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Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage

  1. Gina Westhoff1,*,
  2. Amanda M Cotter2,3,
  3. Jorge E Tolosa3,4

Editorial Group: Cochrane Pregnancy and Childbirth Group

Published Online: 30 OCT 2013

Assessed as up-to-date: 24 JUN 2013

DOI: 10.1002/14651858.CD001808.pub2


How to Cite

Westhoff G, Cotter AM, Tolosa JE. Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD001808. DOI: 10.1002/14651858.CD001808.pub2.

Author Information

  1. 1

    Stanford University and University of California-San Francisco, Stanford, CA, USA

  2. 2

    University of Limerick, Department of Obstetrics and Gynaecology, Limerick, Ireland

  3. 3

    Global Network for Perinatal and Reproductive Health, Portland, OR, USA

  4. 4

    Oregon Health and Science University, Department of Obstetrics and Gynecology, Portland, Oregon, USA

*Gina Westhoff, Stanford University and University of California-San Francisco, 300 Pasteur Dr. HH333, Stanford, CA, 94305-5317, USA. ginaw@stanford.edu. ginawesthoff@gmail.com.

Publication History

  1. Publication Status: New search for studies and content updated (conclusions changed)
  2. Published Online: 30 OCT 2013

SEARCH

 
Characteristics of included studies [ordered by study ID]
Abdel-Aleem 2010

MethodsRandomised controlled trial.

Women were randomly allocated to 1 of 3 groups by selecting the next number in a computer-generated random number sequence. The allocated group was noted inside opaque sealed envelopes. Not blinded.


ParticipantsPregnant woman who were expected to have a vaginal delivery at Women's Health Center Assiut, Egypt and the Department of Obstetrics and Gynecology, East London Hospital Complex, East London South Africa between September 1, 2006 and February 28, 2009. Women were excluded for medical complications as follows; hypertension, diabetes, previous cesarean section, abdominal wall not thin enough to allow adequate palpation of uterus after delivery.


InterventionsAll interventions were given after delivery of the anterior shoulder or after delivery of the neonate.

1) 10 IU IM oxytocin.

2) Sustained uterine massage shortly after delivery performed by the research midwives; massage was sustained for 30 minutes an involved manual stimulation of the whole surface of the uterus.

3) Combined management with 10 IU IM oxytocin plus uterine massage.

In all 3 groups active management was performed: the umbilical cord was clamped soon after delivery of the neonate and the placenta was delivered by controlled cord traction when the uterus became contracted. A plastic drape or a low profile plastic bedpan was placed under the mother's buttocks after delivery of the neonate to collect the blood lost within 30 minutes of delivery. For the group that did not initially receive oxytocin, injections of oxytocin were given if blood loss > 500 mL occurred during the 30-minute collection time.

Comparison for review is groups 1 and 3 combined vs group 2.


OutcomesBlood loss > 300 mL, > 500 mL or > 1000 mL within 30 minutes of delivery, delivery of the placenta within 30 minutes of neonate delivery, use of additional uterotonics or other procedures to manage haemorrhage, Hb level after 12-24 hours of < 8 g in 100 mL or < 10 g in 100 mL (South Africa only), blood transfusion, MRP or placenta not delivered in 30 minutes, maternal morbidity and adverse effects (nausea, vomiting, pain or discomfort).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskWomen were randomly allocated to 1 of 3 groups by selecting the next number in a computer-generated random number sequence.

Allocation concealment (selection bias)Low riskThe allocated group was noted inside opaque sealed envelopes.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNo mention of blinding procedures.

Incomplete outcome data (attrition bias)
All outcomes
Low riskMinimal loss.

Selective reporting (reporting bias)Unclear riskUnclear.

Other biasUnclear riskUnclear.

Bader 2000

MethodsQuasi-randomised controlled trial.

Women were randomly allocated. No further information is given aside from confirmation that the allocation was randomised.

Not blinded.


Participants180 women in the third stage of labour at the Gynaecological Clinic of the University of Witten/Herdecke, part of the Marienhospital Witten.

Primary grounds for exclusion included complicated pregnancies requiring oxytocin stimulation during delivery, multiple pregnancies, weight over 100 kg, uterus myomatosus, previous treatment with oxytocin and conditions tending to increased blood loss.

Secondary grounds were the need for surgical intervention (forceps or vacuum) in delivery, unusually high levels of blood loss of unknown origin and placenta delivery times longer than 30 min after delivery.


InterventionsAfter delivery of the fetus, women were randomly assigned to receive;

1) acupuncture: 2 needles (0.3 x 25 mm) applied 1.5 cm on either side of the navel (point Ni16);

2) oxytocin: 3 units administered intravenously directly after delivery;

3) control: no treatment.

After the birth, waterproof bedding was laid down in order to measure blood loss. The time between delivery of the baby and delivery of the placenta was measured in minutes. After delivery of the placenta the waterproof bedding was removed and weighed (to measure blood loss). The Hb levels of each patient were measured on arrival in the delivery room and on leaving the hospital.

The midwives involved were advised not to interfere postpartum with the uterus and umbilical cord--expectant management.

Comparison for review is group 2 vs group 3.


OutcomesPrimary outcomes included blood loss and the length of the placental delivery period. The duration of the birth and the delivery period were also recorded.


NotesOnly the oxytocin and control group data is used in the analysis.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskMethod of randomisation not described other than "allocation was randomised".

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
High riskThere were a total of 20 exclusions on various secondary exclusion grounds: 1 in the control group, 12 in the acupuncture group and 7 in the oxytocin group, leaving a total of 160 patients.

Selective reporting (reporting bias)Low riskAll outcomes reported.

Barbaro 1961

MethodsQuasi-randomised controlled trial.

No randomisation methodology described.
Timing of randomisation not stated.
Not blinded.


ParticipantsWomen admitted for delivery in 1 of 2 obstetric units in hospital in Melbourne, Australia. Over 28 weeks. No antepartum or labour complications.


