed T, et al.Umbilical vein oxytocin for the treatment of retained placenta (Release Study): a double-blind, randomised controlled trial. Lancet 2010; 375(9709): 141–7. Weeks AD, Alia G, Vernon G, et al.The Release trial: A multi-centre double blind trial of umbilical oxytocin to treat retained placenta. Personal communication 2009.

Hauksson 1986

Hauksson A. Oxytocin injection into the umbilical vein in women with retained placenta. A questionable method. American Journal of Obstetrics and Gynecology 1986; 125: 1140. Heinonen 1985

Heinonen PK, Pihkala H. Pharmacologic management and controlled cord traction in the third stage of labour. Annales Chirurgiae et Gynaecologiae 1985; 74(197):31–5.

∗

Wilken-Jensen 1989 {published data only}

Higgins 2008

Higgins JPT, Green S, editors. Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1 [updated September 2008]. The Cochrane Collaboration, 2008. Available from www.cochrane-handbook.org.

Wilken-Jensen C, Strom V, Nielsen MD, Rosenkilde-Gram B. Removing placenta by oxytocin - a controlled study. American Journal of Obstetrics and Gynecology 1989;161: 155–6.

References to studies excluded from this review

Jarcho 1928

Jarcho A. Management of retained placenta. Surgery Gynecology and Obstetrics 1928;46:265–72.

Das 2008 {published data only}

Das S. Management of retained placentas using umbilical vein oxytocin injection by Pipingas technique. BJOG: an international journal of obstetrics and gynaecology 2008;115 (s1):242.

Koerting 1926

Koerting W. El metodo de Mojon Gabaston en el tratamiento de las complicaciones del alumbramiento. Semana Medica 1926;33:353–65.

Habek 2001 {published data only}

Habek D, Hrgovic Z, Ivanisevic M, Delmis J. Treatment of a retained placenta with intraumbilical oxytocin injection. Zentralblatt fur Gynakologie 2001;123:415–7.

References to studies awaiting assessment

Neri 1966

Neri A, Goldman J, Gans B. Intra-umbilical vein injection of pitocin. A new method in the management of the third stage of labor. Harefuah 1966; 70:351–3. RevMan 2008

The Nordic Cochrane Centre, The Cochrane Collaboration. Review Manager (RevMan). 5.0. Copenhagen: The Nordic Cochrane Centre, The Cochrane Collaboration, 2008.

Chauhan 2004 {published data only}

Chauhan P, Rosendahl M, Sorensen B, Westergaard JG. Randomised controlled study of treatment of retained placenta with 100 IE intraumbilical oxytocin via and infant mucus aspiration tube. XXXIV Congress of Nordic Federation of Societies of Obstetrics and Gynecology; 2004 June 12-15; Helsinki, Finland. 2004:56.

WHO 1990

World Health Organization. The prevention and management of postpartum haemorrhage. Report of a technical working group, Geneva. 3-6 July 1989. Document WHO/ MCM/90.7 . Geneva: World Health Organization, 1990.

Additional references Carroli 1991

Carroli G. Management of retained placenta by umbilical vein injection. British Journal of Obstetrics and Gynaecology 1991;98:348–50.

References to other published versions of this review Carroli 2001

Carroli G, Bergel E. Umbilical vein injection for the management of retained placenta. Cochrane Database of Systematic Reviews 2001, Issue 4. [DOI: 10.1002/ 14651858.CD001337]

Gabaston 1914

Gabaston JA. Eine neue Methode kuenstlicher Plazentaloeung. Muenchener Mediziner Wochenzchrift 1914; 61:651. Golan 1983

Elbourne 1995

Elbourne DR. Umbilical vein injection (oxytocin or saline) for retained placenta. [revised 03 April 1992]. In: Enkin MW, Keirse MJNC, Renfrew MJ, Neilson JP, Crowther C (eds.) Pregnancy and Childbirth Module. In: The Cochrane Pregnancy and Childbirth Database [database on disk and CDROM]. The Cochrane Collaboration; Issue 2, Oxford: Update Software; 1995.

Golan A, Lidor AL, Wexler S, David MP. A new method for the management of the retained placenta. American Journal of Obstetrics and Gynecology 1983;146:708–9. Golan 1984

Golan A, Lidor AL, Wexler S, David MP. Reply to Liner [letter]. American Journal of Obstetrics and Gynecology 1984; 148:232.

∗

Indicates the major publication for the study


15

C HA R AC TE RI S TI CS O F S TU DI ES

Characteristics of included studies [ordered by study ID] Bider 1996

Methods

Random generation: computerized. Allocation concealment: not stated.

Participants

37womenwithsingletonvaginaldeliverywithretainedplacenta60minutesafterdelivery of the baby

Interventions

Group 1: UVI of prostaglandin F2α 20 mg + saline solution 20 ml. Group 2: UVI of oxytocin 30 IU 3 ml + solution 20 ml. Group 3: UVI of saline solution 20 ml and then either prostaglandin or oxytocin ’randomly’ after 30 minutes if still undelivered Group 4: manual removal (’Control’).

Outcomes

Manual removal of placenta30 minutes after entry to thetrial, time toplacental delivery, blood loss, fever, abdominal pain, addition of therapeutic uterotonics

Notes

Group 3 and 4 were excluded from analysis.

Risk of bias Bias

Authors’ judgement

Support for judgement

Random sequence generation (selection Low risk bias) Allocation concealment (selection bias)

Unclear risk

Not described.

Blinding (performance bias and detection High risk bias) All outcomes High quality study?

High risk

Calderale 1994

Methods

Random generation: not stated. They said: “Randomization list”. Allocation concealment: not stated. They said: “Randomized double blind”

Participants

42 women with vaginal delivery of a singleton fetus between 34-42 weeks of gestation. Retained placenta was diagnosed when it was still undelivered 30 minutes after delivery of the baby

Interventions

Group 1: UVI of oxytocin 10 IU 1 ml + saline solution 20 ml. Group 2: UVI of placebo + saline solution 20 ml.


16

Calderale 1994

(Continued)

Outcomes

Manual removal of the placenta 30 minutes after UVI, blood loss, time to placental delivery

Notes Risk of bias Bias



Random sequence generation (selection Unclear risk bias)

“Randomized”. No further description.

Allocation concealment (selection bias)

Not described.

Unclear risk

Blinding (performance bias and detection Low risk bias) All outcomes High quality study?

“il doppio cieco” (double blind).

Low risk

Carroli 1998

Methods

Random generation: customized computer program in a ratio of 1/1/1 within balanced blocks of 3-9, stratified by centre. Allocation concealment: sealed treatment packs consecutively numbered. The packs were prepared by the statistician who kept the personnel involved in the recruitment unaware of the pack content. The packs were similar in size, shape, weight, and feel and were sealed with wax after preparation. Contents in both packs were identical: 1 ampoule and a bottle but in the expectant management inside the lid and on the bottles was a label saying: ’do not use! expectant management’; furthermore, to be sure the fluid would not be injected, the bottles contained small black particles in the fluid

Participants

286 women with retained placenta 30 minutes after a vaginal delivery and no uterine scar or signs of hypovolaemic shock

Interventions

Group 1: UVI of oxytocin 20 IU 2 ml + saline solution 18 ml. Group 2: UVI of saline solution 2 ml + saline solution 18 ml. Group 3: expectant management. After the first 64 women recruited the injected volume was increased to 40 ml

Outcomes

Manual removal of placenta 30 minutes after entry to the trial, blood loss after entry to the trial, time to placental delivery, haemoglobin level at 24-48 hours and at 40-45 days after delivery, blood transfusion, curettage, infection and hospital stay

Notes Risk of bias Umbilical vein injection for management of retained placenta (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

17

Carroli 1998

(Continued)

Bias




Low risk

Blinding (performance bias and detection Low risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes

Low risk

Selective reporting (reporting bias)

Low risk

Other bias

Low risk

High quality study?

Low risk

Adequate. Oxytocin vs saline blinded, expectant not blinded.

