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Postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia in preterm infants

Posted: Jul 31, 2020


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Principal author(s)

Brigitte Lemyre, Michael Dunn, Bernard Thebaud, Fetus and Newborn Committee

Paediatr Child Health 2020 25(5):322–326.

Abstract

Historically, postnatal corticosteroids have been used to prevent and treat bronchopulmonary dysplasia (BPD), a significant cause of morbidity and mortality in preterm infants. Administering dexamethasone to prevent BPD in the first 7 days post-birth has been associated with increasing risk for cerebral palsy, while early inhaled corticosteroids appear to be associated with an increased risk of mortality. Neither medication is presently recommended to prevent BPD. New evidence suggests that prophylactic hydrocortisone, when initiated in the first 48 h post-birth, at a physiological dose, and in the absence of indomethacin, improves survival without BPD, with no adverse neurodevelopmental effects at 2 years. This therapy may be considered by clinicians for infants at highest risk for BPD. Routine dexamethasone therapy for all ventilator-dependent infants is not recommended, but after the first week post-birth, clinicians may consider a short course of low-dose dexamethasone (0.15 mg/kg/day to 0.2 mg/kg/day) for individual infants at high risk for, or with evolving, BPD. There is no evidence that hydrocortisone is an effective or safe alternative to dexamethasone for treating evolving or established BPD. Current evidence does not support inhaled corticosteroids for the treatment of BPD. 

Keywords: Bronchopulmonary dysplasia (BPD); Dexamethasone; Hydrocortisone; Inhaled corticosteroids; Postnatal corticosteroids; Preterm infants

Background

Bronchopulmonary dysplasia (BPD) is a serious complication of preterm birth, affecting around 40% of infants born before 29 weeks gestational age (GA) [1][2]. Recent advances in neonatal care have improved the survival of extremely preterm infants. At least in part due to improved survival, the incidence of BPD has not decreased in Canada in the past 10 years [2]. BPD is associated with life-long respiratory and neurodevelopmental morbidity.

Historically, postnatal corticosteroids have been used in the first week post-birth for prevention, or later for treatment, of evolving or established BPD. However, clinical trials and systematic reviews of this practice have highlighted its long-term side effects and specifically, an increased risk for cerebral palsy (CP). The previous revision of this statement in 2012 recommended against the routine use of corticosteroids in the first week after birth to prevent BPD, due to safety concerns [3], and recommended caution when using corticosteroids after the first week post-birth. It further suggested having an informed discussion with parents about risks and benefits, and underlined the need for evidence regarding the safety and efficacy of low-dose dexamethasone and inhaled corticosteroids.

This statement reviews studies published since 2012 to guide clinical use of postnatal corticosteroids in infants at risk for or with evolving or established BPD.

Statement development

Searches were designed and conducted by a librarian experienced with systematic review. MEDLINE searches included e-publications ahead of print, papers in-process, and other non-indexed citations (1946 to June 14, 2018). Embase (1980 to June 14, 2018) and the CENTRAL Trials Registry of the Cochrane Collaboration (May 2018 issue) were also searched. Randomized controlled trials (RCTs), cohort studies, and systematic reviews were sought specifically. Searches were not restricted by language, but were limited to material entering the databases since 2012. Search terms included ‘bronchopulmonary dysplasia’, ‘chronic lung disease’, ‘dexamethasone’, ‘hydrocortisone’, ‘inhaled corticosteroids’, ‘postnatal corticosteroids’, and ‘preterm infants’.

In general, studies to prevent BPD have examined potential therapies administered in the first week post-birth, whereas studies aiming to treat evolving or established BPD have examined therapies administered beyond this period. This statement makes the same differentiation.

Levels of evidence and grading of recommendations are based on criteria from the Canadian Task Force on Preventive Health [4].

Systemic corticosteroids in the first 7 days post-birth to prevent BPD

No new clinical trials of dexamethasone use in neonates to prevent BPD have been published since 2012. One large clinical trial of early hydrocortisone use, with two ancillary publications and one follow-up at 5 to 7 years of an RCT, have been published since [5][8]. One updated Cochrane systematic review and an individual patient data meta-analysis of four trials assessing physiological doses of hydrocortisone (HC) in the first days post-birth to prevent BPD, have been recently published [9][10]. Details of these studies are shown in Table 1.

