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 of a Cochrane review, prepared and maintained by The Cochrane Collaboration and 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.
TABLE OF CONTENTS
HEADER . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
ABSTRACT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
PLAIN LANGUAGE SUMMARY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
BACKGROUND . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
OBJECTIVES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
METHODS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Figure 1. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6
Figure 2. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
RESULTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7
Figure 3. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
Figure 4. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
DISCUSSION . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
AUTHORS CONCLUSIONS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
ACKNOWLEDGEMENTS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
REFERENCES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
CHARACTERISTICS OF STUDIES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 16
DATA AND ANALYSES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
Analysis 1.1. Comparison 1 Saline solution versus expectant management, Outcome 1 Manual removal of the placenta. 32
Analysis 1.2. Comparison 1 Saline solution versus expectant management, Outcome 2 Blood loss. . . . . . . . 32
Analysis 1.3. Comparison 1 Saline solution versus expectant management, Outcome 3 Blood loss = or > 500 ml after
entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Analysis 1.4. Comparison 1 Saline solution versus expectant management, Outcome 4 Blood loss = or > 1000 ml after
entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 33
Analysis 1.5. Comparison 1 Saline solution versus expectant management, Outcome 5 Blood transfusion. . . . . 34
Analysis 1.6. Comparison 1 Saline solution versus expectant management, Outcome 6 Haemoglobin 24-48 hours
postpartum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
Analysis 1.7. Comparison 1 Saline solution versus expectant management, Outcome 7 Haemoglobin 40-45 days
postpartum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 35
Analysis 1.8. Comparison 1 Saline solution versus expectant management, Outcome 8 Maternal mortality. . . . . 35
Analysis 1.9. Comparison 1 Saline solution versus expectant management, Outcome 9 Serious maternal morbidity. . 36
Analysis 1.10. Comparison 1 Saline solution versus expectant management, Outcome 10 Surgical evacuation of retained
products of conception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
Analysis 1.11. Comparison 1 Saline solution versus expectant management, Outcome 11 Infection. . . . . . . 37
Analysis 1.12. Comparison 1 Saline solution versus expectant management, Outcome 12 Stay at hospital more than two
days. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 37
Analysis 2.1. Comparison 2 Oxytocin solution versus expectant management, Outcome 1 Manual removal of the
placenta. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
Analysis 2.2. Comparison 2 Oxytocin solution versus expectant management, Outcome 2 Blood loss. . . . . . . 38
Analysis 2.3. Comparison 2 Oxytocin solution versus expectant management, Outcome 3 Blood loss = or > 500 ml after
entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Analysis 2.4. Comparison 2 Oxytocin solution versus expectant management, Outcome 4 Blood loss = or > 1000 ml after
entry. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 39
Analysis 2.5. Comparison 2 Oxytocin solution versus expectant management, Outcome 5 Blood transfusion. . . . 40
Analysis 2.6. Comparison 2 Oxytocin solution versus expectant management, Outcome 6 Haemoglobin 24-48 hours
postpartum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 40
Analysis 2.7. Comparison 2 Oxytocin solution versus expectant management, Outcome 7 Haemoglobin 40-45 days
postpartum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
Analysis 2.8. Comparison 2 Oxytocin solution versus expectant management, Outcome 8 Maternal mortality. . . . 41
Analysis 2.9. Comparison 2 Oxytocin solution versus expectant management, Outcome 9 Serious maternal morbidity. 42
Analysis 2.10. Comparison 2 Oxytocin solution versus expectant management, Outcome 10 Surgical evacuation of retained
products of conception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
Umbilical vein injection for management of retained placenta (Review) i
Analysis 2.11. Comparison 2 Oxytocin solution versus expectant management, Outcome 11 Infection. . . . . . 43
Analysis 2.12. Comparison 2 Oxytocin solution versus expectant management, Outcome 12 Stay at hospital more than
two days. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Analysis 3.1. Comparison 3 Oxytocin solution versus saline solution, Outcome 1 Manual removal of the placenta - by
study quality. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
Analysis 3.2. Comparison 3 Oxytocin solution versus saline solution, Outcome 2 Manual removal of the placenta - by
oxytocin dose. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
Analysis 3.3. Comparison 3 Oxytocin solution versus saline solution, Outcome 3 Additional therapeutic uterotonics. 46
Analysis 3.4. Comparison 3 Oxytocin solution versus saline solution, Outcome 4 Blood loss. . . . . . . . . . 46
Analysis 3.5. Comparison 3 Oxytocin solution versus saline solution, Outcome 5 Blood loss = or > 500 ml after entry. 47
Analysis 3.6. Comparison 3 Oxytocin solution versus saline solution, Outcome 6 Blood loss = or > 1000 ml after entry. 48
Analysis 3.7. Comparison 3 Oxytocin solution versus saline solution, Outcome 7 Blood transfusion. . . . . . . 49
Analysis 3.8. Comparison 3 Oxytocin solution versus saline solution, Outcome 8 Haemoglobin 24-48 hours postpartum. 49
Analysis 3.9. Comparison 3 Oxytocin solution versus saline solution, Outcome 9 Haemoglobin 40-45 days postpartum. 50
Analysis 3.10. Comparison 3 Oxytocin solution versus saline solution, Outcome 10 Haemoglobin levels fall. . . . 50
Analysis 3.11. Comparison 3 Oxytocin solution versus saline solution, Outcome 11 Maternal mortality. . . . . . 51
Analysis 3.12. Comparison 3 Oxytocin solution versus saline solution, Outcome 12 Serious maternal morbidity. . . 51
Analysis 3.13. Comparison 3 Oxytocin solution versus saline solution, Outcome 13 Surgical evacuation of retained products
of conception. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
Analysis 3.14. Comparison 3 Oxytocin solution versus saline solution, Outcome 14 Nausea following injection. . . 53
Analysis 3.15. Comparison 3 Oxytocin solution versus saline solution, Outcome 15 Infection. . . . . . . . . 53
Analysis 3.16. Comparison 3 Oxytocin solution versus saline solution, Outcome 16 Fever. . . . . . . . . . 54
Analysis 3.17. Comparison 3 Oxytocin solution versus saline solution, Outcome 17 Abdominal pain. . . . . . . 54
Analysis 3.18. Comparison 3 Oxytocin solution versus saline solution, Outcome 18 Stay at hospital more than two days. 55
Analysis 3.19. Comparison 3 Oxytocin solution versus saline solution, Outcome 19 Length of third stage of labour. . 55
Analysis 3.20. Comparison 3 Oxytocin solution versus saline solution, Outcome 20 Headache following injection. . 56
Analysis 3.21. Comparison 3 Oxytocin solution versus saline solution, Outcome 21 Shivering following injection. . 56
Analysis 3.22. Comparison 3 Oxytocin solution versus saline solution, Outcome 22 Hypertension following injection. 57
Analysis 4.1. Comparison 4 Oxytocin solution versus plasma expander, Outcome 1 Manual removal of the placenta. 57
Analysis 4.2. Comparison 4 Oxytocin solution versus plasma expander, Outcome 2 Blood loss > 1000 ml. . . . . 58
Analysis 5.1. Comparison 5 Prostaglandin solution versus saline solution, Outcome 1 Manual removal of the placenta. 58
Analysis 5.2. Comparison 5 Prostaglandin solution versus saline solution, Outcome 2 Additional therapeutic uterotonics. 59
Analysis 5.3. Comparison 5 Prostaglandin solution versus saline solution, Outcome 3 Blood loss. . . . . . . . 59
Analysis 5.4. Comparison 5 Prostaglandin solution versus saline solution, Outcome 4 Abdominal pain. . . . . . 60
Analysis 5.5. Comparison 5 Prostaglandin solution versus saline solution, Outcome 5 Fever. . . . . . . . . . 60
Analysis 6.1. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 1 Manual removal of the placenta. 61
Analysis 6.2. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 2 Additional therapeutic
uterotonics. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 61
Analysis 6.3. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 3 Blood loss. . . . . . . 62
Analysis 6.4. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 4 Fever. . . . . . . . . 62
Analysis 6.5. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 5 Abdominal pain. . . . . 63
Analysis 6.6. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 6 Time from injection to placental
delivery. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
WHATS NEW . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 63
HISTORY . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
CONTRIBUTIONS OF AUTHORS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
DECLARATIONS OF INTEREST . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 64
SOURCES OF SUPPORT . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
DIFFERENCES BETWEEN PROTOCOL AND REVIEW . . . . . . . . . . . . . . . . . . . . . 65
NOTES . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
INDEX TERMS . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 65
Umbilical vein injection for management of retained placenta (Review) ii

[Intervention Review]
Juan Manuel Nardin1 , Andrew Weeks2 , Guillermo Carroli1

1 Centro Rosarino de Estudios Perinatales, Rosario, Argentina. 2 Department of Womens and Childrens Health, The University of
Liverpool, Liverpool, UK
Contact address: Juan Manuel Nardin, Centro Rosarino de Estudios Perinatales, Moreno 878 piso 6, Rosario, Santa Fe, 2000, Argentina.
jmnardin@crep.org.ar. jmnardin@yahoo.com.
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.
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 Groups 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) 1
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.
PLAIN LANGUAGE SUMMARY
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.
BACKGROUND plus an uterotonic drug (to induce uterine contractions) seems a

