Neurodevelopment at 2 years of extremely preterm infants who received early intratracheal budesonide
Brett Manley, MBBS, PhD
BACKGROUND: Preterm birth rates are increasing around the world and currently represent ~10% of all births. Extremely preterm infants are born before 28 weeks’ gestation (at least 3 months early) and are at the highest risk of death and morbidity. Half of extremely preterm infants admitted to intensive care develop bronchopulmonary dysplasia (BPD), the inflammatory chronic lung disease of extreme prematurity. There are few therapies that safely reduce BPD and none that prevent it. GAP: Systemic (intravenous or enteral) corticosteroids are effective against BPD but may increase the risk of cerebral palsy when used in the first week of life: a safe, early treatment is urgently required. Intratracheal budesonide mixed with surfactant is a simple, inexpensive therapy that may increase survival free of BPD and result in improved longer-term outcomes for this high-risk population. HYPOTHESIS: In extremely preterm infants, intratracheal budesonide mixed with surfactant soon after birth will increase survival free of moderate-severe neurodevelopmental disability at 2 years of age (corrected for prematurity). METHODS: This study will assess surviving children at 2 years (corrected for prematurity) who were born extremely preterm and enrolled in an international, double-blind, randomized trial (the PLUSS trial) of intratracheal budesonide mixed with surfactant soon after birth. The primary outcome is survival free of moderate-severe neurodisability, defined as any one or more of: moderate-severe developmental delay, moderate-severe cerebral palsy, blindness or deafness. PLUSS will recruit 1060 extremely preterm infants. We expect ~850 infants to survive and be assessed at 2 years’ corrected age for the current study. RESULTS: Pending. IMPACT: If this simple, readily available and inexpensive intervention is efficacious and safe in the longer-term, it will be quickly translated into worldwide clinical practice by our internationally recognized team, potentially improving longer-term outcomes for 10,000s of extremely preterm infants each year.