Methods

RCT with randomisation of individual women.

Participants

Irish hospital setting. High‐income country.

Inclusion criteria: all women at low risk of haemorrhage (< 35 years; parity < 5; 1^st stage of labour < 15 hours; no previous history of PPH; Hb > 11 g/dL (or 10.6 g/dL for capillary sample)) with singleton, cephalic presentation, 35 to 36 weeks at recruitment; no medical complications which would contraindicate ergometrine or would increase the risk of bleeding (cardiac disease, use of heparin, hypertension), and expected to give birth vaginally.

1429 women randomised out of 2901 eligible.

Exclusion criteria: women with hypertension in pregnancy or 1st or 2nd stage; epidural anaesthesia (included in separate study); APH; 1st stage > 15 hours; OVB; women attending private care.

Clinician responsible for third stage: midwives.

Interventions

Intervention:  active management of third stage (N = 705):

1. prophylactic ergometrine 0.5 mg IV immediately following birth (once 2^nd twin excluded);

2. try to clamp cord within 30 sec;

3. delivery of the placenta by CCT when uterus contracted;

4. try not to give any special instructions re posture.

 For retained placenta: 1 hour after birth:

• ensure empty bladder;

• attempt delivery again using CCT;

• manual removal of placenta under GA.

Comparison: expectant management of third stage (N = 724):

1. no oxytocic drug to be given routinely;

2. try to leave cord attached to baby until pulsation has ceased. When cord is cut milk any placental blood into bowl and discard;

3. encourage mother to breastfeed;

4. watch for signs of placental separation and ask women to tell you when she feels a contraction or urge to push. DO NOT touch the abdomen or manipulate the uterus at this stage;

5. placenta may be delivered by maternal effort or gentle CCT;

6. if mother does not experience a contraction within 8 minutes, place hand gently on fundus to determine intrauterine bleeding and await separation.

Special circumstances:

if baby’s cord is clamped and cut before pulsation ceases (due to cord round neck, asphyxia etc) do not give ergometrine. Milk any placental blood into bowl and discard it. Watch for signs of placental separation and deliver placenta by CCT.

 Retained placenta > 1 hour after birth:

• ensure empty bladder;

• attempt delivery again using CCT;

• give ergometrine 0.5 mg IV and re‐attempt delivery;

• manual removal under GA.

Data entered into Comparisons 1 and 2.

Outcomes

Pre‐specified outcomes: manual removal of placenta; PPH (> 500 mL); mean blood loss; length 3^rd stage; Hb < 10 g/dL at 48‐72 hours; and difference between 32 weeks and 48‐72 hours PP: PP blood transfusions; side effects 1‐2 hours post birth; PP complications; breastfeeding; serum prolactin; women’s views. No neonatal outcomes.

(Information from Oxford Database of Perinatal Trials registration sheet) and from [Begley 1990]): morbidity; blood loss during 3^rd stage; method of placental delivery; complications occurring in first 1‐2 hours post birth (haemorrhage, nausea, vomiting, raised BP, pain); Hb on 3^rd postnatal day; prolactin levels on 3^rd postnatal day, duration of breastfeeding.

Notes

Between 1 Oct ’87 and 31 Oct ’88, 2901 women were deemed eligible for initial inclusion, 2650 agreed to take part. 1221 of these were excluded prior to randomisation because of epidural (399); OVB (354); CS (132); rapid birth (95); hypertension (77); missed (53); low Hb (40); woman’s request (28); miscellaneous (23); breech (20).

Actual management used in the active arm:

all given IV ergometrine 0.5 mg before delivery of placenta; 89% cord clamped and cut; 93% CCT and 5% maternal effort; 7% upright and 93% recumbent.

Actual management used in the expectant arm:

14% got ergometrine for treatment, not prophylactically, 6 (0.83%) before placenta delivered; cord left unclamped till pulsation ceased 42%; placenta delivered by maternal effort 32% and CCT 66%; 11% upright.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Unpublished information from author: random number tables were used (Fleiss 1981). The first number was selected from the table by a disinterested observer and the numbers were allocated in blocks of 100 following in sequence.

Allocation concealment (selection bias)

Low risk

“...a numbered, sealed envelope containing the randomly allocated group was stapled to the woman’s chart in readiness for admission...The envelope remained sealed until the women was in second stage of labour and the midwife was certain a normal delivery would ensue.  The envelope was then opened...”