Normally the uterine contractions that occur immediately after promising intervention. Uterotonic drugs are those that increase
the delivery of the baby result in the spontaneous detachment of the uterine tone and/or contractility and include ergot alkaloids,
the placenta from the uterine wall and subsequent delivery. The oxytocin and prostaglandins. Injection of the solution into the
term retained placenta is used when the placenta has not been de- umbilical vein in the cord after delivery of the baby is an inexpen-
livered within one hour after the birth of the baby (WHO 1990). sive and simple intervention.
Retained placenta is a potentially life-threatening complication of UVI for the management of retained placenta was first described
the third stage of labour. If untreated, as may happen after home by Mojon and Asdrubali in 1826 (Koerting 1926). In the early
births in developing countries, there is a high risk of maternal twentieth century, various authors reported the use of UVI of
death from haemorrhage or infection. The current standard man- saline solution with volumes that have varied widely between 200
agement of retained placenta, by manual removal, aims to prevent ml and 400 ml (Gabaston 1914; Jarcho 1928). Subsequent studies
these problems, but it is unsatisfactory. Manual removal involves have concentrated on smaller volumes of UVI of saline solution
the clinician passing a hand through the vagina into the cavity plus oxytocin, although most of these were uncontrolled (Golan
of uterus, and usually requires general or regional anaesthesia in 1983; Golan 1984; Hauksson 1986; Heinonen 1985; Neri 1966).
hospital. It is an invasive procedure with its own serious complica-
The hypothesized beneficial effect of the UVI is that it may reduce
tions of haemorrhage, infection or genital tract trauma. Any man-
the need for manual removal of the placenta (Carroli 1991).
agement simple and safe enough to be performed at the place of
delivery which reduces the need for manual removal of placenta The aim of this review was to evaluate the available evidence about
could be of major benefit to women worldwide. The umbilical the possible benefits and risks of the use of UVI versus expectant
vein injection (UVI) of saline solution or any other fluid alone or management for retained placenta. We also evaluated benefits and
risks of the use of umbilical injection with different fluids and Primary outcomes
uterotonic drugs. 1. Manual removal of the placenta.
2. Maternal mortality.
3. Severe postpartum haemorrhage (PPH) (defined as
OBJECTIVES clinically estimated blood loss greater than or equal to 1000 ml).
4. Blood transfusion.
To determine the possible benefits and risks of the use of UVI 5. Addition of therapeutic uterotonics.
for retained placenta. We considered UVI as an intervention for
retained placenta when the latter remained undelivered 15 minutes
or more after the delivery of the baby. Also, to assess the effects of Secondary outcomes
alternative fluids and uterotonic drugs. 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
METHODS 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
Criteria for considering studies for this review
concentration according to local standards).
4. Mean blood loss (ml).
5. Mean time from injection to placental removal (minutes).
Types of studies 6. Perinatal fall in haemoglobin levels (defined as decrease in
Any adequately randomized controlled trial comparing UVI of previous haemoglobin concentration levels by at least 10%).
saline solution or other fluids, with or without uterotonic drugs, 7. Iron tablets during the puerperium.
either with expectant management or with an alternative solution 8. Subsequent surgical evacuation of retained products of
or other uterotonic agent, in the management of retained placenta. conception.
9. Diastolic blood pressure greater than 100 mmHg between
injection and discharge from the labour ward.
Types of participants 10. Vomiting between injection and discharge from the labour
All women having a vaginal delivery with a retained placenta. ward.
For this review, we consider trials including women in whom the 11. Shivering between injection and discharge from the labour
placenta was not delivered spontaneously at least 15 minutes after ward.
delivery of the baby. 12. Nausea between injection and discharge from the labour
ward.
13. Headache between injection and discharge from the labour
Types of interventions ward.
1. UVI of saline solution versus expectant management. 14. Maternal pain between injection and discharge from the
2. UVI of oxytocin plus saline solution versus expectant labour ward.
management. 15. Maternal dissatisfaction with third stage management.
3. UVI of oxytocin plus saline solution versus UVI of saline 16. Secondary PPH (after 24 hours and before six weeks).
solution. 17. Bleeding needing readmission.
4. UVI of oxytocin plus saline solution versus UVI of plasma 18. Need for treatment with antibiotics.
expander. 19. Maternal fatigue.
5. UVI of prostaglandin plus saline solution versus UVI of 20. Breastfeeding at discharge from hospital.
saline solution.
6. UVI of prostaglandin plus saline solution versus UVI of
oxytocin plus saline solution. Search methods for identification of studies
Types of outcome measures Electronic searches

We evaluated the following maternal outcomes. We chose five We searched the Cochrane Pregnancy and Childbirth Groups
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).

The Cochrane Pregnancy and Childbirth Groups Trials Register (1) Sequence generation (checking for possible selection
is maintained by the Trials Search Co-ordinator and contains trials bias)
identified from: We described for each included study the method used to generate
1. quarterly searches of the Cochrane Central Register of the allocation sequence in sufficient detail to allow an assessment
Controlled Trials (CENTRAL); of whether it should produce comparable groups.
2. weekly searches of MEDLINE; We assessed the method as:
3. weekly searches of EMBASE; low risk of bias (any truly random process, e.g. random
4. handsearches of 30 journals and the proceedings of major number table; computer random number generator),
conferences; high risk of bias (any non-random process, e.g. odd or even
5. weekly current awareness alerts for a further 44 journals date of birth; hospital or clinic record number) or,
plus monthly BioMed Central email alerts. unclear risk of bias.
Details of the search strategies for CENTRAL, MEDLINEand
EMBASE, the list of handsearched journals and conference pro-
ceedings, and the list of journals reviewed via the current aware- (2) Allocation concealment (checking for possible selection
ness service can be found in the Specialized Register section bias)
within the editorial information about the Cochrane Pregnancy We described for each included study the method used to conceal
and Childbirth Group. the allocation sequence in sufficient detail and determine whether
Trials identified through the searching activities described above intervention allocation could have been foreseen in advance of, or
are each assigned to a review topic (or topics). The Trials Search during recruitment, or changed after assignment.
Co-ordinator searches the register for each review using the topic We assessed the methods as:
list rather than keywords. low risk of bias (e.g. telephone or central randomisation;
We did not apply any language restrictions. consecutively numbered sealed opaque envelopes);
high risk of bias (open random allocation; unsealed or non-
opaque envelopes, alternation; date of birth);
Data collection and analysis unclear risk of bias,
(3) Blinding (checking for possible performance bias)

Selection of studies
We described for each included study the methods used, if any, to
Two review authors (JM Nardin, A Weeks) independently assessed blind study participants and personnel from knowledge of which
for inclusion all the potential studies identified as a result of the intervention a participant received. We judged studies at low risk
search strategy. We resolved any disagreement through discussion of bias if they were blinded, or if we judge that the lack of blinding
or, if required, by consulting a third person (G Carroli). 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 third person (G Carroli). We entered data into Review
Manager software (RevMan 2008) and checked for accuracy. (4) Incomplete outcome data (checking for possible attrition
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 ex-
clusions from the analysis. We stated whether attrition and exclu-
sions 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 attrition or exclusion where reported, and whether missing data
risk of bias for each study using the criteria outlined in the 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 involving a third authors, we re-included missing data in the analyses. We assessed
assessor. methods as:

low risk of bias (e.g. no missing outcome data; missing Continuous data
outcome data balanced across groups);
For continuous data, we used the mean difference if outcomes were
high risk of bias (e.g. numbers or reasons for missing data
measured in the same way between trials. We used the standardized
imbalanced across groups; as treated analysis done with
mean difference to combine trials that measure the same outcome,
substantial departure of intervention received from that assigned
but use different methods.
at randomization)
unclear risk of bias.
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: Cluster-randomized trials
low risk of bias (where it is clear that all of the studys pre- The search included cluster-randomized trials along with indi-
specified outcomes and all expected outcomes of interest to the vidually randomized trials. Their sample sizes would have been
review have been reported); adjusted according to the methods described in the Handbook
high risk of bias (where not all the studys pre-specified (Higgins 2008) using an estimate of the intracluster correlation co-
outcomes have been reported; one or more reported primary efficient (ICC) derived from the trial (if possible), or from another
outcomes were not pre-specified; outcomes of interest are source. However, we found no cluster randomized trials with this
reported incompletely and so cannot be used; study fails to search strategy.
include results of a key outcome that would have been expected
to have been reported);
unclear risk of bias.
Dealing with missing data
For included studies, we noted levels of attrition. We explored the
(6) Other sources of bias impact of including studies with high levels of missing data in the
We described for each included study any important concerns we overall assessment of treatment effect by using sensitivity analysis.
have about other possible sources of bias. For all outcomes we carried out analyses, as far as possible, on an
We assessed whether each study was free of other problems that intention-to-treat basis, i.e. we attempted to include all partici-
could put it at risk of bias: pants randomized to each group in the analyses. The denominator
low risk of other bias; for each outcome in each trial was the number randomized minus
high risk of other bias; any participants whose outcomes are known to be missing.
unclear whether there is risk of other bias.
Assessment of heterogeneity
(7) Overall risk of bias
We applied tests of heterogeneity between trials, if appropriate, us-
We made explicit judgements about whether studies are at high risk
ing I statistic. If we identified high levels of heterogeneity among
of bias, according to the criteria given in the Handbook (Higgins
the trials (I exceeding 50%), we performed prespecified sensitiv-
2008). With reference to (1) to (6) above, we assessed the likely
ity analyses according to the methodological quality of the studies.
magnitude and direction of the bias and whether we consider it is
We used a random-effect meta-analysis as an overall summary if
likely to impact on the findings. We explored the impact of the level
this was considered appropriate.
of bias through undertaking sensitivity analyses - see Sensitivity
analysis.
Assessment of reporting biases

Measures of treatment effect
Where we suspected reporting bias (see Selective reporting bias
above), we attempted to contact study authors asking them to pro-
vide missing outcome data. Where this was not possible, and the
Dichotomous data missing data were thought to introduce serious bias, we explored
For dichotomous data, we presented results as summary risk ratio the impact of including such studies in the overall assessment of
with 95% confidence intervals. results by a sensitivity analysis.