Frappell 1988

Methods

Random generation: random number table. Allocation concealment: sequentially randomly numbered ampoules prepared by pharmacist who took no further participation in the study

Participants

50 women with singleton vaginal delivery. Retained placenta was diagnosed by vaginal exam if the placenta was not located in the vagina or the cervix 15 minutes after the delivery of the baby

Interventions

Group 1: UVI of oxytocin 10 IU 1 ml + saline solution 20 ml. Group 2: UVI of placebo (saline solution) 1 ml + saline solution 20 ml

Outcomes

Manual removal of the placenta 15 minutes after the UVI, PPH, blood loss





Low risk


Adequate.

18

Frappell 1988

(Continued)


High risk


High risk

High quality study?

Low risk

9 women (18%) post randomization exclusions, ITT not used.

It does have a high exclusion rate, but double-blind nature means bias is unlikely

Gazvani 1998

Methods

Random generation: table of random numbers. Allocation concealment: consecutively numbered opaque sealed e nvelopes

Participants

81 women with placentaundelivered 20 minutes after completion of the second stage of labour and the following criteria: intact umbilical cord, maternal age more than 18 years, gestational age equal or more than 28 weeks, no PPH requiring immediate intervention, no known uterine malformations, no previous caesarean delivery

Interventions

Intraumbilical vein injection was given 30 minutes after delivery of the baby: Group 1: UVI of oxytocin 20 IU 2 ml + saline solution 20 ml. Group 2: UVI of saline solution 20 ml. Group 3: no injection was given.

Outcomes

Manual removal of the placenta, expulsion of the placenta within 45 minutes, PPH, blood transfusion, maternal morbidity





Low risk

Adequate.

Blinding (performance bias and detection High risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes

Low risk


19

Gazvani 1998

(Continued)


Low risk

High quality study?

High risk

Hansen 1987

Methods

Random generation: not stated. Allocation concealment: identical consecutively numbered vials containing oxytocin or saline solution coded by pharmaceutical company that was broken after completion of the trial

Participants

60 women with retained placenta 30 minutes after delivery of the baby. 1 woman with heavy bleeding was not entered

Interventions

Group 1: UVI of oxytocin 10 IU 1 ml + saline solution 20 ml. Group 2: UVI of placebo (saline solution) 1 ml + saline solution 20 ml

Outcomes

Manual removal of placenta 15 min after UVI.

Notes

No response to a letter sent for additional information.

Risk of bias Bias






Adequate.

Low risk

Blinding (performance bias and detection Low risk bias) All outcomes High quality study?

Low risk

Huber 1991

Methods

Random generation: not stated. A ’blocking procedure’ was used to allow balance within small blocks (n = 6). Allocation concealment: identical white sealed boxes in numeric order that bore a serial code, by which randomization occurred in 3 groups. Each box contained an unmarked ampoule. The code was kept by the principal investigator and was broken after completion of the trial

Participants

220 women with a vaginal delivery of a singleton baby of equal or more than 28 weeks’ gestational age and placenta undelivered 30 minutes or more after delivery of the baby


20

Huber 1991

(Continued)

Interventions

Group 1: UVI of oxytocin 10 IU 1 ml + saline solution 20 ml. Group 2: UVI of saline solution 1 ml + saline solution 20 ml. Group 3: expectant management.

Outcomes

Manual removal of placenta after a time based on the clinical judgement of the obstetrician, time interval from injection to spontaneous expulsion of placenta, blood loss

Notes


Risk of bias Bias






Adequate.

Low risk

Blinding (performance bias and detection Low risk bias) All outcomes

Expectant management group not blinded.

Incomplete outcome data (attrition bias) All outcomes

High risk

20 women (9.1%) excluded out of 220,

High quality study?

Low risk

Kristiansen 1987

Methods

Random generation: not stated. Allocation concealment: not stated. The authors said ’randomized’

Participants

51 women with retained placenta for more than 20 minutes after delivery of the baby

Interventions

Group 1: UVI of oxytocin 10 IU 1 ml + saline solution 10 ml. Group 2: UVI of saline solution 10 ml. Group 3: expectant management.

Outcomes

Manual removal of placenta.

Notes


Risk of bias Bias




21

Kristiansen 1987

(Continued)




Unclear.

Unclear risk


Participant blinded, but investigator not blind.

High risk

Makkonen 1995

Methods

Random generation: not stated. Allocation concealment: not stated.

Participants

109 women with retained placenta 30 minutes after delivery of the baby

Interventions

Group 1: UVI of oxytocin 50 IU 5 ml + saline solution 15 ml. Group 2: UVI of plasma expander (Dextran 70) 20 ml.

Outcomes

Manual removal of the placenta 30 minutes after entry to the trial, duration of third stage, blood loss







Unclear.

Unclear risk


Unclear risk


It is not clear whether this is a high-quality study.

22

Rogers 2007

Methods

Random generation: tableof computer-generated random numbers. Allocation concealment: series of randomized treatment packs with a 50 ml syringe of one of the three preparations. They stated misoprostol suspension was not ’clear’ as the other 2 solutions

Participants

54 women with retained placenta 45 min after vaginal delivery of a single fetus of more than 37 weeks of gestation

Interventions

Group 1: UVI of oxytocin 50 IU 5 ml + saline solution 25 ml. Group 2: UVI of prostaglandin E1 analogue (misoprostol) 800 mcg + saline solution 30 ml Group 3: UVI of saline solution 30 ml. All intra-umbilical injections given through an umbilical catheter

Outcomes

Manual removal of the placenta 30 min after trial entry.





Low risk

Adequate.

Blinding (performance bias and detection High risk bias) All outcomes

Investigator not blinded. Participant and outcome assessor blinded

Incomplete outcome data (attrition bias) All outcomes

Low risk

ITT used.


Low risk

High quality study?

High risk

Selinger 1986

Methods

Random generation: not stated. Allocation concealment: randomly numbered ampoules.

Participants

30 women with vaginal delivery, singleton pregnancy and diagnosis of retained placenta by bimanual exam 20 minutes after delivery of the baby. Women shocked or heavily bleeding were excluded

Interventions

Group 1: UVI of oxytocin 10 IU 1 ml + saline solution 19 ml. Group 2: UVI of saline solution 20 ml.


23

Selinger 1986

(Continued)

Outcomes

Manual removal of placenta 15 minutes after injection, duration of third stage of labour, postpartum blood loss

Notes

Response to a letter sent for additional information specified ’fully blinded’

Risk of bias Bias






Adequate.

Low risk


High risk

5 women (17%) excluded, ITT not used.

High quality study?

Low risk

Exclusions made whilst still blinded.

Sivalingam 2001

Methods

Random generation: box with equal number of sealed opaque envelopes. Allocation concealment: sealed opaque envelopes

Participants

35 women with retainedplacenta 20 min after vaginal delivery of single fetus with gestational age equal or higher than 28 weeks.Reasons for exclusionincluded: placenta previa, primary PPH, snapped umbilical cord, emergency caesarean section, h aemodynamically unstable or ill patients, severe anaemia, chorioamnionitis

Interventions


Outcomes

Manual removal of placenta after 30 min of UVI, addition of therapeutic uterotonics, blood transfusion, blood loss, curettage



Random sequence generation (selection Unclear risk bias) Umbilical vein injection for management of retained placenta (Review) Copyright © 2012 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.


Box of equal number of envelopes.

24

Sivalingam 2001

(Continued)


Low risk

Adequate.


Low risk

High quality study?

Low risk

Thiery 1987

Methods

Random generation: not stated. Allocation concealment: sealed numbered envelopes.

Participants

32 women with diagnosis of retained placenta 15 minutes after delivery of the baby

Interventions

Group 1: UVI of oxytocin 10 IU 1 ml + saline solution 20 ml. Group 2: expectant management.

Outcomes

Manual removal of placenta 15 minutes after entry to the trial

Notes

Unpublished data only.

Risk of bias Bias






Sealed numbered envelopes.

Unclear risk

Blinding (performance bias and detection High risk bias) All outcomes Incomplete outcome data (attrition bias) All outcomes

Low risk


Low risk

High quality study?

High risk


ITT used.