Summary

Overall, the potential benefits of dexamethasone in the first week post-birth are offset by substantial side effects. Dexamethasone is therefore not recommended for prevention of BPD. (Level of evidence 1.)

Based on current evidence, physiological HC, at replacement doses, initiated in the first 24 to 48 h post-birth in infants born ˂28 weeks GA, when not associated with prophylactic indomethacin, increases survival without BPD at 36 weeks and survival before discharge without harmful effects on neurodevelopment at 2 years. These beneficial effects were more pronounced in infants exposed to maternal chorioamnionitis and in those born ≥26 weeks. An increased incidence of late-onset sepsis was observed in hydrocortisone-treated infants, a finding which was more pronounced in infants exposed to chorioamnionitis and in those born ˂26 weeks GA. Conversely, in the largest trial, infants born ˂26 weeks had better neurodevelopmental outcomes than those who received placebo. High-risk infants (e.g., those born ˂28 weeks GA, and particularly those exposed to chorioamnionitis) may benefit from physiological HC at replacement doses. Clinician assessment of each individual case is advised.

Table 1. Trials and systematic reviews of systemic corticosteroid use in the first week post-birth to prevent BPD

Study

Methods

Sample size and number of centres

Eligibility criteria

Intervention

Results

Baud et al. [5][6][8]

Randomized controlled trial (RCT)

523

21 centres

Planned sample of 786; DSMB  stopped recruitment due to technical and financial issues

24+0-27+6 weeks GA, <24 h of age; small for GA (<3rd centile) were excluded

Hydrocortisone hemisuccinate 1 mg/kg per day x 7 days, then 0.5 mg/kg per day x 3 days (total: 8.5 mg/kg)

Survival without BPD* 60% vs. 51% (RR 1.48, 95% CI 1.02 to 2.16)

No difference in rates of GI perforation

Sub-group analysis:

More sepsis in 24 to 25 weeks in treatment group

Follow-up at 2 years:

No difference in neurodevelopmental impairment or CP†

Sub-group analysis: Better global neurodevelopment in infants born at 24 to 25 weeks who received hydrocortisone vs. those who did not

Peltoniemi et al. [7]

RCT

51 (37 followed up at 5 to 7 years)

single-centre

501 to 1250 g, 23+0 to 30+0 weeks GA, ventilated in first 24 h after birth

Hydrocortisone 2.0 mg/kg per day x 2 days, 1.5 mg/kg per day x 2 days, 0.75 mg/kg per day x 6 days (total: 11.5 mg/kg)

Study interrupted due to higher rate of GI perforations in the hydrocortisone-treated infants

Follow-up at 5 to 7 years:

Mean verbal IQ and functional IQ not different. Mean performance IQ lower in the hydrocortisone-treated children (88.3 (14.5) vs. 99.1 (14.0); p = 0.034)

Doyle, LW et al. [9]

Systematic review

4395

32 trials

Follow-up data for 13 trials

Preterm infants at risk for developing BPD

21 trials of dexamethasone

11 trials of hydrocortisone

Earlier extubation, decreased risk for BPD, patent ductus arteriosus (PDA), and severe retinopathy of prematurity (ROP) offset by short- (GI perforation) and long-term (increased risk for CP) harms.

Most benefits and harms attributed to dexamethasone. Risk of GI perforation attributed to hydrocortisone

Methodological quality of follow-up studies limited, due to follow-up before school age or lack of power

Shaffer et al. [10]

Individual patient data meta-analysis (includes trials by Baud and Peltoniemi)

982 patients, 4 trials

Preterm infants (<30 weeks GA) or birth weight under 1 kg in first 48 h post-birth

Hydrocortisone prophylactic replacement for adrenal insufficiency over 10 to 15 days (total dose 8.5 to 13.5 mg/kg)

Hydrocortisone treated infants had:

  1. Improved survival without BPD at 36 weeks: OR 1.45 (95% CI 1.11 to 1.9); p = 0.007; NNT 11
  2. Less death before discharge: OR 0.70 (95% CI 0.51 to 0.97); p = 0.0327
  3. Less treatment for PDA: OR 0.72 (95% CI 0.56 to 0.93); p = 0.012
  4. More late-onset sepsis: OR 1.34 (95% CI 1.02 to1.75); p = 0.0357

Sub-group analysis: Spontaneous GI perforation increased with indomethacin and hydrocortisone, but not with hydrocortisone alone.

