Collaborative 1981

Methods	Type of study: RCT Method of treatment allocation: method of randomisation not stated. Coded drug boxes with sequentially‐numbered vials containing study drug were used. Sealed envelope containing the identity of the contents of was attached to each vial "to be opened in emergency only in case of an emergency". The manuscripts do not state how often these were opened. Stratification: yes, within each hospital Placebo: yes, identical appearance Sample size calculation: yes Intention‐to‐treat analyses: no Losses to follow‐up: yes, 2 (0%) infants in the control arm were lost to RDS follow‐up as neonates and 240 (37%) children were lost to follow‐up at age 3 (124 in the treatment arm and 116 in the control arm) Funding: National Institutes of Health, USA
Participants	Location: 5 university hospitals in the USA Timeframe: March 1977‐March 1980 Eligibility criteria: women at high risk of preterm delivery. L/S ratio < 2.0 in cases of uncertain gestation, hyperthyroidism, hypertension, placental insufficiency, drug addiction, methadone use or gestational age > 34 weeks Gestational age range: 26‐37 weeks Exclusion criteria: > 5 cm of cervical dilatation, anticipated delivery < 24 h or > 7 d, intrauterine infection, previous glucocorticoid treatment, history of peptic ulcer disease, active tuberculosis, viral keratitis, severe fetal Rhesus sensitisation, infant unlikely to be available for follow‐up Total recruited: 696 women and 757 infants; 349 women and 378 infants in the treatment arm and 347 women and 379 infants in the control arm
Interventions	4 doses of 5 mg dexamethasone phosphate IM 12 h apart Control group received placebo
Outcomes	Maternal outcomes (postnatal fever), fetal/neonatal outcomes (fetal death, neonatal death, RDS, birthweight, interval between trial entry and delivery, systemic infection in the first 48 h of life, proven infection while in the NICU, necrotising enterocolitis), childhood outcomes (death, lung function, developmental delay, intellectual impairment, cerebral palsy) and health service outcomes were reported (length of neonatal hospitalisation)
Notes	Further information was requested from the authors but there was no reply
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Method of randomisation not stated
Allocation concealment (selection bias)	High risk	Sealed envelope containing the identity of the contents of was attached to each vial "to be opened in emergency only in case of an emergency". The manuscripts do not state how often these were opened.
Blinding of participants and personnel (performance bias) All outcomes	Low risk	"Both placebo and steroid were dispensed as 10 ml clear, colourless solutions which differed only in that one contained the steroid". It is likely that participants were blinded.
Blinding of outcome assessment (detection bias) All outcomes	Unclear risk	Blinding of outcome assessors was not described.
Incomplete outcome data (attrition bias) All outcomes	Unclear risk	2 (0.27%) infants in the control arm were lost to RDS follow‐up as neonates. At age 3, 240 (37%) children were lost to follow‐up (124 in the treatment arm and 116 in the control arm), or had died (47 in the treatment arm and 46 in the control arm).
Selective reporting (reporting bias)	Low risk	Study protocol not available, but appears to report on all pre‐specified outcomes
Other bias	Unclear risk	Insufficient information to asses if other sources of bias exist.