634 - Health and Neurodevelopmental Outcomes at 2 Years of Extremely Preterm Infants Enrolled in the International PLUSS Trial of Intratracheal Budesonide

Publication Number: 2619.634

Brett J. Manley, The University of Melbourne, Kensington, Victoria, Australia; C. Omar F. Kamlin, University of Melbourne, London, England, United Kingdom; Peter G. Davis, University of Melbourne, Melbourne, Victoria, Australia; Kate L. Francis, Murdoch children's research institute, Melbourne, Victoria, Australia; Renae Allen, MCRI, Parkvile, Victoria, Australia; Katinka P. Bach, Starship Children's Hospital, Auckland, Auckland, New Zealand; Risha Bhatia, The Royal Women's Hospital, Melbourne, Australia, Melbourne, Victoria, Australia; Pita Birch, Mater Health, South Brisbane, Queensland, Australia; Jennifer A. Dawson, The Royal Women's Hospital, Melbourne, Victoria, Australia; Koert de Waal, John Hunter Children's Hospital, Newcastle, New South Wales, Australia; Callum Gately, University of Otago, Wellington, Wellington, New Zealand; Gayatri Jape, King Edward Memorial Hospital, Perth, Western Australia, Australia; Brenda Law, University of Alberta Faculty of Medicine and Dentistry, Edmonton, AB, Canada; Steven Resnick, King Edward Memorial Hospital, Perth, Western Australia, Australia; Georg Schmolzer, University of Alberta Faculty of Medicine and Dentistry, Edmonton, AB, Canada; Lex W. Doyle, Prof. Lex Doyle, Parkville, Victoria, Australia; Christopher JD. McKinlay, University of Auckland, Auckland, Auckland, New Zealand; Jeanie Cheong, Murdoch Children's Research Institute, Melbourne, Victoria, Australia

Background: Early intratracheal budesonide mixed with surfactant has emerged as a promising intervention to increase survival free of bronchopulmonary dysplasia (BPD) in extremely preterm (EP) infants, and is routinely used in some units. The international PLUSS trial (Manley et al, JAMA 2024;332(22):1889) enrolled 1059 EP infants and found no significant improvement in survival free of BPD from intratracheal budesonide mixed with surfactant. Recently, the NICHD “BiB” primary trial results were published and were very similar to PLUSS (Ambalavanan et al, JAMA 2025) . Surviving children enrolled in PLUSS were followed up at 2 years’ corrected age (CA) to assess longer-term health and neurodevelopment. These results will be the first large-scale, longer-term outcome data from trials of intratracheal budesonide.

Objective: To evaluate, in EP infants born < 28 weeks’ gestation, the effect of intratracheal budesonide mixed with surfactant on survival free of neurodevelopmental disability (NDD) at 2 years' CA.

Design/Methods: In this blinded RCT, EP infants requiring surfactant were randomly allocated to receive intratracheal budesonide (0.25 mg/kg) mixed with surfactant (poractant alfa) or surfactant alone. Assessments were scheduled in survivors at 24-30 months' CA, incl: 1) physical examination & health assessment; 2) Bayley Scales of Infant and Toddler Development for cognitive, language, and motor development; 3) Gross Motor Function Classification System to determine the severity of any cerebral palsy; 4) Infant-Toddler Social & Emotional Assessment; and 5) the Predicting Asthma Risk in Children questionnaire.

The primary outcome at 2 years is survival without moderate-severe NDD, defined as any one or more of moderate-severe developmental delay, moderate-severe cerebral palsy, deafness, or blindness. Secondary outcomes incl: death; the components of NDD; moderate or severe neurosensory disabilities; emotional-behavioral scores; body size; and asthma risk score.

Results: 842/1059 (80%) children were alive at 2 years' CA, and the primary outcome is available for 967/1059 (91%). Assessed infants had a mean (SD) gestational age of 25.6 (1.4) weeks and birth weight 774 (197) g. Data are being analyzed in late 2025, and the primary outcome will be presented by group overall, and by gestational age subgroups ( < 26 weeks; 26-27 weeks).

Conclusion(s): It is critical to assess longer-term outcomes for EP infants enrolled in randomized trials of corticosteroid medications. We will present the 2 year outcomes for the 1059 EP infants enrolled in the PLUSS trial of intratracheal budesonide mixed with surfactant.