Results of the search

For the current update of this review, database searches for the calendar years 2016‐2020 identified 3760 references; other search sources identified no additional references. After removing 404 duplicate records, 3356 title abstracts were screened, 3351 full texts were excluded, five full text articles were assessed for eligibility, and two new studies were included. See Figure 1.

Figure 1

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Study flow diagram: review update.

 With addition of the two new RCTs, we have included in this updated review 23 RCTs, in total, that have recruited 1817 infants. These trials enrolled preterm infants who were oxygen‐ or ventilator‐dependent (or both) beyond six days of age. Investigators typically used dexamethasone at an initial dose of 0.5 to 1.0 mg/kg/d, with initial duration of therapy ranging from three days to six weeks. In two studies, the corticosteroid was hydrocortisone (Onland 2019; Parikh 2013). Details are given below and in the Characteristics of included studies table.

We discuss the excluded trials below and in the Characteristics of excluded studies table.

We identified two ongoing RCTs of hydrocortisone to prevent or treat BPD (He 2020; NCT01353313). See Characteristics of ongoing studies.

Included studies

We included 23 RCTs (1817 infants) in this updated review.

Ariagno 1987 was updated with more data provided by investigators in September 2000. Investigators randomised 34 preterm infants of less than 1501 grams birth weight who were ventilator‐dependent and were not weaning from mechanical ventilation at three weeks of age to parenteral dexamethasone (n = 17) or placebo (n = 17) groups. Treated babies received one of two regimens: a 10‐day course of 1.0 mg/kg/d for four days and 0.5 mg/kg/d for six days ((total dose 7 mg/kg dexamethasone over 10 days), or a seven‐day course of 1.0 mg/kg/d for three days followed by 0.5 mg/kg/d for four days (total dose 8.5 mg/kg dexamethasone over 10 days). Researchers calculated total respiratory system compliance from a pneumotachometer and made airway pressure measurements during mechanical inflation before and after seven days of treatment. Outcomes included mortality, duration of ventilation and oxygen therapy, and complications of prematurity and treatment. Country: USA.

Avery 1985 enrolled 16 infants with birth weight less than 1500 grams, a clinical and radiographic diagnosis of respiratory distress syndrome, inability to be weaned from the ventilator after two weeks, and radiological evidence of stage II or III BPD (Northway 1967). Researchers excluded babies if they had patent ductus arteriosus, congenital heart disease, sepsis, or pneumonia; had received intravenous lipids for at least 24 hours; and were over six weeks of age. To those randomised to receive dexamethasone (n = 8), investigators gave 0.5 mg/kg/d intravenously in two divided doses for three days, followed by 0.3 mg/kg/d for a further three days, thereafter decreased by 10% of the current dose every three days until a dose of 0.1 mg/kg/d was reached. At that point, they gave the drug on alternate days for one week, then discontinued (total dose approximately 8 mg/kg dexamethasone over 42 days). Control infants (n = 8) did not receive a placebo. Country: USA.

Brozanski 1995 was a prospective randomised double‐blind trial conducted to assess the efficacy and safety of pulse doses of dexamethasone for survival without supplemental oxygen given to very low birth weight infants at high risk of BPD. Trial authors randomly assigned 78 infants with birth weight less than 1501 grams, who were ventilator‐dependent at seven days, to receive pulse doses of dexamethasone 0.5 mg/kg/d 12‐hourly or an equivalent volume of a saline placebo for three days at 10‐day intervals, until they no longer required supplemental oxygen or mechanical ventilation, or had reached 36 weeks' postmenstrual age (total minimum dose 3 mg/kg dexamethasone over three days). Infants were excluded from the study if they had complex congenital anomalies, pulmonary hypoplasia, or haemodynamic instability. Country: USA. Participants were recruited between March 1991 and April 1993. Supported by grants from the Magee‐Women's Health Foundation Research Fund and the GCRC/National Institutes of Health 5M0 IRR00084.

CDTG 1991 (Collaborative Dexamethasone Trial Group 1991) was a multi‐centre trial conducted at 31 centres in six countries (UK, Ireland, Belgium, Germany, Canada, and USA) over a period of two and a half years from August 1986 to January 1989. A total of 287 infants who were oxygen‐dependent and had been in a static or deteriorating condition over the preceding week were eligible for trial entry from around three weeks of age. Study authors excluded infants with major malformations (n = 2), and they delayed trial entry to allow treatment of any intercurrent infection or heart failure. Infants did not have to require mechanical ventilation ‐ at the time of entry approximately two‐thirds of infants were intubated and one‐third were not. Those allocated to the dexamethasone group (n = 143) received 0.6 mg/kg/d intravenously (or orally if there was no intravenous line) for one week (total dose 4.2 mg/kg dexamethasone over seven days). There was an option to give a second tapering nine‐day course (0.6, 0.4, and 0.2 mg/kg/d for three days each) if, after initial improvement, relapse occurred. Control infants (n = 142) received an equivalent volume of saline placebo. Supported by Action Research for Crippled Children.

Cummings 1989 randomised 36 preterm infants with birth weight less than 1251 grams and gestational age less than 31 weeks, who were dependent on oxygen (> 29%) and mechanical ventilation (rate > 14 per minute with no evidence of weaning during the previous 72 hours) at two weeks of age, to receive a 42‐day course of dexamethasone or an 18‐day course of dexamethasone or saline placebo. They did not include infants with symptomatic patent ductus arteriosus, renal failure, or sepsis. To infants in the 42‐day group (n = 13), researchers administered dexamethasone at a dose of 0.5 mg/kg/d for three days and 0.3 mg/kg/d for the next three days. They then reduced the dose by 10% every three days until a dose of 0.1 mg/kg was reached on Day 34. After three days at this dose, the drug was given on alternate days for one week and then was stopped (total dose 7.9 mg/kg dexamethasone over 42 days). Infants in the 18‐day dexamethasone group (n = 12) received the same initial dose of 0.5 mg/kg/d for three days, but their dose was then decreased more rapidly by 50% every three days until a dose of 0.06 mg/kg was reached on Day 10. After three days at this dose, study authors gave the drug on alternate days for one week and then stopped (total dose 3 mg/kg dexamethasone over 18 days). For the remaining four treatment days, those infants received saline placebo. Infants in the control group (n = 11) received saline placebo for 42 days. Researchers combined the two treatment groups for the purposes of this meta‐analysis and provided additional data on some short‐term and long‐term outcomes for inclusion in this review. Country: USA. Participants were recruited between January 1986 and June 1987.