Interventions(1) IM SE505 (synthetic preparation-mixture of 5 units of syntocin and 0.5 mg ergometrine maleate in 1 mL) given immediately after delivery of the baby (n = 300).
(2) IV 0.5 mg ergometrine maleate given immediately after delivery of the baby + IM 0.5 mg ergometrine maleate after delivery of placenta (n = 300).

No comment regarding other actions performed relating to active management of the third stage.

Blood loss was carefully measured; allowances were made for contamination with liquor or urine and for blood contained within swabs and packs.


OutcomesPPH (> 600 mL); average blood loss 266 vs 219 mL (SD not given); average duration of 3rd stage 16 vs 13 minutes (SD not given).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo randomisation method described.

Allocation concealment (selection bias)Unclear riskNo concealment method described.

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAdequate.

Selective reporting (reporting bias)Low riskAll outcomes reported.

Other biasUnclear riskUnclear.

Bonham 1963

MethodsRandomised controlled trial.

Selection of drug was made by random numbers. Timing of randomisation not stated.
Not blinded.


ParticipantsAll vaginal deliveries April 1961 to October 1962 in hospital in London, except: multiple pregnancies, previous PPH or manual removal, forceps and breech deliveries must be post-randomisation exclusions but does not state how many were randomised), parity 4 or more, induction or augmentation with syntocinon.


Interventions(1) IM 0.5 mg ergometrine + 5 units synthetic oxytocin, given at crowning of the head (n = 391).
(2) IM 0.5 mg ergometrine, given at crowning of the head (n = 416).
[Third group of ergometrine + hyaluronidase not considered for this review.]
Women were also selected in random 2-week groups to either controlled cord traction (n = 199 ergometrine + oxytocin vs 217 ergometrine alone) or maternal effort/fundal pressure (192 vs 199)--combination of both active and expectant management.
No information about timing of cord clamping/cutting.

Blood loss was estimated by adding to the measured quantity a figure for loss on linen and swabs used during the perineal repair.


OutcomesPrimary PPH (> 568 mL estimated by adding to measured quantity a figure for loss on linen and swabs used for perineal repair); mean blood loss (154 vs 178 mL, SD not given); mean length of third stage (6.3 vs 6.2 minutes, SD not given); prolonged third stage (> 30 minutes); MRP.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation by numbers; procedure not described in detail.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
High riskInadequate.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition described; no loss of data.

Selective reporting (reporting bias)Low riskAll outcomes reported.

Other biasUnclear riskUnclear.

De Groot 1996

MethodsRandomised controlled trial.

Hospital pharmacy supplied numbered boxes of tablets and ampoules according to computer-generated randomisation list. Informed consent asked in early labour. Assigned before delivery of baby's head. Double-blind for oral ergometrine vs placebo and unblinded for ergometrine and/or placebo vs oxytocin. Randomisation 1:2:2, oxytocin to ergometrine to placebo. Multicentre.


Participants2 university hospitals, a midwifery school and independent midwives in and around Nijmegen, Netherlands. Women expecting to deliver in one of these settings, and who did not develop following exclusion criteria: refusal, cardiovascular disease/hypertension, multiple pregnancy, non-cephalic presentation, polyhydramnios, tocolysis 2 hours prior to delivery, anticoagulant therapy, stillbirth, APH, chemical induction or augmentation (oxytocin, prostaglandins), instrumental/operative delivery (some of these must have been post-randomisation exclusions), anaemia Hb < 6.8 mmol/L (timing not stated), previous third stage complications.
4 of 371 women were assigned to the study erroneously (3 forceps, 1 augmentation) and were excluded post-randomisation. Otherwise eligible women wishing a natural childbirth refused to enter the trial (numbers not stated).


InterventionsAll 3 interventions given immediately after birth of baby:
(1) IM 5 IU oxytocin;
(2) oral 0.4 mg ergometrine;
(3) oral placebo.
Other third stage management expectant (although no information given about timing of cord clamping/cutting). When mother feels contractions or there are signs of separation, maternal effort encouraged, adopting position to aid gravity. If necessary, flat hand on abdomen to act as brace to aid pushing. Re-attempt if placenta does not deliver spontaneously. If haemorrhage, administer extra oxytocics and/or controlled cord traction.

Blood loss measured gravimetrically--fresh perineal pad under perineum to absorb blood or fluid; gauzes and pads collected until 1 hour after delivery of placenta and weighed. 100 g increase in weight considered equivalent to 100 mL blood.

Comparison for review is group 1 vs. group 2 and group 1 vs group 3.


OutcomesMean blood loss (mL); PPH (>= 500 mL); severe PPH (>= 1000 mL); length of third stage (11 (range 4-90), 15 (2-90), 14 (3-55) in oxytocin, ergometrine and placebo groups respectively. No information about whether mean or median, and SD not given); blood pressure 15, 30, 45 and 60 minutes after delivery of placenta, in institutional deliveries only (oral ergometrine showed no significant elevation); use of further oxytocics; MRP; transfusion.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskNumbered boxes of tablets and ampoules according to computer-generated randomisation list.

Allocation concealment (selection bias)Low riskNo difference could be detected between boxes.

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAttrition minimal and described.

Selective reporting (reporting bias)Low riskAll outcomes described.

Other biasUnclear riskUnclear.

Francis 1965

MethodsQuasi-randomised controlled trial.

'Ampoules used in rotation and participants were unselected'.
Blinded.


Participants2 maternity hospitals in Liverpool, UK. in 1961.
All women expected to deliver except those in whom an abnormal third stage was anticipated (previous PPH, instrumental or breech deliveries, twin pregnancies, APH, severe anaemia, IV oxytocin for induction or augmentation).


