WHO 2020.

Study characteristics
Methods	Type of study: multicountry, multicentre, individually‐randomised, parallel‐group, double‐blind, placebo‐controlled trial Method of treatment allocation: 1:1 Stratification: site‐stratified individual randomisation with balanced permuted blocks of size 10 were used Placebo: yes Sample size calculation: yes
Participants	Location: Bangladesh, India, Kenya, Nigeria and Pakistan Inclusion criteria: pregnant women (with confirmed live fetuses) who were at risk of preterm birth between 26 weeks 0 days and 33 weeks 6 days; birth planned or expected in the next 48 hours (following preterm prelabour rupture of membranes, spontaneous labor, or provider‐initiated preterm birth). Exclusion criteria: clinical signs of severe infection; major congenital fetal anomalies; concurrent or recent (within the past two weeks) use of systemic glucocorticoids; participation in another trial; or contraindication to glucocorticoids Total recruited: 2852 women (3070 infants) randomised (A 1429 women, 1544 infants; B 1423 women, 1526 infants) Gestational age range: between 26 weeks 0 days and 33 weeks 6 days
Interventions	Group A: 6 mg dexamethasone administered every 12 hours, to a maximum of four doses, or until hospital discharge or birth Group B: placebo administered every 12 hours, to a maximum of four doses, or until hospital discharge or birth Women were eligible for a repeat course if they had not given birth after seven completed days but still met inclusion criteria. The repeat course was identical to the first course, and the same as the initial allocation
Outcomes	Neonatal death Any baby death Possible maternal bacterial infection For the neonate: Stillbirth Early neonatal death Severe respiratory distress Neonatal sepsis Severe Intraventricular haemorrhage (sIVH) Neonatal hypoglycaemia Apgar score at 5 minutes Major neonatal resuscitation at birth Timing of breast milk feeding initiation Time to full enteral feeding Use of oxygen therapy Length of oxygen therapy Use of continuous CPAP)ventilation Length of use of CPAP ventilation Use of mechanical ventilation Length of use of mechanical ventilation Any use of parenteral therapeutic antibiotic therapy Length of use of parenteral therapeutic antibiotic therapy Use of surfactant treatment Number of doses of surfactant treatment Length of hospital stay after birth Admission to a special care unit (SCU) Length of admission to SCU (days) Newborn readmission for health care at facility Length of stay for newborn readmission Number of newborn readmission for health care at facility Cause of neonatal readmission for health care at facility For the woman: Maternal death Maternal fever Chorioamnionitis Postpartum endometritis Wound infection Non‐obstetric infection Therapeutic antibiotics Number of days of therapeutic antibiotic use Any antibiotic use Length of total maternal hospitalisation for birth Any postpartum maternal readmission to facility Number of maternal readmissions to facility Cause of maternal readmission to facility Any referral of woman to another facility for treatment of complications
Notes	Study dates: December 2017 through November 2019 Funding sources: Quote:“This trial was primarily funded by the Bill and Melinda Gates Foundation (Grant OPP1136821). Additional support was provided by UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research; and Department of Maternal, Newborn, Child, Adolescent Health, and Ageing, of the World Health Organization, Geneva, Switzerland.” Declarations of interest: Quote:“The authors declare that they have no competing interests.” Trial stopped early: the Data Safety Monitoring Monitoring board "recommended the trial be stopped for infant mortality benefits, and strong evidence of a graded dose‐response effect, in the context of existing evidence of benefits of antenatal glucocorticoids."
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote:“The computer‐generated randomization sequence was prepared centrally at WHO”
Allocation concealment (selection bias)	Low risk	Quote:“All sites received serially numbered identical treatment packs containing 4mg/mL ampules of dexamethasone or placebo for two full courses” "The assignment schedule was stored at WHO. Once eligibility was confirmed and consent obtained, trained study staff randomized a woman by taking the next numbered treatment pack from the dispenser (which was designed to ensure packs were taken sequentially"
Blinding of participants and personnel (performance bias) All outcomes	Low risk	Quote:“Trial participants, care providers, and investigators were not aware of group assignments.”
Blinding of outcome assessment (detection bias) All outcomes	Low risk	Quote:“Trial participants, care providers, and investigators were not aware of group assignments.”
Incomplete outcome data (attrition bias) All outcomes	Low risk	Low attrition. Quote:“Over 99% of randomized women and infants completed follow‐up”
Selective reporting (reporting bias)	Low risk	All outcomes that were pre‐specified in the protocol are reported in full
Other bias	Low risk	Nothing to indicate any other source of bias

CPAP: continuous positive airways pressure
GDM: gestational diabetes mellitus
HPA: hypothalamic‐pituitary‐adrenal
ICU: intensive care unit
IM: intramuscular
ITT: intention‐to‐treat
IQR: interquartile range
IUGR: Iintrauterine growth restriction
IV: intravenous
IVH: intraventricular haemorrhage
LMP: last menstrual period
NICU: neonatal intensive care unit
PIH: pregnancy induced hypertension
PROM: premature rupture of membranes
PPROM: prolonged premature rupture of membranes
RCT: randomised controlled trial
RDS: respiratory distress syndrome
SD: standard deviation