Doyle 2006 included a total of 70 infants of less than 1000 grams birth weight or born at less than 28 weeks' gestation, who were at least seven days of age and were ventilator‐dependent and considered eligible for postnatal corticosteroids. Exclusions were few and comprised only those with congenital anomalies likely to adversely affect long‐term neurological outcomes. Trialists worked at 11 collaborating centres within Australia, New Zealand, and Canada and performed stratification by centre. They randomly allocated infants to twice‐daily doses of a 10‐day tapering course of dexamethasone sodium phosphate (0.15 mg/kg/d for three days, 0.10 mg/kg/d for three days, 0.05 mg/kg/d for two days, 0.02 mg/kg/d for two days (total dose 0.89 mg/kg dexamethasone over 10 days) (n = 35 infants)) or to an equivalent volume of 0.9% saline placebo (n = 35 infants). A repeat course of the same blinded drug was a therapeutic option for attending physicians. The dexamethasone preparation did not contain bisulphite preservative. Researchers based the sample size calculation for the original trial on detecting improvement in survival free of major neurosensory disability from 50% to 60%, with a two‐sided type I error rate of 5% and 80% power, and required that a total of 814 infants be recruited. This study was stopped early at 70 infants, not only because less than 10% of the initial sample had been recruited after 2.5 years (March 2000 to October 2002), making it unlikely that the total sample size of 814 would be achieved within a reasonable time, but also because the rate of recruitment had fallen ‐ not increased ‐ even though more centres had entered the study from the time of its inception. Countries: Australia, New Zealand, Canada. Supported by the National Health ad Medical Research Council of Australia (Project Grant 108700).

Durand 1995 was a prospective randomised trial of 44 infants of birth weight 501 grams to 1500 grams and gestational age between 24 and 32 weeks who failed to be weaned from the ventilator at 7 to 14 days; one infant was excluded after randomisation because of birth weight < 500 grams, and hence data were reported for 43 infants. Their oxygen requirement was > 29% and ventilator rate > 14 per minute. Investigators excluded infants with documented sepsis, evidence of systemic hypertension, congenital heart disease, renal failure, intraventricular haemorrhage (grade IV), and multiple congenital anomalies. Infants in the treatment group (n = 23) received dexamethasone 0.5 mg/kg/d 12‐hourly intravenously for the first three days, 0.25 mg/kg/d for the next three days, and 0.10 mg/kg/d on the seventh day of treatment (total dose 2.35 mg/kg dexamethasone over seven days). Controls (n = 20) received no placebo and no dexamethasone during the seven‐day study period. At the end of the study week, the attending clinician could start dexamethasone treatment for controls. Country: USA. Participants were recruited between December 1990 and November 1992.

Harkavy 1989 randomised 21 preterm infants who were ventilator‐ and oxygen‐dependent at 30 days of age to receive dexamethasone or placebo. They gave dexamethasone 0.5 mg/kg/d in two or more doses either intravenously or by mouth (total dose 1 mg/kg dexamethasone or more over 2 days), and they gave an equivalent volume of saline to controls. Country: USA. Participants were recruited between April 1983 and July 1987. Supported by a grant from the Columbia Hospital for Women Research Foundation.

Kari 1993 was a randomised double‐blind placebo‐controlled trial that enrolled 41 infants with birth weight less than 1501 grams, gestational age greater than 23 weeks, dependence on mechanical ventilation at 10 days, and no signs of patent ductus arteriosus, sepsis, gastrointestinal bleeding, or major malformations. Infants in the dexamethasone group (n = 17) received 0.5 mg/kg/d intravenously in two doses for seven days (total dose 3.5 mg/kg dexamethasone over seven days), whereas the placebo group (n = 24) received normal saline. Country: Finland. Participants were recruited between January 1989 and February 1991. Supported by The Foundation for Pediatric Research, The Academy of Finland, and The Sigfrid Juselius Foundation.

In Kazzi 1990, 23 preterm infants with birth weight less than 1500 grams and radiological findings consistent with a diagnosis of BPD who were ventilator‐dependent at three to four weeks of age were eligible for study entry provided they needed more than 34% oxygen and had a ventilator rate greater than 14 per minute or peak inspiratory pressure > 17 cmH₂O. Infants had to show lack of improvement in ventilator dependency during the preceding five days. Infants in the treatment group (n = 12) received dexamethasone 0.50 mg/kg/d for three days, given as a single daily dose by nasogastric tube. The dose was tapered to 0.40 mg/kg/d for two days, then to 0.25 mg/kg/d for two days (total dose 2.8 mg/kg dexamethasone over seven days). Thereafter, infants received hydrocortisone administered in four divided doses every six hours, beginning with 8 mg/kg/d for two days and tapered by 50% of the dose every other day until 0.5 mg/kg/d was reached (total dose 31 mg/kg hydrocortisone over 10 days). After a total of 17 days, treatment was discontinued. Infants in the control group (n = 11) received equal volumes of saline. In subgroup analysis by type of corticosteroid, this study is included in the dexamethasone subgroup because the dose of corticosteroid received comprised more dexamethasone than it did hydrocortisone. Country: USA. Participants were recruited between August 1986 and February 1989.

Kothadia 1999 randomly allocated 118 preterm infants (birth weight < 1501 grams) between 15 and 25 days of age who were ventilator‐dependent to receive a 42‐day tapering course of dexamethasone (n = 57) or saline placebo (n = 61). The dosage schedule was 0.25 mg/kg 12‐hourly for three days and 0.15 mg/kg 12‐hourly for three days, followed by a 10% reduction in dose every three days until a dose of 0.1 mg/kg had been received for three days, from which time they received 0.1 mg/kg every other day until 42 days after entry (total dose 7.9 mg/kg dexamethasone over 42 days). Study authors provided additional data on some short‐term outcomes for inclusion in this review. Country: USA. Participants were recruited between April 1992 and May 1995. Supported by the Brenner Children's Hospital, Winston‐Salem, North Carolina.

Kovacs 1998 was a double‐blind RCT conducted to assess the efficacy of a combination of prophylactic systemic dexamethasone and nebulised budesonide in reducing the incidence and severity of BPD in infants at less than 30 weeks' gestation and weighing less than 1501 grams who were ventilator‐dependent at the age of seven days. Thirty infants received dexamethasone 0.25 mg/kg twice daily for three days (total dose 1.5 mg/kg dexamethasone over three days), followed by nebulised budesonide 500 µg twice daily for 18 days. Thirty control infants received systemic and inhaled saline. Study authors provided additional data on some short‐term and long‐term outcomes for inclusion in this review. Country: Canada. Participants were recruited between March 1993 and October 1995.