Interventions(1) 1 mL IM ergometrine-oxytocin (5 IU oxytocin + 0.5 mg per 1 mL ergometrine) after delivery of baby and cord divided, AND 1 mL water after placental delivery (n = 171).
(2) 0.5 mg IM ergometrine after delivery of baby and cord divided, AND 1 mL water after placental delivery (n = 183).
(3) 1 mL IM water after delivery of baby and cord divided, AND 0.5 mg IM ergometrine after placental delivery (n = 167).
The collection of blood commenced with birth of the baby and continued for one hour after delivery. Swabs were rung out manually. Blood loss was measured in a graduated jug.

When signs of descent became apparent, the placenta delivered with uterine massage and cord traction--active management.
Comparison in review is between groups 1 and 2.


OutcomesBlood loss (average 4.9, 6.4, 7.0 in groups 1, 2 and 3 respectively - no SD given); for the review, loss of > 20 oz has been taken as PPH; retained placenta (> 20 minutes).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskTreatments were rotated, no random sequence generated.

Allocation concealment (selection bias)Unclear riskNot described.

Blinding (performance bias and detection bias)
All outcomes
Low riskVials were blinded to personnel, participants and outcome assessors.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll outcomes reported.

Selective reporting (reporting bias)Low riskNo attrition.

Other biasUnclear riskUnclear.

Fugo 1958

MethodsRandomised controlled trial.

Numbered identical drug packages administered in rotation. Number meaningless to obstetrician.
Blinded.


ParticipantsWomen delivering in a hospital in Chicago, USA.
No details given of inclusion/exclusion criteria, but description of study participants showed that half had labour over 8 hours, and 98% received some anaesthetic agent.


InterventionsAll administered intravenously in 2 mL with anterior shoulder.
(1) 2 IU oxytocin (natural oxytocin) n = 168.
(2) 2 IU syntocinon (synthetic oxytocin) n = 156.
(3) 4 mg ergonovine 149.
(4) 80 mg U3772 (alpha, alpha diphenyl gamma dimethylamino N-methyl valeramide-HCl) n = 151.
Blood lost when the placenta separated was collected in a basin containing 200 mL of 4% sodium oxalate solution as an anticoagulant and was measured in a graduated jug.

Expectant management of the third stage with MRP at 10 minutes for teaching purposes.
Comparison for review is groups 1 and 2 combined vs group 3.


OutcomesMethod of placental delivery (high % of manual removals for teaching purposes if haemorrhage or undelivered within 10 minutes); length of third stage (not significantly different between groups but data only given for those delivered spontaneously, i.e. within 10 minutes); blood loss with placenta; (1 hour postpartum (?) average blood loss 50.2 vs 40.8 mL; no SDs given).


NotesGiven the high number of manual placental removals for teaching purposes, the data from this trial were not used due to concern for methodologic bias and lack of clinical translatability of this trial as MRP this early in the third stage is not standard of care.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation method not described.

Allocation concealment (selection bias)Low riskIdentical packages were used.

Blinding (performance bias and detection bias)
All outcomes
Low riskBlinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll outcomes reported.

Selective reporting (reporting bias)Low riskNo significant attrition.

Other biasUnclear riskUnclear.

Ilancheran 1990

MethodsQuasi-randomised controlled trial.

'Consecutive participants divided equally into 4 subgroups, distribution being done on a random basis'.


ParticipantsWomen in spontaneous labour between 38 and 42 weeks' gestation with normal vertex deliveries in hospital in Singapore. 17/20 were multigravid.


InterventionsControl group and 3 groups given IV uterotonic in 'standard' doses with the delivery of the anterior shoulder.

A. No oxytocic in third stage.
B. Oxytocin.
C. Ergometrine-oxytocin.
D. Ergometrine.

Blood loss estimation technique not described.

Other methods to manage third stage of labour not described.

Comparisons for this review are: B vs A; B vs D; C vs D.


OutcomesProstaglandin levels 5, 15b and 30 minutes after delivery (significant rise in all 4 groups but no differences between the groups); PPH.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskWomen randomly assigned into groups; no computer sequence.

Allocation concealment (selection bias)Unclear riskUnclear.

Blinding (performance bias and detection bias)
All outcomes
Unclear riskNot described.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot described.

Selective reporting (reporting bias)Unclear riskNot described.

Jago 2007

MethodsRandomised controlled trial.

Randomisation was performed using a computer-generated table of random numbers, which were labelled on envelopes containing the drug (ergometrine or oxytocin).


Participants510 consenting normotensive women with singleton pregnancies and no proteinuria at a Hospital in Nigeria.

Excluded those with history of hypertensive disorders of pregnancy, hypertension, chronic renal disease, endocrine disorders, vascular or cardiac disease, on anticoagulant therapy, having epidural anaesthesia, with allergy to one of the drugs under study, and those with intended instrumental/operative delivery.


InterventionsAt delivery of the anterior shoulder:

A. oxytocin 10 IU IV (n = 256).

B. ergometrine 0.5 mg IM (n = 254).

Management of the third stage of labour not otherwise described.

Technique for measurement of blood loss not described.


OutcomesElevated blood pressure (> 140/90 mmHg).

Estimated blood loss (mL).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskComputer-generated table of random numbers.

Allocation concealment (selection bias)Low riskLabelled envelopes containing the drug.

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo loss to follow-up reported for the outcome included in the review.

Selective reporting (reporting bias)Unclear riskNo data.

Other biasUnclear riskNo data.

Jerbi 2007

MethodsQuasi randomised trial.

Not stated. Authors say: "...women were randomly allocated to...".


Participants130 women with singleton pregnancies at term who were expected to deliver vaginally in a hospital in Tunisia.

Excluded: placenta previa, APH, non-cephalic presentation, history of PPH, intrauterine death, parity > 5, caesarean section, uterine fibroids, anticoagulant therapy.


InterventionsAt the time of delivery of the anterior shoulder:

A. oxytocin 5 IU IV (n = 65);

B. no oxytocin (n = 65).

Authors say that the comparison arms are active vs expectant management--active is defined as receiving prophylactic oxytocin. The third stage of labour was managed in the same way for all women: immediate cord clamping and cutting, controlled cord traction and gentle fundal pressure.


