RT Journal Article SR Electronic T1 Neuronal exosome proteins: novel biomarkers for predicting neonatal response to therapeutic hypothermia JF Archives of Disease in Childhood - Fetal and Neonatal Edition JO Arch Dis Child Fetal Neonatal Ed FD BMJ Publishing Group Ltd and Royal College of Paediatrics and Child Health SP 60 OP 64 DO 10.1136/archdischild-2020-321096 VO 107 IS 1 A1 Beth Pineles A1 Arunmani Mani A1 Livia Sura A1 Candace Rossignol A1 Mehmet Albayram A1 Michael David Weiss A1 Laura Goetzl YR 2022 UL http://fn.bmj.com/content/107/1/60.abstract AB Objective Central nervous system (CNS) derived exosomes can be purified from peripheral blood and have been used widely in adult neurological disease. Application to neonatal neurological disease deserves investigation in the setting of hypoxic–ischaemic encephalopathy (HIE).Design Observational cohort.Setting Level III neonatal intensive care unit.Participants Term/near-term neonates undergoing therapeutic hypothermia (TH) for HIE.Interventions Blood samples were collected at 0–6, 12, 24, 48 and 96 hours of life.Main outcomes and measures CNS exosomes were purified from serum using previously described methods. Biomarker protein levels were quantified using standard ELISA methods and normalised to exosome marker CD-81. The slope of change for biomarker levels was calculated for each time interval. Our primary outcome was MRI basal ganglia/watershed score of ≥3.Results 26 subjects were included (umbilical artery pH range 6.6–7.29; 35% seizures). An increasing MRI injury score was significantly associated with decreasing levels of synaptopodin between 0–6 and 12 hours (p=0.03) and increasing levels of lipocalin-2 (NGAL) between 12 and 48 hours (p<0.0001). Neuronal pentraxin was not significant. The negative predictive values for increasing synaptopodin and decreasing NGAL was 70.0% and 90.9%, respectively.Conclusions and relevance Our results indicate that CNS exosome cargo has the potential to act as biomarkers of the severity of brain injury and response to TH as well as quantify pharmacological response to neuroactive therapeutic/adjuvant agents. Rigorous prospective trials are critical to evaluate potential clinical use of exosome biomarkers.Data are available on reasonable request. All study data are available on reasonable request. Please contact Laura Goetzl at laura.goetzl@uth.tmc.edu. Data reuse is permitted on agreement from all authors.