Long-chain omega-3 polyunsaturated fatty acids are reduced in neonates with substantial brain injury undergoing therapeutic hypothermia after hypoxic-ischemic encephalopathy

Simon C Dyall; Isabell Nessel; Jennine A Sharpe; Ping K Yip; Adina T Michael-Titus; Divyen K Shah

doi:10.3389/fneur.2023.1231743

Long-chain omega-3 polyunsaturated fatty acids are reduced in neonates with substantial brain injury undergoing therapeutic hypothermia after hypoxic-ischemic encephalopathy

Front Neurol. 2023 Aug 30:14:1231743. doi: 10.3389/fneur.2023.1231743. eCollection 2023.

Authors

Simon C Dyall¹, Isabell Nessel², Jennine A Sharpe¹, Ping K Yip², Adina T Michael-Titus², Divyen K Shah^{2

3}

Affiliations

¹ School of Life and Health Sciences, University of Roehampton, London, United Kingdom.
² Centre for Neuroscience, Surgery and Trauma, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, United Kingdom.
³ Royal London Hospital, Barts Health NHS Trust, London, United Kingdom.

Abstract

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Although therapeutic hypothermia is an effective treatment, substantial chronic neurological impairment often persists. The long-chain omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, offer therapeutic potential in the post-acute phase. To understand how PUFAs are affected by HIE and therapeutic hypothermia we quantified for the first time the effects of HIE and therapeutic hypothermia on blood PUFA levels and lipid peroxidation. In a cross-sectional approach, blood samples from newborns with moderate to severe HIE, who underwent therapeutic hypothermia (sHIE group) were compared to samples from newborns with mild HIE, who did not receive therapeutic hypothermia, and controls. The sHIE group was stratified into cerebral MRI predictive of good (n = 10), or poor outcomes (n = 10; nine developed cerebral palsy). Cell pellets were analyzed for fatty acid content, and plasma for lipid peroxidation products, thiobarbituric acid reactive substances and 4-hydroxy-2-nonenal. Omega-3 Index (% DHA + EPA) was similar between control and HIE groups; however, with therapeutic hypothermia there were significantly lower levels in poor vs. good prognosis sHIE groups. Estimated Δ-6 desaturase activity was significantly lower in sHIE compared to mild HIE and control groups, and linoleic acid significantly increased in the sHIE group with good prognosis. Reduced long-chain omega-3 PUFAs was associated with poor outcome after HIE and therapeutic hypothermia, potentially due to decreased biosynthesis and tissue incorporation. We speculate a potential role for long-chain omega-3 PUFA interventions in addition to existing treatments to improve neurologic outcomes in sHIE.

Keywords: DHA; EPA; Omega-3 Index; hypoxic–ischemic encephalopathy; lipid peroxidation; mild therapeutic hypothermia; newborns; omega-3 polyunsaturated fatty acids.