Data synthesis the risk of spurious results, have not presented these in the review.
We carried out statistical analysis using the Review Manager soft-
ware (RevMan 2008). We used fixed-effect meta-analysis for com- Sensitivity analysis
bining data where trials were examining the same intervention,
We carried out sensitivity analyses to explore the effect of trial
and the trials populations and methods were judged sufficiently
quality (Figure 1). This involved analyses based on each trials
similar. Where we suspect clinical or methodological heterogene-
risk of bias rating (adequate/inadequate/unclear) for allocation,
ity between studies sufficient to suggest that treatment effects may
incomplete outcome data, and blinding (Figure 2). We excluded
differ between trials, we used random-effects meta-analysis.
studies of poor quality in the analysis (those rated as inadequate
If we identified substantial heterogeneity in a fixed-effect meta-
or unclear) in order to assess for any substantive difference to the
analysis, we have noted this and repeated the analysis using a ran-
overall result. We considered only studies which were rated as
dom-effects method.
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
Subgroup analysis and investigation of heterogeneity or unclear for incomplete outcome data) and selected for the
We did not plan to perform subgroup analyses in advance. We report of the sensitivity analysis. We also analyzed data according
performed analyses by study size and dosage post hoc, but due to 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.

Figure 2. Methodological quality graph: review authors judgements about each methodological quality
item presented as percentages across all included studies.
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
RESULTS trial with 109 women. Prostaglandin plus saline solution versus
Description of studies saline solution alone was compared in two small trials (51 women).
Prostaglandin plus saline solution versus oxytocin plus saline so-
See: Characteristics of included studies; Characteristics of excluded lution was compared in the same two small studies (62 women).
studies; Characteristics of studies awaiting classification. The volume injected into the umbilical vein was mostly 20 ml (10
For a detailed description of studies see table of Characteristics of
studies) whereas four trials used a higher dose (30 ml) and only
included studies and Figure 2. The following text summarizes the trial used a lower dose (10 ml). Seven studies used 10 IU of oxy-
main characteristics. tocin, two studies used 20 IU, two used 30 IU, three trials used 50
The search strategy identified 18 relevant studies that we assessed IU and only one used a dose of 100 IU of oxytocin (Wilken-Jensen
for inclusion. Of these, 15 (1704 women) fulfilled the selection 1989). Prostaglandin doses used were 20 mg of F2 in one study
criteria and were included in the meta-analyses. We incorporated (Bider 1996) and 800 mcg of E1 analog (misoprostol) in another
three of them (659 women) in this update since the last publication
study (Rogers 2007). Plasma expander (Dextran 70) 20 ml was
of this review. Five trials were published in the late 1980s, six in administered in one trial (Makkonen 1995).
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 Time to trial entry
into six subgroups according to the type of fluids or drugs being
The time to trial entry after delivery of the baby was 15 minutes
compared (see below).
in two studies; 20 minutes in five studies; 30 minutes in other six;
Interventions 45 minutes in one study; and 60 minutes in another study.
The agents and uterotonic drugs used in these trials include: saline
solution alone, plasma expander alone, oxytocin plus saline solu-
tion and prostaglandin plus saline solution injected into the um- Limit time for manual removal of the placenta
bilical vein. The limit time for manual removal of the placenta was 15 minutes
Saline solution alone versus expectant management was compared in four trials, 30 minutes in six trials and 40 to 45 minutes in
in four trials including 403 women. Oxytocin plus saline solution two trials. In one trial, timing of the procedure was left to the

judgement of attending clinicians and in two trials it was not pre- Blinding
specified.
Bider 1996 and Makkonen 1995 are likely to suffer assessment
bias because they did not describe the masking procedure between
Included studies both arms of the trial. In an effort to diminish the bias, a time limit
of 40 minutes and 30 minutes, respectively, for manual removal
See Characteristics of included studies.
of placenta was established, but they did not measure compliance
with the protocol.
Excluded studies Calderale 1994 is not prone to assessment bias because both arms
are indistinguishable and a limit time for manual removal of the
See Characteristics of excluded studies.
placenta was established. There is limited details in the report of
blinding except to state that a double-blind methodology was
used.
Risk of bias in included studies 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 estab-
Selection bias at entry to the trial lished for manual removal the placenta; to assess compliance with
Four trials describe clearly the random method generation and the protocol, the time that had elapsed from entry to the trial to
concealment of allocation, making selection bias at entry to the manual removal of the placenta was measured.
trials unlikely (Carroli 1998; Frappell 1988; Rogers 2007; Weeks Frappell 1988 and Wilken-Jensen 1989 are potentially free of as-
2009). In another four trials, concealment of allocation (coded by sessment bias because, in both arms of the trials, the treatments
the pharmacist) was sound; the possibility of selection bias is un- given to the women were indistinguishable to the physician and
likely but none of them describe the random generation method also because they established a time limits of 15 minutes and 40
(Hansen 1987; Huber 1991; Selinger 1986; Wilken-Jensen 1989). minutes respectively, for manual removal of placenta but they did
Calderale 1994, although described as double blind with a placebo not describe any method to control for protocol compliance.
administered, does not clearly state the allocation concealment. Gazvani 1998 could suffer assessment bias because the observer
Gazvani 1998 describes clearly the random generation and the was aware of the treatment given to each patient but a time limit for
concealment of allocation by sealed envelopes. Thiery 1987 de- manual removal of the placenta was established to try to minimize
scribes only the concealment allocation method which is by sealed the bias.
envelopes. Finally, three trials did not describe the random gener- Hansen 1987 is likely to be free of assessment bias because the
ation nor the allocation concealment method and, consequently, physicians were not aware of the treatment given to the women but
are open to selection bias at entry (Bider 1996; Kristiansen 1987; they did not set a limit time for manual removal of the placenta.
Makkonen 1995). In Sivalingam 2001, the method of random- Huber 1991 is not prone to assessment bias in the comparison
ization is described as use of box containing equal number of en- between the two injection arms of the trial, but is prone to bias
velopes that were taken randomly; however, no attempt to conceal in the comparison to the expectant management arm because the
the randomization sequence is described and, therefore, this study treatment given was known by the physician and a limit time for
could be prone to selection bias. manual removal of the placenta was not established in the protocol;
furthermore, timing was determined by the clinical judgement of
the obstetrician.
Selection bias after entry to the trial Kristiansen 1987 is prone to assessment bias because the physicians
No withdrawals were stated to have occurred from 10 trials were aware of the treatment given and there was not an established
(Calderale 1994; Gazvani 1998; Hansen 1987; Kristiansen 1987; limit time for manual removal of placenta.
Makkonen 1995; Rogers 2007; Selinger 1986; Sivalingam 2001; Rogers 2007 is prone to assessment bias because the physicians
Thiery 1987; Weeks 2009), so the likelihood of selection bias after were aware of the treatment given as solutions were not similar in
entry to these trials is low. In Huber 1991, 4.5% of the women colour but the established time limit of 30 minutes for manual
were excluded from the analyses for violations of the treatment removal of the placenta could minimize the bias.
protocol, and in Carroli 1998, 1.7% of the participants were lost Selinger 1986 is potentially free of assessment bias because both
to follow-up, giving these two trials a very low risk of selection arms of the trial were indistinguishable and also they did establish
bias after entry. In the remaining trials, the withdrawals were as a time limit of 20 minutes for manual removal of the placenta, al-
follows: Bider 1996, 8%; Frappell 1988, 18%; and Wilken-Jensen though they described three women delivering the placenta spon-
1989, 7.5%, without any explanation about the reason for the ex- taneously at 30, 55 and 80 minutes after entry to the trial.
clusions leaving open the potential for serious selection bias after Sivalingam 2001 is unlikely to suffer from assessment bias as solu-
entry into the trials. tions, similar in colour and consistency, were prepared by a mid-

wife, which kept the physician unaware of the content of the sy- the treatment given and a time limit of 30 minutes was established
ringe. A limit time of 30 minutes for manual removal of the pla- for manual removal of the placenta.
centa was also established. In summary, according to the criteria applied for the sensitivity
Thiery 1987 is prone to assessment bias because the physicians analysis, eight trials were methodologically sound (Calderale 1994;
were aware of the treatment given. To alleviate this problem a Carroli 1998; Frappell 1988; Hansen 1987; Huber 1991; Selinger
time limit of 15 minutes was set up for manual removal of the 1986; Sivalingam 2001; Weeks 2009) and seven trials were of poor
placenta but the researchers did not describe any effort to measure methodological quality or there was insufficient information for
compliance with the protocol. inclusion into the high-quality group (Bider 1996; Gazvani 1998;
Weeks 2009 is unlikely to suffer assessment bias between both Kristiansen 1987; Makkonen 1995; Rogers 2007; Thiery 1987;
injection arms of the trial because the physicians were not aware of Wilken-Jensen 1989) (Figure 3).