25

Weeks 2009

Methods

Random generation: computer randomization in a ratio of 1/1 within randomly sized blocks of between 2 and 6. Allocation concealment: sealed treatment packs consecutively numbered. The packs were prepared by a commercial company who were uninvolved with the remainder of the study. The packs were similar in size, shape, weight, and feel and were sealed after preparation. The contents of both packs were identical with 5, 1 ml ampoules labelled with the study name and recruit number. Each pack also contained an extra emergency ampoule hidden in a side compartment for use only in case of breakages

Participants

577 women with retained placenta 30 min after a vaginal delivery of a single fetus of more than 34 weeks of gestation or more than 2 kg birthweight. Exclusion criteria: heavy bleeding, evidence of shock (pulse > 100 or systolic BP < 100 mmHg), stillbirth

Interventions

Group 1 : UVI o f oxytocin 5 0 IU ( 5 ml) + saline s olution 25 m l. Group 2 : UVI o f placebo (5 ml sterile water) + saline solution 25 ml

Outcomes

Manual removal of placenta, blood loss, blood transfusion, haemoglobin fall, time to placental delivery, maternal mortality, maternal morbidity, curettage, use of antibiotics

Notes

Unpublished data only.

Risk of bias Bias




Low risk

Adequate.


Low risk


Low risk

Other bias

Low risk

High quality study?

Low risk


26

Wilken-Jensen 1989

Methods

Random generation: not stated. Allocation concealment: similar ampoules supplied by pharmaceutical company

Participants

40 women with diagnosis of retained placenta 20 minutes after deliveryof thebaby vaginally after by intermittent traction on the umbilical cord and light suprapubic pressure

Interventions


Outcomes

Manual removal of placenta 40 min after trial entry, time from injection to delivery of the placenta, postpartum blood loss

Notes


Risk of bias Bias




Not described.


Unclear risk

Not described.

High quality study?

Unclear risk

It is not clear whether this is a high-quality study.

ITT: intention to treat min: minutes PPH: postpartum haemorrhage IU: international unit UVI: umbilical vein injection vs: versus Characteristics of excluded studies [ordered by study ID]

Study

Reason for exclusion

Das 2008

Comparison of 2 different method of injection of the same solution. Also inadequate data and unclear if randomized

Habek 2001

Non-randomized prospective study.


27

Characteristics of studies awaiting assessment [ordered by study ID] Chauhan 2004

Methods

Randomized.

Participants

60 patients with retained placenta 30 minutes after vaginal delivery

Interventions

Group 1: UVI of oxytocin 100 IU 10 ml + saline solution 20 ml. Group 2: UVI of saline solution 30 ml. Group 3: no active treatment was given during 30 minutes.

Outcomes

Time from injection to placental delivery, blood loss.

Notes

Only abstract found. Data presented as percentages with results favourable to oxytocin group. Raw data are not available for extraction

IU: international unit UVI: umbilical vein injection


28

D A T A A N D A N A L Y SE S

Comparison 1. Saline solution versus expectant management

Outcome or subgroup title

No. of No. of studies participants

Statistical method

Effect size

1 Manual removal of the placenta 2 Blood loss

4 1

403 122

Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

3 Blood loss = or > 500 ml after entry 4 Blood loss = or > 1000 ml after entry 5 Blood transfusion 6 Haemoglobin 24-48 hours postpartum 7 Haemoglobin 40-45 days postpartum 8 Maternal mortality 9 Serious maternal morbidity 10 Surgical evacuation of retained products of conception 11 Infection 12 Stay at hospital more than two days

2

177

Risk Ratio (M-H, Fixed, 95% CI)

0.99 [0.84, 1.16] -44.0 [-168.51, 80. 51] 0.98 [0.52, 1.82]

1

122


0.73 [0.17, 3.11]

2 1

235 163


0.76 [0.41, 1.39] 0.10 [-0.59, 0.79]

1

93

Mean Difference (IV, Fixed, 95% CI)

0.40 [-0.23, 1.03]

2 2 1

87 87 178

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.79 [0.51, 1.22]

1 1

176 176

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.48 [0.09, 2.54] 1.19 [0.66, 2.15]

Comparison 2. Oxytocin solution versus expectant management



Statistical method

Effect size

1 Manual removal of the placenta 2 Blood loss

5 1

444 130


3 Blood loss = or > 500 ml after entry 4 Blood loss = or > 1000 ml after entry 5 Blood transfusion 6 Haemoglobin 24-48 hours postpartum 7 Haemoglobin 40-45 days postpartum 8 Maternal mortality 9 Serious maternal morbidity

2

185


0.87 [0.74, 1.03] 89.0 [-51.35, 229. 35] 1.51 [0.87, 2.60]

1

130


1.29 [0.38, 4.34]

2 1

237 166


0.89 [0.50, 1.58] 0.0 [-0.61, 0.61]

1

96


0.5 [-0.14, 1.14]

2 2

93 90


0.0 [0.0, 0.0] 0.0 [0.0, 0.0]


29

10 Surgical evacuation of retained products of conception 11 Infection 12 Stay at hospital more than two days

1

182


0.69 [0.44, 1.09]

1 1

179 180


1.16 [0.32, 4.16] 1.09 [0.60, 1.97]

Comparison 3. Oxytocin solution versus saline solution



Statistical method

Effect size

1 Manual removal of the placenta - by study quality 1.1 High-quality studies 1.2 Low-quality studies 2 Manual removal of the placenta - by oxytocin dose 2.1 High dose (> 30 IU) 2.2 Low dose (< 30 IU) 3 Additional therapeutic uterotonics 4 Blood loss

12

1276


0.91 [0.82, 1.00]

8 4 12

1119 157 1276


0.92 [0.83, 1.01] 0.84 [0.64, 1.10] 0.91 [0.82, 1.00]

4 8 4

682 594 678


0.97 [0.86, 1.09] 0.83 [0.71, 0.96] 0.85 [0.59, 1.23]

3

180


5 Blood loss = or > 500 ml after entry 6 Blood loss = or > 1000 ml after entry 7 Blood transfusion 8 Haemoglobin 24-48 hours postpartum 9 Haemoglobin 40-45 days postpartum 10 Haemoglobin levels fall 11 Maternal mortality 12 Serious maternal morbidity 13 Surgical evacuation of retained products of conception 14 Nausea following injection 15 Infection 16 Fever 17 Abdominal pain 18 Stay at hospital more than two days 19 Length of third stage of labour

5

829


48.84 [-13.16, 110. 84] 1.01 [0.83, 1.24]

4

766


1.08 [0.70, 1.68]

5 1

880 167


1.18 [0.84, 1.65] -0.10 [-0.76, 0.56]

1

91


0.10 [-0.58, 0.78]

1 4 4 4

541 724 724 826

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

1.01 [0.90, 1.14] 2.93 [0.12, 71.59] 0.33 [0.01, 7.95] 0.89 [0.56, 1.40]

1 3 2 1 1

60 820 78 18 184

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI)

0.0 [0.0, 0.0] 1.35 [0.87, 2.09] 2.0 [0.09, 43.22] 2.0 [0.09, 43.22] 0.91 [0.52, 1.59]

1

30


20 Headache following injection 21 Shivering following injection 22 Hypertension following injection

1 1 1

60 60 60


16.20 [-15.22, 47. 62] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0] 0.0 [0.0, 0.0]


30

Comparison 4. Oxytocin solution versus plasma expander


1 Manual removal of the placenta 2 Blood loss > 1000 ml


1 1

109 109

Statistical method


Effect size

1.34 [0.97, 1.85] 0.96 [0.34, 2.75]

Comparison 5. Prostaglandin solution versus saline solution



Statistical method

Effect size

1 Manual removal of the placenta 2 Additional therapeutic uterotonics 3 Blood loss

2 1

51 17


0.42 [0.22, 0.82] 1.05 [0.46, 2.38]

1

17


4 Abdominal pain 5 Fever

1 1

17 17


-21.0 [-120.18, 78. 18] 5.09 [0.30, 85.39] 2.18 [0.10, 46.92]

Comparison 6. Prostaglandin solution versus oxytocin solution



Statistical method

Effect size

1 Manual removal of the placenta 2 Additional therapeutic uterotonics 3 Blood loss

2 1

62 21


0.43 [0.25, 0.75] 1.32 [0.58, 3.00]