OutcomesDecrease in haematocrit, decrease in Hb concentration, duration of the third stage of labour (min), MRP, maternal Hb concentration, postpartum anaemia.

Total blood loss was not an outcome.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated.

Allocation concealment (selection bias)Unclear riskNot stated. Authors only say: "...women were randomly allocated to...".

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo loss to follow-up reported for the outcomes included in the review.

Selective reporting (reporting bias)Unclear riskNo data.

Other biasUnclear riskNo data.

McGinty 1956

MethodsQuasi-randomised trial.

'Cases picked at random'.
Unblinded.


ParticipantsAll vaginally delivered under pudendal block and demerol/scopolamine, in hospital in United States of America.


InterventionsDrug given at birth of anterior shoulder:
A. 1 mL normal saline intravenously (n = 50);
B. 0.2 mg methergine intravenously (n = 50);
C. 0.2 mg ergonovine intravenously (n = 50);
D. oxytocin 5 IU each intravenously and intramuscularly (n = 50).
Comparisons for this review:
D vs A; D vs B and C.

No information about other aspects of third stage management.


OutcomesDiastolic and systolic blood pressure 5, 15 and 60 minutes after administration - although data not provided for control group; estimated severe blood loss over 1000 mL mentioned for 1 women in methergine series and 1 in control group (not included in data tables as unlikely to have been systematically recorded).


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"cases picked at random". Randomisation technique not described.

Allocation concealment (selection bias)Unclear riskAllocation concealment not described.

Blinding (performance bias and detection bias)
All outcomes
High riskUnblinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear.

Selective reporting (reporting bias)Unclear riskUnclear.

Moodie 1976

MethodsQuasi-randomised trial.

Not stated, authors say "...the allocation being at random..."..


Participants148 women with instrumental deliveries (143 forceps, 5 vacuum) under epidural anaesthesia in a Hospital in New Zeland.

Excluded multiple births and breech presentation.


InterventionsAt delivery of the anterior shoulder:

A. oxytocin 5 IU IV (n = 70);

B. ergometrine 0.5 mg IV (n = 78).

No mention of other aspects of the management of the third stage of labour.


OutcomesBlood loss (mL).

Emetic sequelae (retching or vomiting and nausea).


NotesBlood loss was measured only in 54% of women (80/148), so this outcome was not included in this review.


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNot stated.

Allocation concealment (selection bias)Unclear riskNot stated. Authors only say: "...the allocation being at random...".

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo (for nausea and vomiting). 46% of women excluded from outcome "blood loss", thus this outcome was not included in the review.

Selective reporting (reporting bias)Unclear riskNo data.

Other biasUnclear riskNo data.

Nordstrom 1997

MethodsDouble-blind randomised trial.
2 sets of ampoules prepared and numbered according to computer-generated schedule. Contents unknown to women or caregivers.


ParticipantsHospital in Sweden.
Singleton cephalic vaginal deliveries.


Interventions1 mL IV after delivery of baby of either;
1) 10 IU oxytocin.
2) Saline.

Passive (expectant) management of the placenta.

Blood loss was calculated by measuring collected blood and adding what was estimated to have been absorbed by surgical cloths and tissues.


OutcomesBlood loss; additional oxytocin (data tables give methylergometrine; clarification about other oxytocics sought from authors), Hb, blood transfusion; manual removal.


NotesAdditional oxytocin (data tables give methylergometrine; clarification about other oxytocics sought from authors).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk2 sets of ampoules prepared and numbered according to computer-generated schedule.

Allocation concealment (selection bias)Low riskNo difference in appearance of ampoules.

Blinding (performance bias and detection bias)
All outcomes
Low riskContents unknown to women or caregivers.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo significant attrition.

Selective reporting (reporting bias)Low riskAll outcomes reported.

Orji 2008

MethodsRandomised controlled trial.

Eligible participants who gave informed consent were randomly allocated to either oxytocin or ergometrine group. Allocation was done by opening a sealed envelope from a pack that had been arranged serially. Not blinded.


Participants600 consenting women in labour with no illnesses or added risk in the active phase at 2 tertiary hospitals in Nigeria.

Excluded those with hypertensive disorders of pregnancy, packed cell volume < 30%, history of PPH, haemoglobinopathy, heart disease or caesarean section.


InterventionsAt delivery of the anterior shoulder:

A. oxytocin 10 IU IV (n = 297);

B. ergometrine 0.25 mg IV (n = 303).

In both groups the third stage of labour was managed actively.

Blood loss was measured using a pre-weighed guaze that was weighed again after delivery.


OutcomesPrimary outcomes: PPH (> 500 mL), severe PPH (> 1000 mL).

Secondary outcomes: retained placenta, need for blood transfusion, MRP, estimated blood loss (mL, nausea, vomiting, headaches, elevated blood pressure, need for additional oxytocics.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskRandomly assigned to previously determined sequence.

Allocation concealment (selection bias)Low risk"...sealed envelopes arranged serially...".

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo (for the outcomes reported).

Selective reporting (reporting bias)Unclear riskNo data.

Other biasUnclear riskNo data.

Pierre 1992

MethodsQuasi-randomised trial.

Leaflets marked from 1-1000 alternate allocation 'this made possible a control of selection bias at entry by the authors as the order in the trial had the same chronology as the date and time of entry in the labour ward'.


ParticipantsWomen expecting to deliver vaginally in hospital in France. Only exclusions - breech, twins, APH, refusal.


InterventionsActive management of third stage with (n = 488) and without 5 IU IV oxytocin (n = 488) with the anterior shoulder.

Blood loss was estimated by placing a large plastic sheet under the patient's bottom from delivery of the infant until delivery of the placenta.

Third stage managed actively.


OutcomesBlood loss; length of third stage, MRP, maternal side effects.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskEnvelopes labelled in sequence. selection at entry into the hospital. no random sequence.

