Hemananda Muniraman1,2, Danielle Gardner3, Jane Skinner4, Anna Paweletz3, Anitha Vayalakkad5, Ying Hui Chee6, Clare Clifford5, Sunil Sanka1, Vidheya Venkatesh6, Anna Curley6,7, Suresh Victor5,8, Mark A Turner3,9, Paul Clarke10,11. 1. Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK. 2. Division of Neonatology, Department of Pediatrics, Keck School of Medicine, Los Angeles County Medical Center, University of Southern California, Los Angeles, USA. 3. Neonatal Unit, Liverpool Women's Hospital NHS Foundation Trust, Liverpool, UK. 4. Norwich Medical School, University of East Anglia, Norwich, UK. 5. Neonatal Unit, Central Manchester NHS Foundation Trust (St Mary's Hospital), Manchester, UK. 6. Neonatal Unit, Cambridge University NHS Foundation Trust (Addenbrooke's Hospital), Cambridge, UK. 7. Neonatal Unit, National Maternity Hospital, Dublin, Ireland. 8. Centre for Developing Brain, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, UK. 9. Department of Women's and Children's Health, Institute of Translational Medicine, University of Liverpool, Liverpool, UK. 10. Neonatal Unit, Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, UK. paul.clarke@nnuh.nhs.uk. 11. Norwich Medical School, University of East Anglia, Norwich, UK. paul.clarke@nnuh.nhs.uk.
Abstract
Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemic encephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001). CONCLUSION: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemic encephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.
Therapeutic hypothermia (TH) is now provided as standard care to infants with moderate-severe hypoxic ischemicencephalopathy (HIE). The role of TH in limiting neuronal injury is well recognized, but its effect on hepatic injury which occurs frequently in neonatal HIE is not known. Our objective was to characterize biomarkers of liver injury and function in the setting of neonatal HIE and to describe whether HIE severity and provision of TH influence these hepatic biomarkers. We performed a multicenter retrospective study and compared hepatic biomarkers obtained during the first postnatal week, according to the severity of HIE and whether treated with TH. Of a total of 361 infants with HIE, 223 (62%) received TH and 138 (38%) were managed at normal temperature. Most hepatic biomarkers and C-reactive protein (CRP) were significantly associated with the severity of HIE (p < 0.001). Infants treated with TH had lower peak alanine aminotransferase (ALT) concentrations (p = 0.025) and a delay in reaching peak CRP concentration (p < 0.001). CONCLUSION: We observed a significant association between the clinical grade of HIE and biomarkers of liver metabolism and function. Therapeutic hypothermia was associated with delayed CRP responses and with lower ALT concentrations and so may have the potential to modulate hepatic injury. What is Known: • Ischemic hepatic injury occurs frequently as a part of multiorgan dysfunction in infants with hypoxic ischemicencephalopathy (HIE). • The neuroprotective role of therapeutic hypothermia in management of infants with HIE is well recognized, but the potential hepato-protective effects of hypothermia are unclear. What is New/What this study adds: • Therapeutic hypothermia was associated with lower alanine aminotransferase and albumin concentrations and a delayed C-reactive protein (CRP) response and so may have the potential to modulate hepatic injury. • An elevated CRP concentration during the first postnatal week may be regarded as an expected finding in moderate and severe HIE and, in the overwhelming majority of cases, occurs secondary to hepatic hypoxia-ischemia in the absence of blood culture-positive sepsis.
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