1

21


4 Fever 5 Abdominal pain 6 Time from injection to placental delivery

1 1 1

21 21 21

Risk Ratio (M-H, Fixed, 95% CI) Risk Ratio (M-H, Fixed, 95% CI) Mean Difference (IV, Fixed, 95% CI)

-19.0 [-118.19, 80. 19] 1.1 [0.08, 15.36] 3.3 [0.41, 26.81] -6.0 [-8.78, -3.22]


31

Analysis 1.1. Comparison 1 Saline solution versus expectant management, Outcome 1 Manual removal of the placenta. Review:


Comparison:

1 Saline solution versus expectant management

Outcome: 1 Manual removal of the placenta

Study or subgroup

Experimental

Control

n/N

n/N

Carroli 1998

60/95

59/93

52.4 %

1.00 [ 0.80, 1.24 ]

Gazvani 1998

22/26

26/29

21.6 %

0.94 [ 0.77, 1.16 ]

Huber 1991

25/69

19/59

18.0 %

1.13 [ 0.69, 1.83 ]

7/16

9/16

7.9 %

0.78 [ 0.38, 1.57 ]

206

197

100.0 %

0.99 [ 0.84, 1.16 ]

Kristiansen 1987

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI

Risk Ratio M-H,Fixed,95% CI

Total events: 114 (Experimental), 113 (Control) Heterogeneity: Chi2 = 0.93, df = 3 (P = 0.82); I 2 =0.0% Test for overall effect: Z = 0.12 (P = 0.91) Test for subgroup differences: Not applicable

0.5

0.7

1

1.5

Favours treatment

2

Favours control

Analysis 1.2. Comparison 1 Saline solution versus expectant management, Outcome 2 Blood loss. Review:


Comparison:


Outcome: 2 Blood loss

Study or subgroup

E xperimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Carroli 1998

62

394 (305)

60

438 (390)

Total (95% CI)

62

Weight

IV,Fixed,95% CI

Mean Difference IV,Fixed,95% CI

100.0 %

60

-44.00 [ -168.51, 80.51 ]

100.0 % -44.00 [ -168.51, 80.51 ]

Heterogeneity: not applicable Test for overall effect: Z = 0.69 (P = 0.49) Test for subgroup differences: Not applicable

-100

-50

0

Favours experimental


50

100

Favours control

32

Analysis 1.3. Comparison 1 Saline solution versus expectant management, Outcome 3 Blood loss = or > 500 ml after entry. Review:


Comparison:


Outcome: 3 Blood loss = or > 500 ml after entry

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Weight

Carroli 1998

15/62

14/60

90.9 %

1.04 [ 0.55, 1.96 ]

Gazvani 1998

0/26

1/29

9.1 %

0.37 [ 0.02, 8.71 ]

Total (95% CI)

88

89

100.0 %

0.98 [ 0.52, 1.82 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 1.4. Comparison 1 Saline solution versus expectant management, Outcome 4 Blood loss = or > 1000 ml after entry. Review:


Comparison:


Outcome: 4 Blood loss = or > 1000 ml after entry

Study or subgroup

Experimental

Control

Risk Ratio

Weight

n/N

n/N

Carroli 1998

3/62

4/60

100.0 %

0.73 [ 0.17, 3.11 ]

Total (95% CI)

62

60

100.0 %

0.73 [ 0.17, 3.11 ]

M-H,Fixed,95% CI


Total events: 3 (Experimental), 4 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.43 (P = 0.67) Test for subgroup differences: Not applicable

0.1 0.2

0.5

favours treatment

1

2

5

10

Favours control


33

Analysis 1.5. Comparison 1 Saline solution versus expectant management, Outcome 5 Blood transfusion. Review:


Comparison:


Outcome: 5 Blood transfusion

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Risk Ratio

Carroli 1998

15/92

19/88

0.76 [ 0.41, 1.39 ]

Gazvani 1998

0/26

0/29

0.0 [ 0.0, 0.0 ]

Total (95% CI)

118

117

0.76 [ 0.41, 1.39 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

Analysis 1.6. Comparison 1 Saline solution versus expectant management, Outcome 6 Haemoglobin 24-48 hours postpartum. Review:


Comparison:


Outcome: 6 Haemoglobin 24-48 hours postpartum

Study or subgroup

Experimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Carroli 1998

82

9.8 (2.4)

81

9.7 (2.1)

Total (95% CI)

82

Weight

IV,Fixed,95% CI


81

100.0 %

0.10 [ -0.59, 0.79 ]

100.0 %

0.10 [ -0.59, 0.79 ]


-10

-5

Favours treatment


0

5

10

Favours control

34

Analysis 1.7. Comparison 1 Saline solution versus expectant management, Outcome 7 Haemoglobin 40-45 days postpartum. Review:


Comparison:


Outcome: 7 Haemoglobin 40-45 days postpartum

Study or subgroup

Experimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Carroli 1998

44

10.8 (1.6)

49

10.4 (1.5)

Total (95% CI)

44

Weight

IV,Fixed,95% CI


49

100.0 %

0.40 [ -0.23, 1.03 ]

100.0 %

0.40 [ -0.23, 1.03 ]


-10

-5

0

Favours treatment

5

10

Favours control

Analysis 1.8. Comparison 1 Saline solution versus expectant management, Outcome 8 Maternal mortality. Review:


Comparison:


Outcome: 8 Maternal mortality

Study or subgroup

Experimental

Control

n/N

n/N

Gazvani 1998

0/26

0/29

0.0 [ 0.0, 0.0 ]

Kristiansen 1987

0/16

0/16

0.0 [ 0.0, 0.0 ]

42

45

0.0 [ 0.0, 0.0 ]

Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI

Total events: 0 (Experimental), 0 (Control) Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I 2 =0.0% Test for overall effect: Z = 0.0 (P < 0.00001) Test for subgroup differences: Not applicable

0.01

0.1



1

10

100

Favours control

35

Analysis 1.9. Comparison 1 Saline solution versus expectant management, Outcome 9 Serious maternal morbidity. Review:


Comparison:


Outcome: 9 Serious maternal morbidity

Study or subgroup

Experimental

Control

n/N

n/N

Gazvani 1998

0/26

0/29

0.0 [ 0.0, 0.0 ]

Kristiansen 1987

0/16

0/16

0.0 [ 0.0, 0.0 ]

42

45

0.0 [ 0.0, 0.0 ]

Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.01

0.1


1

10

100

Favours control

Analysis 1.10. Comparison 1 Saline solution versus expectant management, Outcome 10 Surgical evacuation of retained products of conception. Review:


Comparison:


Outcome: 10 Surgical evacuation of retained products of conception

Study or subgroup

Carroli 1998

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

25/90

31/88

100.0 %

0.79 [ 0.51, 1.22 ]

90

88

100.0 %

0.79 [ 0.51, 1.22 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


36

Analysis 1.11. Comparison 1 Saline solution versus expectant management, Outcome 11 Infection. Review:


Comparison:


Outcome: 11 Infection

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Weight

Carroli 1998

2/90

4/86

100.0 %

0.48 [ 0.09, 2.54 ]

Total (95% CI)

90

86

100.0 %

0.48 [ 0.09, 2.54 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 1.12. Comparison 1 Saline solution versus expectant management, Outcome 12 Stay at hospital more than two days. Review:


Comparison:


Outcome: 12 Stay at hospital more than two days

Study or subgroup

Carroli 1998

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

20/90

16/86

100.0 %

1.19 [ 0.66, 2.15 ]

90

86

100.0 %

1.19 [ 0.66, 2.15 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

favours control


37

Analysis 2.1. Comparison 2 Oxytocin solution versus expectant management, Outcome 1 Manual removal of the placenta. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 1 Manual removal of the placenta

Study or subgroup

Experimental

Control

n/N

n/N

Carroli 1998

57/98

59/93

47.4 %

0.92 [ 0.73, 1.15 ]

Gazvani 1998

14/26

26/29

19.3 %

0.60 [ 0.41, 0.88 ]

