Guinn 2002.

Methods	Type of study: randomised controlled trial.
Participants	Location: 13 academic centres in USA. Timeframe: February 1996‐April 2000. Eligibility criteria: 502 women (502 babies) at 24 weeks to < 33 weeks' gestation at high risk of preterm birth who remained undelivered 1 week following an initial course of antenatal corticosteroids (defined as 2 doses of 12 mg/dose intramuscular betamethasone, repeated at 24 hours; or 4 doses of 6 mg/dose intramuscular dexamethasone, given at 12 hour‐intervals. To be at high risk of preterm birth qualifying criteria were: preterm labour with intact membranes (either a history of regular uterine contractions associated with cervical dilatation of > 2 cm and effacement > 80% in a nulliparous participant or cervical dilatation of > 3 cm and > 80% effacement in a multiparous participant at the time of presentation: or regular uterine contractions with documented cervical change); preterm premature rupture of the membranes (rupture of the membranes occurring > 1 hour prior to the onset of preterm labour); maternal medical illness (pre‐eclampsia, hypertension, diabetes, renal disease, systemic lupus erythematosus, trauma); or suspected fetal jeopardy (intrauterine growth restriction < 10th percentile, oligohydramnios, abnormal antepartum testing, progression of a fetal anomaly compatible with like, twin‐twin transfusion syndrome). Gestational age range: 24 weeks to < 33 weeks' gestation. Exclusion criteria: women were excluded if they required immediate delivery, there were fetal anomalies incompatible with life, documented fetal lung maturity, and maternal active tuberculosis or human immunodeficiency virus infection. Total recruited: 502‐256 in the weekly‐course group and 246 in the single‐course group.
Interventions	In the weekly‐course group: a weekly course of betamethasone (2 doses of 12 mg/dose betamethasone repeated after 24 hours, intramuscularly), until 34 weeks or birth whichever came first. In the single‐course group: a similarly administered placebo.
Outcomes	Primary outcomes: composite neonatal morbidity defined as presence of any of the following: severe RDS, BPD, severe IVH, PVL, necrotising enterocolitis, proven sepsis or death between randomisation and nursery discharge. Secondary outcomes: frequency and severity of RDS; need for and duration of oxygen therapy; need for and duration of ventilatory support; BPD (defined as need for oxygen > 21% and usually ventilatory therapy for at least 28 days of life; in cases were no additional ventilatory support was needed but oxygen was required, chest radiographs consistent with BPD were used; in the case of neonatal death, BPD was diagnosed on autopsy findings); severe IVH was defined as intraventricular bleeding with dilatation of the cerebral ventricles (grade 3) or parenchymal haemorrhage (grade 4), as diagnosed with an imaging technique or autopsy, PVL was defined as the presence of more than 1 obvious hypoechoic cyst in the periventricular white matter; necrotising enterocolitis (defined as proven); proven sepsis; perinatal death defined as death of a fetus or neonate at any time between randomisation and nursery discharge.
Funding Support	Funding: March of Dimes grant, the Berlex Foundation, the Wisconsin Perinatal Association, the Perinatal Clinical Research Center at the University of Colorado Health Sciences Center (grant from the General Clinical Research Centers Program, National Centers for Research Resources, National Institutes of Health), and the participating departments.
Notes	Sample‐size calculation: yes. A sample of 1000 women was required to have a 90% power to detect a one‐third reduction in composite morbidity from 25.0% to 16.5% (2‐tailed alpha = 0.05). 2 interim analyses were planned for efficacy and safety. Recruitment was stopped early based on safety concerns.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Computer‐generated randomisation logs prepared centrally and distributed to the research pharmacist at each clinical site. Stratification: by centre.
Allocation concealment (selection bias)	Low risk	Method of treatment allocation: participants were assigned by the pharmacy to a treatment group.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	The placebo syringes were indistinguishable from the syringes containing betamethasone. Patients and healthcare workers were blinded to study group.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	No details reported
Incomplete outcome data (attrition bias) All outcomes	Low risk	Intention‐to‐treat analyses: yes. Losses to follow‐up: 16 women and 1 neonate were lost to follow‐up. Partial data were available for participants who were lost to follow‐up. In some cases the investigators were able to ascertain the birth date, weight, and health status for the neonate. The denominators presented very slightly from 1 variable to another because of missing data.
Selective reporting (reporting bias)	Low risk	No obvious risk of selective reporting.
Other bias	High risk	After the first interim analysis when 308 women have been randomised the decision was made to stop recruitment at 500 women, because of "safety concerns" and the finding of only a marginal difference in short‐term outcomes between treatment groups.