Effects on survival to 36 weeks without BPD, death before discharge more pronounced in infants exposed to chorioamnionitis or those born at ≥26 weeks.

* Physiologic definition of BPD
† Standardized neurological examination and revised Brunet-Lezine scale
BPD Bronchopulmonary dysplasia; CI Confidence interval; CP cerebral palsy; DSMB Data and Safety Monitoring Board; GI Gastro-intestinal; NNT Number needed to treat; OR Odds ratio; RR Relative risk

Early inhaled corticosteroids to prevent BPD

Two RCTs and one systematic review have been published since 2012 [11][14]. Details of these studies are shown in Table 2.

Table 2. Trials and systematic reviews of early inhaled corticosteroids to prevent BPD

Study

Methods

Sample size and number of centres

Eligibility criteria

Intervention

Results and effect size

Bassler et al. [11][14]

Randomized controlled trial (RCT)

863 (40 centres)

23+0-27+6 weeks GA, <12 h  post-birth on positive pressure respiratory support

Budesonide by metered-dose inhaler

800 mcg per day x 14 days; 400 micrograms per day until 32 weeks GA or no longer needing oxygen or respiratory support

Death or BPD reduced in infants who received budesonide: 40% vs. 46% (RR 0.71, 95% CI 0.53 to 0.97)

Survival without BPD higher in infants who received budesonide: 27.8% vs. 38%; p = 0.004

Death 16.9% vs. 13.8%; p = 0.17

Neurodevelopmental disability at 18 to 22 months corrected age:

48.1% vs. 51.4%; p = 0.40

Death by 18 to 22 months 19.9% vs. 14.5%; p = 0.04, favoring the control group

Nakamura et al. [12]

RCT

211 (12 centres)

Birth weight (BW)<1000 g, requiring intubation and ventilation in first 24 h post-birth

Fluticasone propionate 100 mcg per day x 6 weeks, or until extubation

Death or oxygen dependence at discharge 14% vs. 22%; p = 0.15

Shah et al. [13] (includes studies by Bassler and Nakamura)

Cochrane systematic review

1644 (10 trials)

Preterm infants with BW˂1501 g, on respiratory support, and randomized within the first 1 to 2 weeks post-birth (only 2 trials allowed enrollment from 7 to 14 days of age)

Budesonide, beclomethasone dipropionate, fluticasone propionate, or flunisolide by inhalation for at least 2 weeks

Infants treated with inhaled corticosteroids had:

  • No difference in BPD overall at 36 weeks: RR 0.97 (95% CI 0.62 to 1.52)
  • Less BPD at 36 weeks among survivors: RR 0.76 (95% CI 0.63 to 0.93); NNT 14 (95% CI 8 to 50)
  • Less death or BPD at 36 weeks: RR 0.86 (95% CI 0.75 to 0.99); (p = 0.04); NNTB 17 (95% CI 9 to infinity)
BPD Bronchopulmonary dysplasia; CI Confidence interval; NNT Number needed to treat; NNTB Number needed to benefit; RR Relative risk

Although a reduction in BPD in survivors was observed in the largest trial performed to date [11], more infants randomized to inhaled corticosteroids had died by the 2-year follow-up time point [14]. Trial authors have cautioned that reducing the incidence of BPD may have been achieved at the expense of increased mortality.

Summary

Based on current evidence, any beneficial effects on BPD rates appear to be offset by increased risk for mortality. Administering inhaled corticosteroids (such as budesonide and fluticasone) the first 2 weeks post-birth to prevent BPD is not recommended. (Level of evidence 1.)

Systemic corticosteroids after the first week post-birth to treat evolving or established BPD

No new trial of later dexamethasone treatment has been published since 2012. One single centre pilot RCT and one multi-centre RCT investigating hydrocortisone succinate were reported since then [15][16]. A 2019 RCT reported no difference in the combined outcome of death or BPD at 36 weeks corrected GA, but found a decrease in death in infants who received hydrocortisone (16% versus 24%) [16]. These results are encouraging and suggest that later hydrocortisone may benefit preterm infants with evolving BPD. However, more research to confirm this possibility is required before treatment can be recommended.