Allocation concealment (selection bias)Low riskEnvelopes sealed and randomly labelled.

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll outcomes reported.

Poeschmann 1991

MethodsRandomised trial.

Hospital pharmacy supplied numbered boxes. Allocation of boxes was by order of entry to the labour ward. A nurse not working in the labour room prepared the injection.


ParticipantsApril 1986 -88, 2 hospitals in Netherlands.
Uncomplicated singleton term pregnancies in spontaneous labour with spontaneous vaginal deliveries and Hobel score of less than 10.


InterventionsAfter birth of baby:
A. IM 5 IU oxytocin;
B. 500 micrograms sulprostone;
C. saline.

Comparison in this review is A vs C.

Cord was clamped within 1 min of birth; otherwise expectant management of the third stage was performed.

Blood loss was calculated by measuring the amount of blood and clots collected in the bedpan and by weighing the bloodstained swabs and linen obtained during 1 hr postpartum.


OutcomesBlood loss; need for additional oxytocics; length of third stage.


Notes77 women were entered into the trial; 3 were excluded because of induction of labour (2) and vacuum extractin (1).


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskA random treatment allocation list was previously prepared.

Allocation concealment (selection bias)Low riskAdequate.

Blinding (performance bias and detection bias)
All outcomes
Low riskNurse not working in labour room prepared the injection. injection type blinded to participant and personnel.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll outcomes reported.

Other biasHigh riskTrial stopped at 2 years due to organisational issues.

Saito 2007

MethodsQuasi random: "...women were allocated to a group in a temporal manner (...) selected weekly or monthly, as determined by each hospital, in alternate shifts".


Participants343 consenting women with low risk of PPH at 4 hospitals in Japan

Excluded: contraindication for ergometrine, multiple pregnancies, non-cephalic presentation, uterine fibroids or deformity, placenta previa, history of PPH, parity > 4, previous caesarean section, severe anaemia, preeclampsia, epidural anaesthesia, use of oxytocics, anticoagulation therapy, estimated baby weight < 2000 g or > 4000 g.


InterventionsShortly after delivery of the baby:

A. oxytocin 5 IU IM (n = 156);

B. methylergometrine 0.2 mg IM (n = 187).

Active management of the third stage of labour in both groups. immediate cord clamping and cutting, controlled cord traction.

Blood loss was calculated objectively by measuring the amount of collected blood and by the weighting of surgical sponges, clothes and drapes by experienced attending midwives who were not involved in the administration of prophylactic oxytocics.


OutcomesBlood loss (mL), maternal blood pressure, nausea, vomiting, headache, chest pain, dyspnoea, duration of the third stage (min), additional oxytocics, blood transfusion, MRP.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskQuasi random: "...women were allocated to a group in a temporal manner (...) selected weekly or monthly, as determined by each hospital, in alternate shifts.".

Allocation concealment (selection bias)High riskInadequate. "...women were allocated to a group in a temporal manner (...) selected weekly or monthly, as determined by each hospital, in alternate shifts."

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo loss to follow-up reported for the outcomes included in the review.

Selective reporting (reporting bias)Unclear riskNo data.

Other biasUnclear riskNo data.

Soiva 1964

MethodsQuasi-randomised trial.

Every third normal parturient.


ParticipantsHospital, Finland.
Spontaneous, singleton, cephalic.


InterventionsImmediately after birth of baby.
No efforts to expel placenta during first contraction of third stage.
IV methergine 0.12-0.2 mg
IM ergometrine-oxytocin (IU oxytocin + 0.5 ergometrine).
Not clear whether rest of third stage managed actively or expectantly.


OutcomesBlood loss; duration of third stage, retained placenta, complications, MRP.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High risk"every third participant". No random sequence generation used.

Allocation concealment (selection bias)Unclear riskNo allocation concealment described.

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskUnclear.

Selective reporting (reporting bias)Unclear riskUnclear.

Sorbe 1978

MethodsQuasi-randomised trial.

Alternate - odd and even numbers of mothers' hospital records.
Not blinded.


ParticipantsHospital in Sweden.


InterventionsIV after delivery of anterior shoulder.
0.2 mg ergometrine.
10 IU oxytocin.
Expectant management of the third stage was routine.

Blood was collected in a specially designed bedpan which was placed under the buttocks of the women immediately after the delivery of the child. The measurement of the blood loss during the 2 hour period was then performed with a graduated glass.


OutcomesBlood loss; MRP, placental separation time.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)High riskRandomisation by odd/even hospital record numbers.

Allocation concealment (selection bias)Unclear riskNo allocation concealment described.

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded.

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot described.

Vaughan Williams1974

MethodsQuasi-randomised trial.

"Patients were randomly assigned to one of six treatment groups." No information about blinding or allocation concealment described.


Participants51 women in labour at the Royal Sussex County Hospital, Brighton, who required an IV infusion. Inclusion criteria was no known antenatal complications and expectation to have a spontaneous vaginal delivery. Patients with complications during labour were excluded. Informed consent was obtained.


InterventionsWomen were randomly assigned to 1 of 6 treatment groups:

1) no treatment, control;

2) 0.5 mg ergometrine IV with delivery of the anterior shoulder;

3) 0.5 mg ergometrine IV with delivery of the baby;

4) 10 IU oxytocin IV with delivery of the anterior shoulder;

5) ergometrine 0.5 mg plus 5 IU oxytocin IM with delivery of the anterior shoulder;

6) 10 mg diazepam IM in the late first stage of labour followed by ergometrine 0.5 mg plus 5 IU oxytocin IM with delivery of the anterior shoulder.

Placenta was delivered actively by controlled cord traction.

Blood loss was measured by collection in a kidney dish placed below the perineum after delivery of the infant.

Comparisons for this review are group 1 vs. 4, groups 2 and 3 vs. group 4, and groups 5 and 6 vs group 2 and 3.


