Crowther 2006.

Methods	Type of study: ACTORDS randomised controlled trial.
Participants	Location: 23 hospitals in Australia and New Zealand. Timeframe: April 1998 to July 2004. Included: single, twin or triplet pregnancy at less than 32 weeks' gestation if women had received an initial treatment of corticosteroid 7 or more days previously and their responsible clinician regarded them to be at continued risk of preterm birth, and there was no contraindication to further corticosteroid therapy. Exclusion criteria: in second stage of labour, had chorioamnionitis needing urgent delivery, or if further corticosteroid therapy was judged to be essential. Gestational age recruited up to less than 32 weeks. Total recruited 982 women (1146 babies). 489 women in the repeat corticosteroid group and 493 women in the placebo group.
Interventions	Repeat corticosteroids: 11.4 mg Celestone Chronodose (as 7.8 mg betamethasone sodium phosphate and 6 mg betamethasone acetate. Placebo: saline intramuscular injection. Every week, if the woman remained undelivered and less than 32 weeks' gestation, and the responsible clinician regarded her as at continued risk of preterm birth, a further treatment pack from the same treatment group was allocated by the telephone randomisation service.
Outcomes	To time of primary hospital discharge: primary outcomes: frequency and severity of RDS (defined as clinical signs of respiratory distress and a ground‐glass appearance on chest radiograph); weight, length and head circumference at birth and primary discharge from hospital. Secondary outcomes included clinical chorioamnionitis (defined as requiring intrapartum antibiotics); maternal postpartum pyrexia (38.0 degrees Centrigrade or greater); any side effects of the injection for the mother and other measures of neonatal morbidity. Composite outcome was post hoc (defined as one of air leak syndrome, patent ductus arteriosus, need for oxygen at 36 weeks' post menstrual age, severe IVH (grade 3 or 4), periventricular haemorrhage, proven necrotising enterocolitis, or retinopathy of prematurity). For the early childhood follow‐up at 2 years' corrected age: primary outcomes: survival at 2 years' corrected age free of major neurosensory disability, defined as survival free of moderate to severe disability. Body size (weight, height and head circumference). Secondary outcomes were general health, including the use of health services since primary hospital discharge; respiratory morbidity; blood‐pressure; child behaviour; incidence of neurosensory impairments and disabilities; total number of deaths by 2 years of corrected age; and the combined adverse outcome of death or any neurosensory disability at 2 years' corrected age.
Funding Support	Funding: Australian National Health and Medical Research Council, The Channel 7 Research Foundation of South Australia, The Women's and Children's Hospital Research Foundation, Adelaide, and The Department of Obstetrics and Gynaecology, The University of Adelaide, South Australia.
Notes	Sample‐size calculation: yes. 980 women needed to detect a 25% reduction in the risk of respiratory distress syndrome form 30% to 22.5% with 80% power and a 2‐sided significance level of 5%.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Random‐number sequence generated by computer with variable block sizes and stratification by centre, gestational age and number of fetuses.
Allocation concealment (selection bias)	Low risk	Method of treatment allocation: central telephone randomisation.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Normal saline placebo was used. Study treatment packs and study syringes identical appearance (opaque study‐labelled syringe).
Blinding of outcome assessment (detection bias) All outcomes	Low risk	At the follow‐up at 2 years' corrected age: staff making the assessments and the families "were unaware of group assignment."
Incomplete outcome data (attrition bias) All outcomes	Low risk	Losses to follow‐up to time of primary hospital discharge: none. Losses to follow‐up to time of 2 year corrected age assessment: 38 survivors (4%) had no paediatric assessment, 18 in the repeat corticosteroid group and 20 in the placebo group; 86 (8%) had no psychological tests, 44 in the repeat corticosteroid group and 42 in the placebo group. Intention‐to‐treat analyses: yes.
Selective reporting (reporting bias)	Low risk	All expected outcomes reported. No obvious risk of selective reporting.
Other bias	Low risk	No other obvious risk of bias identified. Pre‐specified that analyses would be adjusted for gestational age at trial entry and for prognostic variables with imbalance (antepartum haemorrhage and preterm, prelabour rupture of the membranes).