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

bin, blood transfusion, curettage, infection and hospital stay (for
Effects of interventions 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
3. Oxytocin solution versus saline
analysed), while the other 36 reported results correspond to single-
trial analyses. Twelve trials were included in this comparison. Oxytocin solution
compared with saline alone showed a reduction in manual removal
1. Saline versus expectant management of the placenta, but this was not statistically significant and the 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; I = 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
95% CI see data and analyses tables). either individually or combined (RR 0.98; 95% CI 0.88 to 1.09).
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 trials were included in this comparison. UVI of oxytocin solu- to have no effect as the four studies that used 30 units of oxytocin
tion compared with expectant management showed no statistically or more (Rogers 2007; Sivalingam 2001; Weeks 2009; Wilken-
significant 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).

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 morbid- uterotonics (for treatment effects and 95% CI see data and anal-
ity, addition of therapeutic uterotonics, blood loss, postpartum yses tables).
haemorrhage, haemoglobin fall, blood transfusion, curettage, in-
fection, hospital stay, fever, abdominal pain and length of third
6. Prostaglandin solution versus oxytocin solution
stage of labour (for treatment effects and 95% CI see data and
analyses tables). 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 effects and 95% CI see data and analyses data and analyses tables).
tables).
5. Prostaglandin solution versus saline

DISCUSSION
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
Saline versus expectant management
placenta (RR 0.42; 95% CI 0.22 to 0.82) but no difference in One question is whether UVI of saline compared with expectant
blood loss, fever, abdominal pain, and addition of therapeutic management reduces the need for manual removal of the placenta.

Although this is based in the only four available randomized con- Oxytocin solution versus plasma expander
trolled trials with a small overall sample size, the answer extracted
UVI of oxytocin solution compared with UVI of plasma expander
from this systematic review is that there seem to be no advantages
showed higher, but not statistically significant, incidence of man-
in using this intervention to reduce the above-mentioned main
ual removal of placenta and did not show any difference in blood
outcome. There was a similar lack of effect on secondary endpoints
loss but, as it was shown, there is only one trial available to date
such as blood loss, blood transfusion curettage, hospital stay or
and considering the poor methodological quality and the small
any difference in postpartum haemoglobin level.
size of it, these results should be interpreted cautiously.
Oxytocin solution versus expectant

management Prostaglandin solution versus saline
The use of UVI of prostaglandin solution compared with UVI of
In this comparison, UVI of oxytocin solution showed a 13% risk
saline alone showed a statistically significant risk reduction in man-
reduction in the incidence of manual removal of placenta, but
ual removal of placenta but did not show any difference in blood
this benefit is not statistically significant with confidence intervals
loss, fever, abdominal pain, and addition of therapeutic uteroton-
compatible with a risk reduction of 26% and a marginal risk of
ics. The results of this comparison should be taken cautiously as
increase of 3%. There was no advantage with regards to secondary
there were only two small trials with 51 women in total and both
endpoints such as blood loss, haemoglobin, blood transfusion,
studies were considered of low methodological quality due to the
curettage, infection and hospital stay.
lack of proper blinding and therefore, prone to bias.
Oxytocin solution versus saline

Prostaglandin solution versus oxytocin solution
This is the comparison in which most studies have been done and
contributes the largest sample size of all the comparisons included The UVI of prostaglandin solution compared with UVI oxytocin
in this systematic review. Overall the results are complex as they solution showed again a significant difference in manual removal
show the need for manual removal to be of borderline statistical of placenta as well as for time to placental delivery favourable to the
significance of beneficial effect to the oxytocin solution group and first group. No other differences reached statistical significance.
of borderline heterogeneity. When subgroup analysis by quality However, as for the previous comparison, these results should be
of studies was performed, the high-quality group showed low het- interpreted guardedly as only two small unblinded trials were in-
erogeneity and confidence intervals compatible with anything be- cluded in the meta-analysis.
tween 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. Deal-
ing with this data will, therefore, be controversial, especially as two
AUTHORS CONCLUSIONS
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
Implications for practice
oxytocin injection on main outcomes. However, with a number Given that the meta-analysis of all the main three comparisons
needed to treat of 18 (95% confidence interval 9.00 to 948), it showed no major effect, it would not be appropriate to suggest
could be argued that with no harmful effects found with its ad- widespread implementation of intra-umbilical oxytocin injection
ministration, and as an inexpensive and simple intervention that for the treatment of retained placenta. Furthermore, if there is an
could be performed while placental delivery is awaited, it would effect, it does not appear to be large; the number of cases that need
still have a role in the management of retained placenta. If the in- to be treated to prevent one manual removal is unlikely to be less
tervention is performed within 15 to 30 minutes after delivery of than nine and could be high as 948. However, those who currently
the baby, it may slightly reduce the need for further interventions use the technique can be reassured that there is no evidence of
for retained placenta. This small potential beneficial effect could harm, and they may therefore, wish to continue using it. Indeed,
still be important in settings where resources are scarce and there with many retained placenta delivering spontaneously with no
is no immediate availability of facilities for manual removal. intervention at all, there may be a benefit to just waiting for a
It should be noted that we found no differences in length of third further 30 minutes to allow time for this spontaneous expulsion.
stage of labour, blood loss, postpartum haemorrhage, haemoglo- However, the risk of bleeding increases with the length of the third
bin, blood transfusion, curettage, infection, hospital stay, fever, stage and so facilities for manual removal and blood transfusion
abdominal pain and addition of therapeutic uterotonics. should be readily available.

Implications for research ACKNOWLEDGEMENTS
There is little evidence of the optimal time to wait prior to man-
ual 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 Groups 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 the Cochrane Pregnancy and Childbirth Group team for their
to expectant management. constant support.
REFERENCES
References to studies included in this review Kristiansen 1987 {published data only}
Kristiansen FV, Frost L, Kaspersen P, Moller BR. The
Bider 1996 {published data only} effect of oxytocin injection into the umbilical vein for the
Bider D, Dulitzky M, Goldenberg M, Lipitz S, Mashiach management of retained placenta. American Journal of
S. Intraumbilical vein injection of prostaglandin F2alpha Obstetrics and Gynecology 1987;156:97980.
in retained placenta. European Journal of Obstetrics &
Gynecology and Reproductive Biology 1996;64:5961. Makkonen 1995 {published data only}
Calderale 1994 {published data only} Makkonen M, Suoino S, Saarikoski S. Intraumbilical
Calderale L, Dalle NF, Franzoi R, Vitalini R. Is oxytocin for management of retained placenta. International
intraumbilical vein administration with oxytocin useful Journal of Gynecology & Obstetrics 1995;48:16972.
in the treatment of retained placenta? [ utile la
Rogers 2007 {published data only}
somministrazione di ossitocina nella vena ombelicale per il
Rogers MS, Yuen PM, Wong S. Avoiding manual removal
trattamento della placenta ritenuta?]. Giornale Italiano di
of placenta: evaluation of intra-umbilical injection
Ostetricia e Ginecologia 1994;16(5):2836.
of uterotonics using the Pipingas technique for the
Carroli 1998 {published data only} management of adherent placenta. Acta Obstetricia et
Carroli G, Belizan JM, Grant A, Gonzalez L, Campodonico Gynecologica 2007;86:4854.
L, Bergel E. Intra-umbilical vein injection and retained
placenta: evidence from a collaborative large randomised Selinger 1986 {published data only}
controlled trial. Grupo Argentino de Estudio de Placenta Selinger M, Mackenzie IZ, Dunlop P, James D. Intra-
Retenida. British Journal of Obstetrics and Gynaecology 1998; umbilical vein oxytocin in the management of retained
105(2):17985. placenta. A double blind placebo controlled study. Journal
Frappell 1988 {published data only} of Obstetrics and Gynaecology 1986;7:1157.
Frappell JM, Pearce JM, McParland P. Intra-umbilical
Sivalingam 2001 {published data only}
vein oxytocin in the management of retained placenta:
Sivalingam N, Surinder S. Is there a place for intra-umbilical
a random, prospective, double blind, placebo controlled
oxytocin for the management of retained placenta?. Medical
study. Journal of Obstetrics and Gynaecology 1988;8:3224.
Journal of Malaysia 2001;56(4):4519.
Gazvani 1998 {published data only}
Gazvani MR, Luckas MJM, Drakeley AJ, Emery SJ, Thiery 1987 {unpublished data only}
Alfirevic Z, Walkinshaw SA. Intraumbilical oxytocin for the Thiery M. Management of retained placenta with oxytocin
management of retained placenta: a randomized controlled injection into the umbilical vein. Personal communication
trial. Obstetrics & Gynecology 1998;91:2037. 1987.
Hansen 1987 {published data only} Weeks 2009 {published and unpublished data}
Hansen P, Jorgensen L, Dueholm M, Hansen S. Weeks A, Mirembe F, Alfirevic Z. The release trial: a
Intraumbilical oxytocin in the treatment of retained randomised controlled trial of umbilical vein oxytocin versus
placenta. Ugeskrift for Laeger 1987;149:33189. placebo for the treatment of retained placenta. BJOG: an
Huber 1991 {published data only} international journal of obstetrics and gynaecology 2005;115
Huber MGP, Wildschut HIJ, Boer K, Kleiverda G, Hoek (10):1458.
FJ. Umbilical vein administration of oxytocin for the Weeks AD, Alia G, Vernon G, Namavanja A, Gosakan R,
management of retained placenta: is it effective?. American Majeed T, et al.The release trial: a multi-centre double blind
Journal of Obstetrics and Gynecology 1991;164:12169. trial of umbilical oxytocin to treat retained placenta. BJOG:
an international journal of obstetrics and gynaecology 2008; Hauksson 1986
115(s1):32. Hauksson A. Oxytocin injection into the umbilical vein in
Weeks AD, Alia G, Vernon G, Namayanja A, Gosakan R, women with retained placenta. A questionable method.
Majeed T, et al.Umbilical vein oxytocin for the treatment American Journal of Obstetrics and Gynecology 1986;125:
of retained placenta (Release Study): a double-blind, 1140.
randomised controlled trial. Lancet 2010;375(9709): Heinonen 1985
1417. Heinonen PK, Pihkala H. Pharmacologic management and

