Methods	Type of study: randomised trial. Small pilot study to determine the feasibility of a larger trial
Participants	Location: 2 hospitals in Toronto, Canada. Timeframe: September 1999-August 2000. Eligibility criteria: women at 24-30 weeks’ gestation at continued increased risk of preterm birth who remained undelivered 7 or more days following a single course of antenatal corticosteroids (defined as 2 doses of 12 mg/dose intramuscular betamethasone, given at 12- or 24-hour intervals; or 4 doses of 5-6 mg/dose intramuscular dexamethasone, given at 12-hour intervals. To be at increased risk of preterm birth, women had to have one or more of the following: regular uterine contractions; a shortened cervical length or cervical dilatation; preterm prelabour rupture of the membranes; antepartum bleeding secondary to placental separation or placenta praevia; history of preterm birth; maternal hypertension; other medical condition increasing the risk of preterm delivery or intrauterine growth restriction; or other fetal conditions increasing the risk of preterm delivery. Gestational age range: 24-30 weeks. Exclusion criteria: women were excluded if they required chronic doses of corticosteroids secondary to medical conditions, had a contra-indication to corticosteroids, had clinical evidence of chorioamnionitis, or of their fetus(es) had a known lethal congenital anomaly. Total recruited: 12 in total: 6 in the multiple course of antenatal corticosteroid group and 6 in the placebo group
Interventions	Multiple course of antenatal corticosteroid group: a weekly course of betamethasone (2 doses of 12 mg/dose betamethasone (Celestone Soluspan; Schering Canada Inc) intramuscularly, 24 hours apart) until 33 weeks or delivery if the woman remained at increased risk of preterm birth. In the placebo group: a weekly course of placebo consisting of 2 doses of normal saline, intramuscularly 24 hours apart, until 33 weeks or birth if the woman remained at increased risk of preterm birth
Outcomes	Outcomes: rate of recruitment over 12-month period, risk of complications requiring discontinuation of study treatment, concentrations of plasma cortisol and ACTH in cord blood and in maternal blood immediately following birth. Perinatal or neonatal mortality or significant neonatal morbidity, defined as one or more of the following: stillborn or neonatal death during the first 28 days of life or prior to hospital discharge, whichever was sooner; respiratory distress syndrome; bronchopulmonary dysplasia (requiring oxygen at 36 corrected postnatal gestational age); intraventricular haemorrhage (grade 3 or 4; and necrotising enterocolitis
Funding Support	Funding: support from Canadian Institutes of Health Research Senior Scientist Award
Notes	Sample-size calculation: no.
Risk of bias
Bias	Authors’ judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Randomisation sequence was computer-generated and was centrally controlled by one pharmacist at each hospital who kept the randomisation code Stratification: by gestational age (24-27 weeks; 28-30 weeks) and by hospital using block sizes of 2
Allocation concealment (selection bias)	Low risk	Method of treatment allocation: one pharmacist at each hospital who kept the randomisation code
Blinding (performance bias and detection bias) All outcomes	Low risk	The injection of the study treatment was given by a designated research nurse in each hospital who was not caring for the woman. Placebo of normal saline was used. The physical appearance of the study solutions had to be kept masked since the betamethasone is opaque, while saline is clear. To minimise unblinding, the pharmacist prepared the study treatments in a syringe covered with yellow tape
Incomplete outcome data (attrition bias) All outcomes	Low risk	No losses to follow up reported. Intention-to-treat analyses: yes.
Selective reporting (reporting bias)	Low risk	All expected outcomes reported.
Other bias	Low risk	The study appears to be free of other sources of bias.