Noble‐Jamieson 1989 enrolled 18 infants over four weeks of age who required more than 30% oxygen delivered by a headbox (oxyhood). Congenital infection, gastric erosion, and necrotising enterocolitis were absolute contraindications to trial entry; investigators excluded one infant because of necrotising enterocolitis. Entry was postponed if an infant had a central venous catheter, active infection, untreated patent ductus arteriosus, glucose intolerance, or major segmental pulmonary collapse. Trial entry was postponed for 11 infants, mainly because of suspected sepsis. Researchers randomly allocated infants to receive either dexamethasone (n = 9) or saline (n = 9). They gave dexamethasone orally or intravenously at a dose of 0.25 mg/kg twice daily for the first week, 0.125 mg/kg twice daily for the second week, and 0.10 mg/kg daily for the third week (total dose 3.325 mg/kg dexamethasone over 21 days). Twice‐weekly cranial ultrasound scans were performed on all infants, with scans analysed blinded to treatment allocation after completion of the study. Country: England.

Ohlsson 1992 enrolled 25 infants with birth weight less than 1501 grams after receiving parental informed consent, if the following criteria were met: postnatal age 21 to 35 days, inspired oxygen greater than 29%, chest radiograph consistent with BPD, and treatment with diuretics resulting in no signs of improvement in ventilator requirements during the previous 72 hours. Researchers excluded infants if they had a diagnosis of suspected or proven infection, significant congenital malformation, or clinical evidence of patent ductus arteriosus, necrotising enterocolitis, and gastrointestinal haemorrhage or perforation. The treatment group (n = 12) received dexamethasone 0.50 mg/kg 12‐hourly for three days, 0.25 mg/kg 12‐hourly for three days, 0.125 mg/kg 12‐hourly for three days, and 0.125 mg/kg daily for three days (total dose 5.625 mg/kg dexamethasone over 12 days). Investigators gave dexamethasone intravenously at a standard volume of 1 mL. The Research Ethical Committee did not permit use of an intravenous placebo, so a physician not involved in subsequent care of the infant gave a sham injection of 1 mL of normal saline into the bed in the control group (n = 13). Study authors provided additional data for some short‐term outcomes for inclusion in this review. Country: Canada. Participants were recruited between April 1986 and June 1988. Supported by a grant from the Dean's Fund of the University of Toronto.

Onland 2019 was a double‐blind RCT conducted to compare hydrocortisone with placebo in infants < 1250 grams birth weight or < 30 weeks' gestational age who were ventilator‐dependent between 7 and 14 days of age and at high risk of developing BPD. Infants were ineligible if they had chromosomal defects or major congenital malformations or had received corticosteroids for improving lung function in the first week of life. A total of 181 infants received a total dose of 72.5 mg/kg of hydrocortisone over 22 days, and 190 infants received placebo. The primary endpoint was mortality or BPD at 36 weeks' postmenstrual age. Countries: Netherlands and Belgium. Participants were recruited from 15 November 2011 to 23 December 2016. Supported by a project grant from The Netherlands Organization for Health Research and Development (priority medicines for children grant 11‐32010‐02).

Papile 1998 was a double‐blind RCT conducted to compare the benefits and hazards of initiating dexamethasone therapy at two weeks of age versus four weeks of age to 371 ventilator‐dependent very low birth weight (501 grams to 1500 grams) infants who had respiratory index scores (mean airway pressure (MAP) × fraction of inspired oxygen) ≥ 2.4 at 13 to 15 days of age that had been increasing or minimally decreasing during the previous 48 hours, or a score of 4.0, even if there had been improvement during the preceding 48 hours; had received no glucocorticoid treatment after birth; had no evidence or suspicious signs of sepsis as judged by the treating physician; and had no major congenital anomaly of the cardiovascular, pulmonary, or central nervous system. A total of 182 infants received dexamethasone for two weeks followed by placebo for two weeks, and 189 infants received placebo for two weeks followed by either dexamethasone (those with a respiratory index score ≥ 2.4 on treatment Day 14) or additional placebo for two weeks. The dexamethasone dose was 0.5 mg/kg/d intravenously or orally for five days, then 0.3 mg/kg for three days, 0.14 mg/kg for three days, and 0.06 mg/kg for three days (total dose 4.0 mg/kg dexamethasone over 14 days). Only outcome data at 28 days were eligible for inclusion in this review (see below). Country: USA. Participants were recruited from September 1992 to July 1995. Supported by cooperative agreements (U10 HD27881, U10 HD21373, U10 HD27851, U10 HD27853, U10 HD21397, U10 HD19897, U10 HD21415, U10 HD27856, U10 HD21364, U10 HD27880, U10 HD27904, U10 HD27871, and U10 HD21385) with the National Institute of Child Health and Human Development and by General Clinical Research Center grants MO1 RR 00997, MO1 RR 08084, MO1 RR 00750, MO1 RR 00070, and MO1 RR 06022. Dexamethasone was provided by Merck Sharp & Dohme.

Parikh 2013 was a double‐blind RCT of hydrocortisone versus saline placebo given to 64 infants with birth weight ≤ 1000 grams who were ventilator‐dependent between 10 and 21 days of age and at high risk of developing BPD, with the primary outcome of differences in brain tissue volumes on magnetic resonance imaging (MRI) at term‐equivalent age. Infants were excluded if they were at < 23 weeks' gestation at birth, were previously treated with corticosteroids, were receiving indomethacin treatment or were likely to receive it within seven days, had presumed sepsis or necrotising enterocolitis, or had a major congenital anomaly of the cardiopulmonary or central nervous system. Thirty‐one infants received a total of 17 mg/kg of hydrocortisone over seven days, and 33 infants received an identical volume of saline placebo. This trial included follow‐up at 18 to 22 months of age, corrected for prematurity. Country: USA. Participants were recruited between 11 October 2005 and 8 September 2008. Supported by National Institutes of Neurological Disorders and Stroke (K23‐NS048152) and National Center for Research Resources (UL1RR024148 to University of Texas Health Science Center at Houston Center for Clinical and Translational Sciences).

Romagnoli 1997 was a randomised trial of 30 preterm infants who were ventilator‐ and oxygen‐dependent at 10 days and were at 90% risk of developing BPD based on the trial authors' own scoring system. Fifteen infants received dexamethasone 0.5 mg/kg/d for six days, 0.25 mg/kg/d for six days, and 0.125 mg/kg/d for two days (total dose 4.75 mg/kg dexamethasone over 14 days). Control infants (n = 15) did not receive any steroid. Study authors provided additional data on some short‐term outcomes for inclusion in this review. Country: Italy. Participants were recruited between April 1996 and June 1997.

Scott 1997 was a double‐blind RCT of dexamethasone versus saline placebo given to 15 infants who were ventilator‐dependent between 11 and 14 days of age with an inspired oxygen requirement greater than 60%. The primary outcome was cortisol response to adrenocorticotrophic hormone (ACTH). Infants with lethal anomalies were excluded. Ten infants received a total of 1.9 mg/kg of dexamethasone over five days, and five infants received an identical volume of saline placebo. Country: USA. Participants were recruited between 11 October 2005 and 8 September 2008. Supported by a Bristol‐Myers Research Grant and the General Clinical Research Center of the University of New Mexico, Program DRR (NIH 5M01RR00997‐14‐18).