Huber 1991

27/72

19/59

16.4 %

1.16 [ 0.72, 1.87 ]

Kristiansen 1987

10/19

9/16

7.7 %

0.94 [ 0.51, 1.72 ]

9/19

10/13

9.3 %

0.62 [ 0.35, 1.08 ]

234

210

100.0 %

0.87 [ 0.74, 1.03 ]

Thiery 1987

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI


Total events: 117 (Experimental), 123 (Control) Heterogeneity: Chi2 = 6.88, df = 4 (P = 0.14); I 2 =42% Test for overall effect: Z = 1.62 (P = 0.10) Test for subgroup differences: Not applicable

0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

Analysis 2.2. Comparison 2 Oxytocin solution versus expectant management, Outcome 2 Blood loss. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 2 Blood loss

Study or subgroup

Experimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Carroli 1998

70

527 (426)

60

438 (390)

Total (95% CI)

70

Weight

IV,Fixed,95% CI


60

100.0 %

89.00 [ -51.35, 229.35 ]

100.0 %

89.00 [ -51.35, 229.35 ]


-100

-50



0

50

100

Favours control

38

Analysis 2.3. Comparison 2 Oxytocin solution versus expectant management, Outcome 3 Blood loss = or > 500 ml after entry. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 3 Blood loss = or > 500 ml after entry

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Weight

Carroli 1998

25/70

14/60

94.1 %

1.53 [ 0.88, 2.67 ]

Gazvani 1998

1/26

1/29

5.9 %

1.12 [ 0.07, 16.95 ]

Total (95% CI)

96

89

100.0 %

1.51 [ 0.87, 2.60 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 2.4. Comparison 2 Oxytocin solution versus expectant management, Outcome 4 Blood loss = or > 1000 ml after entry. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 4 Blood loss = or > 1000 ml after entry

Study or subgroup

Experimental

Control

Risk Ratio

Weight

n/N

n/N

Carroli 1998

6/70

4/60

100.0 %

1.29 [ 0.38, 4.34 ]

Total (95% CI)

70

60

100.0 %

1.29 [ 0.38, 4.34 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


39

Analysis 2.5. Comparison 2 Oxytocin solution versus expectant management, Outcome 5 Blood transfusion. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 5 Blood transfusion

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Risk Ratio

Carroli 1998

18/94

19/88

0.89 [ 0.50, 1.58 ]

Gazvani 1998

0/26

0/29

0.0 [ 0.0, 0.0 ]

Total (95% CI)

120

117

0.89 [ 0.50, 1.58 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

Analysis 2.6. Comparison 2 Oxytocin solution versus expectant management, Outcome 6 Haemoglobin 2448 hours postpartum. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 6 Haemoglobin 24-48 hours postpartum

Study or subgroup

Experimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Carroli 1998

85

9.7 (1.9)

81

9.7 (2.1)

Total (95% CI)

85

Weight

IV,Fixed,95% CI


81

100.0 %

0.0 [ -0.61, 0.61 ]

100.0 %

0.0 [ -0.61, 0.61 ]


-10

-5

Favours treatment


0

5

10

Favours control

40

Analysis 2.7. Comparison 2 Oxytocin solution versus expectant management, Outcome 7 Haemoglobin 4045 days postpartum. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 7 Haemoglobin 40-45 days postpartum

Study or subgroup

Experimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Carroli 1998

47

10.9 (1.7)

49

10.4 (1.5)

Total (95% CI)

47

Weight

IV,Fixed,95% CI


49

100.0 %

0.50 [ -0.14, 1.14 ]

100.0 %

0.50 [ -0.14, 1.14 ]


-10

-5

0

Favours treatment

5

10

Favours control

Analysis 2.8. Comparison 2 Oxytocin solution versus expectant management, Outcome 8 Maternal mortality. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 8 Maternal mortality

Study or subgroup

Experimental

Control

n/N

n/N

Gazvani 1998

0/26

0/29

0.0 [ 0.0, 0.0 ]

Kristiansen 1987

0/19

0/19

0.0 [ 0.0, 0.0 ]

45

48

0.0 [ 0.0, 0.0 ]

Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.01

0.1



1

10

100

Favours control

41

Analysis 2.9. Comparison 2 Oxytocin solution versus expectant management, Outcome 9 Serious maternal morbidity. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 9 Serious maternal morbidity

Study or subgroup

Experimental

Control

n/N

n/N

Gazvani 1998

0/26

0/29

0.0 [ 0.0, 0.0 ]

Kristiansen 1987

0/19

0/16

0.0 [ 0.0, 0.0 ]

45

45

0.0 [ 0.0, 0.0 ]

Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.01

0.1


1

10

100

Favours control

Analysis 2.10. Comparison 2 Oxytocin solution versus expectant management, Outcome 10 Surgical evacuation of retained products of conception. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 10 Surgical evacuation of retained products of conception

Study or subgroup

Carroli 1998

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

23/94

31/88

100.0 %

0.69 [ 0.44, 1.09 ]

94

88

100.0 %

0.69 [ 0.44, 1.09 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


42

Analysis 2.11. Comparison 2 Oxytocin solution versus expectant management, Outcome 11 Infection. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 11 Infection

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Weight

Carroli 1998

5/93

4/86

100.0 %

1.16 [ 0.32, 4.16 ]

Total (95% CI)

93

86

100.0 %

1.16 [ 0.32, 4.16 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 2.12. Comparison 2 Oxytocin solution versus expectant management, Outcome 12 Stay at hospital more than two days. Review:


Comparison: 2 Oxytocin solution versus expectant management Outcome: 12 Stay at hospital more than two days

Study or subgroup

Carroli 1998

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

19/94

16/86

100.0 %

1.09 [ 0.60, 1.97 ]

94

86

100.0 %

1.09 [ 0.60, 1.97 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


43

Analysis 3.1. Comparison 3 Oxytocin solution versus saline solution, Outcome 1 Manual removal of the placenta - by study quality. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 1 Manual removal of the placenta - by study quality

Study or subgroup

Umbilical oxytocin

Saline

n/N

n/N

Risk Ratio

Weight

1/22

9/20

2.5 %

0.10 [ 0.01, 0.73 ]

Carroli 1998

57/98

60/95

16.0 %

0.92 [ 0.73, 1.16 ]

Frappell 1988

14/22

15/19

4.2 %

0.81 [ 0.54, 1.19 ]

Hansen 1987

14/32

20/28

5.6 %

0.61 [ 0.39, 0.97 ]

Huber 1991

27/72

25/69

6.7 %

1.04 [ 0.67, 1.59 ]

Selinger 1986

9/15

8/15

2.1 %

1.13 [ 0.60, 2.11 ]

Sivalingam 2001

9/19

10/16

2.9 %

0.76 [ 0.41, 1.39 ]

179/292

177/285

47.1 %

0.99 [ 0.87, 1.12 ]

572

547

87.2 %

0.92 [ 0.83, 1.01 ]

M-H,Fixed,95% CI


1 High-quality studies Calderale 1994

Weeks 2009

Subtotal (95% CI)

Total events: 310 (Umbilical oxytocin), 324 (Saline) Heterogeneity: Chi2 = 10.56, df = 7 (P = 0.16); I 2 =34% Test for overall effect: Z = 1.71 (P = 0.088) 2 Low-quality studies Gazvani 1998

14/26

22/26

5.8 %

0.64 [ 0.43, 0.94 ]

Kristiansen 1987

10/19

7/16

2.0 %

1.20 [ 0.60, 2.42 ]

Rogers 2007

16/20

7/13

2.2 %

1.49 [ 0.86, 2.57 ]

Wilken-Jensen 1989

5/18

11/19

2.8 %

0.48 [ 0.21, 1.11 ]

Subtotal (95% CI)

83

74

12.8 %

0.84 [ 0.64, 1.10 ]

621

100.0 %

0.91 [ 0.82, 1.00 ]

Total events: 45 (Umbilical oxytocin), 47 (Saline) Heterogeneity: Chi2 = 8.80, df = 3 (P = 0.03); I 2 =66% Test for overall effect: Z = 1.25 (P = 0.21)

Total (95% CI)

