Issue 14 – November 2022

Exposing very preterm infants to postnatal steroids reduces the risk of chronic lung disease, or bronchopulmonary dysplasia, but increases the risk of cognitive impairment and cerebral palsy^1,2. We examined exposure to systemic (not inhaled) steroids for treatment or prevention of chronic lung disease after birth.

We evaluated 851,138 infants born at 22-29 weeks’ gestational age who were admitted to a Vermont Oxford Network member center within 28 days of birth from 1991 to 2021. In 1991, 28.1% were exposed to postnatal steroids. That number reached a high of 41.5% in 1996, a low of 11.4% in 2009, and was 19.1% by 2021. The dose, type, timing, and duration of exposure were not collected.

The pendulum of care swings as neonatologists continue to grapple with the quandary of when and how to use pulmonary corticosteroids for very preterm infants. Significant decreases in bronchopulmonary dysplasia (BPD) were demonstrated in the early trials of dexamethasone and hydrocortisone. In the 1990s, the frequency of use of these drugs approached 25-40%,^3,4 but concerns for increased cerebral palsy and gastrointestinal perforation led to curtailment of this practice.⁵ Notable during this swing away from treatment was the untimely closure of the last large randomized controlled trial (RCT) on corticosteroids for a respiratory indication, which was closed when less than 10% of its intended sample size had been enrolled, due to a lack of equipoise among participating clinicians.⁶ Very few trials on the topic have been published subsequently.⁷ This lack of literature to reassure clinicians about the safety and efficacy to prescribing initially resulted in a period of very infrequent administration of postnatal corticosteroids. However, as depicted in this snapshot on corticosteroid trends in NICU by Numbers, the clinical community has more recently increased its use of this treatment.

Perhaps the willingness to expose more preterm infants to postnatal steroids comes from an appreciation of the competing risks and benefits. Both BPD and steroids may be considered to pose risks to neurodevelopment.⁸ Without adequate RCT evidence, clinicians are left to guess at what represents an optimal approach. While recent attempts at gleaning additional comparative data through innovative techniques like network meta-analysis can hold some promise, conclusions drawn are severely limited by multiple factors, including the heterogeneity of these, often small, trials in both treatments and patient populations.^9,10 Moreover, even the extant data suffers steady losses in relevance, as NICU care continues to evolve at a rapid pace, with arguably a different population of neonates now in question than those studied in corticosteroid trials decades ago. An RCT adequately powered to answer the question of long-term neurodevelopmental effects of postnatal corticosteroids is desperately needed. Our community’s recent increased use of corticosteroids without any changes in the evidence base suggests that we have the equipoise to pursue this.

1. Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL, Soll R. Early (< 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database of Systematic Reviews. 2021;(10). doi:10.1002/14651858.CD001146.pub6
2. Doyle LW, Cheong JL, Hay S, Manley BJ, Halliday HL. Late (≥ 7 days) systemic postnatal corticosteroids for prevention of bronchopulmonary dysplasia in preterm infants. Cochrane Database of Systematic Reviews. 2021;(11). doi:10.1002/14651858.CD001145.pub5
3. Stoll BJ, Hansen NI, Bell EF, et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA. 2015;314(10):1039-1051. doi:10.1001/jama.2015.10244
4. Walsh MC, Yao Q, Horbar JD, Carpenter JH, Lee SK, Ohlsson A. Changes in the use of postnatal steroids for bronchopulmonary dysplasia in 3 large neonatal networks. Pediatrics. 2006;118(5):e1328-1335. doi:10.1542/peds.2006-0359
5. Watterberg KL, American Academy of Pediatrics. Committee on Fetus and Newborn. Policy statement–postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia. Pediatrics. 2010;126(4):800-808. doi:10.1542/peds.2010-1534
6. Doyle LW, Davis PG, Morley CJ, McPhee A, Carlin JB, DART Study Investigators. Outcome at 2 years of age of infants from the DART study: a multicenter, international, randomized, controlled trial of low-dose dexamethasone. Pediatrics. 2007;119(4):716-721. doi:10.1542/peds.2006-2806
7. Hay S, Kunz S, Samad A, et al. The NeoCanon Project: Lessons from two decades of neonatal randomized clinical trials. Presented at: Pediatric Academic Societies Meeting; May 2018; Toronto, Canada.
8. Doyle LW, Halliday HL, Ehrenkranz RA, Davis PG, Sinclair JC. Impact of postnatal systemic corticosteroids on mortality and cerebral palsy in preterm infants: effect modification by risk for chronic lung disease. Pediatrics. 2005;115(3):655-661. doi:10.1542/peds.2004-1238
9. Ramaswamy VV, Bandyopadhyay T, Nanda D, et al. Assessment of Postnatal Corticosteroids for the Prevention of Bronchopulmonary Dysplasia in Preterm Neonates: A Systematic Review and Network Meta-analysis. JAMA Pediatr. 2021;175(6):e206826. doi:10.1001/jamapediatrics.2020.6826
10. Bamat NA, Jensen EA, Mitra S. EBNEO Commentary: A network meta-analysis of postnatal corticosteroids for bronchopulmonary dysplasia: Has the most appropriate treatment been revealed? Acta Paediatr. 2022;111(4):903-904. doi:10.1111/apa.16228

This report is made possible by Vermont Oxford Network members who voluntarily contribute data in a global effort to improve the care of high-risk newborns. VON members can view center-specific data by logging on to Nightingale and benchmark against this NICU by the Numbers report.

Editor: Erika Edwards, PhD, MPH

Analyst: Lucy Greenberg, MS

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