Vento 2004 was a randomised trial of 20 neonates with birth weight < 1251 grams and gestation < 33 weeks who were oxygen‐ and ventilator‐dependent on the 10th day of life. Infants received dexamethasone 0.5 mg/kg/d for three days, 0.25 mg/kg/d for three days, and 0.125 mg/kg/d for one day (total dose 2.375 mg/kg dexamethasone over seven days) (n = 10), or they received no steroid treatment (n = 10). Country: Italy. Participants were recruited between August 1998 and July 2000.

In Vincer 1998, researchers randomly assigned 20 very low birth weight infants who were ventilator‐dependent at 28 days to receive either a six‐day course of intravenous dexamethasone 0.5 mg/kg/d for three days followed by 0.3 mg/kg/d for the final three days (total dose 2.4 mg/kg dexamethasone over six days) (n = 11), or an equal volume of saline placebo (n = 9). This trial included a two‐year follow‐up. Study authors provided additional data on some short‐term outcomes for inclusion in this review. Country: Canada.

Walther 2003 was a double‐blind randomised clinical trial involving 36 preterm infants with birth weight > 599 grams, gestation of 24 to 32 weeks, and respiratory distress syndrome requiring mechanical ventilation with oxygen > 29% or respiratory index > 1.7 between 7 and 14 days of life. Exclusion criteria were sepsis or other documented infection, congenital heart disease, systemic hypertension, unstable clinical status (renal failure, grade IV intraventricular haemorrhage), or multiple congenital anomalies. Eligible infants received dexamethasone 0.2 mg/kg/d for four days, 0.15 mg/kg/d for four days, 0.1 mg/kg for four days, and 0.05 mg/kg for two days (total dose 1.9 mg/kg over 14 days) (n = 19 infants), or saline placebo (n = 17 infants). Country: USA. Participants were recruited between December 1996 and November 1999. Supported by NIH grant P20 RR11145 and GCRC grant M01 RR00425.

Yates 2019 was a multi‐centre randomised blinded parallel‐group placebo‐controlled feasibility study, designed to be the forerunner of a larger RCT. Eligible infants were at < 30 weeks’ gestational age with postnatal age from 10 to 24 days, were ventilator‐dependent and receiving at least 30% inspired oxygen, and were at high risk of developing BPD. Excluded were infants who had received previous courses of postnatal steroids for respiratory disease; and those who had a severe congenital anomaly affecting the lungs, heart, or central nervous system; who had a surgical abdominal procedure or patent ductus arteriosus ligation; or who had an illness or medication for which postnatal corticosteroid would be contraindicated. Eligible infants were randomised to very low‐dose dexamethasone (0.05 mg/kg daily for 10 days, then every second day on Days 12, 14, and 16 after trial entry (total dose 0.65 mg/kg dexamethasone over 16 days) (n = 12 infants)), or saline placebo (n = 10 infants). Country: England. Participants were recruited between 21 July 2017 and 14 April 2018. Supported by the Efficacy and Mechanism Evaluation (EME) programme ‐ a Medical Research Council and National Institute for Health Research (NIHR) partnership.

Excluded studies

In total, we excluded 46 studies. Vento 2004 was listed as excluded and provided data for two separate cohorts of infants ‐ the first cohort randomised at 10 days of age (those data are included in this "Late" review), and the second cohort randomised at four days of age (hence these data are included in the "Early" review (Doyle 2021)).

We excluded 32 studies that were included in Doyle 2021. That Cochrane Review addressed the use of postnatal corticosteroids commenced in the first six days after birth to prevent BPD in preterm infants (Anttila 2005; Baden 1972; Batton 2012; Baud 2016; Biswas 2003; Bonsante 2007; Efird 2005; Garland 1999; Halac 1990; Hochwald 2014; Kopelman 1999; Lauterbach 2006; Lin 1999; Mukhopadhyay 1998; Ng 2006; Peltoniemi 2005; Rastogi 1996; Romagnoli 1999; Sanders 1994; Shinwell 1996; Sinkin 2000; Soll 1999; Stark 2001; Subhedar 1997; Suske 1996; Tapia 1998; Vento 2004a; Wang 1996; Watterberg 1999; Watterberg 2004; Yeh 1990; Yeh 1997).

We excluded an additional study because it compared two different dosages of dexamethasone only (Marr 2019). We excluded other studies for a variety of reasons. See Characteristics of excluded studies.

Allocation

We found little evidence of allocation bias overall; most studies had no evidence of allocation bias, and in a small minority the risk was unclear.

Blinding

We found little evidence of blinding bias overall; most studies had no evidence of blinding bias, but small minorities had unclear or high risk of blinding bias.

Incomplete outcome data

We found little evidence of attrition bias overall; most studies had no evidence of attrition bias, and a small minority had unclear risk.

Selective reporting

Just over one‐half of studies had no evidence of selective reporting bias, and the remainder had unclear risk of selective reporting bias.

Other potential sources of bias

A majority of studies used a valid method of random sequence generation, but in approximately 40% of studies, the methods used for randomisation were unclear.

Results of meta‐analysis

Meta‐analysis of these 23 studies yielded the following results.

Mortality

Evidence indicates that late systemic corticosteroid treatment was associated with reduced mortality at all ages: 28 days (typical risk ratio (RR) 0.60, 95% confidence interval (CI) 0.40 to 0.89; typical risk difference (RD) ‐0.04, 95% CI ‐0.09 to ‐0.00; 7 studies, 970 infants; Analysis 1.1), 36 weeks' postmenstrual age (typical RR 0.70, 95% CI 0.52 to 0.94; typical RD ‐0.05, 95% CI ‐0.10 to ‐0.01; 15 studies, 1029 infants; Analysis 1.2), before hospital discharge (typical RR 0.79, 95% CI 0.63 to 0.98; typical RD ‐0.04, 95% CI ‐0.08 to ‐0.00; 20 studies, 1406 infants; Analysis 1.3), and at latest reported age (RR 0.81, 95% CI 0.66 to 0.99; RD ‐0.05, 95% CI ‐0.09 to ‐0.00; 21 studies, 1428 infants; Analysis 1.4).

No evidence suggests publication bias for mortality at latest reported age upon examination of a funnel plot (Egger test, P = 0.78) (Figure 4).

Figure 4

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Funnel plot of comparison: 1 Mortality, outcome: 1.4 Mortality at latest reported age.

