Peltoniemi 2007.

Methods	Type of study: placebo‐controlled randomised trial.
Participants	Location: 5 Finnish university and 3 central hospitals. Time frame: May 2001 to March 2005. Included: women at < 34 weeks' gestation who had received a single course of betamethasone > 7 days previously and were to have elective delivery within 48 hours or were at very high risk of spontaneous delivery within 48 hours (cervical opening 3 cm or more, and regular contractions at 5‐ to 10‐minute intervals). Exclusion criteria: long‐term maternal corticosteroid use, clinical chorioamnionitis, or lethal disease of the fetus. Total recruited: 249 women (125 betamethasone, 124 placebo), 326 infants (159 betamethasone, 167 placebo).
Interventions	Repeat corticosteroid: a single dose of betamethasone 12 mg intramuscularly. Placebo: isotonic saline intramuscularly.
Outcomes	To time of primary hospital discharge: primary outcome: survival without severe RDS or severe IVH (grade 3 or 4) during the first hospital admission. RDS was defined on the basis of typical chest radiograph findings, requirement for continuous distending airway pressure, supplemental oxygen for 48 hours or more, or requirement for surfactant in cases of established respiratory failure. Severe IVH was defined as IVH with ventricular dilation (grade 3) or parenchymal haemorrhage (grade 4). Cranial ultrasound was performed for all infants at 4 to 8 days of age and at 36 weeks post‐menstrual age or before discharge. The most severe grade of IVH was recorded. Secondary outcomes: cystic PVL; necrotising enterocolitis grade 2 or higher; BPD (defined as a requirement for supplemental oxygen or any form of ventilation with continuous distending pressures at postnatal age of 36 weeks or at postnatal age of 4 weeks for those born after postmenstrual age of 31 weeks); patent ductus arteriosus requiring treatment (defined as a requirement for prostaglandin inhibitor therapy or surgery for closure). For the early childhood follow‐up at 2 years' corrected age: a range of outcomes were assessed. Survival without serious neurological, cognitive or sensory impairment (NDI); respiratory problems; infections, medical history; child's weight, length and head circumference; cerebral palsy; speech; deafness; blindness; child behaviour.
Funding Support	Funding: foundation for paediatric research in Finland, Alma and KA Snellmann Foundation, Sigrid Juselius foundation, hospital research funds.
Notes	Tocolytics were not used and 79% of mothers gave birth < 24 hours after the intervention. All infants were born < 36 weeks' gestation. Sample‐size calculation: yes. Sample size based on a 25% increase in the primary outcome rate, from an estimated 50% in the control group to 62.5% in the repeat group. The planned sample size was 220 women in each arm (2 tailed alpha 0.05, beta 0.2). Recruitment was terminated early, after 249 women had been enrolled, primarily because of safety concerns due a decrease in intact survival in the repeat corticosteroid group. In addition, recruitment was slower than expected.
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	The method by which the sequence was generated was not described.
Allocation concealment (selection bias)	Low risk	"Randomization was performed centrally and was stratified according to centre by using 4 sets of sequentially‐labelled, opaque, sealed envelopes ( for the 4 strata of gestational age (< 28 weeks or between 28 and ≤ 34 weeks and multiple gestation), which were sent to each centre." "Both gestation groups were stratified additionally on the basis of number of fetuses (singleton or multiple pregnancies)." "The sealed envelopes were opened after informed consent was obtained."
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"The doctors and nurses as well as the study investigators were blinded."
Blinding of outcome assessment (detection bias) All outcomes	Low risk	At the follow‐up at 2 years' corrected age: "The examiners and families were unaware of treatment‐group assignment."
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	Losses to follow‐up to time of primary hospital discharge: none reported. Analysis was by "intention‐to‐treat". Losses to follow‐up to time of 2‐year corrected age assessment: 259 of 312 (83%) survivors completed 2‐year follow‐up. 66 survivors (21%) had no paediatric assessment, 32 (21%) in the repeat corticosteroid group and 34 (21%) in the placebo group; 116 (37%) had no psychological tests, 61 (41%) in the repeat corticosteroid group and 56 (34%) in the placebo group.
Selective reporting (reporting bias)	Low risk	No obvious risk of selective reporting detected.
Other bias	High risk	Recruitment was terminated early, after 249 women had been enrolled, primarily because of safety concerns due a decrease in intact survival in the repeat corticosteroid group. There were additional concerns about the long‐term adverse effects of glucocorticoid. Potential imbalance at trial entry for multiple pregnancy and gestational age not addressed.