Methods	Type of study: open-label, randomised trial.
Participants	Location: tertiary hospital in northern India. Time frame: August 2004 onwards. Included: mothers from 26 to 33 weeks’ gestation who were at risk of preterm birth and who had received a course of betamethasone 7 or more days previously. Mothers had to be available for follow-up every week until birth Exclusion criteria: unreliable gestational age, frank chorioamnionitis, and major fetal malformation Total recruited: 76 mothers (38 repeat steroid, 38 control). 83 babies were born to 75 mothers but only the first born of multiple pregnancies were assessed (37 repeat steroid, 38 control)
Interventions	Repeat steroid: betamethasone 12 mg intramuscularly, 2 doses, 24 hours apart. The course was repeated every 7 days until delivery or the end of the 33rd week of gestation Control: no intervention.
Outcomes	Primary outcome: severe RDS. RDS was defined as respiratory distress within 6 hours of birth in a preterm infant with either a negative gastric shake test or a typical chest radiograph. Severe RDS was defined as requiring mechanical ventilation for at least 12 hours. Mechanical ventilation was started in infants with hypoxaemia (Pa02 < 50 mmHg) or hypercapnic acidosis (PaC02 > 50mmHg with pH < 7.25) or worsening acidosis or clinically worsening respiratory fatigue/apnoea/work of breathing despite continuous positive airway pressure (maximum 8 cm water pressure) Secondary outcomes: RDS; intraventricular haemorrhage; necrotising enterocolitis (not defined); patent ductus arteriosus (not defined); bronchopulmonary dysplasia (not defined), sepsis (not defined), retinopathy of prematurity, stillbirth and neonatal death, weight, length and occipital-frontal circumference at birth and at 6 months’ corrected age, and body size and development (evaluated by the Denver Development Screening Test II) at 6 months’ corrected age
Funding Support	None.
Notes	Sample-size calculation: yes, based on a reduction in severe RDS from an estimated 33% in the control group to 6% in the repeat steroid group (2 tailed alpha 0.05, beta 0.2). The planned sample size was 70 (35 women in each arm)
Risk of bias
Bias	Authors’ judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Website-generated random number list.
Allocation concealment (selection bias)	Low risk	Subjects were “randomised” to receive by a process of simple randomisation. “Slips bearing the random allocation” (generated from the random number list) “were placed in opaque envelopes, sealed and numbered serially on the outside”
Blinding (performance bias and detection bias) All outcomes	High risk	Placebo not used so no blinding of participants or staff.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	One mother in the repeat steroid group was lost to follow-up before birth. Outcomes were recorded only for the firstborn of multiple pregnancies. Intention-to-treat analysis was performed on babies with known outcomes. Neonatal outcomes reported on 75 (99%) infants, 37 in the repeat steroid group and 38 in the control group. Infant outcomes reported to date for 44 (58%) infants, 21 in the repeat steroid group and 23 in the control group
Selective reporting (reporting bias)	Unclear risk	Insufficient detail to permit judgement. Outcomes specified in the research methods reported
Other bias	Low risk	No other obvious risk of bias identified.