Weeks AD, Alia G, Vernon G, et al.The Release trial: A controlled cord traction in the third stage of labour. Annales
multi-centre double blind trial of umbilical oxytocin to treat Chirurgiae et Gynaecologiae 1985;74(197):315.
retained placenta. Personal communication 2009.
Wilken-Jensen 1989 {published data only} Higgins 2008
Wilken-Jensen C, Strom V, Nielsen MD, Rosenkilde-Gram Higgins JPT, Green S, editors. Cochrane Handbook for
B. Removing placenta by oxytocin - a controlled study. Systematic Reviews of Interventions Version 5.0.1 [updated
American Journal of Obstetrics and Gynecology 1989;161: September 2008]. The Cochrane Collaboration, 2008.
1556. Available from www.cochrane-handbook.org.
References to studies excluded from this review Jarcho 1928

Jarcho A. Management of retained placenta. Surgery
Das 2008 {published data only} Gynecology and Obstetrics 1928;46:26572.
Das S. Management of retained placentas using umbilical
Koerting 1926
vein oxytocin injection by Pipingas technique. BJOG: an
Koerting W. El metodo de Mojon Gabaston en el
international journal of obstetrics and gynaecology 2008;115
tratamiento de las complicaciones del alumbramiento.
(s1):242.
Semana Medica 1926;33:35365.
Habek 2001 {published data only}
Habek D, Hrgovic Z, Ivanisevic M, Delmis J. Treatment of Neri 1966
a retained placenta with intraumbilical oxytocin injection. Neri A, Goldman J, Gans B. Intra-umbilical vein injection
Zentralblatt fur Gynakologie 2001;123:4157. of pitocin. A new method in the management of the third
stage of labor. Harefuah 1966;70:3513.
References to studies awaiting assessment
RevMan 2008
Chauhan 2004 {published data only} The Nordic Cochrane Centre, The Cochrane Collaboration.
Chauhan P, Rosendahl M, Sorensen B, Westergaard JG. Review Manager (RevMan). 5.0. Copenhagen: The Nordic
Randomised controlled study of treatment of retained Cochrane Centre, The Cochrane Collaboration, 2008.
placenta with 100 IE intraumbilical oxytocin via and WHO 1990
infant mucus aspiration tube. XXXIV Congress of Nordic World Health Organization. The prevention and
Federation of Societies of Obstetrics and Gynecology; 2004 management of postpartum haemorrhage. Report of a technical
June 12-15; Helsinki, Finland. 2004:56. working group, Geneva. 3-6 July 1989. Document WHO/
MCM/90.7. Geneva: World Health Organization, 1990.
Additional references
Carroli 1991 References to other published versions of this review
Carroli G. Management of retained placenta by umbilical
vein injection. British Journal of Obstetrics and Gynaecology Carroli 2001
1991;98:34850. Carroli G, Bergel E. Umbilical vein injection for the
Gabaston 1914 management of retained placenta. Cochrane Database
Gabaston JA. Eine neue Methode kuenstlicher of Systematic Reviews 2001, Issue 4. [DOI: 10.1002/
Plazentaloeung. Muenchener Mediziner Wochenzchrift 1914; 14651858.CD001337]
61:651.
Elbourne 1995
Golan 1983 Elbourne DR. Umbilical vein injection (oxytocin or saline)
Golan A, Lidor AL, Wexler S, David MP. A new method for for retained placenta. [revised 03 April 1992]. In: Enkin
the management of the retained placenta. American Journal MW, Keirse MJNC, Renfrew MJ, Neilson JP, Crowther
of Obstetrics and Gynecology 1983;146:7089. C (eds.) Pregnancy and Childbirth Module. In: The
Golan 1984 Cochrane Pregnancy and Childbirth Database [database on
Golan A, Lidor AL, Wexler S, David MP. Reply to Liner disk and CDROM]. The Cochrane Collaboration; Issue 2,
[letter]. American Journal of Obstetrics and Gynecology 1984; Oxford: Update Software; 1995.
148:232.
Indicates the major publication for the study

CHARACTERISTICS OF STUDIES
Characteristics of included studies [ordered by study ID]
Bider 1996
Methods Random generation: computerized.

Allocation concealment: not stated.
Participants 37 women with singleton vaginal delivery with retained placenta 60 minutes after delivery
of the baby
Interventions Group 1: UVI of prostaglandin F2 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 ran-
domly after 30 minutes if still undelivered
Group 4: manual removal (Control).
Outcomes Manual removal of placenta 30 minutes after entry to the trial, time to placental 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.

Calderale 1994 (Continued)
Outcomes Manual removal of the placenta 30 minutes after UVI, blood loss, time to placental
delivery
Notes
Risk of bias
Random sequence generation (selection Unclear risk Randomized. No further description.

bias)
Blinding (performance bias and detection Low risk il doppio cieco (double blind).
bias)
All outcomes
High quality study? 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

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

Carroli 1998 (Continued)

bias)
Allocation concealment (selection bias) Low risk Adequate.
Blinding (performance bias and detection Low risk Oxytocin vs saline blinded, expectant not
bias) blinded.
All outcomes
Incomplete outcome data (attrition bias) Low risk

All outcomes
Selective reporting (reporting bias) Low risk
Other bias Low risk
Frappell 1988
Methods Random generation: random number table.

Allocation concealment: sequentially randomly numbered ampoules prepared by phar-
macist 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

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
Notes
Risk of bias

bias)

Frappell 1988 (Continued)
Blinding (performance bias and detection Low risk

bias)
All outcomes
Incomplete outcome data (attrition bias) High risk 9 women (18%) post randomization exclu-
All outcomes sions, ITT not used.
Selective reporting (reporting bias) High risk
High quality study? Low risk It does have a high exclusion rate, but dou-
ble-blind nature means bias is unlikely
Gazvani 1998
Methods Random generation: table of random numbers.

Allocation concealment: consecutively numbered opaque sealed envelopes
Participants 81 women with placenta undelivered 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
Notes
Risk of bias

bias)

bias)
All outcomes

All outcomes

Gazvani 1998 (Continued)
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

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)

bias)
All outcomes
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 comple-
tion 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

Huber 1991 (Continued)

Group 2: UVI of saline solution 1 ml + saline solution 20 ml.
Outcomes Manual removal of placenta after a time based on the clinical judgement of the obstetri-
cian, time interval from injection to spontaneous expulsion of placenta, blood loss
Risk of bias

bias)
Blinding (performance bias and detection Low risk Expectant management group not blinded.
bias)
All outcomes
Incomplete outcome data (attrition bias) High risk 20 women (9.1%) excluded out of 220,
All outcomes
Kristiansen 1987

Allocation concealment: not stated. The authors said randomized
Participants 51 women with retained placenta for more than 20 minutes after delivery of the baby

Outcomes Manual removal of placenta.
Risk of bias

Kristiansen 1987 (Continued)

bias)
Allocation concealment (selection bias) Unclear risk Unclear.
Blinding (performance bias and detection High risk Participant blinded, but investigator not
bias) blind.
All outcomes
Makkonen 1995

Allocation concealment: not stated.
Participants 109 women with retained placenta 30 minutes after delivery of the baby

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
Notes
Risk of bias

bias)
Allocation concealment (selection bias) Unclear risk Unclear.

bias)
All outcomes
High quality study? Unclear risk It is not clear whether this is a high-quality
study.

Rogers 2007
Methods Random generation: table of computer-generated random numbers. Allocation conceal-

ment: 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

Group 2: UVI of prostaglandin E1 analogue (misoprostol) 800 mcg + saline solution 30
ml
All intra-umbilical injections given through an umbilical catheter
Outcomes Manual removal of the placenta 30 min after trial entry.
Notes
Risk of bias

bias)
Blinding (performance bias and detection High risk Investigator not blinded. Participant and
bias) outcome assessor blinded
All outcomes
Incomplete outcome data (attrition bias) Low risk ITT used.

All outcomes
Selinger 1986

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


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)

bias)
All outcomes
Incomplete outcome data (attrition bias) High risk 5 women (17%) excluded, ITT not used.
All outcomes
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 retained placenta 20 min after vaginal delivery of single fetus with gesta-
tional age equal or higher than 28 weeks. Reasons for exclusion included: placenta previa,
primary PPH, snapped umbilical cord, emergency caesarean section, haemodynamically
unstable or ill patients, severe anaemia, chorioamnionitis

Outcomes Manual removal of placenta after 30 min of UVI, addition of therapeutic uterotonics,
blood transfusion, blood loss, curettage
Notes
Risk of bias
Random sequence generation (selection Unclear risk Box of equal number of envelopes.
bias)

Sivalingam 2001 (Continued)

bias)
All outcomes

All outcomes
Thiery 1987

Allocation concealment: sealed numbered envelopes.
Participants 32 women with diagnosis of retained placenta 15 minutes after delivery of the baby

Outcomes Manual removal of placenta 15 minutes after entry to the trial
Notes Unpublished data only.
Risk of bias

bias)
Allocation concealment (selection bias) Unclear risk Sealed numbered envelopes.

bias)
All outcomes
Incomplete outcome data (attrition bias) Low risk ITT used.