"When a woman was excluded from the study, her envelope was returned, unopened, to the researcher. All returned envelopes were re‐allocated in numerical order prior to starting the next batch of 100 envelopes."

Blinding of participants and personnel (performance bias)
All outcomes

High risk

It was not possible to blind women or clinicians in this study. The outcome assessor was often the caregiver for many important outcomes, e.g. blood loss and PPH. Even though blood loss was measured and not estimated, there may have been bias in measuring.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Describes the differences in measuring blood loss in non‐blinded staff and attempts to standardise methods. Hb measurement was conducted by assessors blinded to allocation (personal communication) thus some outcomes were blinded but for some it was not possible.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Some missing data for some postnatal Hb measurements  (618 out of 705 in the active group (12% attrition) and 645 out of 724 in the expectant (11% attrition).

ITT not mentioned but no loss to follow‐up for outcomes measured during labour. Some outcome data are taken from the unpublished thesis.

Selective reporting (reporting bias)

Low risk

None apparent, outcomes on trial registration sheet all reported.

Other bias

Low risk

No significant difference in baseline characteristics, but more women in the physiological arm had pethidine in labour (46% cf 52%, P = 0.05). This may impact on outcomes in the physiological arm where the sight and sound of the baby may be the stimulus for the hormonal release needed for natural 3^rd stage and pethidine may impact here.

1^st and 2^nd stage management similar and no obvious differences overall.

Methods

RCT with randomisation of individual women.

Participants

Setting: University hospital, Sweden. High‐income country.

Inclusion criteria:  healthy women with normal pregnancies, a gestational age of 34 to 43 weeks, singleton, cephalic presentation and expected vaginal birth (included ventouse deliveries).  

Exclusion criteria: non‐Swedish speaking, previous PPH, elective CS, pre‐eclampsia, grand multiparity (> 5) or IUFD.

Subgroups: high‐income, not low‐risk

Clinician responsible for third stage: midwives.

Interventions

Experimental intervention: active management  of third stage (N = 903, but analysed 810).

1. Uterotonic ‐ drug/dose/route/timing ‐ oxytocin 10 U, IV, within 2 minutes of birth.

2. Cord clamping ‐ timing  Immediate.

3. CCT ‐ yes, and encouragement to push.

4. Uterine massage ‐ after expulsion of placenta.

Control/Comparison intervention:  mixed management of third stage (N = 899, but analysed 821).

Description: mixed: (no routine uterotonic; early cord clamping, no CCT):

1. clamping the cord immediately after birth;

2. administration of 2 mL saline solution, IV within 2 minutes;

3. waiting for signs of placental detachment and encouraging the mother to push out the placenta without cord traction;

4. uterine massage after placenta deliver.

Data used in Comparison 11.

Outcomes

Pre‐specified outcomes: primary outcome was the incidence of blood loss > 1000 mL during the third stage of labour. Other outcomes: Hb at 24 hours and women's views.

Reported outcomes: blood loss > 1000 mL and > 500 mL during the third stage of labour, blood loss > 1000 mL and > 500 mL in first 2 hours PP, Hb at 24 hours, change in Hb from antenatal to 24 hours postnatal, retained placenta/retained part of placenta or membranes, additional uterotonics, duration of 3^rd stage. Blood transfusion, units transfused, experience of mothers, after‐pains.

Outcomes obtained by email response 28^thApril 2011 manual removal of placenta alone, cross‐over in additional uterotonics, Hb < 9 g/dL at 24‐48 hours, length of third stage > 60 minutes.

Outcomes obtained by email response 26^th May 2011 clarification of cross‐over in additional uterotonics, blood loss > 500 mL and > 1000 mL during third stage of labour separated from blood loss > 500 mL and > 1000 mL in first 2 hours PP.

Notes

We wrote to the author for additional information which was provided as follows:

"In the active group, 41  women had extra Synt, therapeutically, before the placenta (some went on to have a second dose, and/or Methergin) = 41

767 had no extra Synt before the placenta. Of these, 26 had a second dose after the placenta was delivered, 6 had a second dose of Synt and a dose of Methergin and 48 had Methergin but no Synt = 80                                                             

IN TOTAL, IN THE ACTIVE GROUP, 121 WOMEN HAD THERAPEUTIC UTEROTONICS.