One Cochrane systematic review and meta-analysis to assess both dexamethasone and hydrocortisone succinate was updated in 2017 [17]. Details are presented in Table 3. Concerns have been raised about the potential toxicity of dexamethasone, including the possible toxic effects of sulfite preservatives used in its preparation. While some investigators have studied betamethasone or methylprednisolone as an alternative to dexamethasone for infants with evolving BPD, the quality of evidence provided by these studies is insufficient to endorse these medications [18][22].

Table 3. Studies of systemic corticosteroids initiated after the first week post-birth to treat evolving BPD

Study

Methods

Sample size and number of centres

Eligibility criteria

Intervention

Results and effect size

Parikh et al. [15]

Randomized controlled trial (RCT)

64, single centre

BW ≤1000 g at birth, ventilator dependent at 10 to 21 days of age with a  respiratory index score ≥2 or score ≥3 with improvement in last 24 h

Hydrocortisone succinate 3 mg/kg/day x 4 days; 2 mg/kg/day x 2 days; 1 mg/kg/day x 1 day (cumulative dose: 17 mg/kg over 7 days)

Brain volume at 38 weeks of age: no difference

No difference in BPD or duration of mechanical ventilation

Onland et al. (abstract) [16]

RCT

372, multi-centre

<30 weeks at birth, ventilated at 7 to14 days, respiratory index score ≥2.5

Hydrocortisone weaning over 22 days; cumulative dose 72 mg/kg. Open label steroids permitted: 28% in treatment group; 56% in placebo group

Death or BPD at 36 weeks:

70% vs. 74%: RR 0.95 (95% CI 0.84 to 1.08)

Mortality at 36 weeks: 16% vs. 24%: RR 0.65 (95% CI 0.43 to 0.99)

Doyle LW et al. [17] (does not include the trial by Onland et al.)

Cochrane systematic review

1424 patients; 21 trials

Preterm infants with evolving or established BPD, defined as oxygen-dependent, ventilator-dependent (or both), with or without radiographic changes in BPD status

Dexamethasone or hydrocortisone, IV or per os for 7 to 42 days. Total dose varied across trials

Infants treated with late corticosteroids had:

  • Facilitated extubation on study days 3, 7, and 28
  • Less BPD at 36 weeks: RR 0.77; 95% CI 0.67 to 0.88
  • Less need for rescue corticosteroids
  • Less discharge on home oxygen: RR 0.71; 95% CI 0.54 to 0.94
  • Increased risk of severe ROP (no increase in blindness)
  • No difference in death rates at 36 weeks: RR 0.82 (95% CI 0.50 to 1.35)
  • No difference in CP rates
BPD Bronchopulmonary dysplasia; CI Confidence interval; CP Cerebral palsy; ROP Retinopathy of prematurity; RR Relative risk

Summary

The routine use of dexamethasone for all infants who require assisted ventilation after 7 days of age to treat evolving BPD is not recommended. Nor can hydrocortisone to treat evolving BPD be recommended at this time. The results of ongoing trials are awaited.

Inhaled corticosteroids after the first week post-birth to treat evolving or established BPD

No post-2012 trial of late inhaled steroids was identified. One updated Cochrane systematic review in 2017 included eight trials and 232 patients [23]. Some infants were ventilated while others were not. Treatment was initiated between 7 and 21 days post-birth. Meta-analysis showed a reduced risk of failure to extubate at 7 days (RR 0.80, 95% CI 0.66 to 0.98; 5 studies, 79 infants) in infants who received inhaled corticosteroids. No difference was noted in the rate of death or BPD, in death at 36 weeks of age, or in BPD at 36 weeks of age. Conclusions are limited by the small number of infants enrolled and heterogeneity of patients and inhalation therapy.

Inhaled corticosteroids cannot be recommended to treat BPD. (Level of evidence 1.)

Ancillary analyses conducted to help guide practice for prevention or treatment of evolving or established BPD

Although an adequate number of trials have been conducted with a sufficient number of infants enrolled to allow for meta-analyses and help guide practice, the widespread use of open-label treatments and significant variance among  patients being assessed (e.g., regarding eligibility criteria, type and course of steroid used, comparison groups, and outcomes) have prompted a number of ancillary analyses to help refine recommendations for clinical use.

