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PRISM: PReterm Infection and SysteMic inflammation and neonatal outcomes (2014-7)

PI: E Molloy, Dr. Dave Coghlan, Dr. Denise McDonald, Dr. John Kelleher, Dr. Suzanne Kelleher, Dr. David Rea, Prof J Meaney, Dr. Arun Bodke, Prof. John O'Leary, Prof. Jan Miletin, Dr. Jana Sembrova

PhD student: Dr. Murwan Omer

Institutions: CWIUH, Tallaght hospital, TCD

Background: Despite rapid progress in neonatal intensive care over the past decades, neonatal mortality from sepsis remains unacceptably high and morbidity includes brain injury and developmental delay. Systemic inflammation related to sepsis has been implicated in many common neonatal complications such as brain, lung, or gastrointestinal injury especially in preterm infants. Modulation of inflammatory signalling during sepsis may improve survival in preterm infants and prevent related neurodevelopmental complications. Activated leucocytes, infection and persistent inflammation have been implicated in the pathogenesis of brain injury and also cerebral palsy. Antenatal inflammation and neonatal outcome: We will evaluate antenatal inflammation using placental pathology results and blood culture results from mother and baby. Detailed clinical multiorgan outcomes including novel renal biomarkers and echocardiography will be quantified using the Modified Neonatal Multi -Organ Dysfunction (NEOMOD) score. Neuroimaging with cranial ultrasound and/or MRI will be performed and developmental followup including 2-year Bayley's developmental scales (BSID III). Inflammatory response to infection and immunomodulation: We will examine pro and anti-inflammatory cytokine responses using whole blood from preterm infants over the first few weeks of life and correlate with antenatal inflammation. We will evaluate neonatal inflammatory cell phenotype and activation of the inflammasome, which is crucial for inflammatory responses and host defense to pathogens as well as being implicated in several inflammatory diseases such as inflammatory bowel disease, rheumatoid arthritis and atherosclerosis. Immunomodulators such as melatonin and specific inflammasome inhibitors will be assessed in vitro as possible methods to ameliorate persistent inflammation.

Conclusion: This research will improve the understanding of the systemic inflammatory response in preterm infants and the potential for newer adjunctive therapies. In addition these immune markers will assist in prognosis of multi-organ outcomes in preterm infants. This project is funded by NCHF and TCD.


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