655

Total events: 355 (Umbilical oxytocin), 371 (Saline) Heterogeneity: Chi2 = 19.85, df = 11 (P = 0.05); I 2 =45% Test for overall effect: Z = 2.05 (P = 0.041) Test for subgroup differences: Chi2 = 0.35, df = 1 (P = 0.55), I 2 =0.0%

0.5

0.7

1

Favours treatment


1.5

2

Favours control

44

Analysis 3.2. Comparison 3 Oxytocin solution versus saline solution, Outcome 2 Manual removal of the placenta - by oxytocin dose. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 2 Manual removal of the placenta - by oxytocin dose

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Weight

16/20

7/13

2.2 %

1.49 [ 0.86, 2.57 ]

9/19

10/16

2.9 %

0.76 [ 0.41, 1.39 ]

179/292

177/285

47.1 %

0.99 [ 0.87, 1.12 ]

Wilken-Jensen 1989

5/18

11/19

2.8 %

0.48 [ 0.21, 1.11 ]

Subtotal (95% CI)

349

333

55.0 %

0.97 [ 0.86, 1.09 ]

1/22

9/20

2.5 %

0.10 [ 0.01, 0.73 ]

Carroli 1998

57/98

60/95

16.0 %

0.92 [ 0.73, 1.16 ]

Frappell 1988

14/22

15/19

4.2 %

0.81 [ 0.54, 1.19 ]

Gazvani 1998

14/26

22/26

5.8 %

0.64 [ 0.43, 0.94 ]

Hansen 1987

14/32

20/28

5.6 %

0.61 [ 0.39, 0.97 ]

Huber 1991

27/72

25/69

6.7 %

1.04 [ 0.67, 1.59 ]

Kristiansen 1987

10/19

7/16

2.0 %

1.20 [ 0.60, 2.42 ]

9/15

8/15

2.1 %

1.13 [ 0.60, 2.11 ]

306

288

45.0 %

0.83 [ 0.71, 0.96 ]

621

100.0 %

0.91 [ 0.82, 1.00 ]

M-H,Fixed,95% CI


1 High dose (> 30 IU) Rogers 2007 Sivalingam 2001 Weeks 2009

Total events: 209 (Experimental), 205 (Control) Heterogeneity: Chi2 = 5.74, df = 3 (P = 0.13); I 2 =48% Test for overall effect: Z = 0.50 (P = 0.62) 2 Low dose (< 30 IU) Calderale 1994

Selinger 1986

Subtotal (95% CI)

Total events: 146 (Experimental), 166 (Control) Heterogeneity: Chi2 = 11.64, df = 7 (P = 0.11); I 2 =40% Test for overall effect: Z = 2.47 (P = 0.014)

Total (95% CI)

655

Total events: 355 (Experimental), 371 (Control) Heterogeneity: Chi2 = 19.85, df = 11 (P = 0.05); I 2 =45% Test for overall effect: Z = 2.05 (P = 0.041) Test for subgroup differences: Chi2 = 2.55, df = 1 (P = 0.11), I 2 =61%

0.01

0.1


1

10

100

Favours control


45

Analysis 3.3. Comparison 3 Oxytocin solution versus saline solution, Outcome 3 Additional therapeutic uterotonics. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 3 Additional therapeutic uterotonics

Study or subgroup

Experimental

Control

n/N

n/N

Bider 1996

5/11

4/7

10.0 %

0.80 [ 0.32, 1.98 ]

Hansen 1987

0/32

6/28

14.2 %

0.07 [ 0.00, 1.15 ]

Sivalingam 2001

7/19

10/16

22.2 %

0.59 [ 0.29, 1.19 ]

31/284

26/281

53.6 %

1.18 [ 0.72, 1.93 ]

346

332

100.0 %

0.85 [ 0.59, 1.23 ]

Weeks 2009

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

1

2

Favours treatment

5

10

Favours control

Analysis 3.4. Comparison 3 Oxytocin solution versus saline solution, Outcome 4 Blood loss. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 4 Blood loss

Study or subgroup

Experimental

Mean Difference

Control

Weight

IV,Fixed,95% CI

Mean Difference

N

Mean(SD)

N

Mean(SD)

IV,Fixed,95% CI

Bider 1996

11

229 (102.8)

7

231 (82)

52.1 %

-2.00 [ -87.91, 83.91 ]

Carroli 1998

70

527 (426)

62

394 (305)

24.4 %

133.00 [ 7.61, 258.39 ]

Selinger 1986

15

360 (221)

15

286 (123)

23.5 %

74.00 [ -53.99, 201.99 ]

Total (95% CI)

96

100.0 %

48.84 [ -13.16, 110.84 ]

84

Heterogeneity: Chi2 = 3.22, df = 2 (P = 0.20); I 2 =38% Test for overall effect: Z = 1.54 (P = 0.12) Test for subgroup differences: Not applicable

-10

-5

Favours treatment


0

5

10

Favours control

46

Analysis 3.5. Comparison 3 Oxytocin solution versus saline solution, Outcome 5 Blood loss = or > 500 ml after entry. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 5 Blood loss = or > 500 ml after entry

Study or subgroup

Experimental

Control

n/N

n/N

Carroli 1998

25/70

15/62

12.5 %

1.48 [ 0.86, 2.54 ]

Frappell 1988

4/22

5/19

4.2 %

0.69 [ 0.22, 2.21 ]

Gazvani 1998

1/26

0/26

0.4 %

3.00 [ 0.13, 70.42 ]

Sivalingam 2001

2/19

5/16

4.3 %

0.34 [ 0.08, 1.51 ]

99/287

99/282

78.6 %

0.98 [ 0.78, 1.23 ]

424

405

100.0 %

1.01 [ 0.83, 1.24 ]

Weeks 2009

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


47

Analysis 3.6. Comparison 3 Oxytocin solution versus saline solution, Outcome 6 Blood loss = or > 1000 ml after entry. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 6 Blood loss = or > 1000 ml after entry

Study or subgroup

Experimental

Control

n/N

n/N

Carroli 1998

6/70

3/62

9.2 %

1.77 [ 0.46, 6.79 ]

Selinger 1986

0/15

1/15

4.3 %

0.33 [ 0.01, 7.58 ]

Sivalingam 2001

0/19

1/16

4.7 %

0.28 [ 0.01, 6.51 ]

31/287

28/282

81.8 %

1.09 [ 0.67, 1.76 ]

391

375

100.0 %

1.08 [ 0.70, 1.68 ]

Weeks 2009

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


48

Analysis 3.7. Comparison 3 Oxytocin solution versus saline solution, Outcome 7 Blood transfusion. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 7 Blood transfusion

Study or subgroup

Experimental

Control

n/N

n/N

Carroli 1998

18/94

15/92

1.17 [ 0.63, 2.19 ]

Gazvani 1998

0/26

0/26

0.0 [ 0.0, 0.0 ]

Selinger 1986

1/15

0/15

3.00 [ 0.13, 68.26 ]

Sivalingam 2001

1/19

1/16

0.84 [ 0.06, 12.42 ]

43/292

36/285

1.17 [ 0.77, 1.76 ]

446

434

1.18 [ 0.84, 1.65 ]

Weeks 2009

Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 3.8. Comparison 3 Oxytocin solution versus saline solution, Outcome 8 Haemoglobin 24-48 hours postpartum. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 8 Haemoglobin 24-48 hours postpartum

Study or subgroup

Experimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Carroli 1998

85

9.7 (1.9)

82

9.8 (2.4)

Total (95% CI)

85

Weight

IV,Fixed,95% CI


82

100.0 %

-0.10 [ -0.76, 0.56 ]

100.0 %

-0.10 [ -0.76, 0.56 ]


-10

-5

Favours treatment


0

5

10

Favours control

49

Analysis 3.9. Comparison 3 Oxytocin solution versus saline solution, Outcome 9 Haemoglobin 40-45 days postpartum. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 9 Haemoglobin 40-45 days postpartum

Study or subgroup

Experimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Carroli 1998

47

10.9 (1.7)

44

10.8 (1.6)

Total (95% CI)

47

Weight

IV,Fixed,95% CI


44

100.0 %

0.10 [ -0.58, 0.78 ]

