Mistry, PriyalMellet, JuanitaDurandt, ChrisnaSmuts, IzellePepper, Michael Sean2026-02-252026-02-252025-12-08Mistry, P., Mellet, J., Durandt, C. et al. 2025, 'An epigenetic perspective on neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy', Clinical EpigeneticsClinical Epigenetics, vol. 15, no. 1, art. 15, pp. 1-22. doi : 10.1186/s13148-025-01984-z.1868-7075 (print)1868-7083 (online)10.1186/s13148-025-01984-zhttp://hdl.handle.net/2263/108635DATA AVAILABILITY : No datasets were generated or analysed during the current study.Neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy (NESHIE) is a neurological disorder caused by oxygen deprivation and limited blood flow to a neonate's brain. Although various antenatal and perinatal factors have been identified, their precise role in NESHIE pathogenesis remains unclear. The pathophysiology involves multiple molecular pathways that can be explored using a multi-omics approach, including epigenetics. Epigenetics involves heritable changes in gene expression without altering the DNA sequence, encompassing chemical modifications to DNA and histone proteins, as well as changes mediated by non-coding RNAs (ncRNAs). These epigenetic changes regulate gene expression and can be influenced by environmental factors, offering crucial insights into gene regulation and disease mechanisms. This review examines the role of epigenetic mechanisms in NESHIE, focusing on the modulation of hypoxia-inducible factor-1 alpha (HIF-1α) and ncRNA during hypoxic conditions. Additionally, epigenetic-mediated foetal programming may shed light on how maternal and antenatal risk factors contribute to NESHIE susceptibility. Understanding these epigenetic signatures could advance biomarker discovery and the development of novel therapeutic strategies for NESHIE.en© 2025 The Author(s). This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND).Neonatal encephalopathy with suspected hypoxic ischaemic encephalopathy (NESHIE)EpigeneticsHypoxia-inducible factor-1 alpha (HIF-1α)Foetal programmingArticle