In the expectant group, 160 women had a dose of Synt, therapeutically, before the placenta (some went on to have a second dose, and/or Methergin) = 160
655  had no Synt before the placenta. Of these, 102 had a dose of Synt after the placenta was delivered, 32 had a dose of Synt and a dose of Methergin and 17 had Methergin but no Synt. = 151

IN TOTAL, IN THE EXPECTANT GROUP, 311 WOMEN HAD THERAPEUTIC UTEROTONICS.

Blood loss before and during placenta delivery: IN ACTIVE GROUP:  0 to 500 mL = 86.57% ( n = 696) > 500 mL = 13.43% (n = 108) and  0 to 1000 mL = 96.39% (n = 775) > 1000 mL = 3.61% (n = 29)
Blood loss before and during placenta delivery: IN EXPECTANT GROUP: 0 to 500 mL = 76.25% (n = 623) > 500 mL = 23.75% (n = 194) and 0 to 1000 mL = 95.3% (n = 779) > 1000 mL = 4.65% (n = 38)

26 women in the active group and 21 in the expectant had manual removal of placenta.

34 women in the active and 28 in the expectant group had maternal Hb < 9 g/dL at 24‐48 hrs.

31 women in the active and 23 in the expectant group had third stage > 60 minutes.

"mean blood loss before placenta" was clarified as meaning "mean blood loss 'before and during expulsion' of the placenta."

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Computer‐generated randomisation.

Allocation concealment (selection bias)

Low risk

Sealed envelopes containing the computer‐generated randomisation group were prepared in consecutive order and kept in another unit. At randomisation, midwives phoned the staff at the other unit who opened the sealed envelopes and disclosed the assigned intervention and trial number.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Received an injection in both groups to “blind”, but expectant group were asked to push and did not have CCT, active group had CCT.

Clinicians not blinded.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Clinicians not blinded and clinicians involved in many important outcomes decisions/assessments, e.g. blood loss, therapeutics uterotonics, blood transfusions. Other outcomes could have been blinded, e.g. Hb.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Of the 903 women randomised to the active group and 899 women randomised to the mixed management group:

• 4 women withdrew from the active group and 2 from the mixed management group;

• 75 women had CS in active group and 56 in the mixed management group, so were excluded;

• A further14 women in the active group and 20 in the mixed management group were lost to follow‐up.

Overall 10% and 9%.

Was the analysis ITT? Yes, apart from above exclusions.

Selective reporting (reporting bias)

Unclear risk

Proposal not seen, and not registered before the trial commenced.                                                                                                      

Other bias

High risk

There were more inductions in the active group (10% versus 7%). 

Describe any differential diagnosis: none.

Although 11,000 women were potentially eligible, of whom at least half would usually be considered eligible, only 1802 were entered into the study. Numbers excluded due to ineligibility are not recorded, and other reasons given are 'excessive workload' or 'admission in advanced labour'. Email response from Jangsten 28^th April 2001: "the hard workload was one reason that the women were not included and that all eligible women were not asked to participate. Few women refused in participating but I don't have the number".

This has the potential to have biased the study, as midwives would have had the choice of not asking the women to participate and may unconsciously have not offered participation to some women who they felt were not suitable for physiological management.

Methods

RCT of individual women in low‐income setting.

Participants

Setting: Sousse, Tunisia. Low‐income country.

Women with singleton pregnancies expecting to give birth vaginally.

Exclusion criteria: placenta praevia, APH, non‐cephalic presentation, intrauterine death, parity > 5, uterine fibroids, anticoagulation therapy, history of PPH, history of CS.

Interventions

Intervention: active management of 3rd stage (N = 65):

1. IV flash injection of 5 IU oxytocin at time of delivery of anterior shoulder;

2. immediate cord clamping and cutting;

3. CCT with gentle fundal pressure when signs of separation appeared;

4. manual removal if not delivered by 30 minutes or if haemorrhaging.

Comparison: mixed management of 3rd stage (N = 65):

1. no routine uterotonic (not stated in publication, but author provided information on 19th March 2011);

2. immediate cord clamping and cutting;

3. CCT plus gentle fundal pressure when signs of separation appeared;

4. manual removal if not delivered by 30 minutes or if haemorrhaging.

