Jangsten 2011.

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 34‐43 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) Uterotonic drug/dose/route/timing: oxytocin 10 U, IV, within 2 min of birth Cord clamping timing: immediate CCT: yes, and encouragement to push Uterine massage: after expulsion of placenta Control/comparison intervention: mixed management of 3rd stage (N = 899, but analysed 821) Description: mixed: (no routine uterotonic; early cord clamping, no CCT) clamping the cord immediately after birth administration of 2 mL saline solution, IV within 2 min waiting for signs of placental detachment and encouraging the mother to push out the placenta without cord traction uterine massage after placenta delivered Data used in comparison 11
Outcomes	Pre‐specified outcomes: primary outcome was the incidence of blood loss > 1000 mL during the 3rd stage of labour. Other outcomes: Hb at 24 h and women's views Reported outcomes: blood loss > 1000 mL and > 500 mL during the 3rd stage of labour, blood loss > 1000 mL and > 500 mL in first 2 h PP, Hb at 24 h, change in Hb from antenatal to 24 h postnatal, retained placenta/retained part of placenta or membranes, additional uterotonics, duration of 3rd stage. Blood transfusion, units transfused, experience of mothers, afterpains Outcomes obtained by email response 28 April 2011: manual removal of placenta alone, cross‐over in additional uterotonics, Hb < 9 g/dL at 24‐48 h, length of 3rd stage > 60 min Outcomes obtained by email response 26 May 2011 clarification of cross‐over in additional uterotonics, blood loss > 500 mL and > 1000 mL during 3rd stage of labour separated from blood loss > 500 mL and > 1000 mL in first 2 h PP
Notes	We wrote to the study 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." In further correspondence, the author replied: "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)" And also: Question: Number of women having retained placenta and manual removal of placenta (excluding those who had retained pieces of membrane, etc, if possible) Answer: "in total 47 manual removal of the placenta were performed. In active group 26 in expectant group 21." Question: Number of maternal haemoglobin <9gm/dl at 24‐48 hrs Answer: "In total there were 62 women with Hb < 90. In active group 34 women, and in expectant group 28 women" Question: Number of lengths of third stage > 60 minutes. Answer: "In total there were 54 women with third stge that exceede 60 min. In active group 31 women and in expectant group 23 women." Question: Was 'mean blood loss before placenta' actually 'blood loss up to and including expulsion of placenta'? Answer: "mean bloodloss before placenta was expelled is refered to as before and during expulsion." Dates of study: November 2006‐April 2008 Funding sources: "The study was supported by grants from the Research and Development Board in Göteborg and Bohuslän Baby Bag and the SU foundation". Declarations of interest: "The authors have no conflicts of interest and are independent from industrial funding"
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 study 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% The analysis was ITT, apart from above exclusions
Selective reporting (reporting bias)	Unclear risk	All outcomes listed in the methods are reported, but no protocol for the study is available.
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 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.