Systemic glucocorticoid activity in extremely preterm neonates after antenatal betamethasone and intratracheal budesonide: a sub-study of the PLUSS trial

OBJECTIVE: To quantify systemic exposure to budesonide following intratracheal administration; evaluate the impact of intratracheal budesonide on blood glucocorticoid activity (cortisol plus betamethasone as cortisol equivalents); and relate the latter to outcomes. STUDY DESIGN: Sub-study of the PLUSS randomized trial(ACTRN12617000322336) of intratracheal budesonide with surfactant versus surfactant alone. RESULT: Among 63 infants enrolled at Kidz First Neonatal Care, Auckland, systemic exposure to intratracheal budesonide was low, and cortisol equivalents were similar between intervention groups at 36-48 h (adjusted-ratio-geometric-means = 1.16, 95% CI 0.52-2.57). Antenatal betamethasone <24 h before birth contributed to neonatal blood glucocorticoid activity for up to 24-48 h. Infants above the upper tertile for cortisol equivalents at <60 h, compared with those below the lower tertile, had increased likelihood of severe intraventricular hemorrhage and possibly death. CONCLUSION: Systemic exposure to intratracheal budesonide has little to no effect on cortisol equivalents at 36-48 h. High glucocorticoid activity after birth may be associated with poorer neonatal outcomes.