OutcomesPrimary outcomes were mean CVP and blood loss.


Notes


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation not described.

Allocation concealment (selection bias)Unclear riskAllocation concealment not described.

Blinding (performance bias and detection bias)
All outcomes
High riskNo blinding.

Incomplete outcome data (attrition bias)
All outcomes
Low riskAll outcomes reported.

Selective reporting (reporting bias)Unclear riskUnclear.

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Boucher 2004Comparison of intramuscular carbetocin to a 2-hour IV oxytocin infusion administered after delivery of the placenta.

Dickinson 2009Comparison of oxytocin, misoprostol and no additional medication for the third-stage management after second trimester medical termination.

Docherty 1982Oxytocin versus ergometrine-oxytocin (subject of separate review).

Dommisse 1980No randomisation of treatment groups.

Dumoulin 1981Oxytocin (different doses) versus ergometrine-oxytocin (subject of separate review).

Friedman 1957Likely to be considerable bias after entry to study as 27% of the 1221 were 'deleted from the study' as inadequate observations were obtained. No other reasons given, and no indication of whether these women were missing in similar proportions from the 5 intervention groups.

Gerstenfeld 2001Comparison of oxytocin with misoprostol (subject of separate review).

Hacker 1979No randomisation of treatment groups.

Hoffman 2006bComparison of oxytocin within the context of active vs expectant management (subject of a separate review).

Howard 1964Oxytocin, methergine or placebo given after delivery of the placenta.

Huh 2000Excluded as only different timing of administration.

Irons 1994Comparison of nipple stimulation to ergometrine-oxytocin which is not a subject of this review.

Jackson 2001Comparison of oxytocin administered before and after placental delivery so the only difference is timing of administration.

Khan 1997Comparison of prophylactic oxytocin within context of active management vs oxytocin after placental delivery within context of expectant management (subject of separate review by Prendiville et al: Active versus expectant management of third stage of labour - see Prendiville 2000).

Kundodyiwa 2001Comparison of oxytocin with misoprostol (subject of separate review).

Lokugamage 2001Comparison of oxytocin to misoprostol (subject of separate review) and at caesarean section.

Muller 19965 IU IV oxytocin with crowning of head and Brandt-Andrews vs expectant. Abstract only, in French and German. No clinical data available from authors.

Newton 1961Oxytocin or placebo given after delivery of the placenta.

Nieminen 1963No randomisation of treatment groups.

Parsons 2004Comparison of oxytocin with misoprostol (subject of separate review).

Porter 1991Only difference is different route of administration.

Ramirez 2001Inadequate information available about randomisation and available only as abstract.

Rouse 2011Comparison between different doses of oxytocin without placebo or alternate uterotonic.

Sariganont 1999No randomisation of treatment groups.

Schaefer 2004Excluded as only difference is timing of administration.

Schemmer 2001Comparison of oxytocin administered before and after placental delivery so the only difference is timing of administration.

Soriano 1995Compares oxytocin with oxytocin plus ergometrine (subject of separate review).

Stanton 2012Manuscript published is of study protocol only, data planned to be analysed in 2013.

Stearn 1963Allocation was to 2 different consultants, 1 of whom gave all patients ergometrine-oxytocin, and the other to give 'normal' cases ergometrine with hyalase and abnormal given IV ergometrine.

Symes 1984Compares oxytocin with oxytocin plus ergometrine (subject of separate review).

Tessier 2000Excluded as only different routes of administration.

Thornton 1988Strong likelihood of post-entry bias as alternate allocation used for 65, but 40 were withdrawn 40 as did not meet inclusion criteria, leaving 10 and 15 in trial comparing oxytocin vs no oxytocin within active management. Primary outcome plasma oxytocin concentration.

Tita 2012Comparison between different doses of oxytocin without placebo or alternate uterotonic.

Vasegh 2005Comparison of active vs expectant management of the third stage of labour (subject of a separate review). Study design information not available.

Wetta 2011Comparison between different doses of oxytocin without placebo or alternate uterotonic

Yuen 1995Oxytocin vs ergometrine-oxytocin (subject of separate review).

 
Comparison 1. Oxytocin versus no uterotonics

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PPH (clinically estimated blood loss > or = 500 mL)64203Risk Ratio (M-H, Random, 95% CI)0.53 [0.38, 0.74]

 2 Therapeutic uterotonics43174Risk Ratio (M-H, Random, 95% CI)0.56 [0.36, 0.87]

 3 Severe PPH (clinically estimated blood loss > or = 1000 mL)54162Risk Ratio (M-H, Random, 95% CI)0.62 [0.44, 0.87]

 4 Mean blood loss (mL)51402Mean Difference (IV, Random, 95% CI)-99.46 [-181.97, -16.95]

 5 Maternal haemoglobin concentration (Hb) < 9 g/dL 24 to 48 hours postpartum31645Risk Ratio (M-H, Random, 95% CI)0.78 [0.60, 1.00]

 6 Blood transfusion33120Risk Ratio (M-H, Random, 95% CI)0.89 [0.44, 1.78]

 7 Third stage greater than 30 minutes11947Risk Ratio (M-H, Fixed, 95% CI)2.55 [0.88, 7.44]

 8 Mean length of third stage (minutes)3294Mean Difference (IV, Random, 95% CI)-3.61 [-9.06, 1.83]

 9 Manual removal of the placenta64320Risk Ratio (M-H, Random, 95% CI)1.26 [0.88, 1.81]

10 Diastolic blood pressure >100 mm Hg between delivery of the baby and discharge from the labour ward00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

11 Vomiting between delivery of the baby and discharge from the labour ward00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 12 Nausea between delivery of the baby and discharge from the labour ward152Risk Ratio (M-H, Fixed, 95% CI)0.29 [0.01, 6.74]

13 Headace between delivery of the baby and discharge from the labour ward00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 2. Oxytocin versus no uterotonics--subgroup analyses

