Literature

From Pages to Practice


By Clement Lee, MD, MSc

Published July 20, 2022

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Bronchopulmonary dysplasia (BPD) is a common morbidity in preterm infants. At the core of the disease, an insult leads to disruption of normal lung development and ultimately presents as respiratory insufficiency. In the past few decades, the epidemiology of BPD has shifted as our understanding of the disease has evolved, and surfactant therapy has emerged as a mainstay of prevention.

There is no cure for BPD, and management currently relies on respiratory support for chronic hypercarbic and/or hypoxemic respiratory failure, strategies to optimize airway clearance, and the judicious use of diuretics. Respiratory support requirements vary from weaning to ambient air to tracheostomy for ventilator dependence. Given the complexities of BPD care, mitigating the upstream processes that lead to disease development is an important focus. 

The use of corticosteroids in neonatology has been marked by controversy. Corticosteroids demonstrate mechanistic plausibility, accelerating the production of surfactant and development of pneumocytes. When given antenatally, corticosteroids have been shown to reduce neonatal respiratory distress syndrome (RDS), which is often a precursor to BPD. Mounting enthusiasm for postnatal corticosteroids led to the landmark DART trial, in which dexamethasone shortened the duration of intubation in very preterm or extremely low birth weight infants who were ventilator-dependent. Unfortunately, the trial was stopped early due to poor enrollment, and there was no evidence of improvement in mortality rates or oxygen dependence at 36 weeks. 

Nonetheless, many neonatologists subsequently cited the DART study as rationale for the continued use of postnatal steroids, even after concerning data emerged regarding an excess risk of cerebral palsy. Some researchers hypothesize that the use of dexamethasone, which crosses the blood-brain barrier, poses a higher risk of poor neurodevelopmental outcomes than hydrocortisone. Herein lies the excitement for a recent trial conducted by Watterberg et al. and published in NEJM. In this NIH-funded multicenter trial, 800 premature infants (gestational age, <30 weeks) who had been intubated for ≥7 days at age 14–28 days were randomized to receive hydrocortisone (tapered over 10 days) or placebo. Strict protocols for extubation were followed and primary outcomes included both efficacy and the safety outcome of neurodevelopmental impairment.

Overall, survival without BPD was similar in the two groups, an unsurprising outcome given the prior negative results of the DART trial. Neurodevelopmental outcomes were also similar, supporting the notion that hydrocortisone is more neurologically neutral than dexamethasone.

Another adverse event in the trial was the development of hypertension requiring medication in 4.3% of hydrocortisone-treated patients. This finding aligns with what we know about the systemic effects of corticosteroids in adults and provides even more impetus for the halting of corticosteroid administration postnatally.

Pediatricians are no strangers to the principle that doing less is sometimes the best option. Bronchodilators for bronchiolitis, prolonged courses of antibiotics for osteomyelitis, and costly workups for failure to thrive and brief resolved unexplained events (BRUEs) are all examples of interventions that were once standard but are now being phased out due to lack of efficacy and signal of harm. I would argue that prescribing corticosteroids for the prevention of BPD has now entered this category and should be discontinued in neonatal intensive care units. The evidence does not support the routine usage of hydrocortisone for BPD prevention and should cause clinicians to rethink postnatal corticosteroid administration, regardless of formulation, to prevent the development of BPD.

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Clement Lee, MD, MSc, is a 2021–2022 NEJM Editorial Fellow. He is currently an internal medicine hospitalist at Beth Israel Deaconess Medical Center and a pediatric hospitalist at Lowell General Hospital. He completed his internal medicine-pediatrics residency at Penn-CHOP.
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