Data included in Comparison 12.

Outcomes

Pre‐specified: reduction in HCT and Hb.

Notes

We contacted the authors again on 14th March 2011, for further information on the management in the comparison arm, the methodology they used and data obtained. Reply received 19th March 2011. No publication has emanated, no further data were provided, but methodology was clarified.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

As per www.randomization.com (not stated in publication but information provided by author on 19 March 2011).

Allocation concealment (selection bias)

High risk

Not concealed in any way (not stated in publication, but in information provided by author on 19 March 2011).

Blinding of participants and personnel (performance bias)
All outcomes

High risk

None. Unblinded assessment made.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

No loss described in publication and confirmed by information from author on 19 March 2011. Authors also provided information that the analysis was by 'intention to treat'.

Selective reporting (reporting bias)

Unclear risk

We did not assess the trial protocol.

Other bias

High risk

Women reported to have been allocated to groups after placental delivery yet active management group supposedly had oxytocin with the anterior shoulder.

Methods

RCT with randomisation of individual women.

Participants

Abu Dhabi hospital setting. High‐income country.

Inclusion criteria: all women expected to give birth vaginally. 1657 women randomised out of a possible 4239.

Exclusion criteria:  refusal or CS in second stage (9 excluded, final sample 1648).

Interventions

Intervention:  active management of 3rd stage (N = 827):

1. prophylactic oxytocin 10 units IM at birth of anterior shoulder (OR if breech, soon after delivery of baby);

2. cord clamped and cut immediately;

3. CCT as soon as the uterus was contracted firmly. Repeated every 2‐3 minutes.

Comparison: mixed management of 3rd stage (N = 821):

1. no IM/IV oxytocic;

2. cord clamped and cut after delivery;

3. no cord traction. No fundal massage or pressure. Signs of separation awaited, then maternal expulsion of placenta;

4. IV infusion of oxytocin 10 units in 500 mL normal saline given slowly after delivery.

In both groups, if placenta not delivered after 30 minutes, CCT or digital removal attempted, with IV oxytocin infusion if bleeding present.

Data included in Comparison 10.

Outcomes

Primary: PPH.

Secondary: duration of third stage, retained placenta, shock, blood transfusion, methylergonovine or 15‐methyl‐a‐prostaglandin to control haemorrhage.

Notes

Not readily comparable to other studies as IV oxytocin infusion given to all women in expectant management group after delivery of placenta. This is the practice in the US but not elsewhere.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Unclear risk

No detail.

Allocation concealment (selection bias)

Low risk

Numbered sealed opaque envelopes.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Attempted with 2^nd MW recording blood loss – however, no guarantee that the first MW could/would not have altered the amount of blood in the receptacle, so not any better than just 1 clinician measuring.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

No information provided.

Presumed blinded, but unclear.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

2582 excluded prior to randomisation due to refusal.

9 excluded after randomisation due to emergency CS.

Selective reporting (reporting bias)

Unclear risk

No trial protocol reviewed. Most reported outcomes were pre‐specified. Mean change in HCT was reported, but not pre‐specified.

Other bias

High risk

2582 out of 4239 refused to participate. Those that did agree may have been biased.

It is unknown whether or not the midwives had sufficient training in physiological third stage before the trial started.

This trial has been criticised for including all women (including high parity, all age groups, previous PPH, epidural, long labour, operative delivery) and not confining inclusion criteria to women who were low risk. Women at high risk of PPH will have a higher blood loss using expectant management; clinicians experiencing this may respond by anxiety in subsequent births, even of low‐risk women, which may result in higher intervention (mixed management) rates.

Also, the minimal intervention (control) group had the cord clamped and cut immediately after delivery, which is suspected to lead to an increase in blood loss.

Methods

RCT with randomisation of individual women.

Participants

UK hospital setting. High‐income country.

Inclusion criteria: all women expected to give birth vaginally. 1695 women randomised out of a possible 4709.

Exclusion criteria: refusal, cardiac disease, APH, non‐cephalic presentation, multiple pregnancy, IUFD, if clinician had good reason not to include women.

After the first 5 months, exclusions included women with ritodrine given 2 hours before birth; anticoagulant treatment; any condition needing  a particular management of 3rd stage (e.g. meconium‐stained liquor, dural tap).