Comparisons between various treatment regimens

One recent meta-analysis concluded that evidence was insufficient to determine an optimal dexamethasone dosing regimen (i.e., higher versus lower cumulative dose, in the first week versus after 1 week, pulse versus a continuous regimen) [24]. Two further meta-analyses comparing inhaled with systemic corticosteroids reported no advantage for either medication [25][26].

Efficacy and safety in relation to risk of developing BPD

One updated meta-regression found that the higher the rate of BPD in the control group, the lower the risk difference  in the rate of death or CP between the control and dexamethasone-treated groups, suggesting that with a high baseline risk of BPD, treatment with dexamethasone may convey benefit [27]. Study authors concluded that when the risk for BPD was >60%, dexamethasone treatment appeared to lower the rate of death or CP. This possibility has an important clinical implication: for a sub-group of infants at high risk for BPD, the benefits of the treatment appear to outweigh risks.

Determining the effect of open-label use of corticosteroids on study outcomes

To adjust for the confounding effect of open-label corticosteroid use in RCTs, one meta-regression was performed to compare dexamethasone with placebo in infants over 7 days old [28]. Twenty-seven per cent  to 65% of infants assigned to the placebo group, and 10% to 33% of those assigned to active treatment, received open-label dexamethasone. Overall, infants in the active treatment group had lower rates of death or BPD without increasing the incidence of adverse neurodevelopmental outcomes, and this apparent benefit was inversely related to the degree of open-label usage in the placebo group (i.e., the more the use of open label, the less observed benefit). As an additional caution, dexamethasone treatment was associated with an increase in CP when treatment was delayed beyond 21 days of age.

Summary

These findings strongly suggest that for a sub-group of infants at high risk for BPD (e.g., who remain ventilated beyond the first week post-birth with increasing oxygen requirements and worsening lung disease), a short course of dexamethasone (0.15 mg/kg/day to 0.2 mg/kg/day tapered over 7 to 10 days) should be considered. The timing of initiation and initial dose should be based on postnatal age and severity of condition. Treatment before BPD is fully established and titration based on illness severity are advised (Level of Evidence 5).

Future treatments

Recent trials have reported on mixing corticosteroids with surfactant and administering this combination early via endotracheal tube for infants born very preterm [29][30]. Although the beneficial effects of this combined therapy on reducing death or BPD were marked, relatively few infants were being studied. Results from ongoing research are needed before a recommendation on this practice can be issued.

Recommendations

  • The use of dexamethasone in the first week post-birth to prevent BPD is not recommended. (Grade A recommendation.)
  • Clinicians may consider prescribing a course of low-dose hydrocortisone (physiologic replacement dose: 1 mg/kg per day x 7 days, then 0.5 mg/kg per day x 3 days) beginning in the first 24 to 48 h after birth, for 10 days, to infants at the highest risk for BPD (e.g., <28 weeks GA or exposed to chorioamnionitis). There may be an increased risk for late-onset sepsis associated with this practice. Hydrocortisone should not be combined with indomethacin prophylaxis. (Grade B recommendation.)
  • The routine use of inhaled corticosteroids to prevent BPD is not recommended. (Grade A recommendation.)
  • The routine use of dexamethasone after the first week of life for evolving BPD is not recommended. (Grade A recommendation.) For infants who remain ventilated after the first week post-birth with increasing oxygen requirements and worsening lung disease, the benefits of dexamethasone therapy appear to outweigh the potential adverse effects. In these circumstances, low-dose dexamethasone (with an initial dose of 0.15 mg/kg/day to 0.2 mg/ kg/day, tapered over a short course [7 to 10 days]) should be considered. (Grade C recommendation.)
  • Hydrocortisone to treat infants with evolving BPD beyond the first week post-birth, or infants with prolonged ventilator dependence, is not recommended. (Grade B recommendation.)
  • Use of inhaled corticosteroids to treat BPD is not recommended. (Grade B recommendation.)
  • More research is needed to identify the most at-risk population and on the utility of alternative corticosteroid preparations and regimens. (Grade A recommendation.)

