Postnatal Glucocorticoids in Very Preterm Infants: “The Good, the Bad, and the Ugly”?

Abstract

Premature births represent 7% to 10% of all births, but account for >85% of all perinatal complications and death. Survival of extremely premature newborns (<28 weeks' gestation) has increased because of the widespread use of surfactant treatment for respiratory distress syndrome, together with antenatal glucocorticoids and new ventilator strategies.1 However, these infants are at high risk for long-term injury of both the lungs and the brain. Bronchopulmonary dysplasia (BPD) is one of the most frequent sequelae in extremely premature infants and results in increased health care costs, prolonged hospital stays with frequent rehospitalizations, and deleterious effects on subsequent growth and neurodevelopment.2 Periventricular leukomalacia, the most severe form of white matter brain damage, is a frequent cause of cerebral palsy in children surviving preterm birth, with lifelong consequences.3 Recent data suggest that a common treatment for one, dexamethasone for BPD, may have deleterious effects on both sequelae. Northway et al4 first described BPD as severe lung injury resulting from mechanical ventilation and oxygen exposure. With improved prenatal and postnatal care, preterm infants developing BPD now are generally very immature, and have antenatal and postnatal histories that differ from those of preterm infants in previous eras. The “new BPD,” as described by Jobe,5 is characterized by an arrest of lung development and interference with alveolarization. This more complex view of the pathogenesis of BPD includes prenatal lung inflammation in response to proinflammatory cytokine exposure in utero, together with postnatal exposure to proinflammatory stimuli, such as ventilation and oxygen. Jobe5 postulates that these stimuli, together with glucocorticoid exposure and inadequate nutrition, can result in inhibition of alveolar and vascular development. Therein lies the irony: the postnatal dexamethasone (DXM) widely used for the treatment or prevention of BPD may suppress inflammation, but also may impair alveolarization and interfere …