100.0 %

0.10 [ -0.58, 0.78 ]


-10

-5

0

Favours treatment

5

10

Favours control

Analysis 3.10. Comparison 3 Oxytocin solution versus saline solution, Outcome 10 Haemoglobin levels fall. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 10 Haemoglobin levels fall

Study or subgroup

Weeks 2009

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

185/274

178/267

100.0 %

1.01 [ 0.90, 1.14 ]

274

267

100.0 %

1.01 [ 0.90, 1.14 ]

M-H,Fixed,95% CI



0.01

0.1


1

10

100

Favours control


50

Analysis 3.11. 3.11. Comparison 3 Oxytocin Oxytocin solution versus versus saline solution, Outcome 11 Maternal mortality. mortality. Review: Umbilical vein vein injection for for management management of retained retained placenta Comparison: Comparison: 3 Oxytocin Oxytocin solution versus versus saline saline solution solution Outcome: Outcome: 11 Materna Maternall mortality mortality

Study or subgroup

Experimental

Control

n/N

n/N

Gazvani 1998

0/26

0/26

0.0 [ 0.0, 0.0 ]

Hansen 1987

0/32

0/28

0.0 [ 0.0, 0.0 ]

Kristiansen 1987

0/19

0/16

0.0 [ 0.0, 0.0 ]

1/292

0/285

2.93 [ 0.12, 71.59 ]

369

355

2.93 [ 0.12, 71.59 ]

Weeks Weeks 2009

Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.01

0.1

1

10

Favou Favours rs experi experimen mental tal

100

Favo Favours urs contro controll

Analysis 3.12. 3.12. Comparison 3 Oxytocin Oxytocin solution solution versus saline solution, Outcome Outcome 12 Serious Serious maternal morbidity. Review: Umbilical vein vein injection for for management management of retained placenta Comparison: Comparison: 3 Oxytocin Oxytocin solution versus versus saline saline solution solution Outcome: Outcome: 12 Serious Serious maternal maternal morbidi morbidity ty

Study or subgroup

Experimental

Control

n/N

n/N

Gazvani 1998

0/26

0/26

0.0 [ 0.0, 0.0 ]

Hansen 1987

0/32

0/28

0.0 [ 0.0, 0.0 ]

Kristiansen 1987

0/19

0/16

0.0 [ 0.0, 0.0 ]

0/292

1/285

0.33 [ 0.01, 7.95 ]

369

355

0.33 [ 0.01, 7.95 ]

Weeks Weeks 2009

Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.01

0.1

Favo Favours urs experim experiment ental al


1

10

100

Favou Favours rs contro controll

51

Analysis 3.13. 3.13. Comparison 3 Oxytocin Oxytocin solution versus saline saline solution, Outcome 13 Surgical evacuation evacuation of retained products of conception. Review: Umbilical vein vein injection for for management management of retained placenta Comparison: Comparison: 3 Oxytocin Oxytocin solution versus versus saline saline solution solution Outcome: Outcome: 13 Surgical Surgical evacuation evacuation of retained retained products of conception conception

Study or subgroup

Experimental

Control

n/N

n/N

Carroli 1998

23/94

25/90

84.5 %

0.88 [ 0.54, 1.43 ]

Selinger 1986

1/15

0/15

1.7 %

3.00 [ 0.13, 68.26 ]

Sivalingam 2001

1/19

2/16

7.2 %

0.42 [ 0.04, 4.23 ]

2/292

2/285

6.7 %

0.98 [ 0.14, 6.88 ]

420

406

100.0 %

0.89 [ 0.56, 1.40 ]

Weeks Weeks 2009

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours Favours treatment treatment

1

2

5

10

Favours Favours control control


52

Analysis 3.14. 3.14. Comparison 3 Oxytocin Oxytocin solution versus saline saline solution, Outcome 14 Nausea following following injection. Review: Umbilical vein vein injection for for management management of retained placenta Comparison: Comparison: 3 Oxytocin Oxytocin solution versus versus saline saline solution solution Outcome: Outcome: 14 Nausea Nausea following following injectio injection n

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Risk Ratio

Hansen 1987

0/32

0/28

0.0 [ 0.0, 0.0 ]

Total (95% CI)

32

28

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI

Total events: 0 (Experimental), 0 (Control) Heterogeneity: not applicable Test for overall effect: Z = 0.0 (P < 0.00001) Test for subgroup differences: Not applicable

0.01

0.1

1

10

Favo Favours urs experim experiment ental al

100

Favo Favours urs contro controll

Analysis 3.15. 3.15. Comparison 3 Oxytocin solution solution versus saline saline solution, Outcome Outcome 15 Infection. Infection. Review: Umbilical vein vein injection for for management management of retained retained placenta Comparison: Comparison: 3 Oxytocin Oxytocin solution versus versus saline saline solution solution Outcome: Outcome: 15 Infection Infection

Study or subgroup

Experimental

Control

n/N

n/N

Carroli 1998

5/93

2/90

2.42 [ 0.48, 12.15 ]

Hansen 1987

0/32

0/28

0.0 [ 0.0, 0.0 ]

38/292

29/285

1.28 [ 0.81, 2.02 ]

417

403

1.35 [ 0.87, 2.09 ]

Weeks Weeks 2009

Total (95% CI)

Risk Ratio

Risk Ratio

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.1 0.2

0.5

Favours Favours treatment treatment


1

2

5

10

Favours Favours control control

53

Analysis 3.16. Comparison 3 Oxytocin solution versus saline solution, Outcome 16 Fever. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 16 Fever

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Risk Ratio

Bider 1996

1/11

0/7

2.00 [ 0.09, 43.22 ]

Hansen 1987

0/32

0/28

0.0 [ 0.0, 0.0 ]

Total (95% CI)

43

35

2.00 [ 0.09, 43.22 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

Analysis 3.17. Comparison 3 Oxytocin solution versus saline solution, Outcome 17 Abdominal pain. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 17 Abdominal pain

Study or subgroup

Bider 1996

Total (95% CI)

Experimental

Control

n/N

n/N

Risk Ratio

Weight

1/11

0/7

100.0 %

2.00 [ 0.09, 43.22 ]

11

7

100.0 %

2.00 [ 0.09, 43.22 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


54

Analysis 3.18. Comparison 3 Oxytocin solution versus saline solution, Outcome 18 Stay at hospital more than two days. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 18 Stay at hospital more than two days

Study or subgroup

Experimental

Control

n/N

n/N

19/94

20/90

100.0 %

0.91 [ 0.52, 1.59 ]

94

90

100.0 %

0.91 [ 0.52, 1.59 ]

Carroli 1998

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control

Analysis 3.19. Comparison 3 Oxytocin solution versus saline solution, Outcome 19 Length of third stage of labour. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 19 Length of third stage of labour

Study or subgroup

Experimental

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

Selinger 1986

15

111.4 (43.2)

15

95.2 (44.6)

Total (95% CI)

15

Weight

IV,Fixed,95% CI


15

100.0 %

16.20 [ -15.22, 47.62 ]

100.0 %

16.20 [ -15.22, 47.62 ]


-10

-5

Favours treatment


0

5

10

Favours control

55

Analysis 3.20. Comparison 3 Oxytocin solution versus saline solution, Outcome 20 Headache following injection. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 20 Headache following injection

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Risk Ratio

Hansen 1987

0/32

0/28

0.0 [ 0.0, 0.0 ]

Total (95% CI)

32

28

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.01

0.1

1


10

100

Favours control

Analysis 3.21. Comparison 3 Oxytocin solution versus saline solution, Outcome 21 Shivering following injection. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 21 Shivering following injection

Study or subgroup

Experimental

Control

Risk Ratio

Risk Ratio

n/N

n/N

Hansen 1987

0/32

0/28

0.0 [ 0.0, 0.0 ]

Total (95% CI)

32

28

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.01

0.1



1

10

100

Favours control

56

Analysis 3.22. Comparison 3 Oxytocin solution versus saline solution, Outcome 22 Hypertension following injection. Review:


Comparison: 3 Oxytocin solution versus saline solution Outcome: 22 Hypertension following injection