All outcomes

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 of oxytocin 50 IU (5 ml) + saline solution 25 ml. Group 2: UVI of 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)

bias)
All outcomes

All outcomes
Other bias Low risk

Wilken-Jensen 1989

Allocation concealment: similar ampoules supplied by pharmaceutical company
Participants 40 women with diagnosis of retained placenta 20 minutes after delivery of the baby vagi-
nally after by intermittent traction on the umbilical cord and light suprapubic pressure

Outcomes Manual removal of placenta 40 min after trial entry, time from injection to delivery of
the placenta, postpartum blood loss
Risk of bias
Random sequence generation (selection Unclear risk Not described.

bias)
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.

Characteristics of studies awaiting assessment [ordered by study ID]
Chauhan 2004
Methods Randomized.
Participants 60 patients with retained placenta 30 minutes after vaginal delivery

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

DATA AND ANALYSES
Comparison 1. Saline solution versus expectant management
No. of No. of
Outcome or subgroup title studies participants Statistical method Effect size
1 Manual removal of the placenta 4 403 Risk Ratio (M-H, Fixed, 95% CI) 0.99 [0.84, 1.16]
2 Blood loss 1 122 Mean Difference (IV, Fixed, 95% CI) -44.0 [-168.51, 80.
51]
3 Blood loss = or > 500 ml after 2 177 Risk Ratio (M-H, Fixed, 95% CI) 0.98 [0.52, 1.82]
entry
entry
5 Blood transfusion 2 235 Risk Ratio (M-H, Fixed, 95% CI) 0.76 [0.41, 1.39]
6 Haemoglobin 24-48 hours 1 163 Mean Difference (IV, Fixed, 95% CI) 0.10 [-0.59, 0.79]
postpartum
7 Haemoglobin 40-45 days 1 93 Mean Difference (IV, Fixed, 95% CI) 0.40 [-0.23, 1.03]
postpartum
8 Maternal mortality 2 87 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
9 Serious maternal morbidity 2 87 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
10 Surgical evacuation of retained 1 178 Risk Ratio (M-H, Fixed, 95% CI) 0.79 [0.51, 1.22]
products of conception
11 Infection 1 176 Risk Ratio (M-H, Fixed, 95% CI) 0.48 [0.09, 2.54]
12 Stay at hospital more than two 1 176 Risk Ratio (M-H, Fixed, 95% CI) 1.19 [0.66, 2.15]
days
Comparison 2. Oxytocin solution versus expectant management
No. of No. of
2 Blood loss 1 130 Mean Difference (IV, Fixed, 95% CI) 89.0 [-51.35, 229.
35]
entry
entry
6 Haemoglobin 24-48 hours 1 166 Mean Difference (IV, Fixed, 95% CI) 0.0 [-0.61, 0.61]
postpartum
postpartum
days
Comparison 3. Oxytocin solution versus saline solution
No. of No. of
- by study quality
1.1 High-quality studies 8 1119 Risk Ratio (M-H, Fixed, 95% CI) 0.92 [0.83, 1.01]
1.2 Low-quality studies 4 157 Risk Ratio (M-H, Fixed, 95% CI) 0.84 [0.64, 1.10]
- by oxytocin dose
2.1 High dose (> 30 IU) 4 682 Risk Ratio (M-H, Fixed, 95% CI) 0.97 [0.86, 1.09]
2.2 Low dose (< 30 IU) 8 594 Risk Ratio (M-H, Fixed, 95% CI) 0.83 [0.71, 0.96]
3 Additional therapeutic 4 678 Risk Ratio (M-H, Fixed, 95% CI) 0.85 [0.59, 1.23]
uterotonics
4 Blood loss 3 180 Mean Difference (IV, Fixed, 95% CI) 48.84 [-13.16, 110.
84]
entry
entry
8 Haemoglobin 24-48 hours 1 167 Mean Difference (IV, Fixed, 95% CI) -0.10 [-0.76, 0.56]
postpartum
postpartum
10 Haemoglobin levels fall 1 541 Risk Ratio (M-H, Fixed, 95% CI) 1.01 [0.90, 1.14]
14 Nausea following injection 1 60 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
16 Fever 2 78 Risk Ratio (M-H, Fixed, 95% CI) 2.0 [0.09, 43.22]
17 Abdominal pain 1 18 Risk Ratio (M-H, Fixed, 95% CI) 2.0 [0.09, 43.22]
days
19 Length of third stage of labour 1 30 Mean Difference (IV, Fixed, 95% CI) 16.20 [-15.22, 47.
62]
20 Headache following injection 1 60 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
21 Shivering following injection 1 60 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
22 Hypertension following 1 60 Risk Ratio (M-H, Fixed, 95% CI) 0.0 [0.0, 0.0]
injection

Comparison 4. Oxytocin solution versus plasma expander
No. of No. of
2 Blood loss > 1000 ml 1 109 Risk Ratio (M-H, Fixed, 95% CI) 0.96 [0.34, 2.75]
Comparison 5. Prostaglandin solution versus saline solution
No. of No. of
uterotonics
18]
Comparison 6. Prostaglandin solution versus oxytocin solution
No. of No. of
uterotonics
19]
6 Time from injection to placental 1 21 Mean Difference (IV, Fixed, 95% CI) -6.0 [-8.78, -3.22]
delivery

Analysis 1.1. Comparison 1 Saline solution versus expectant management, Outcome 1 Manual removal of
the placenta.
Review: Umbilical vein injection for management of retained placenta
Comparison: 1 Saline solution versus expectant management
Outcome: 1 Manual removal of the placenta
Study or subgroup Experimental Control Risk Ratio Weight Risk Ratio

n/N n/N M-H,Fixed,95% CI M-H,Fixed,95% CI
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 ]
Kristiansen 1987 7/16 9/16 7.9 % 0.78 [ 0.38, 1.57 ]
Total (95% CI) 206 197 100.0 % 0.99 [ 0.84, 1.16 ]

Total events: 114 (Experimental), 113 (Control)
Heterogeneity: Chi2 = 0.93, df = 3 (P = 0.82); I2 =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 2

Favours treatment Favours control
Analysis 1.2. Comparison 1 Saline solution versus expectant management, Outcome 2 Blood loss.
Outcome: 2 Blood loss
Mean Mean
Study or subgroup Experimental Control Difference Weight Difference
N Mean(SD) N Mean(SD) IV,Fixed,95% CI IV,Fixed,95% CI
Carroli 1998 62 394 (305) 60 438 (390) 100.0 % -44.00 [ -168.51, 80.51 ]
Total (95% CI) 62 60 100.0 % -44.00 [ -168.51, 80.51 ]

Heterogeneity: not applicable
-100 -50 0 50 100

Favours experimental Favours control

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

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 ]

0.1 0.2 0.5 1 2 5 10

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

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 ]

0.1 0.2 0.5 1 2 5 10

favours treatment Favours control

Analysis 1.5. Comparison 1 Saline solution versus expectant management, Outcome 5 Blood transfusion.
Outcome: 5 Blood transfusion
Study or subgroup Experimental Control 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 ]

0.1 0.2 0.5 1 2 5 10

Analysis 1.6. Comparison 1 Saline solution versus expectant management, Outcome 6 Haemoglobin 24-48
hours postpartum.
Outcome: 6 Haemoglobin 24-48 hours postpartum
Mean Mean
Carroli 1998 82 9.8 (2.4) 81 9.7 (2.1) 100.0 % 0.10 [ -0.59, 0.79 ]
Total (95% CI) 82 81 100.0 % 0.10 [ -0.59, 0.79 ]

-10 -5 0 5 10

Analysis 1.7. Comparison 1 Saline solution versus expectant management, Outcome 7 Haemoglobin 40-45
days postpartum.
Outcome: 7 Haemoglobin 40-45 days postpartum
Mean Mean
Carroli 1998 44 10.8 (1.6) 49 10.4 (1.5) 100.0 % 0.40 [ -0.23, 1.03 ]
Total (95% CI) 44 49 100.0 % 0.40 [ -0.23, 1.03 ]

-10 -5 0 5 10
Analysis 1.8. Comparison 1 Saline solution versus expectant management, Outcome 8 Maternal mortality.
Outcome: 8 Maternal mortality

Gazvani 1998 0/26 0/29 0.0 [ 0.0, 0.0 ]
Kristiansen 1987 0/16 0/16 0.0 [ 0.0, 0.0 ]
Total (95% CI) 42 45 0.0 [ 0.0, 0.0 ]

Heterogeneity: Chi2 = 0.0, df = 0 (P<0.00001); I2 =0.0%
Test for overall effect: Z = 0.0 (P < 0.00001)
0.01 0.1 1 10 100


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

Gazvani 1998 0/26 0/29 0.0 [ 0.0, 0.0 ]
Kristiansen 1987 0/16 0/16 0.0 [ 0.0, 0.0 ]
Total (95% CI) 42 45 0.0 [ 0.0, 0.0 ]

0.01 0.1 1 10 100

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

Carroli 1998 25/90 31/88 100.0 % 0.79 [ 0.51, 1.22 ]
Total (95% CI) 90 88 100.0 % 0.79 [ 0.51, 1.22 ]