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PPH (clinically estimated blood loss > or = 500 mL); randomised v. quasi-randomised trials64203Risk Ratio (M-H, Random, 95% CI)0.53 [0.38, 0.74]

    1.1 Randomised trials only (low risk of bias)
33171Risk Ratio (M-H, Random, 95% CI)0.61 [0.48, 0.77]

    1.2 Quasi-randomised trials (high risk of bias)
31032Risk Ratio (M-H, Random, 95% CI)0.38 [0.19, 0.76]

 2 PPH (clinically estimated blood loss > or = 500 mL); active v. expectant management54193Risk Ratio (M-H, Random, 95% CI)0.53 [0.38, 0.74]

    2.1 Active management
22920Risk Ratio (M-H, Random, 95% CI)0.39 [0.22, 0.72]

    2.2 Expectant management
31273Risk Ratio (M-H, Random, 95% CI)0.64 [0.49, 0.84]

 3 PPH (clinically estimated blood loss > or = 500 mL); IM v. IV oxytocin64203Risk Ratio (M-H, Random, 95% CI)0.53 [0.38, 0.74]

    3.1 IV oxytocin
31980Risk Ratio (M-H, Random, 95% CI)0.41 [0.21, 0.79]

    3.2 IM oxytocin
32223Risk Ratio (M-H, Random, 95% CI)0.65 [0.47, 0.89]

 4 PPH (clinically estimated blood loss > 500 mL); oxytocin dose < 10 IU v. 10 IU54193Odds Ratio (M-H, Random, 95% CI)0.44 [0.30, 0.64]

    4.1 Oxytocin dose < 10 IU
31243Odds Ratio (M-H, Random, 95% CI)0.42 [0.17, 1.01]

    4.2 Oxytocin dose 10 IU
22950Odds Ratio (M-H, Random, 95% CI)0.47 [0.38, 0.59]

 5 Therapeutic uterotonics; randomised v. quasi-randomised trials43174Risk Ratio (M-H, Random, 95% CI)0.56 [0.36, 0.87]

    5.1 Randomised trials (low risk of bias)
33122Risk Ratio (M-H, Random, 95% CI)0.58 [0.36, 0.92]

    5.2 Quasi-randomised trials (high-risk of bias)
152Risk Ratio (M-H, Random, 95% CI)0.17 [0.01, 3.42]

 6 Therapeutic uterotonics; active v. expectant management43174Risk Ratio (M-H, Random, 95% CI)0.56 [0.36, 0.87]

    6.1 Active management
11901Risk Ratio (M-H, Random, 95% CI)0.39 [0.26, 0.58]

    6.2 Expectant management
31273Risk Ratio (M-H, Random, 95% CI)0.68 [0.41, 1.12]

 7 Therapeutic uterotonics; IM v. IV oxytocin43174Risk Ratio (M-H, Random, 95% CI)0.56 [0.36, 0.87]

    7.1 IV oxytocin
11000Risk Ratio (M-H, Random, 95% CI)0.57 [0.39, 0.82]

    7.2 IM oxytocin
32174Risk Ratio (M-H, Random, 95% CI)0.56 [0.24, 1.27]

 8 Therapeutic uterotonics; oxytocin dose < 10 IU v. 10 IU43174Risk Ratio (M-H, Random, 95% CI)0.56 [0.36, 0.87]

    8.1 Oxytocin dose < 10 IU
2273Risk Ratio (M-H, Random, 95% CI)0.77 [0.23, 2.56]

    8.2 Oxytocin dose 10 IU
22901Risk Ratio (M-H, Random, 95% CI)0.48 [0.33, 0.68]

 
Comparison 3. Oxytocin versus ergot alkaloids

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PPH (clinically estimated blood loss > or = 500 mL)52226Risk Ratio (M-H, Random, 95% CI)0.76 [0.61, 0.94]

 2 Therapeutic uterotonics31167Risk Ratio (M-H, Random, 95% CI)0.70 [0.38, 1.29]

 3 Severe PPH (clinically estimated blood loss > or = 1000 mL)31616Risk Ratio (M-H, Random, 95% CI)1.07 [0.62, 1.85]

 4 Mean blood loss (mL)62748Mean Difference (IV, Random, 95% CI)-12.49 [-37.66, 12.68]

5 Maternal haemoglobin concentration (Hb) < 9 g/dL 24 to 48 hours postpartum00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Blood transfusion2567Risk Ratio (M-H, Random, 95% CI)3.74 [0.34, 40.64]

7 Third stage > 30 minutes00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Mean length of third stage (minutes)31992Mean Difference (IV, Random, 95% CI)-0.43 [-0.89, 0.04]

 9 Manual removal of the placenta42216Risk Ratio (M-H, Random, 95% CI)0.59 [0.29, 1.17]

 10 Diastolic blood pressure > 100 mm Hg between delivery of the baby and discharge from the labour ward2660Risk Ratio (M-H, Random, 95% CI)0.53 [0.19, 1.52]

 11 Vomiting between delivery of the baby and discharge from the labour ward31091Risk Ratio (M-H, Random, 95% CI)0.07 [0.02, 0.25]

 12 Nausea between delivery of the baby and discharge from the labour ward31091Risk Ratio (M-H, Random, 95% CI)0.18 [0.06, 0.53]

 13 Headaches between delivery of the baby and discharge from the labour ward2943Risk Ratio (M-H, Random, 95% CI)0.08 [0.00, 9.46]

 
Comparison 4. Oxytocin versus ergot alkaloids--subgroup analyses

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PPH (clinically estimated blood loss > or = 500 mL); randomised v. quasi-randomised trials52226Risk Ratio (M-H, Random, 95% CI)0.76 [0.61, 0.94]

