Briery 2009.

Study characteristics
Methods	Placebo‐controlled, double‐blind randomised controlled trial. Participants were recruited from University of Mississippi Obstetric Clinics or Antenatal Diagnostic Unit, Mississippi. Dates of study not reported
Participants	30 women with twin gestations were randomised Inclusion criteria: between 20 – 30 weeks’ gestation, intact membranes, ability to understand and sign the consent form Exclusion criteria: severe medical disorders such as sickle cell disease, insulin‐dependent diabetes mellitus, chronic hypertension, cervical dilatation 1 cm, intrauterine growth restriction (10th percentile), growth discordancy between twins (20%), cerclage, uterine abnormalities or unwillingness to participate in the study protocol
Interventions	Intervention group: participants received weekly injections of 250 mg 17‐alphahydroxyprogesterone caproate from the time of randomisation until 34 weeks' gestation or delivery (whichever came first) Control group: participants received weekly injections of placebo (castor oil) from the time of randomisation until 34 weeks' gestation or delivery (whichever came first)
Outcomes	Primary outcome: delivery before 35 completed weeks’ of gestation Preselected secondary outcomes: development of preterm labour, preterm rupture of the membranes and gestational age at delivery Selected infant data, including birthweight, Apgar score, total days in the NICU and occurrence of neonatal morbidity such as RDS, PDA, IVH, or NEC were also recorded. Those infants who died or were discharged with a neurologic handicap were also noted
Notes	PharmaAmerica donated the 17‐OHPC Funding sources: not reported Declarations of interest: not reported
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	"Women who met the above criteria were randomised when they presented to our outpatient facility by the selection of sequentially numbered, sealed, opaque envelopes generated and opened by a disinterested third party (UMC Pharmacy)" Assume random sequence generation.
Allocation concealment (selection bias)	Low risk	"Sequentially numbered, sealed, opaque envelopes."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"An order was written by the treating physician that the patient was participating in the Twins‐progesterone trial. This order was submitted to pharmacy and an opaque, number‐coded syringe was returned to the treatment area." ...."The participating women, as well as research personnel and physicians/nurses, were unaware of the study group assessment."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	"research personnel and physicians/nurses, were unaware of the study group assessment."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Data available for all women who were randomised
Selective reporting (reporting bias)	High risk	Trial was not registered and no published protocol
Other bias	Low risk	Sample size calculation met. ITT not stated. IRB (ethics) approval for study obtained.