[Skip to Navigation]
Original Investigation
March 15, 2021

Assessment of Postnatal Corticosteroids for the Prevention of Bronchopulmonary Dysplasia in Preterm Neonates: A Systematic Review and Network Meta-analysis

Author Affiliations
  • 1Newborn Services, John Radcliffe Hospital, Oxford University Hospitals National Health Service (NHS) Foundation Trust, Oxford, United Kingdom
  • 2Ankura Hospital for Women and Children, Hyderabad, India
  • 3Department of Neonatology, Dr Ram Manohar Lohia Hospital and Post Graduate Institute of Medical Education and Research, New Delhi, India
  • 4Department of Neonatology, Institute of Medical Sciences and SUM Hospital, Orissa, India
  • 5Department of Neonatology, Indira Gandhi Institute of Child Health, Bengaluru, India
  • 6Women’s Wellness and Research Centre, Hamad Medical Corporation, Doha, Qatar
  • 7Department of Neonatology, James Cook University Hospital, Middlesbrough, United Kingdom
  • 8National Perinatal Epidemiology Unit, Nuffield Department of Population Health, Medical Sciences Division, University of Oxford, Oxford, United Kingdom
  • 9Department of Neonatology, Lady Hardinge Medical College, New Delhi, India
JAMA Pediatr. 2021;175(6):e206826. doi:10.1001/jamapediatrics.2020.6826
Key Points

Question  Which is the most appropriate postnatal corticosteroid regimen for preventing mortality or bronchopulmonary dysplasia (BPD) in preterm neonates at 36 weeks’ postmenstrual age?

Findings  In this systematic review and network meta-analysis of 62 studies with 5559 neonates, a moderately early-initiated, medium cumulative dose of systemic dexamethasone had the highest relative risk reduction of mortality or BPD among 14 regimens, with a low confidence in the evidence.

Meaning  Results of this study suggested that a moderately early-initiated, medium cumulative dose of systemic dexamethasone appeared to be the best regimen for preventing mortality or BPD at 36 weeks’ postmenstrual age.

Abstract

Importance  The safety of postnatal corticosteroids used for prevention of bronchopulmonary dysplasia (BPD) in preterm neonates is a controversial matter, and a risk-benefit balance needs to be struck.

Objective  To evaluate 14 corticosteroid regimens used to prevent BPD: moderately early-initiated, low cumulative dose of systemic dexamethasone (MoLdDX); moderately early-initiated, medium cumulative dose of systemic dexamethasone (MoMdDX); moderately early-initiated, high cumulative dose of systemic dexamethasone (MoHdDX); late-initiated, low cumulative dose of systemic dexamethasone (LaLdDX); late-initiated, medium cumulative dose of systemic dexamethasone (LaMdDX); late-initiated, high cumulative dose of systemic dexamethasone (LaHdDX); early-initiated systemic hydrocortisone (EHC); late-initiated systemic hydrocortisone (LHC); early-initiated inhaled budesonide (EIBUD); early-initiated inhaled beclomethasone (EIBEC); early-initiated inhaled fluticasone (EIFLUT); late-initiated inhaled budesonide (LIBUD); late-initiated inhaled beclomethasone (LIBEC); and intratracheal budesonide (ITBUD).

Data Sources  PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Embase, World Health Organization’s International Clinical Trials Registry Platform (ICTRP), and CINAHL were searched from inception through August 25, 2020.

Study Selection  In this systematic review and network meta-analysis, the randomized clinical trials selected included preterm neonates with a gestational age of 32 weeks or younger and for whom a corticosteroid regimen was initiated within 4 weeks of postnatal age. Peer-reviewed articles and abstracts in all languages were included.

Data Extraction and Synthesis  Two independent authors extracted data in duplicate. Network meta-analysis used a bayesian model.

Main Outcomes and Measures  Primary combined outcome was BPD, defined as oxygen requirement at 36 weeks’ postmenstrual age (PMA), or mortality at 36 weeks’ PMA. The secondary outcomes included 15 safety outcomes.

Results  A total of 62 studies involving 5559 neonates (mean [SD] gestational age, 26 [1] weeks) were included. Several regimens were associated with a decreased risk of BPD or mortality, including EHC (risk ratio [RR], 0.82; 95% credible interval [CrI], 0.68-0.97); EIFLUT (RR, 0.75; 95% CrI, 0.55-0.98); LaHdDX (RR, 0.70; 95% CrI, 0.54-0.87); MoHdDX (RR, 0.64; 95% CrI, 0.48-0.82); ITBUD (RR, 0.73; 95% CrI, 0.57-0.91); and MoMdDX (RR, 0.61; 95% CrI, 0.45-0.79). Surface under the cumulative ranking curve (SUCRA) value ranking showed that MoMdDX (SUCRA, 0.91), MoHdDX (SUCRA, 0.86), and LaHdDX (SUCRA, 0.76) were the 3 most beneficial interventions. ITBUD (RR, 4.36; 95% CrI, 1.04-12.90); LaHdDX (RR, 11.91; 95% CrI, 1.64-44.49); LaLdDX (RR, 6.33; 95% CrI, 1.62-18.56); MoHdDX (RR, 4.96; 95% CrI, 1.14-14.75); and MoMdDX (RR, 3.16; 95% CrI, 1.35-6.82) were associated with more successful extubation from invasive mechanical ventilation. EHC was associated with a higher risk of gastrointestinal perforation (RR, 2.77; 95% CrI, 1.09-9.32). MoMdDX showed a higher risk of hypertension (RR, 3.96; 95% CrI, 1.10-30.91). MoHdDX had a higher risk of hypertrophic cardiomyopathy (RR, 5.94; 95% CrI, 1.95-18.11).

Conclusions and Relevance  This study suggested that MoMdDX may be the most appropriate postnatal corticosteroid regimen for preventing BPD or mortality at a PMA of 36 weeks, albeit with a risk of hypertension. The quality of evidence was low.

Limit 200 characters
Limit 25 characters
Conflicts of Interest Disclosure

Identify all potential conflicts of interest that might be relevant to your comment.

Conflicts of interest comprise financial interests, activities, and relationships within the past 3 years including but not limited to employment, affiliation, grants or funding, consultancies, honoraria or payment, speaker's bureaus, stock ownership or options, expert testimony, royalties, donation of medical equipment, or patents planned, pending, or issued.

Err on the side of full disclosure.

If you have no conflicts of interest, check "No potential conflicts of interest" in the box below. The information will be posted with your response.

Not all submitted comments are published. Please see our commenting policy for details.

Limit 140 characters
Limit 3600 characters or approximately 600 words
    ×