Bronchopulmonary dysplasia

The incidence of BPD was significantly decreased at 28 days of life (typical RR 0.90, 95% CI 0.84 to 0.95; typical RD ‐0.11, 95% CI ‐0.17 to ‐0.05; 7 studies, 994 infants; Analysis 2.1), and at 36 weeks' postmenstrual age (typical RR 0.89, 95% CI 80 to 0.99; typical RD ‐0.07, 95% CI ‐0.13 to ‐0.01; 14 studies, 988 infants; Analysis 2.2), but the evidence was not as strong at 36 weeks' postmenstrual age among survivors (typical RR 0.91, 95% CI 0.82 to 1.01; typical RD ‐0.06, 95% CI ‐0.13 to 0.01; 9 studies, 624 infants; Analysis 2.3). We noted strong evidence of publication bias upon examining a funnel plot for BPD at 36 weeks (Egger test, P < 0.001) (Figure 5). Data show reduced need for late rescue with corticosteroids (typical RR 0.48, 95% CI 0.41 to 0.57; typical RD ‐0.20, 95% CI ‐0.24 to ‐0.16; 15 studies, 1489 infants; Analysis 2.4) and reduced need for home oxygen both overall (typical RR 0.71, 95% CI 0.54 to 0.94; typical RD ‐0.08, 95% CI ‐0.14 to ‐0.01; 7 studies, 611 infants; Analysis 2.5) and for survivors only (typical RR 0.69, 95% CI 0.51 to 0.94; typical RD ‐0.13, 95% CI ‐0.24 to ‐0.03; 6 studies, 277 infants; Analysis 2.6).

Figure 5

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Funnel plot of comparison: 2 Bronchopulmonary dysplasia (BPD), outcome: 2.2 BPD at 36 weeks' postmenstrual age.

Mortality or bronchopulmonary dysplasia

Strong evidence indicates that the combined outcome of mortality or BPD was decreased both at 28 days of life (typical RR 0.87, 95% CI 0.83 to 0.91; typical RD ‐0.12 to 95% CI ‐0.16 to ‐0.08; 6 studies, 934 infants; Analysis 3.1) and at 36 weeks' postmenstrual age (RR 0.85, 95% CI 0.79 to 0.92; RD ‐0.12, 95% CI ‐0.17 to ‐0.07; 14 studies, 988 infants; Analysis 3.2). We found little evidence of publication bias upon examining a funnel plot for mortality or BPD at 36 weeks (Egger test, P = 0.33) (Figure 6).

Figure 6

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Funnel plot of comparison: 3 Mortality or BPD, outcome: 3.2 Mortality or BPD at 36 weeks' postmenstrual age.

Follow‐up data

• Rates of children with low cut‐off scores for the Mental Developmental Index on the Bayley Scales were little affected overall (typical RR 0.81, 95% CI 0.47 to 1.38; 7 studies, 333 infants; Analysis 6.1) or among survivors assessed (typical RR 0.74, 95% CI 0.45 to 1.22; 7 studies, 232 infants; Analysis 6.2). Rates of children with low cut‐off scores for the Psychomotor Developmental Index on the Bayley Scales were little affected overall (typical RR 0.78, 95% CI 0.34 to 1.80; 1 study, 118 infants; Analysis 6.3) or among survivors assessed (typical RR 0.67, 95% CI 0.30 to 1.50; 1 study, 90 infants; Analysis 6.4)

• The increase in retinopathy of prematurity did not translate into a significant increase in blindness overall (typical RR 0.78, 95% CI 0.35 to 1.73; 13 studies, 784 infants; Analysis 6.5) or among survivors assessed (typical RR 0.77, 95% CI 0.35 to 1.67; 13 studies, 539 infants; Analysis 6.6)

• We found little evidence for a difference in rates of deafness overall (typical RR 0.56, 95% CI 0.26 to 1.27; 9 studies, 936 infants; Analysis 6.7) or among survivors assessed (typical RR 0.62, 95% CI 0.29 to 1.36; 9 studies, 616 infants; Analysis 6.8)

• We found little evidence for a difference in rates of cerebral palsy at the latest reported age overall (typical RR 1.17, 95% CI 0.84 to 1.61; 17 studies, 1290 infants; Analysis 6.10) or among survivors assessed at the latest reported age (typical RR 1.15, 95% CI 0.81 to 1.61; 16 studies, 628 infants; Analysis 6.16). A funnel plot for the outcome of cerebral palsy at latest reported age provided little evidence of publication bias (Egger test, P = 0.13) (Figure 7). Cerebral palsy was not significantly increased in studies limited to the first three years after birth (typical RR 1.11, 95% CI 0.81 to 1.51; 16 studies, 1311 infants; Analysis 6.9), or among survivors assessed at 1‐3 years of age (typical RR 1.08, 95% CI 0.79 to 1.47; 16 studies, 923 infants; Analysis 6.15. The combined rate of mortality or cerebral palsy was little affected in studies limited to the first three years after birth (typical RR 0.89, 95% CI 0.76 to 1.04; 16 studies, 1311 infants; Analysis 6.13). The combined rate of either mortality or cerebral palsy at latest reported age was not significantly different (typical RR 0.90, 95% CI 0.76 to 1.06; 16 studies, 1290 infants; Analysis 6.14). A funnel plot for the outcome mortality or cerebral palsy at latest reported age provided little evidence of publication bias (Egger test, P = 0.99) (Figure 8)

• Major neurosensory disability was not significantly different overall (typical RR 1.09, 95% CI 0.88 to 1.34; 10 studies, 1090 infants; Analysis 6.17) or among survivors assessed (typical RR 1.01, 95% CI 0.83 to 1.22; 10 studies, 778 infants; Analysis 6.20). The combined rate of mortality or major neurosensory disability was not significantly different (typical RR 0.96, 95% CI 0.85 to 1.08; 10 studies, 1090 infants; Analysis 6.19)

• The rate of abnormal neurological examination overall was increased (typical RR 1.81, 95% CI 1.05 to 3.11; typical RD 0.13, 95% CI 0.02 to 0.24; 4 studies, 200 infants; Analysis 6.21), but the clinical importance of this finding is unclear in the absence of important increases in cerebral palsy or major neurosensory disability. Rates of the combined outcome of mortality or abnormal neurological examination were not significantly different between groups (typical RR 0.96, 95% CI 0.71 to 1.31; 4 studies, 200 infants; Analysis 6.23)

• The only study reporting re‐hospitalisation rates over the first five years noted little evidence of a difference between groups (Analysis 6.25; Analysis 6.26). The same study with follow‐up of survivors to five years noted little evidence for increased maternal reports of wheezing (RR 1.47, 95% CI 0.82 to 2.64; 1 study, 74 infants; Analysis 7.1), need for corrective lenses (RR 1.61, 95% CI 0.82 to 3.13; 1 study, 74 infants; Analysis 7.2), and need for physical therapy (RR 1.49, 95% CI 0.71 to 3.11; 1 study, 74 infants; Analysis 7.3), and a non‐significant decrease in the need for speech therapy (RR 0.46, 95% CI 0.21 to 1.02; 1 study, 74 infants; Analysis 7.4)

• Data show no substantial differences between groups for other outcomes in later childhood, including IQ, respiratory health or function, blood pressure, and growth, with the exceptions of a significant reduction in rates of children with FEV₁ < ‐2 SD (typical RR 0.58, 95% CI 0.36 to 0.94; 2 studies, 187 infants; Analysis 8.2), increased standardised mean difference for FEV₁ (standardised mean difference (SMD) 0.28, 95% CI 0.01 to 0.55; 4 studies, 222 participants; Analysis 8.5), and increased mean difference for forced vital capacity (MD 7.68% predicted, 95% CI 1.69 to 13.68; 3 studies, 98 participants; Analysis 8.7).