Interventions

Intervention:  active management of 3rd stage (N = 846):

1. prophylactic syntometrine (5 units oxytocin + 0.5 mg ergometrine) (or 10 units syntocinon if mother had raised BP), administered immediately after birth of anterior shoulder;

2. cord clamping and cutting within 30 seconds of birth;

3. delivery of the placenta by CCT when uterus contracted.

Comparison: expectant management of 3rd stage (N = 849):

1. try not to give oxytocic;

2. try to leave cord attached to baby until placenta delivered;

3. try not to use CCT or any manual interference with uterus at the fundus. Following signs of separation encourage posture aiding delivery by gravity, and maternal effort.

Data included in Comparison 1.

Outcomes

Pre‐specified outcomes: PPH (and “more objective measures of blood loss”, presumably Hb); length 3^rd stage; need for therapeutic oxytocics; manual removal placenta; ERPC; side effects of oxytocics (nausea, vomiting, headaches, hypertension); Apgar scores; PCV; SCBU; jaundice; breastfeeding. Views of a subsample of women.

Notes

Actual management used in the active arm: 99% given prophylactic uterotonic before delivery of placenta; 99% cord clamped and cut before delivery of placenta; 99% CCT; 26% upright.

Actual management used in the expectant arm: 30% received uterotonic for treatment, and 20% prophylactically; cord left unclamped till pulsation ceased 48%; placenta delivered by maternal effort 60% and CCT 40%; 49% upright.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

No description of the randomisation given. However, we believe that unclear sequence generation was a consequence of reporting omission rather than methodological inadequacies and therefore does not give rise to bias.

Allocation concealment (selection bias)

Low risk

“On admission to the labour ward... Correspondingly numbered, sealed opaque envelopes were placed in the woman’s notes...”

Blinding of participants and personnel (performance bias)
All outcomes

High risk

In all the studies, not possible to blind the women or the clinicians in any of the studies. The paper stated “We were concerned that clinical estimates of blood loss might also be subject to systematic bias between the two trial groups as the observer could not be blinded to the management allocated. We therefore studied three maternal haematological variables – namely, postpartum (24‐48 hrs) haemoglobin concentration ≤ 90g/l, mean postpartum packed cell volume and mean change in haemoglobin concentration between about 34 weeks gestation and post partum”. Primary outcome though is still PPH > 500 mL which is subject to systematic bias.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

See above.

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

Missing data for some outcomes, e.g. 19% of Hb results missing in active arm and 18% in the physiological; 25% of antenatal and/or postnatal Hb results (used to calculate drop in mean Hb) missing in the active arm and 26% in the physiological.

Apparently no women were excluded after randomisation but 182 are described as having not entered in the trial due to the cord being cut early for fetal safety reasons. The allocation details, however, state that when the clinician was ready to prepare for delivery, the envelope was opened and "all women for whom an envelope was opened were deemed to have entered the trial and were followed up". The envelope would have been opened before any neonatal need for attention became apparent.

Selective reporting (reporting bias)

Unclear risk

Trial protocol not assessed. Reported outcomes not pre‐specified: blood transfusions; number of units transfused; days' stay; serious problems with 3^rd stage;neonatal respiratory problems; birthweight; number with “serious problems in 3^rd stage” (not pre‐specified), described as PPH, transfusion, manual removal of placenta, ERPC is reported. This is misleading as a number of those problems would co‐exist.

Other bias

High risk

Protocol was modified after 5 months (425 births), due to high blood loss in expectant management group, to allow women in the control arm who needed some active management to be switched to fully active management.  However, data for the first 5 months were still included in analysis.

Trial was stopped early because of potential harm. Sample size was meant to be 3900 but stopped after 1695.

30 women in the control group gave a late maternal refusal, whereas only 1 in the experimental group did so. The outcomes of these women are included in analysis.

It is questioned whether the midwives had sufficient training in physiological third stage before the trial started. Harding et al found that, of 49 midwives responding to a questionnaire, only 1 had practised physiological management as defined in the trial. Only 6 (13%) of the midwives said that they were very confident of physiological management before the trial and 22 (46%) afterwards (Harding 1989; Prendiville 1988 paper).

This trial has been criticised for including all women (including high parity, all age groups, previous PPH, epidural, long labour, operative delivery) and not confining inclusion criteria to women who were low risk. Women at high risk of PPH will have a higher blood loss using expectant management; clinicians experiencing this may respond by anxiety in subsequent births, even of low‐risk women, which may result in higher intervention (mixed management) rates.