Acknowledgements

The authors would like to thank Margaret Sampson, MLIS, PhD, AHIP (with the Children’s Hospital of Eastern Ontario), for developing our electronic search strategies. This position statement has been reviewed by the Respiratory Health Section of the Canadian Paediatric Society. It was also reviewed by the Canadian Thoracic Society and by members of the Canadian Pediatric Endocrine Group: Dr. Rose Girgis (University of Alberta), Dr. Alex Ahmet (Children’s Hospital of Eastern Ontario), and Dr. Julia Von Oettigen (Montreal Children’s Hospital).


CANADIAN PAEDIATRIC SOCIETY FETUS AND NEWBORN COMMITTEE

Members: Heidi Budden MD (Board Representative), Mireille Guillot MD (Resident member), Leonora Hendson MD, Thierry Lacaze-Masmonteil MD, PhD (past Chair), Brigitte Lemyre MD, Michael R. Narvey MD (Chair), Vibhuti Shah MD
Liaisons: Radha Chari MD, The Society of Obstetricians and Gynaecologists of Canada; James Cummings MD, Committee on Fetus and Newborn, American Academy of Pediatrics; William Ehman MD, College of Family Physicians of Canada; Roxanne Laforge RN, Canadian Perinatal Programs Coalition; Chantal Nelson PhD, Public Health Agency of Canada; Eugene H. Ng MD, CPS Neonatal-Perinatal Medicine Section; Doris Sawatzky-Dickson RN, Canadian Association of Neonatal Nurses
Principal authors: Brigitte Lemyre MD, Michael Dunn MD, Bernard Thebaud MD