Figure 7

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Funnel plot of comparison: 6 Long‐term follow‐up, outcome: 6.10 Cerebral palsy at latest reported age.

Figure 8

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Funnel plot of comparison: 6 Long‐term follow‐up, outcome: 6.14 Mortality or cerebral palsy at latest reported age.

Differences by type of corticosteroid used

When such comparisons were possible, there were few outcomes for which evidence shows differences in treatment effects between RCTs involving dexamethasone and those involving only hydrocortisone. Notable exceptions were that effects of corticosteroids in reducing BPD at 36 weeks (Analysis 2.2), in reducing mortality or BPD at 36 weeks (Analysis 3.2), and in increasing the rate of hypertension (Analysis 5.4) all arose from treatment with dexamethasone ‐ not with hydrocortisone. 

Sensitivity analysis, excluding studies with higher risk of bias

Two studies had higher risk of bias largely because they included no control groups, and hence blinding to knowledge of treatment allocation was not possible (Durand 1995; Romagnoli 1997). Both studies involved dexamethasone only. Excluding these two studies from major outcomes of mortality at latest age, BPD at 36 weeks, combined mortality or BPD at 36 weeks, cerebral palsy, or mortality or cerebral palsy had little effect on most odds ratios or on any CIs, and altered no conclusions, with one exception; for outcomes of BPD at 36 weeks for all studies combined, the typical RR was 0.89 (95% CI 0.80 to 0.99) with all studies included (Analysis 2.2), but was changed slightly to typical RR 0.93 (95% CI 0.83 to 1.03) when the two studies were excluded.

Results of individual trials

Ariagno 1987: total respiratory system compliance improved in the dexamethasone group (P < 0.05). Time from initiation of treatment to first extubation was shorter for the dexamethasone group (6 versus 45 days; P = 0.0006), but time to final extubation was not significantly different (30 versus 48 days). Data show 10 deaths ‐ five in the dexamethasone group and five in the control group ‐ all occurring after the treatment period. Proportionate weight gain was greater among control infants (P < 0.003) during treatment. Five dexamethasone‐treated infants had infection, as did two in the control group. Hyperglycaemia and hypertension were similar between groups. At follow‐up, cerebral palsy was detected in one child in the dexamethasone group at 36 months of age and in three controls at 12 months of age.

Avery 1985: sequential analysis exceeded the criterion (P < 0.005) when seven consecutive untied pairs showed weaning with dexamethasone and failure to wean in control infants. Pulmonary compliance improved by 64% in the treated group and by 5% in the control group (P < 0.01). Results show no significant intergroup differences in mortality, length of hospital stay, sepsis, hypertension, hyperglycaemia, or electrolyte abnormalities.

Brozanski 1995: at 36 weeks' postmenstrual age, results show a significant increase in survival rates without oxygen supplementation (17/39 versus 7/39; P = 0.03) and a significant decrease in the incidence of BPD (46% versus 23%; P = 0.047) in the group that received pulse dexamethasone therapy. Supplemental oxygen requirements were less throughout the study period in the dexamethasone group (P = 0.013). Mortality and durations of supplemental oxygen, ventilator support, and hospital stay did not differ significantly between groups. The need for insulin therapy for hyperglycaemia was increased in the dexamethasone group (P < 0.05). At follow‐up, data show no significant differences between groups in rate of cerebral palsy among survivors assessed (20% versus 21%). Rate of death or survival among randomised children with cerebral palsy was lower in the dexamethasone group (23% versus 33%), but this difference was not statistically significant. The mean Mental Developmental Index (MDI) was 89.5 (SD 23.7) in the dexamethasone group and 80.8 (SD 26.0) in the control group ‐ a non‐significant difference.

CDTG 1991: dexamethasone treatment significantly reduced the duration of mechanical ventilation among infants who were ventilator‐dependent at entry (median days for survivors, 11 versus 17.5). Data show no statistically significant differences between total groups of survivors in time receiving supplemental oxygen and length of stay in hospital, although trends favoured the dexamethasone group. Twenty‐five infants in each group died before hospital discharge; most were ventilator‐dependent at trial entry. Open treatment with steroids was later given to 18% of the dexamethasone group and 43% of the placebo group (P < 0.001). We found little evidence of serious side effects and noted that infection rates in particular were similar in the two groups. At follow‐up, results show no clear differences between randomised groups in the original study for outcomes at three years. This conclusion held when data for cerebral palsy, blindness, and deafness were updated on the basis of results obtained at 13 to 17 years of age. Rates of intellectual impairment and moderate and severe disability at 13 to 17 years of age were similar in both groups, and data reveal no substantial differences in lung function or growth z‐scores, nor in proportions with high blood pressure.

Cummings 1989: infants in the 42‐day dexamethasone group, but not those in the 18‐day group, were weaned from mechanical ventilation significantly faster than controls (median 29, 73, and 84 days, respectively; P < 0.05) and from supplemental oxygen (medians 65, 190, and 136 days, respectively; P < 0.05). No clinical complications of steroid administration were noted. At follow‐up, combining both dexamethasone groups revealed no significant differences between dexamethasone‐treated and control children for rates of cerebral palsy, blindness, deafness, developmental delay, or major neurosensory disability among survivors, or for death or survival with cerebral palsy, or for death or survival with major disability among those randomised. Neurological status was confirmed at four years of age for all children (Cummings 2002 (personal communication follow‐up of Cummings 1989)). Data show no significant differences in psychometric test scores at 15 months or 4 years of age. Between 4 and 15 years, one child in the 18‐day group had died, leaving 22 survivors, all of whom (100%) were assessed at 15 years of age. There were no significant differences between dexamethasone groups combined and the placebo group for any of the major neurological outcomes, nor for growth or respiratory function.