0.1 0.2 0.5 1 2 5 10


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

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 ]

0.1 0.2 0.5 1 2 5 10

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

Carroli 1998 20/90 16/86 100.0 % 1.19 [ 0.66, 2.15 ]
Total (95% CI) 90 86 100.0 % 1.19 [ 0.66, 2.15 ]

0.1 0.2 0.5 1 2 5 10

Favours treatment favours control

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

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 ]
Thiery 1987 9/19 10/13 9.3 % 0.62 [ 0.35, 1.08 ]
Total (95% CI) 234 210 100.0 % 0.87 [ 0.74, 1.03 ]

Heterogeneity: Chi2 = 6.88, df = 4 (P = 0.14); I2 =42%
0.1 0.2 0.5 1 2 5 10

Analysis 2.2. Comparison 2 Oxytocin solution versus expectant management, Outcome 2 Blood loss.
Mean Mean
Carroli 1998 70 527 (426) 60 438 (390) 100.0 % 89.00 [ -51.35, 229.35 ]
Total (95% CI) 70 60 100.0 % 89.00 [ -51.35, 229.35 ]

-100 -50 0 50 100


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

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 ]

0.1 0.2 0.5 1 2 5 10

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

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 ]

0.1 0.2 0.5 1 2 5 10


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

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 ]

0.1 0.2 0.5 1 2 5 10

Analysis 2.6. Comparison 2 Oxytocin solution versus expectant management, Outcome 6 Haemoglobin 24-
48 hours postpartum.
Mean Mean
Carroli 1998 85 9.7 (1.9) 81 9.7 (2.1) 100.0 % 0.0 [ -0.61, 0.61 ]
Total (95% CI) 85 81 100.0 % 0.0 [ -0.61, 0.61 ]

-10 -5 0 5 10

Analysis 2.7. Comparison 2 Oxytocin solution versus expectant management, Outcome 7 Haemoglobin 40-
45 days postpartum.
Mean Mean
Carroli 1998 47 10.9 (1.7) 49 10.4 (1.5) 100.0 % 0.50 [ -0.14, 1.14 ]
Total (95% CI) 47 49 100.0 % 0.50 [ -0.14, 1.14 ]

-10 -5 0 5 10
Analysis 2.8. Comparison 2 Oxytocin solution versus expectant management, Outcome 8 Maternal
mortality.

Gazvani 1998 0/26 0/29 0.0 [ 0.0, 0.0 ]
Kristiansen 1987 0/19 0/19 0.0 [ 0.0, 0.0 ]
Total (95% CI) 45 48 0.0 [ 0.0, 0.0 ]

0.01 0.1 1 10 100


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

Gazvani 1998 0/26 0/29 0.0 [ 0.0, 0.0 ]
Kristiansen 1987 0/19 0/16 0.0 [ 0.0, 0.0 ]
Total (95% CI) 45 45 0.0 [ 0.0, 0.0 ]

0.01 0.1 1 10 100

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

Carroli 1998 23/94 31/88 100.0 % 0.69 [ 0.44, 1.09 ]
Total (95% CI) 94 88 100.0 % 0.69 [ 0.44, 1.09 ]

0.1 0.2 0.5 1 2 5 10


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

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 ]

0.1 0.2 0.5 1 2 5 10

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

Carroli 1998 19/94 16/86 100.0 % 1.09 [ 0.60, 1.97 ]
Total (95% CI) 94 86 100.0 % 1.09 [ 0.60, 1.97 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.1. Comparison 3 Oxytocin solution versus saline solution, Outcome 1 Manual removal of the
placenta - by study quality.
Comparison: 3 Oxytocin solution versus saline solution
Outcome: 1 Manual removal of the placenta - by study quality
Study or subgroup Umbilical oxytocin Saline Risk Ratio Weight Risk Ratio
1 High-quality studies
Calderale 1994 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 ]
Weeks 2009 179/292 177/285 47.1 % 0.99 [ 0.87, 1.12 ]
Subtotal (95% CI) 572 547 87.2 % 0.92 [ 0.83, 1.01 ]

Total events: 310 (Umbilical oxytocin), 324 (Saline)
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 ]

Total (95% CI) 655 621 100.0 % 0.91 [ 0.82, 1.00 ]
Test for subgroup differences: Chi2 = 0.35, df = 1 (P = 0.55), I2 =0.0%
0.5 0.7 1 1.5 2


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

1 High dose (> 30 IU)

Rogers 2007 16/20 7/13 2.2 % 1.49 [ 0.86, 2.57 ]
Sivalingam 2001 9/19 10/16 2.9 % 0.76 [ 0.41, 1.39 ]
Weeks 2009 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 ]

2 Low dose (< 30 IU)
Calderale 1994 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 ]
Selinger 1986 9/15 8/15 2.1 % 1.13 [ 0.60, 2.11 ]
Subtotal (95% CI) 306 288 45.0 % 0.83 [ 0.71, 0.96 ]

Total (95% CI) 655 621 100.0 % 0.91 [ 0.82, 1.00 ]
Test for subgroup differences: Chi2 = 2.55, df = 1 (P = 0.11), I2 =61%
0.01 0.1 1 10 100


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

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 ]
Weeks 2009 31/284 26/281 53.6 % 1.18 [ 0.72, 1.93 ]
Total (95% CI) 346 332 100.0 % 0.85 [ 0.59, 1.23 ]

0.1 0.2 0.5 1 2 5 10

Analysis 3.4. Comparison 3 Oxytocin solution versus saline solution, Outcome 4 Blood loss.
Mean Mean
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 84 100.0 % 48.84 [ -13.16, 110.84 ]

-10 -5 0 5 10

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

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 ]
Weeks 2009 99/287 99/282 78.6 % 0.98 [ 0.78, 1.23 ]
Total (95% CI) 424 405 100.0 % 1.01 [ 0.83, 1.24 ]

0.1 0.2 0.5 1 2 5 10


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

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 ]
Weeks 2009 31/287 28/282 81.8 % 1.09 [ 0.67, 1.76 ]
Total (95% CI) 391 375 100.0 % 1.08 [ 0.70, 1.68 ]

0.1 0.2 0.5 1 2 5 10


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

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 ]
Weeks 2009 43/292 36/285 1.17 [ 0.77, 1.76 ]
Total (95% CI) 446 434 1.18 [ 0.84, 1.65 ]

0.1 0.2 0.5 1 2 5 10

Analysis 3.8. Comparison 3 Oxytocin solution versus saline solution, Outcome 8 Haemoglobin 24-48 hours
postpartum.
Mean Mean
Carroli 1998 85 9.7 (1.9) 82 9.8 (2.4) 100.0 % -0.10 [ -0.76, 0.56 ]
Total (95% CI) 85 82 100.0 % -0.10 [ -0.76, 0.56 ]

-10 -5 0 5 10

Analysis 3.9. Comparison 3 Oxytocin solution versus saline solution, Outcome 9 Haemoglobin 40-45 days
postpartum.
Mean Mean
Carroli 1998 47 10.9 (1.7) 44 10.8 (1.6) 100.0 % 0.10 [ -0.58, 0.78 ]
Total (95% CI) 47 44 100.0 % 0.10 [ -0.58, 0.78 ]

-10 -5 0 5 10
Analysis 3.10. Comparison 3 Oxytocin solution versus saline solution, Outcome 10 Haemoglobin levels fall.
Outcome: 10 Haemoglobin levels fall

Weeks 2009 185/274 178/267 100.0 % 1.01 [ 0.90, 1.14 ]
Total (95% CI) 274 267 100.0 % 1.01 [ 0.90, 1.14 ]

0.01 0.1 1 10 100


Analysis 3.11. Comparison 3 Oxytocin solution versus saline solution, Outcome 11 Maternal mortality.

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 ]
Weeks 2009 1/292 0/285 2.93 [ 0.12, 71.59 ]
Total (95% CI) 369 355 2.93 [ 0.12, 71.59 ]

0.01 0.1 1 10 100

Analysis 3.12. Comparison 3 Oxytocin solution versus saline solution, Outcome 12 Serious maternal
morbidity.

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 ]
Weeks 2009 0/292 1/285 0.33 [ 0.01, 7.95 ]
Total (95% CI) 369 355 0.33 [ 0.01, 7.95 ]

0.01 0.1 1 10 100


Analysis 3.13. Comparison 3 Oxytocin solution versus saline solution, Outcome 13 Surgical evacuation of
retained products of conception.

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 ]
Weeks 2009 2/292 2/285 6.7 % 0.98 [ 0.14, 6.88 ]
Total (95% CI) 420 406 100.0 % 0.89 [ 0.56, 1.40 ]

0.1 0.2 0.5 1 2 5 10


Analysis 3.14. Comparison 3 Oxytocin solution versus saline solution, Outcome 14 Nausea following
injection.
Outcome: 14 Nausea following injection

Hansen 1987 0/32 0/28 0.0 [ 0.0, 0.0 ]
Total (95% CI) 32 28 0.0 [ 0.0, 0.0 ]

0.01 0.1 1 10 100

Analysis 3.15. Comparison 3 Oxytocin solution versus saline solution, Outcome 15 Infection.

