PEGASUS - PErsistent inflammation and systemic multiorGAn dySfunction in UnderStanding neonatal encephalopathy

PEGASUS is a translational, multidisciplinary research project investigating how dysregulated inflammation influences brain injury, multiorgan dysfunction and long-term neurodevelopmental outcomes in infants with neonatal encephalopathy (NE). Although therapeutic hypothermia improves survival, many of these infants still develop significant disability, highlighting the need for better risk stratification and adjunctive therapies.

The study combines detailed clinical phenotyping with advanced neuroimaging, serial physiological assessments and comprehensive immunological profiling. Maternal, placental and neonatal inflammatory markers will be analysed alongside cytokines, microRNAs, innate immune cell function, inflammasome activation and Toll-like receptor signalling to characterise the mechanisms driving persistent hyperinflammation. Multiorgan function—including neurological, cardiac, renal, respiratory, gastrointestinal and haematological systems—will be evaluated using conventional measures and novel biomarkers.

By integrating these datasets in a large, well-characterised cohort and applying advanced statistical modelling, PEGASUS aims to identify early predictors of outcome and develop a multiorgan assessment tool for clinical use. The project will also support international consensus on therapeutic hypothermia practice and explore the potential of immunomodulatory agents such as caffeine and pentoxifylline as adjunctive treatments.

Ultimately, PEGASUS seeks to enable personalised management, improve prognostic counselling for families and inform future targeted neuroprotective and anti-inflammatory therapies for this vulnerable population.

Funder

SFI, CPF

Research Team & Collaborators

Prof Eleanor Molloy – Supervisor

Dr Nicoleta Barbu – PhD Student