Doyle 2006: substantially more infants were extubated successfully by 10 days in the dexamethasone group than in the control group (odds ratio (OR) 11.2, 95% confidence interval (CI) 3.2 to 39.0; P < 0.001). Twelve of 21 dexamethasone‐treated infants were re‐intubated after initial extubation compared with one of four placebo‐treated infants. Mortality was reduced but not significantly in the dexamethasone group (OR 0.52, 95% CI 0.14 to 1.95; P = 0.33), and the same was true for BPD among survivors (OR 0.58, 95% CI 0.08 to 3.32; P = 0.71). Combined rates of death or BPD (86% versus 91%; P = 0.45) and death or severe BPD (34% versus 46%; P = 0.33) were not different between groups. During the first 10 days, mean airway pressure (MAP), peak inspiratory pressure, and inspired oxygen concentration all decreased significantly in the dexamethasone group compared with the placebo group. Data show no differences between groups in rates of high blood glucose levels or high blood pressure. Open‐label use of corticosteroids, sepsis, necrotising enterocolitis, patent ductus arteriosus, and severe retinopathy of prematurity were similar for the two groups. No infant had gastrointestinal perforation or bleeding. One infant in the placebo group had cardiac hypertrophy, but none in the dexamethasone group. At follow‐up, rates of cerebral palsy, blindness, and deafness, of Bayley MDI or PDI < ‐1 SD, or of major neurological disability were similar in the two groups, as were combined rates of death or cerebral palsy, or death or major disability.

Durand 1995: data show significant differences in compliance and tidal volume in the dexamethasone group compared with the control group (P < 0.001). Dexamethasone also significantly decreased inspired oxygen concentration and MAP (both P < 0.001) and facilitated successful weaning from mechanical ventilation. BPD (supplemental oxygen at 36 weeks' postmenstrual age, chest radiograph changes) was significantly decreased in the dexamethasone group (2/21 versus 8/17; P < 0.01). Survival with BPD was also better in the dexamethasone group (19/23 versus 9/20; P < 0.02). Except for transient increases in blood pressure and plasma glucose, we found no evidence of adverse effects of treatment and no significant differences in rates of infection, intraventricular haemorrhage, and retinopathy of prematurity. Thirteen infants in the control group subsequently received dexamethasone.

Harkavy 1989: dexamethasone treatment reduced age at extubation (39.4 days versus 57.2 days) compared with placebo. Average oxygen requirements for the steroid‐treated group were significantly lower during the first 10 days of treatment, but data show no significant differences between groups in age of weaning to room air (74.9 days versus 95.5 days), age at discharge (111 days versus 119 days), or number of deaths (1 (11%) versus 2 (17%)). Dexamethasone therapy was associated with a significantly increased incidence of hyperglycaemia (89% versus 8%; P = 0.01) but did not influence significantly the incidence of hypertension, intraventricular haemorrhage, infection, or retinopathy of prematurity. Steroid‐treated infants had a significant delay in weight gain (P < 0.02) during the first three weeks of treatment. Among the small number of children followed up, cerebral palsy was diagnosed in one of three in the dexamethasone group and in two of three controls.

Kari 1993: at 28 days of life, pulmonary outcome was significantly better among girls treated with dexamethasone but not in all infants. Data show no significant differences between groups in long‐term outcomes, except a shorter duration of supplemental oxygen among dexamethasone‐treated female infants. After one week of dexamethasone treatment, results show significant but short‐lived suppression of basal cortisol concentrations and of the adrenal response to ACTH. Investigators observed no serious side effects. At follow‐up, the only hospital providing follow‐up data reported no significant differences between dexamethasone and control children in rates of mortality, cerebral palsy, blindness, deafness, or major neurological disability, nor of death or survival with cerebral palsy or death or survival with major neurological disability, among those randomised. At seven to nine years of age, data show some improvement in lung function among eight steroid‐treated children compared with seven controls, and no substantial differences in height or weight between steroid and placebo groups, but data were not reported in a form that would allow meta‐analysis. No children had hypertrophic cardiomyopathy.

Kazzi 1990: infants who received dexamethasone required less oxygen on Days 8 and 17 (P < 0.005) and were more likely to be extubated eight days after therapy (8/12 versus 3/11; P < 0.05, P = 0.12 after Yates correction) compared with infants in the control group. Dexamethasone significantly shortened the duration of mechanical ventilation (median 4 versus 22 days; P < 0.05), but we found no evidence of effects on duration of oxygen therapy, hospitalisation, or home oxygen therapy, nor on the occurrence and severity of retinopathy of prematurity, rate of growth, or mortality.

Kothadia 1999: infants treated with dexamethasone were on mechanical ventilation and supplemental oxygen for fewer days after study entry (median days on ventilator: 5th and 95th centiles, 13 (1 to 64) versus 25 (6 to 104); days on oxygen: 59 (6 to 247) versus 100 (11 to 346)). Fewer infants in the dexamethasone group had failed to be extubated by the third day (82% versus 97%) or the seventh day (63% versus 90%). Data show no significant differences in rates of death, infection, or severe retinopathy of prematurity. At one‐year follow‐up, more surviving dexamethasone‐treated infants had cerebral palsy (24% versus 7%) and abnormal findings on neurological examination (42% versus 18%). However, deaths before one year were more frequent in the placebo group (26%) than in the dexamethasone group (12%); thus, rates of the combined outcome, death or cerebral palsy at one year, were not significantly different (dexamethasone 33% versus placebo 31%). An additional child in the placebo group was reported to have cerebral palsy at age four to six years. Risk of cerebral palsy was higher among surviving dexamethasone‐treated children at four to six years of age, although cognitive, functional, and medical outcomes were not significantly different between treated and non‐treated survivors. The combined outcome, death or cerebral palsy, was also similar at four‐ to six‐year follow‐up. Results show no substantial differences in rates of asthma, nor in blood pressure or growth. Fewer participants in the dexamethasone group had a low value for FEV₁ at between 8 and 11 years (dexamethasone 40% versus placebo 68%).

Kovacs 1998: mortality in hospital was not significantly different in the two groups (27% dexamethasone versus 17% controls). It is not possible to determine precisely when infants died, and hence this study cannot contribute to mortality at 28 days or at 36 weeks. Steroid‐treated infants required less ventilatory support between 9 and 17 days of age, and less supplemental oxygen between 8 and 10 days of age. Fewer infants in the dexamethasone group had failed to be extubated by the seventh day (73% versus 93%). Infants in this group also had better pulmonary compliance at 10 days, but comparison with controls revealed that all improvements were not maintained over ensuing weeks. Incidences of BPD at 28 days of life and at 36 weeks' postmenstrual age among survivors were not significantly different between groups (80% versus 87% at 28 days of life; 45% versus 56% at 36 weeks' postmenstrual age). We found no evidence of steroid‐related adverse effects, other than transient glycosuria. At follow‐up, data show no significant differences between dexamethasone‐treated and control children in rates of cerebral palsy, blindness, deafness, developmental delay, or major neurosensory disability among survivors assessed, nor in death or survival with cerebral palsy or death or survival with major disability among those randomised.

