Methods	Type of study: randomised placebo-controlled trial.
Participants	Location: 15 private and 3 university centres, USA. The participants were largely private/non-goverment funded Time frame: May 2003 to February 2008. Included: women with singleton or twin pregnancies from 25 weeks’ to less than 33 weeks’ gestation who had received a course of betamethasone 14 or more days previously and who were judged to have recurrent or continued risk of preterm birth Exclusion criteria: major fetal anomaly, cervical dilatation 5 cm or more, higher order multiples, ruptured membranes, documented lung maturity, receiving corticosteroids for other indications, human immunodeficiency virus infection or active tuberculosis Total recruited: 437 women (223 repeat steroid, 214 placebo). 577 infants were enrolled (289 repeat steroid, 288 placebo), although one fetal twin in the steroid group died before randomisation
Interventions	Repeat steroid: a single course of intramuscular betamethasone given as 2 doses of 12mg, 24 hours apart (preparation not specified) Placebo: a similarly administered saline intramuscular injection In some centres betamethasone became unavailable and was replaced with dexamethasone 6 mg intramuscularly, 4 doses, every 12 hours. 31 women received dexamethasone and 30 women received an equivalent placebo
Outcomes	Primary outcome: composite neonatal mortality/morbidity in babies born before 34 weeks’ gestation. The composite outcome was defined as one or more of: perinatal death (defined as stillbirth or death before neonatal discharge); RDS (oxygen requirement, clinical diagnosis and consistent chest radiograph); bronchopulmonary dysplasia (defined as a requirement for oxygen at 30 days of age); severe intraventricular haemorrhage (grades 3 or 4); periventricular leukomalacia; blood culture-proven sepsis; or necrotising enterocolitis (not defined) Secondary outcomes: preterm birth before 34 weeks’ gestation; RDS; gestational age at birth; small-for-gestational age (< 10th percentile); head circumference; birthweight; surfactant therapy; pneumothorax; maternal infectious morbidity
Funding	Support Funding: Pediatrix Medical Group.
Notes	Sample-size calculation: yes, based on a 40% reduction in the primary outcome, which was estimated to be 28% in the control group. The planned sample size was 217 women in each arm (2 tailed alpha 0.05, beta 0.2)
Risk of bias
Bias	Authors’ judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	A “blocked randomisation sequence” was used that was “prepared centrally”. Although not described in the paper, the study protocol states that the random sequence was generated by computer
Allocation concealment (selection bias)	Low risk	The research pharmacist (unblinded) at each site prepared the medication based on the blocked randomisation sequence
Blinding (performance bias and detection bias) All outcomes	Low risk	Normal saline placebo was used. The study syringes (betamethasone or saline) were completely covered by a label to conceal the contents If betamethasone was unavailable it was replaced with dexamethasone 6 mg intramuscularly, 4 doses, every 12 hours, with the placebo group receiving the same volume and frequency of normal saline
Incomplete outcome data (attrition bias) All outcomes	Low risk	Neonatal data was unavailable on 13 babies in the repeat steroid group and 6 babies in the placebo group. No reason was given for the missing data and no sensitivity analysis was performed. Data were missing for some of the secondary outcomes in a few participants (for example BPD missing data for two babies in the repeat steroid group and three in the placebo group; and similarly for PVL, missing data for six versus nine babies) Intention-to-treat analysis was performed on babies with known outcomes
Selective reporting (reporting bias)	Low risk	No obvious risk of selective reporting.
Other bias	Low risk	No other obvious risk of bias identified.