Postnatal Corticosteroids to Treat or Prevent Bronchopulmonary Dysplasia in Preterm Infants

Abstract

Background: The lungs of particularly newborn are fragile and can be easily damaged. With injury, scarring may follow which is translated into difficult breathing and increased oxygen needs, a condition called bronchopulmonary dysplasia (BPD) or Chronic Lung Disease (CLD). Since inflammation plays an important role in the pathogenesis of CLD, corticosteroids, especially dexamethasone, have been extensively used to avert or treat CLD. Thus, several studies suggest that systemic corticosteroids decrease the duration of ventilator dependence. Aim of the Study: investigate the beneficial and harmful effects of the use of steroid in the prevention and treatment of BPD. Methods: A systematic review and meta-analysis of observational studies and randomized controlled trials was conducted. A review of the scientific literature. Pubmed, Embase and Central were searched to identify randomized controlled trials that investigated postnatal corticosteroids treatment for BPD were the primary endpoints. Identification of papers and data extraction were performed by two independent researchers. We searched for relevant trials in the Cochrane Library, MEDLINE (from 1955), Embase (from 1970), the Transfusion Evidence Library (from 1980), and ongoing trial databases; all searches current to September 2017.Results: The search yielded seven RCTs which enrolled a total of 1862 participants eligible for inclusion in the present review. There were significant beneficial outcomes such as lower rates of failure to extubate and decreased risks of chronic lung disease at both 28 days (RR 0.84, 95% CI 0.83 to 0.87) and 36 weeks' postmenstrual age (RR 0.77, 95% CI 0.72 to 0.84), death or chronic lung disease at 28 days (RR 0.9, 95% CI 0.85 to 0.96) and 36 weeks' postmenstrual age (RR 0.91, 95% CI 0.87 to 0.96). Nevertheless, there were no significant differences in the rates of neonatal mortality (RR= 1.06, 95% CI 0.93, 1.26), periventricular leukomalacia (RR 1.16, 95% CI 0.9 to 1.46), necrotizing enterocolitis or pulmonary haemorrhage (RR 1.21, 95% CI 0.83 to 1.62). In contrast, gastrointestinal bleeding (RR 2.13, 95% CI 1.41 to 2.84) and intestinal perforation (RR 1.77, 95% CI 1.46 to 2.1) were imperative adverse effects. Moreover, many adverse neurological effects were found at follow-up examinations, including developmental delay (RR 1.72, 95% CI 1.4 to 2.05) and cerebral palsy (RR 1.56, 95% CI 1.03 to 2.1). Additionally, the rates of the combined outcomes of death or cerebral palsy (1.92, 95% CI 1.18 to 2.67), or of death or major neurosensory disability (RR 1.25, 95% CI 0.98 to 1.53), were not significantly increased. In subgroup analyses by type of corticosteroid, most of the advantageous and disadvantageous effects were related chiefly to dexamethasone whilst hydrocortisone had slight effect on any of the outcomes except for an increase in intestinal perforation and a borderline reduction in patent ductus arteriosus. The overall risk for bias was low as all were RCTs using robust methods. Conclusion: despite the fact that early corticosteroid treatment can have beneficial outcome for BPD management through facilitation of extubation and decreasing the risk of chronic lung disease and patent ductus arteriosus, it ,on the other hand, results in short-term adverse effects including gastrointestinal bleeding, intestinal perforation, hyperglycaemia, hypertension, hypertrophic cardiomyopathy and growth failure. Clinicians should carefully assess the risks of a short course of glucocorticoid therapy to mitigate BPD for premature neonates such that an individualized decision should be made in conjunction with the infant's parents.