Influence of antenatal steroids on the effect of early inhaled postnatal corticosteroids: a post-hoc analysis of the NEuroSIS trial

Background: Few data are available on the interplay of antenatal and early inhaled postnatal corticosteroids. The NEuroSIS trial randomized extremely preterm infants to receive either early inhaled budesonide or placebo and analyzed the effect of study medication on bronchopulmonary dysplasia or death, as well as the effect on neurodevelopmental outcome at 18-22 months corrected age. Application of antenatal steroids may have had an influence on these outcomes. Objective: To analyze if antenatal corticosteroids (ANS) influenced the short- (BPD and death before 36 weeks PMA) and long-term (disability at 18-22 months corrected age or death before time of assessment) effects of early inhaled postnatal budesonide in NEuroSIS study participants. Methods: Post-hoc analysis of the intention-to-treat population of the NEuroSIS study. Generalized logits models were used to (1) predict risk of BPD, death before 36 weeks PMA and survival without BPD with application of ANS, NEuroSIS study treatment and gestational age as independent variables and (2) predict the risk of disability at 18-22 months corrected age, death before time of neurodevelopmental assessment and survival without disability, with ANS and gestational age as independent variables. Results: Application of ANS, added as an independent variable, did not change the effect of study medication on developing BPD (OR 0.79, 95% CI 0.67-0.93) and there was no association with the risk of death (OR 1.03, 95% CI 0.84-1.27) at 36 weeks PMA. ANS added as an independent variable showed an association with a reduced risk of death before time of completion of neurodevelopmental assessment (OR 0.60, 95% CI 0.44-0.81) and was associated with a reduced risk of disability at 18-22 months corrected age(OR 0.63, 95% CI 0.49-0.81). Conclusion: ANS did not alter the reduction of BPD risk by study medication and there was no association with increased mortality in NEuroSIS study participants.