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Review
. 2025 Mar 24.
doi: 10.1038/s41390-025-03986-2. Online ahead of print.

Neonatal encephalopathy and hypoxic-ischemic encephalopathy: the state of the art

Affiliations
Free article
Review

Neonatal encephalopathy and hypoxic-ischemic encephalopathy: the state of the art

Ela Chakkarapani et al. Pediatr Res. .
Free article

Abstract

Neonatal Encephalopathy (NE) remains a major cause of death and long-term severe disabilities, including epilepsy and cerebral palsy in term and near-term infants. The single most common cause is hypoxic-ischemic encephalopathy (HIE). However, there are many other potential causes, including infection, intracranial hemorrhage, stroke, brain malformations, metabolic disorders, and genetic causes. The appropriate management depends on both the specific cause and the stage of evolution of injury. Key tools to expand our understanding of the timing and causes of NE include aEEG, or even better, video EEG monitoring, neuro-imaging including cranial ultrasound and MRI, placental investigations, metabolic, biomarker, and genetic studies. This information is critical to better understand the underlying causes of NE. Therapeutic hypothermia improves outcomes after HIE, but there is still considerable potential to do better. Careful clinical and pre-clinical studies are needed to develop novel therapeutics and to help provide the right treatment at the right time for this high-risk population. IMPACT: Neonatal encephalopathy is complex and multifactorial. This review seeks to expand understanding of the causes, timing, and evolution of encephalopathy in newborns. We highlight key unanswered questions about neonatal encephalopathy.

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Conflict of interest statement

Competing interests: E.C.—research supported by the NIHR, Wellcome studentship funding, and Action Medical Research for children. Support from Chiesi Pharmaceuticals for conference organization. No other conflicts. Ld.V.—Declares no conflict of interest. Received honorarium as a speaker of the “cranial ultrasound course” held at Imperial College London, UK every year and Royalties being a co-author of “an atlas of aEEG in the newborn”; “An atlas of Neonatal Brain Sonography” and “Neurology of the Newborn”. No other conflicts. D.F.—grants from the NIH and honorarium from the LeDucq foundation and Pediatric Research. No other conflicts. A.G.—Declares no conflict of interest. A.G. has received public good grants from the Health Research Council of New Zealand (current, HRC grant 22/559).

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