Carroli 1998 5/93 2/90 2.42 [ 0.48, 12.15 ]
Hansen 1987 0/32 0/28 0.0 [ 0.0, 0.0 ]
Weeks 2009 38/292 29/285 1.28 [ 0.81, 2.02 ]
Total (95% CI) 417 403 1.35 [ 0.87, 2.09 ]

0.1 0.2 0.5 1 2 5 10


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

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 ]

0.1 0.2 0.5 1 2 5 10

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

Bider 1996 1/11 0/7 100.0 % 2.00 [ 0.09, 43.22 ]
Total (95% CI) 11 7 100.0 % 2.00 [ 0.09, 43.22 ]

0.1 0.2 0.5 1 2 5 10


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

Carroli 1998 19/94 20/90 100.0 % 0.91 [ 0.52, 1.59 ]
Total (95% CI) 94 90 100.0 % 0.91 [ 0.52, 1.59 ]

0.1 0.2 0.5 1 2 5 10

Analysis 3.19. Comparison 3 Oxytocin solution versus saline solution, Outcome 19 Length of third stage of
labour.
Outcome: 19 Length of third stage of labour
Mean Mean
Selinger 1986 15 111.4 (43.2) 15 95.2 (44.6) 100.0 % 16.20 [ -15.22, 47.62 ]
Total (95% CI) 15 15 100.0 % 16.20 [ -15.22, 47.62 ]

-10 -5 0 5 10

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

Hansen 1987 0/32 0/28 0.0 [ 0.0, 0.0 ]
Total (95% CI) 32 28 0.0 [ 0.0, 0.0 ]

0.01 0.1 1 10 100

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

Hansen 1987 0/32 0/28 0.0 [ 0.0, 0.0 ]
Total (95% CI) 32 28 0.0 [ 0.0, 0.0 ]

0.01 0.1 1 10 100


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

Hansen 1987 0/32 0/28 0.0 [ 0.0, 0.0 ]
Total (95% CI) 32 28 0.0 [ 0.0, 0.0 ]

0.01 0.1 1 10 100

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

Makkonen 1995 49/68 22/41 100.0 % 1.34 [ 0.97, 1.85 ]
Total (95% CI) 68 41 100.0 % 1.34 [ 0.97, 1.85 ]

0.1 0.2 0.5 1 2 5 10


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

Makkonen 1995 8/68 5/41 100.0 % 0.96 [ 0.34, 2.75 ]
Total (95% CI) 68 41 100.0 % 0.96 [ 0.34, 2.75 ]

0.1 0.2 0.5 1 2 5 10

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

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 ]

0.1 0.2 0.5 1 2 5 10


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

Bider 1996 6/10 4/7 100.0 % 1.05 [ 0.46, 2.38 ]
Total (95% CI) 10 7 100.0 % 1.05 [ 0.46, 2.38 ]

0.1 0.2 0.5 1 2 5 10

Analysis 5.3. Comparison 5 Prostaglandin solution versus saline solution, Outcome 3 Blood loss.
Mean Mean
Bider 1996 10 210 (126.5) 7 231 (82) 100.0 % -21.00 [ -120.18, 78.18 ]
Total (95% CI) 10 7 100.0 % -21.00 [ -120.18, 78.18 ]

-10 -5 0 5 10

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

Bider 1996 3/10 0/7 100.0 % 5.09 [ 0.30, 85.39 ]
Total (95% CI) 10 7 100.0 % 5.09 [ 0.30, 85.39 ]

0.1 0.2 0.5 1 2 5 10

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

Bider 1996 1/10 0/7 100.0 % 2.18 [ 0.10, 46.92 ]
Total (95% CI) 10 7 100.0 % 2.18 [ 0.10, 46.92 ]

0.1 0.2 0.5 1 2 5 10


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

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 ]

0.1 0.2 0.5 1 2 5 10

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

Bider 1996 6/10 5/11 100.0 % 1.32 [ 0.58, 3.00 ]
Total (95% CI) 10 11 100.0 % 1.32 [ 0.58, 3.00 ]

0.1 0.2 0.5 1 2 5 10


Analysis 6.3. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 3 Blood loss.
Mean Mean
Bider 1996 10 210 (126.5) 11 229 (102.8) 100.0 % -19.00 [ -118.19, 80.19 ]
Total (95% CI) 10 11 100.0 % -19.00 [ -118.19, 80.19 ]

-10 -5 0 5 10
Analysis 6.4. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 4 Fever.
Outcome: 4 Fever

Bider 1996 1/10 1/11 100.0 % 1.10 [ 0.08, 15.36 ]
Total (95% CI) 10 11 100.0 % 1.10 [ 0.08, 15.36 ]

0.1 0.2 0.5 1 2 5 10


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

Bider 1996 3/10 1/11 100.0 % 3.30 [ 0.41, 26.81 ]
Total (95% CI) 10 11 100.0 % 3.30 [ 0.41, 26.81 ]

0.1 0.2 0.5 1 2 5 10

Analysis 6.6. Comparison 6 Prostaglandin solution versus oxytocin solution, Outcome 6 Time from
injection to placental delivery.
Outcome: 6 Time from injection to placental delivery
Mean Mean
Bider 1996 10 7 (3.2) 11 13 (3.3) 100.0 % -6.00 [ -8.78, -3.22 ]
Total (95% CI) 10 11 100.0 % -6.00 [ -8.78, -3.22 ]

-10 -5 0 5 10

WHATS NEW
Last assessed as up-to-date: 10 March 2011.
Date Event Description
18 January 2012 Amended 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 New search has been performed Search updated.
6 November 2008 Amended Converted to new review format.
6 July 2001 New search has been performed Search updated.
CONTRIBUTIONS OF AUTHORS
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.

DECLARATIONS OF INTEREST
G Carroli and A Weeks are the authors of two of the trials included in this review.
SOURCES OF SUPPORT
Internal sources
Centro Rosarino de Estudios Perinatales, Argentina.
School of Reproductive and Developmental Medicine, Division of Perinatal and Reproductive Medicine, The University of
Liverpool, UK.
External sources
Department of Reproductive Health and Research, World Health Organization, Switzerland.
Secretaria de Salud Publica, Municipalidad de Rosario, Argentina.
DIFFERENCES BETWEEN PROTOCOL AND REVIEW

The methods have been updated to reflect the Cochrane Handbook (Higgins 2008).
NOTES
None
INDEX TERMS
Medical Subject Headings (MeSH)

Injections, Intravenous; Oxytocics [ administration & dosage]; Oxytocin [ administration & dosage]; Placenta, Retained [ therapy];
Plasma Substitutes [administration & dosage]; Prostaglandins [administration & dosage]; Randomized Controlled Trials as Topic;
Sodium Chloride [administration & dosage]; Umbilical Veins
MeSH check words

Female; Humans; Pregnancy


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Umbilical vein injection for management of retained placenta

Nardin JM, Weeks A, Carroli G

Umbilical vein injection for management of retained placenta (Review)

Umbilical vein injection for management of retained placenta (Review) ii

Umbilical vein injection for management of retained placenta

Juan Manuel Nardin1 , Andrew Weeks2 , Guillermo Carroli1

Editorial group: Cochrane Pregnancy and Childbirth Group.

PLAIN LANGUAGE SUMMARY

Umbilical vein injection for management of retained placenta

BACKGROUND plus an uterotonic drug (to induce uterine contractions) seems a

Types of outcome measures Electronic searches

Umbilical vein injection for management of retained placenta (Review) 3

(3) Blinding (checking for possible performance bias)

Umbilical vein injection for management of retained placenta (Review) 4

Unit of analysis issues

Assessment of reporting biases

Umbilical vein injection for management of retained placenta (Review) 5

Umbilical vein injection for management of retained placenta (Review) 6

was compared to expectant management in five trials with 444

Umbilical vein injection for management of retained placenta (Review) 7

Umbilical vein injection for management of retained placenta (Review) 8

Umbilical vein injection for management of retained placenta (Review) 9

Umbilical vein injection for management of retained placenta (Review) 10

Umbilical vein injection for management of retained placenta (Review) 11

No statistical differences were found for any of the other evaluated

5. Prostaglandin solution versus saline

Umbilical vein injection for management of retained placenta (Review) 12

Oxytocin solution versus expectant

Oxytocin solution versus saline

Umbilical vein injection for management of retained placenta (Review) 13

References to studies excluded from this review Jarcho 1928

Umbilical vein injection for management of retained placenta (Review) 15

Characteristics of included studies [ordered by study ID]

Methods Random generation: computerized.

Interventions Group 1: UVI of prostaglandin F2 20 mg + saline solution 20 ml.

Notes Group 3 and 4 were excluded from analysis.

Bias Authors judgement Support for judgement

Random sequence generation (selection Low risk

Allocation concealment (selection bias) Unclear risk Not described.

Blinding (performance bias and detection High risk

High quality study? High risk

Methods Random generation: not stated. They said: Randomization list.

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

Umbilical vein injection for management of retained placenta (Review) 16

Bias Authors judgement Support for judgement

Random sequence generation (selection Unclear risk Randomized. No further description.

Allocation concealment (selection bias) Unclear risk Not described.

High quality study? Low risk

Interventions Group 1: UVI of oxytocin 20 IU 2 ml + saline solution 18 ml.

Umbilical vein injection for management of retained placenta (Review) 17

Bias Authors judgement Support for judgement

Random sequence generation (selection Low risk

Allocation concealment (selection bias) Low risk Adequate.

Incomplete outcome data (attrition bias) Low risk

Selective reporting (reporting bias) Low risk

Other bias Low risk

High quality study? Low risk

Methods Random generation: random number table.

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

Bias Authors judgement Support for judgement

Random sequence generation (selection Low risk

Allocation concealment (selection bias) Low risk Adequate.

Umbilical vein injection for management of retained placenta (Review) 18