Current and Emerging Therapies for Prevention and Treatment of Bronchopulmonary Dysplasia in Preterm Infants

Abstract

Although advances in the care of extremely preterm born infants have yielded improvements in survival and reductions in important morbidities, rates of bronchopulmonary dysplasia (BPD) have remained relatively unchanged. As BPD can have a long-lasting impact on the quality of life for survivors of prematurity and their families, this remains a continuing challenge. Treatments that have consistently shown efficacy in preventing either BPD or the composite outcome of BPD and death prior to 36 weeks post menstrual age (PMA) in large-scale randomized clinical trials (RCTs) include caffeine [adjusted odds ratio aOR for BPD, 0.63; 95% confidence interval (95% CI) 0.52-0.76; p < 0.001)], vitamin A [relative risk (RR) for death or BPD 0.89; 95% CI 0.80-0.99], low-dose hydrocortisone in the first week of life [OR for survival without BPD, 1.45; 95% CI 1.11-1.90; p = 0.007], and post-natal dexamethasone [RR for BPD or mortality; 0.76; 95% CI 0.66-0.87]. Although early caffeine therapy is now a widely used strategy to prevent BPD, the potentially severe side effects of post-natal glucocorticoids and the concerns regarding the cost-benefit of vitamin A have led to inconsistent use of these drugs in clinical practice. Inhaled bronchodilators and diuretics provide differing degrees of symptomatic relief for patients according to their phenotypic pattern of lung injury; however, these medications do not prevent BPD. Currently available pharmaceuticals do not sufficiently address the degree of structural immaturity and immune dysregulation that is present in the growing population of survivors born prior to 25 weeks gestational age. In this article, we provide both an evidence-based summary of pharmacological treatments currently available to prevent and manage BPD and a discussion of emerging therapies that could help preserve normal lung development in infants born preterm.

Fig. 1

Extreme preterm birth is associated with both immune dysregulation and structural lung immaturity that may necessitate support with invasive mechanical ventilation and supplemental oxygen. Varying combinations of adverse pre- and post-natal environmental exposures together with the unique genetic make-up of individuals and variable epigenetic responses lead to the presence of different BPD phenotypes. As normal lung development is dependent on communication between different cell types, insults to epithelial, endothelial, or interstitial tissues can cause dysregulated growth of adjacent structures. This leads to the development of mixed phenotypes of lung disease. Abx, antibiotics; BPD, bronchopulmonary dysplasia; IMV, invasive mechanical ventilation; IUGR, intrauterine growth restriction; NEC, necrotizing enterocolitis; O₂, oxygen