Only 47% (403/849) of women in physiological arm received the full physiological package (a problem with other studies also). But, in particular, 168/849 = 20% had prophylactic oxytocic, which is a large number for a “prophylactic” treatment as opposed to one in response to clinical need; In addition, 252 (30%) had a uterotonic as a treatment, so in total, 50% of the expectant management group received an oxytocic.

However, 99% (838/846) of women in active management group received allocated management.

Methods

RCT with randomisation of individual women in balanced blocks, with allocation to 1 of 2 delivery postures within each arm.

Participants

UK hospital setting. High‐income country.

Inclusion criteria: 1512 women at low risk of PPH giving birth at study hospital (including water births).   

Exclusion criteria: placenta praevia, previous PPH, APH after 20 weeks’ gestation, Hb < 10 g/dL or MCV < 75 fL, non‐cephalic presentation, multiple pregnancy, intrauterine death, epidural anaesthesia, parity > 5, uterine fibroid, oxytocin augmentation infusion, anticoagulation therapy, intended instrumental or OVB, duration of gestation < 32 weeks, (plus any other contraindication, in clinician’s view).

Interventions

Intervention:  active management of 3rd stage (N = 748).

2 arms: active management ‐ upright position (N = 374); active management ‐ supine position (N = 374):

1. prophylactic oxytocin (19.5%) or ‘oxytocin + ergometrine’ (75%) as soon as possible after birth of anterior shoulder (within 2 minutes of birth). Number of units/mL not given, nor reason for the difference;     

2. immediate cord clamping and cutting;

3. delivery of the placenta by CCT or maternal effort.

Control:  expectant management of 3rd stage (N = 764).

2 arms: expectant management ‐ upright position (N = 381); expectant management ‐ supine position (N = 383):

1. no prophylactic administration of uterotonic drug;

2. no cord clamping until after pulsation ceased;

3. delivery of placenta within 1 hour by maternal effort.

Data included in Comparisons 1 and 2.

Outcomes

Pre‐specified outcomes: PPH (> 500 mL) as assessed/estimated by the attending MW (used for power calculation); severe PPH 1000 mL), blood transfusion, iron tablets postnatally, Hb at 24‐48 hours P/N, self‐completed questionnaire on maternal fatigue and depression at 6 weeks P/N, nausea, vomiting, headache, hypertension, manual removal of placenta, ERPC, neonatal outcomes, views of mothers and staff.

Notes

High‐income setting.

Actual management used in the active arm: 699 (93.4%) had full active management; 95% given prophylactic uterotonic before delivery of placenta; 93% cord clamped before pulsation ceased; 46% CCT; 44% upright.

Actual management used in the expectant arm: 488 (63.9%) had full expectant management; 21% received oxytocic for treatment, and 2.5% prophylactically; cord left unclamped till pulsation ceased 70%; placenta delivered by CCT 12%; 43% upright.

The setting is described as one where the midwives were “similarly confident” in active and expectant management. However, the questionnaire administered to 92 of the 153 midwives prior to the trial commencement showed that, whereas 84% felt “very confident” of active management, only 41% were “very confident” of expectant management.

Maternal mean Hb levels were reported with SEs and so SDs were calculated.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Variable sized balanced blocks

“...randomisation envelopes were prepared in advance..” in an external academic unit ‐ National Perinatal Epidemiology Unit, Oxford.

Allocation concealment (selection bias)

Low risk

Sequentially numbered, opaque, sealed envelopes stored on the ward. Entry to the trial occurred when an envelope was opened.

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not possible to blind participants and personnel.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Partly blinded. The technicians who did antenatal and postnatal blood tests were unaware of allocation.

Incomplete outcome data (attrition bias)
All outcomes

Low risk

Data available on 1507 out of 1512 at discharge (less than 0.5% attrition, approximately equal losses in both groups).

At 6 weeks follow‐up less than 5% attrition.

Selective reporting (reporting bias)

Unclear risk

Both significant and non‐significant results presented but we have not been able to check the trial protocol. Most as above reported plus others. Only a few neonatal outcomes reported.