References

  1. Jobe AH, Bancalari E. Bronchopulmonary dysplasia. Am J Respir Crit Care Med 2001;163(7):1723–9.
  2. Shah PS, Sankaran K, Aziz K, et al; Canadian Neonatal Network. Outcomes of preterm infants <29 weeks gestation over 10-year period in Canada: A cause for concern? J Perinatol 2012;32(2):132–8.
  3. Jefferies AL. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants. Paediatr Child Health 2012;17(10):573–4.
  4. Canadian Task Force on Preventive Health: https://canadiantaskforce.ca/wp-content/uploads/2016/12/procedural-manual-en_2014_Archived.pdf (Accessed January 16, 2020).
  5. Baud O, Maury L, Lebail F, et al. Effect of early low-dose hydrocortisone on survival without bronchopulmonary dysplasia in extremely preterm infants (PREMILOC): A double-blind, placebo-controlled, multicentre, randomised trial. Lancet 2016;387(10030):1827–36.
  6. Baud O, Trousson C, Biran V, Leroy E, Mohamed D, Alberti C; PREMILOC Trial Group. Association between early low-dose hydrocortisone therapy in extremely preterm neonates and neurodevelopmental outcomes at 2 years of age. JAMA 2017;317(13):1329–37.
  7. Peltoniemi OM, Lano A, Yliherva A, Kari MA, Hallman M; Neonatal Hydrocortisone Working Group. Randomised trial of early neonatal hydrocortisone demonstrates potential undesired effects on neurodevelopment at preschool age. Acta Paediatr 2016;105(2):159–64.
  8. Baud O, Trousson C, Biran V, Leroy E, Mohamed D, Alberti C; PREMILOC Trial Group. Two-year neurodevelopmental outcomes of extremely preterm infants treated with early hydrocortisone: Treatment effect according to gestational age at birth. Arch Dis Child Fetal Neonatal Ed 2019;104(1):F30-F35.
  9. Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL. Early (<8 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2017;10:CD001146.
  10. Shaffer ML, Baud O, Lacaze-Masmonteil T, Peltoniemi OM, Bonsante F, Watterberg KL. Effect of prophylaxis for early adrenal insufficiency using low-dose hydrocortisone in very preterm infants: An individual patient data meta-analysis. J Pediatr 2019;201:136-42.
  11. Bassler D, Plavka R, Shinwell ES, et al. Early inhaled budesonide for the prevention of bronchopulmonary dysplasia. N Engl J Med 2015;373(16):1497–506.
  12. Nakamura T, Yonemoto N, Nakayama M, et al. Early inhaled steroid use in extremely low birthweight infants: A randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 2016;101(6):F552-F556.
  13. Shah VS, Ohlsson A, Halliday HL, Dunn M. Early administration of inhaled corticosteroids for preventing chronic lung disease in very low birth weight preterm neonates. Cochrane Database Syst Rev 2017;1:CD001969.
  14. Bassler D, Shinwell ES, Hallman M, Jarreau PH, et al. Long-term effects of inhaled budesonide for bronchopulmonary dysplasia. N Engl J Med 2018;378(2):148–57.
  15. Parikh NA, Kennedy KA, Lasky RE, McDavid GE, Tyson JE. Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: Effects on regional brain volumes. J Pediatr 2013;162(4):685-90.e1.
  16. Onland W, Cools F, Kroon A, et al. Effect of hydrocortisone therapy initiated 7 to 14 days after birth on mortality or bronchopulmonary dysplasia among very preterm infants receiving mechanical ventilation: A randomized clinical trial. JAMA 2019;321(4):354-63.
  17. Doyle LW, Cheong JL, Ehrenkranz RA, Halliday HL. Late (>7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2017;10:CD001145.
  18. DeCastro M, El-Khoury N, Parton L, Ballabh P, LaGamma EF. Postnatal betamethasone vs dexamethasone in premature infants with bronchopulmonary dysplasia: A pilot study. J Perinatol 2009;29(4):297–304.
  19. Ben Said M, Hays S, Loys CM, Coletto L, Godbert I, Picaud JC. Postnatal steroids in extremely low birth weight infants: Betamethasone or hydrocortisone? Acta Paediatr 2013;102(7):689–94.
  20. Smolkin T, Ulanovsky I, Jubran H, Blazer S, Makhoul IR. Experience with oral betamethasone in extremely low birthweight infants with bronchopulmonary dysplasia. Arch Dis Child Fetal Neonatal Ed 2014;99(6):F517–8.
  21. André P, Thébaud B, Odièvre MH, et al. Methylprednisolone, an alternative to dexamethasone in very premature infants at risk of chronic lung disease. Intensive Care Med 2000;26(10):1496–500.
  22. Bhandari A, Schramm CM, Kimble C, Pappagallo M, Hussain N. Effect of a short course of prednisolone in infants with oxygen-dependent bronchopulmonary dysplasia. Pediatrics 2008;121(2):e344–9.
  23. Onland W, Offringa M, van Kaam A. Late (≥ 7 days) inhalation corticosteroids to reduce bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2017;8:CD002311.
  24. Onland W, De Jaegere AP, Offringa M, van Kaam A. Systemic corticosteroid regimens for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database Syst Rev 2017;1:CD010941.
  25. Shah SS, Ohlsson A, Halliday HL, Shah VS. Inhaled versus systemic corticosteroids for preventing bronchopulmonary dysplasia in ventilated very low birth weight neonates. Cochrane Database Syst Rev 2017;10:CD002058.
  26. Shah SS, Ohlsson A, Halliday HL, Shah VS. Inhaled versus systemic corticosteroids for the treatment of bronchopulmonary dysplasia in ventilated very low birth weight preterm infants. Cochrane Database Syst Rev 2017; 10:CD002057.
  27. Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair JC. An update on the impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: Effect modification by risk of bronchopulmonary dysplasia. J Pediatr 2014;165(6):1258–60.
  28. Onland W, van Kaam AH, De Jaegere AP, Offringa M. Open-label glucocorticoids modulate dexamethasone trial results in preterm infants. Pediatrics 2010;126(4):e954-64.
  29. Yeh TF, Lin HC, Chang CH, et al. Early intratracheal instillation of budesonide using surfactant as a vehicle to prevent chronic lung disease in preterm infants: A pilot study. Pediatrics 2008; 121(5):e1310-8.
  30. Yeh TF, Chen CM, Wu SY, et al. Intratracheal administration of budesonide/surfactant to prevent bronchopulmonary dysplasia. Am J Respir Crit Care Med2016;193(1):86–95.

Disclaimer: The recommendations in this position statement do not indicate an exclusive course of treatment or procedure to be followed. Variations, taking into account individual circumstances, may be appropriate. Internet addresses are current at time of publication.

Last updated: Feb 8, 2024