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Risk Ratio

Hansen 1987

0/32

0/28

0.0 [ 0.0, 0.0 ]

Total (95% CI)

32

28

0.0 [ 0.0, 0.0 ]

M-H,Fixed,95% CI

M-H,Fixed,95% CI


0.01

0.1


1

10

100

Favours control

Analysis 4.1. Comparison 4 Oxytocin solution versus plasma expander, Outcome 1 Manual removal of the placenta. Review:


Comparison: 4 Oxytocin solution versus plasma expander Outcome: 1 Manual removal of the placenta

Study or subgroup

Makkonen 1995

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

49/68

22/41

100.0 %

1.34 [ 0.97, 1.85 ]

68

41

100.0 %

1.34 [ 0.97, 1.85 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


57

Analysis 4.2. Comparison 4 Oxytocin solution versus plasma expander, Outcome 2 Blood loss > 1000 ml. Review:


Comparison: 4 Oxytocin solution versus plasma expander Outcome: 2 Blood loss > 1000 ml

Study or subgroup

Makkonen 1995

Total (95% CI)

Experimental

Control

n/N

n/N

Risk Ratio

Weight

8/68

5/41

100.0 %

0.96 [ 0.34, 2.75 ]

68

41

100.0 %

0.96 [ 0.34, 2.75 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 5.1. Comparison 5 Prostaglandin solution versus saline solution, Outcome 1 Manual removal of the placenta. Review:


Comparison: 5 Prostaglandin solution versus saline solution Outcome: 1 Manual removal of the placenta

Study or subgroup

Experimental

Control

Risk Ratio

Weight

n/N

n/N

Bider 1996

0/10

7/7

50.1 %

0.05 [ 0.00, 0.73 ]

Rogers 2007

9/21

7/13

49.9 %

0.80 [ 0.39, 1.61 ]

Total (95% CI)

31

20

100.0 %

0.42 [ 0.22, 0.82 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


58

Analysis 5.2. Comparison 5 Prostaglandin solution versus saline solution, Outcome 2 Additional therapeutic uterotonics. Review:


Comparison: 5 Prostaglandin solution versus saline solution Outcome: 2 Additional therapeutic uterotonics

Study or subgroup

Experimental

Control

n/N

n/N

6/10

4/7

100.0 %

1.05 [ 0.46, 2.38 ]

10

7

100.0 %

1.05 [ 0.46, 2.38 ]

Bider 1996

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

1

2

Favours treatment

5

10

Favours control

Analysis 5.3. Comparison 5 Prostaglandin solution versus saline solution, Outcome 3 Blood loss. Review:


Comparison: 5 Prostaglandin solution versus saline solution Outcome: 3 Blood loss

Study or subgroup

E xperimental

Bider 1996

Total (95% CI)

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

10

210 (126.5)

7

231 (82)

10

Weight

IV,Fixed,95% CI


100.0 %

7

-21.00 [ -120.18, 78.18 ]

100.0 % -21.00 [ -120.18, 78.18 ]


-10

-5

0

Favours treatment


5

10

Favours control

59

Analysis 5.4. Comparison 5 Prostaglandin solution versus saline solution, Outcome 4 Abdominal pain. Review:


Comparison: 5 Prostaglandin solution versus saline solution Outcome: 4 Abdominal pain

Study or subgroup

Bider 1996

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

3/10

0/7

100.0 %

5.09 [ 0.30, 85.39 ]

10

7

100.0 %

5.09 [ 0.30, 85.39 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 5.5. Comparison 5 Prostaglandin solution versus saline solution, Outcome 5 Fever. Review:


Comparison: 5 Prostaglandin solution versus saline solution Outcome: 5 Fever

Study or subgroup

Bider 1996

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

1/10

0/7

100.0 %

2.18 [ 0.10, 46.92 ]

10

7

100.0 %

2.18 [ 0.10, 46.92 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


60

Analysis 6.1. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 1 Manual removal of the placenta. Review:


Comparison: 6 Prostaglandin solution versus oxytocin solution Outcome: 1 Manual removal of the placenta

Study or subgroup

Experimental

Control

n/N

n/N

Risk Ratio

Weight

Bider 1996

0/10

5/11

24.3 %

0.10 [ 0.01, 1.59 ]

Rogers 2007

9/21

16/20

75.7 %

0.54 [ 0.31, 0.92 ]

Total (95% CI)

31

31

100.0 %

0.43 [ 0.25, 0.75 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 6.2. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 2 Additional therapeutic uterotonics. Review:


Comparison: 6 Prostaglandin solution versus oxytocin solution Outcome: 2 Additional therapeutic uterotonics

Study or subgroup

Bider 1996

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

6/10

5/11

100.0 %

1.32 [ 0.58, 3.00 ]

10

11

100.0 %

1.32 [ 0.58, 3.00 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


61

Analysis 6.3. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 3 Blood loss. Review:


Comparison: 6 Prostaglandin solution versus oxytocin solution Outcome: 3 Blood loss

Study or subgroup

E xperimental

Bider 1996

Total (95% CI)

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

10

210 (126.5)

11

229 (102.8)

10

Weight

IV,Fixed,95% CI


100.0 %

11

-19.00 [ -118.19, 80.19 ]

100.0 % -19.00 [ -118.19, 80.19 ]


-10

-5

0

5

Favours treatment

10

Favours control

Analysis 6.4. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 4 Fever. Review:


Comparison: 6 Prostaglandin solution versus oxytocin solution Outcome: 4 Fever

Study or subgroup

Bider 1996

Total (95% CI)

Experimental

Control

Risk Ratio

Weight

n/N

n/N

1/10

1/11

100.0 %

1.10 [ 0.08, 15.36 ]

10

11

100.0 %

1.10 [ 0.08, 15.36 ]

M-H,Fixed,95% CI



0.1 0.2

0.5

Favours treatment

1

2

5

10

Favours control


62

Analysis 6.5. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 5 Abdominal pain. Review:


Comparison: 6 Prostaglandin solution versus oxytocin solution Outcome: 5 Abdominal pain

Study or subgroup

Experimental

Control

n/N

n/N

3/10

1/11

100.0 %

3.30 [ 0.41, 26.81 ]

10

11

100.0 %

3.30 [ 0.41, 26.81 ]

Bider 1996

Total (95% CI)

Risk Ratio

Weight

M-H,Fixed,95% CI



0.1 0.2

0.5

1

Favours treatment

2

5

10

Favours control

Analysis 6.6. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 6 Time from injection to placental delivery. Review:


Comparison: 6 Prostaglandin solution versus oxytocin solution Outcome: 6 Time from injection to placental delivery

Study or subgroup

Experimental

Bider 1996

Total (95% CI)

Mean Difference

Control

N

Mean(SD)

N

Mean(SD)

10

7 (3.2)

11

13 (3.3)

10

Weight

IV,Fixed,95% CI


11

100.0 %

-6.00 [ -8.78, -3.22 ]

100.0 %

-6.00 [ -8.78, -3.22 ]


-10

-5

Favours treatment


0

5

10

Favours control

63

W H A T ’ S N E W

Last assessed as up-to-date: 10 March 2011.

Date

Event

18 January 2012 Amended

Description

Contact details updated.

HISTORY

Protocol first published: Issue 1, 1999 Review first published: Issue 1, 1999

Date

Event

Description

9 March 2011

New citation required and conclusions have changed

The inclusion of high-quality randomized trials show that the use of oxytocin has little or no effect

9 March 2011

New search has been performed

Search updated. Three new trials included (Rogers 2007; Sivalingam 2001; Weeks 2009).

30 August 2009


Search updated.

6 November 2008

Amended

Converted to new review format.

6 July 2001


Search updated.

C ON TR I BU TI ON S O F A UT HO RS

G Carroli (GC) was responsible for the idea, conception and preparation of the review. He and E Bergel reviewed the quality of the trials, extracted the data and wrote the first version of this review. For this update, JM Nardin (JMN) and A Weeks (AW) reviewed the quality of the trials and extracted the data. JMN, AW and GC wrote the paper.


64

Jurnal injeksi vena umbilikan untuk mencegah perdarahan postpartum 1.pdf

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