Other bias

High risk

·Initial power calculation suggested a sample size of 2000. Interim analysis showed a higher PPH rate than expected, so sample size was revised to 1500 and the trial stopped earlier than expected.

· Similar at baseline.

· 93.4% of active management group received active management. Only 63.9% of women in expectant management group received expectant management.

Also:

· MWs not confident re 1 arm, so observer bias.

· the hypothesis was phrased in favour of active management lowering PPH rate and other complications, rather than being a null hypothesis. Also, the setting is described as one where the midwives were “similarly confident” in active and expectant management. However, the questionnaire administered to 92 of the 153 midwives prior to the trial commencement showed that, whereas 84% felt “very confident” of active management, only 41% were “very confident” of expectant management.

Methods

RCT with randomisation of individual women.

Participants

UK hospital setting. High‐income country.

Inclusion criteria: women at "low risk of PPH” (defined only by the exclusion criteria for study) and at term (37‐42 weeks). 193 women randomised, from an unknown population.

Exclusion criteria: grand multiparity; malpresentation, multiple pregnancy; previous CS or PPH; APH; pregnancy‐induced hypertension and intrauterine death. 

Then after randomisation: women who had had augmentation, instrumental or OVB, 3rd degree tear and cervical laceration.

Interventions

Intervention:  active management of 3rd stage (N = 103):

1. 1 mL syntometrine (not stated whether IM or IV) as soon as baby born;

2. cord “was immediately clamped”;

3. placenta delivered by CCT.

Comparison: expectant management of 3rd stage (N = 90):

presumed no oxytocic, though not stated in the published paper.

Authors’ information by letter states:

1. “No oxytocics or placebos were given to the physiological group”;

2. cord not cut or clamped until after pulsation ceased (unless there were contraindications, e.g. cord round neck, after clamping, maternal end clamp removed as soon as possible to allow drainage);

3. once there were signs of placental separation mother was encouraged to adopt an upright position and bear down, “when the placenta could be felt in the vagina, the midwife could then assist delivery of the placenta”.

Both groups: if placenta not delivered in 30 minutes, bladder emptied and medical assistance sought. If delivery not imminent manual removal performed. Medical assistance sought for any excessive blood loss.

Data included in Comparisons 1 and 2.

Outcomes

Pre‐specified outcomes: estimated blood loss; Hb in labour and 3^rd postnatal day; length of 3^rd stage; complications.

Reported outcomes: as above plus therapeutic uterotonics, blood transfusion.

Notes

Drop in Hb is not calculated correctly.

Maternal mean postnatal Hb reported as median and range. Active: 11.7 g/dL (10.7 to 12.6 g/dL) and expectant 11.7 g/dL (10.9 to 12.6 g/dL).

Worrying problems with methodology and analysis.

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

“...randomly allocated using standard randomisation tables...”

Allocation concealment (selection bias)

Low risk

Not described. Not clear when randomisation occurred “...the midwife responsible for the management of her patient was not aware of the proposed allocation until her patient was entered into the study” (authors' information states: "randomised in the late 1^st stage of labour when it was apparent that they were likely to delivery normally").

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Not possible to blind participants and personnel.

Blinding of outcome assessment (detection bias)
All outcomes

Unclear risk

Unknown.

Incomplete outcome data (attrition bias)
All outcomes

High risk

It is not clear how many were randomised. P. 20 states “A total of 193 women completed the study AND had all results available for complete analysis”. This could mean that a larger number were included but that some of their results were missing, and they were therefore excluded. This could lead to significant bias. It is very unlikely that all participants received the allocated management, yet this is not presented. The study groups were also very different sizes (103 and 93), which sounds unlikely.

Women withdrawn after randomisation for operative delivery, 3^rd degree tears and cervical lacerations. Numbers were not given; there is a significant risk of bias here.

It is not stated in the published paper whether or not "intention to treat" analysis was used, but the response to Diana Elbourne’s letter of April 1991 states that they did not analyse on ‘intention to treat’ as it would not answer the aims of this preliminary study.

Selective reporting (reporting bias)

High risk

PPH rates not given and although this outcome was not specified in the trial registration form on 1991, it is key outcome which we would expect to be reported.

Other bias

High risk

Variables age, birthweight and parity said to be equal between the groups but no details given. No power calculation done.

Not a null hypothesis.

The study groups were very different sizes (103 and 90).