Noble‐Jamieson 1989: dexamethasone‐treated infants showed more rapid improvement in ventilation requirements during the first week of treatment, although the overall duration of oxygen therapy was similar in both groups. Cranial ultrasound examination revealed new periventricular abnormalities in three out of five dexamethasone‐treated infants with previous normal scans, compared with none of four placebo‐treated infants.

Ohlsson 1992: dexamethasone facilitated weaning from mechanical ventilation (P = 0.015). The incidence of infection was not significantly increased, although glycosuria (P = 0.0002) and systolic blood pressure (P = 0.003) were increased and heart rate (P = 0.0001) and weight gain (P = 0.0002) were decreased in the dexamethasone‐treated group. At follow‐up among survivors, cerebral palsy was diagnosed in one of 11 children in the dexamethasone group, and in three of 13 controls.

Onland 2019: hydrocortisone was associated with reduction in mortality at 36 weeks' postmenstrual age (15% versus 24%; P = 0.048) but a higher rate of BPD (55% versus 50%; P = 0.31) and no substantial effect on the primary endpoint of death or BPD (71% versus 74%; P = 0.54). Short‐term benefits included higher rates of successful extubation over the first 14 days of treatment and a reduction in treatment with open‐label steroids (28% versus 57%; P < 0.001), but adverse effects included more hyperglycaemia requiring insulin treatment (18% versus 8%; P = 0.004). At follow‐up, rates of neurodevelopmental impairment, cerebral palsy, and visual and hearing impairment were similar in the two groups, as were combined rates of death or cerebral palsy, or death or neurodevelopmental impairment.

Papile 1998: as infants in the early group were given dexamethasone from 14 days, they can be considered as having been treated late by our definition (> 7 days of age). Upon examination of only 28‐day outcomes, babies in this study's late group can be considered as controls, as they did not receive dexamethasone until after 28 days. Mortality at 28 days was 7/182 in the early group (treated) compared with 16/189 in the late group (controls). Oxygen was required on Day 28 in 141/182 versus 168/189, and the combination of 28‐day mortality or oxygen requirement was evident in 147/182 versus 184/189; the latter was significant (P < 0.001). It is not possible to use long‐term follow‐up data in this meta‐analysis, as all infants were eligible for dexamethasone after 28 days.

Parikh 2013: data show no substantial differences in brain tissue volume between groups. Low‐dose hydrocortisone had little effect on any other reported outcomes, including mortality, BPD, and acute complications. The follow‐up rate of survivors was 86% overall (37/43). Cerebral palsy was diagnosed in 15% (3/20) of survivors in the steroid group and in 6% (1/17) of those in the placebo group. Rates of cognitive and language delay, defined as < 80 on the Bayley III, were 21% versus 47% and 50% versus 59% in steroid and placebo groups, respectively. Rates of cognitive and language delay could not be pooled with others in the meta‐analysis that used earlier versions of the Bayley Scales, because tests and definitions were different. Rates of any neurodevelopmental impairment were similar between the two groups.

Romagnoli 1997: treated infants showed an increase in dynamic respiratory compliance and a decreased incidence of BPD at 28 days of life and at 36 weeks' postmenstrual age. Fewer infants in the dexamethasone group had failed to be extubated by the seventh day (40% versus 87%). Dexamethasone‐treated infants had lower weight gain during treatment and a significantly higher incidence of hypertrophic cardiomyopathy compared with controls. Data show no significant differences between groups regarding incidence of hypertension, sepsis, necrotising enterocolitis, or hyperglycaemia. At follow‐up, data show no significant differences between dexamethasone‐treated and control children for rates of cerebral palsy, blindness, deafness, or intellectual impairment among survivors assessed, or for death or survival with cerebral palsy among those randomised.

Scott 1997: cortisol responses to ACTH were lower in the dexamethasone group than in the placebo group. On Day 28 of life, eight of 10 infants in the dexamethasone group no longer required mechanical ventilation, compared with none of five infants in the placebo group (P = 0.04, as reported by trial authors).

Vento 2004: six dexamethasone‐treated infants and five control infants were extubated within seven days. Data show no significant differences between groups regarding respiratory distress syndrome, patent ductus arteriosus, or severe intraventricular haemorrhage (grade 3 or 4), as well as lower absolute cell counts (P ≤ 0.05) and proportions of polymorphonuclear cells (P < 0.001) in tracheal aspirate fluid in the treated group on Day 7. Treated infants also had an increase in dynamic pulmonary compliance, which was significant compared with the control group at seven days (P < 0.05). We noted no significant differences between groups regarding inspired oxygen concentration but found that infants in the dexamethasone group had significantly lower MAP on Day 7 (P < 0.05).

Vincer 1998: two of 11 dexamethasone‐treated infants died before hospital discharge compared with one of nine control infants. The number of days when infants had apnoeic spells (14 versus 2; P = 0.005) was greater in the dexamethasone‐treated group. Fewer infants in the dexamethasone group had failed to be extubated by the third day (27% versus 100%) or the seventh day (27% versus 100%). Data show a trend towards more retinopathy of prematurity in the dexamethasone group (64% versus 22%; P = 0.064) but similarities in all other outcome variables between groups. At follow‐up among survivors, cerebral palsy was diagnosed in four of nine children in the dexamethasone group and in two of eight controls.

Walther 2003: MAP on the first day of life was higher in the control group than in the dexamethasone group (9.1 versus 7.5 cm H₂O; P < 0.05). More infants in the dexamethasone group were successfully extubated within 7 to 14 days than in the placebo group (P < 0.05). Hyperglycaemia occurred more frequently in the dexamethasone group (P < 0.05), and infants in the control group more often received open‐label dexamethasone (P < 0.05). Incidences of hypertension, sepsis, necrotising enterocolitis, spontaneous gastrointestinal perforation, gastrointestinal bleeding, intraventricular haemorrhage, or periventricular leukomalacia were not significantly different between groups. Similarly, data show no significant differences in duration of ventilation or oxygen, BPD, nor mortality or survival without BPD between groups. Two infants in the control group were discharged home while on oxygen.

Yates 2019: two of the 12 infants in the dexamethasone group had received hydrocortisone prior to study entry, compared with none of 10 infants in the placebo group. In infants who remained in the study seven days after trial entry, five of eight dexamethasone‐treated infants were extubated by Day 7, compared with four of six control infants. Two of 12 dexamethasone‐treated infants died before 36 weeks' postmenstrual age compared with one of 10 control infants; 100% of survivors in both groups had BPD at 36 weeks' postmenstrual age or at discharge (if sooner) (dexamethasone 10/10; placebo 9/9).