    1.1 Randomised trials (low risk of bias)
2824Risk Ratio (M-H, Random, 95% CI)0.82 [0.58, 1.15]

    1.2 Quasi-randomised trials (high risk of bias)
31402Risk Ratio (M-H, Random, 95% CI)0.71 [0.53, 0.96]

 2 PPH (clinically estimated blood loss > or = 500 mL); active v. expectant management42216Risk Ratio (M-H, Random, 95% CI)0.76 [0.61, 0.95]

    2.1 Active management
2943Risk Ratio (M-H, Random, 95% CI)0.58 [0.38, 0.89]

    2.2 Expectant management
21273Risk Ratio (M-H, Random, 95% CI)0.84 [0.65, 1.09]

 3 PPH (clinically estimated blood loss > or = 500 mL); IM v. IV oxytocin52226Risk Ratio (M-H, Random, 95% CI)0.76 [0.61, 0.94]

    3.1 IM oxytocin
2567Risk Ratio (M-H, Random, 95% CI)0.71 [0.44, 1.13]

    3.2 IV oxytocin
31659Risk Ratio (M-H, Random, 95% CI)0.78 [0.57, 1.07]

 4 PPH (clinically estimated blood loss > 500 mL); oxytocin dose < 10 IU v. 10 IU42216Risk Ratio (M-H, Random, 95% CI)0.76 [0.61, 0.95]

    4.1 Oxytocin dose < 10 IU
2567Risk Ratio (M-H, Random, 95% CI)0.71 [0.44, 1.13]

    4.2 Oxytocin dose 10 IU
21649Risk Ratio (M-H, Random, 95% CI)0.79 [0.57, 1.08]

 5 Therapeutic uterotonics; randomised v. quasi-randomised trials31167Risk Ratio (M-H, Random, 95% CI)0.70 [0.38, 1.29]

    5.1 Randomised trials (low risk of bias)
2824Risk Ratio (M-H, Random, 95% CI)0.86 [0.43, 1.74]

    5.2 Quasi-randomised trials (high risk of bias)
1343Risk Ratio (M-H, Random, 95% CI)0.42 [0.19, 0.91]

 6 Therapeutic uterotonics; active v. expectant management31167Risk Ratio (M-H, Random, 95% CI)0.70 [0.38, 1.29]

    6.1 Active management
2943Risk Ratio (M-H, Random, 95% CI)0.54 [0.34, 0.85]

    6.2 Expectant management
1224Risk Ratio (M-H, Random, 95% CI)1.25 [0.67, 2.31]

 7 Therapeutic uterotonics; IM v. IV oxytocin31167Risk Ratio (M-H, Random, 95% CI)0.70 [0.38, 1.29]

    7.1 IM oxytocin
2567Risk Ratio (M-H, Random, 95% CI)0.74 [0.25, 2.19]

    7.2 IV oxytocin
1600Risk Ratio (M-H, Random, 95% CI)0.61 [0.35, 1.07]

 8 Therapeutic uterotonics; oxytocin dose < 10 IU v. 10 IU31167Risk Ratio (M-H, Random, 95% CI)0.70 [0.38, 1.29]

    8.1 Oxytocin dose < 10 IU
2567Risk Ratio (M-H, Random, 95% CI)0.74 [0.25, 2.19]

    8.2 Oxytocin dose 10 IU
1600Risk Ratio (M-H, Random, 95% CI)0.61 [0.35, 1.07]

 
Comparison 5. Oxytocin + ergometrine versus ergot alkaloids

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PPH (clinically estimated blood loss > or = 500 mL)52891Risk Ratio (M-H, Random, 95% CI)0.90 [0.34, 2.41]

2 Therapeutic uterotonics00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 3 Severe PPH (clinically estimated blood loss > or = 1000 mL)11120Risk Ratio (M-H, Fixed, 95% CI)1.67 [0.40, 6.94]

 4 Mean blood loss (mL)134Mean Difference (IV, Fixed, 95% CI)61.0 [6.00, 116.00]

5 Maternal haemoglobin concentration (Hb) < 9 g/dL 24 to 48 hours postpartum00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 6 Blood transfusion11120Risk Ratio (M-H, Fixed, 95% CI)0.71 [0.23, 2.24]

7 Third stage > 30 minutes00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 8 Mean length of the third stage (minutes)1372Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 9 Manual removal of the placenta21927Risk Ratio (M-H, Random, 95% CI)1.02 [0.48, 2.20]

10 Diastolic blood pressure >100 mm Hg between delivery of the baby and discharge from the labour ward00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

11 Vomiting between delivery of the baby and discharge from the labour ward00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

12 Nausea between delivery of the baby and discharge from the labour ward00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

13 Headaches between delivery of the baby and discharge from the labour ward00Risk Ratio (M-H, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 6. Oxytocin + ergometrine versus ergot alkaloids--subgroup analyses

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 PPH (clinically estimated blood loss > or = 500 mL); randomised v. quasi-randomised trials52891Risk Ratio (M-H, Random, 95% CI)0.90 [0.34, 2.41]

   1.1 Randomised trials (low risk of bias)
00Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]

    1.2 Quasi-randomised trials (high risk of bias)
52891Risk Ratio (M-H, Random, 95% CI)0.90 [0.34, 2.41]

 2 PPH (clinically estimated blood loss > or = 500 mL); active v. expectant management21474Risk Ratio (M-H, Random, 95% CI)0.80 [0.45, 1.43]

    2.1 Active management
1354Risk Ratio (M-H, Random, 95% CI)0.48 [0.15, 1.52]

    2.2 Expectant management
11120Risk Ratio (M-H, Random, 95% CI)0.95 [0.50, 1.79]

 3 PPH (clinically estimated blood loss > or = 500 mL); IM v. IV oxytocin52891Risk Ratio (M-H, Random, 95% CI)0.90 [0.34, 2.41]

    3.1 IM oxytocin
42881Risk Ratio (M-H, Random, 95% CI)0.98 [0.34, 2.78]

    3.2 IV oxytocin
110Risk Ratio (M-H, Random, 95% CI)0.33 [0.02, 6.65]