Methods	Type of study: randomised trial.
Participants	Location: two centres in USA (Sacred Heart Hospital, University of Florida, Pensacola, Florida recruited first 8 patients; Oregon Health and Science University). Timeframe: From June 2001 to May 2007. Eligibility criteria: women at 26 to < 34 weeks’ gestation; at least 14 days after first course of antenatal steroids (93% received betamethasone); at continued risk of preterm delivery as determined by their care provider; who provided informed consent Gestational age range: 26 to < 34 weeks’ gestation. Exclusion criteria: women were excluded if they were insulin-dependent diabetics, had a major documented fetal or chromosomal abnormality; multiple pregnancy greater than twins; clinical chorioamnionitis; first course of antenatal steroids given < 24 weeks’ gestation; chronic steroid use during pregnancy for clinical care Total recruited: 85 women randomised (113 babies alive at randomisation). 44 women (56 babies) in the rescue steroids group and 41 women (57 babies) in the placebo group
Interventions	In the rescue group: course of antenatal steroids (2 doses of 12 mg/dose betamethasone (Celestone Soluspan; Schering Corporation, Kenilworth, New Jersey), intramuscularly, 24 hours apart. In the placebo group: two doses of placebo (identical in appearance to betamethasone: 25 mg cortisone acetate, an inactive steroid)
Outcomes	Primary outcomes: respiratory compliance and functional residual capacity (measured within 72 hours of birth (before any surfactant) Secondary outcomes: growth measurements including weight, head circumference and length at birth and hospital discharge; surfactant administration; RDS (defined as clinical signs of respiratory distress with radiographic appearance and needing supplemental oxygen with FiO2 > 0.21); respiratory distress requiring ≥ 0.30 and ≥ 0.40 at 24 hours of age; days on mechanical ventilation and days on supplemental oxygen
Funding	Support Oregon Health and Science University, GCRC/PHS Grant 5 MO1 RR000334; OCTRI UL1 RR02414001; and The American Lung Association
Notes
Risk of bias
Bias	Authors’ judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Group assignment performed using a randomisation table. A staff pharmacist performed randomisation and study drug preparation at each institution. Stratification: ≤ 28 versus > 28 weeks’ gestation; multiple gestation (twins versus singletons)
Allocation concealment (selection bias)	Low risk	Method of treatment allocation: “group assignment was performed using a randomisation table. A staff pharmacist performed randomisation and study drug preparation” Stratification: ≤ 28 versus > 28 weeks’ gestation; multiple gestation (twins versus singletons)
Blinding (performance bias and detection bias) All outcomes	Low risk	“All patients, investigators and care providers were unaware of the treatment allocation.” Placebo: 25 mg cortisone acetate, an inactive steroid, identical in appearance to the betamethasone used in the rescue group
Incomplete outcome data (attrition bias) All outcomes	Low risk	Losses to follow up: neonatal data not available for one baby in the placebo group. Intention-to-treat analyses: yes
Selective reporting (reporting bias)	Low risk	No obvious risk of selective reporting.
Other bias	Low risk	No other obvious risk of bias detected.