Wood 2012.

Study characteristics
Methods	Double‐blinded, placebo‐controlled randomised trial Antenatal clinics at a tertiary care centre and an academic community hospital in Calgary, AB, Canada June 2006 and October 2010.
Participants	84 women were randomised Inclusion criteria: 2 or more live fetuses confirmed at their 16‐ to 18‐week ultrasound and were between 16 + 0 and 20 + 6 weeks gestation at the time of randomisation. Pregnancies reduced from higher‐order multiples to twins were also included if the reduction was carried out before 13 weeks gestation Exclusion: placenta previa, pre‐existing hypertension, known major fetal anomaly detected on ultrasound, monoamniotic monozygotic multiple pregnancies, maternal seizure disorder, active or history of thromboembolic disease, maternal liver disease, known or suspected breast malignancy or pathology, known or suspected progesterone‐dependent neoplasia, plans to move to another city during pregnancy, previous participation in this trial or other perinatal clinical trials during this pregnancy, or known sensitivity to progesterone
Interventions	Intervention group: received daily doses of 90 mg progesterone 8% vaginal gel Control/Comparison group: daily doses of identical applicators containing gel without progesterone
Outcomes	Primary outcome: gestational age at delivery Maternal secondary outcomes: preterm birth before 35 weeks ’ gestation; preterm birth before 37 weeks ’ gestation; the proportion of women who had a spontaneous delivery; length of hospital stay; the proportion of women who received tocolytic therapy; and compliance with treatment as measured by diary self‐report and return of unused applicators Infant secondary outcomes were length of hospital stay; RDS, defined as requiring assisted ventilation via endotracheal tube and supplemental oxygen both within the first 24 hours of life and for duration of ≥ 24 hours and either an X‐ray compatible with RDS or surfactant given between the first 2 and 24th hour of life; BPD, defined as requiring oxygen at postnatal GA of 36 completed weeks and X‐ray compatible with BPD; IVH grade III or IV diagnosed by cranial ultrasound or at autopsy; NEC, defined as perforation of the intestine, pneumatosis intestinalis, or air in the portal vein, diagnosed by X‐ray, surgery, or at autopsy; number of days of ventilator therapy; birthweight; stillbirth; and neonatal death. Any possible maternal or infant serious adverse events up to 28 days after delivery.
Notes	Funding sources: This study was funded by the Calgary Health Region Perinatal Funding Competition (peer reviewed funding). We are grateful to Columbia Laboratories (Livingston, NJ, USA) who donated blinded active treatment and placebo gels Declarations of interest: the authors declared no conflicts of interest
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Used a random‐number generator with random block sizes of 2 or 4
Allocation concealment (selection bias)	Low risk	The allocation sequence generated by the trial statistician was provided to the dispensing pharmacy. Once a woman consented, the pharmacy dispensed treatment according to the next randomisation allocation from the stratum to which the woman belonged
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Double‐blinded study
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Research nurse assessing dates was blinded to allocation. Assume true for outcome assessment
Incomplete outcome data (attrition bias) All outcomes	Low risk	Outcomes reported for all randomised women and their infants
Selective reporting (reporting bias)	Low risk	Stated outcomes are reported
Other bias	Unclear risk	Other bias not apparent

17‐OHPC: 17 alpha‐hydroxyprogesterone caproate
BPD: bronchopulmonary dysplasia
ITT: intention to treat
IVH: intraventricular haemorrhage
NEC: necrotising enterocolitis
NICU: neonatal intensive care unit
PDA: patent ductus arteriosus
RDS: respiratory distress syndrome