Postnatal corticosteroid therapy in bronchopulmonary dysplasia - why animal studies disagree with clinical trials?

The systematic review and meta-analysis of newborn animal models by Irene Lok et al. is the first to extensively summarize the literature regarding postnatal systemic corticosteroid use on lung development of newborn rodent models. The meta-analysis showed that the use of postnatal corticosteroids resulted in a reduction in body weight along with persistent alveolar simplification. The most frequently used corticosteroid was dexamethasone. Corticosteroids have been extensively used in clinical trials in preterm newborns. Trials using early systemic administration of corticosteroids reduced the rate of BPD or mortality with no increase in the rates of cerebral palsy. Use of late systemic corticosteroids (administered >7 days after birth) also reduced the rate of BPD, mortality, and combined outcome of mortality or BPD. Late systemic corticosteroids showed no impact on the rates of neurodevelopmental outcomes in later childhood. It is important to note that later stages of inflammation leading to a more severe form of BPD continues to be a problem with no clear therapy in sight. The authors made a critical point in their paper - the negative effects of steroids were greater in the normal lung control animals than in the injured. This conveys caution in using steroids in a prophylactic manner. IMPACT: Use of systemic corticosteroids in clinical trials have shown good response in preterm neonates evidenced by reduced rate of bronchopulmonary dysplasia. Rodent models have not shown a similar beneficial response. Use of systemic corticosteroids have caused greater arrest of lung development in rodent models with normal lungs compared to those with lung damage.