Trinity team leads first international collaboration to define neonatal encephalopathy

An Irish-led international collaboration has produced the first globally agreed definition of neonatal encephalopathy, a serious condition affecting the brains of newborn babies which is associated with significant risks of disability and death. The landmark work, led by researchers at Trinity College Dublin, the Coombe Hospital, and the Health Research Board Neonatal Encephalopathy PhD Training Network (NEPTuNE), has been published in The Lancet Child and Adolescent Health following an extensive international consultation involving clinicians, researchers, and families from 52 countries.

Neonatal encephalopathy affects between one and four infants in every thousand births globally and is even more common in lower-income countries. Yet, despite its prevalence and severity, doctors and researchers have long used different terms such as neonatal encephalopathy, hypoxic-ischaemic encephalopathy (HIE), and perinatal asphyxia interchangeably, and without consistent definitions.

The result has led to difficulties in comparing studies and uncertainty in communication with families. The new consensus definition, developed through the DEFiNE (Definition of Neonatal Encephalopathy) project, involved 378 participants worldwide and represents the first internationally agreed attempt to standardise terminology in the field.

Prof Eleanor Molloy, a Professor of Paediatrics at the School of Medicine in Trinity College Dublin and senior author of the study, said: “Words matter in medicine. When doctors and researchers use different terms to describe the same condition, it can create confusion for families and impede scientific progress. This new definition provides a common language that will improve communication, support research, and ultimately contribute to better care for babies and their families.”

The consensus defines neonatal encephalopathy as a heterogeneous clinical condition characterised by abnormal or impaired brain function with multiple potential causes. It recognises that the condition can arise from a range of factors, including oxygen deprivation, infection, stroke, genetic disorders, and metabolic disease. Importantly, the definition moves beyond earlier approaches that focused largely on babies eligible for cooling therapy after oxygen-related injury, and instead encompasses all infants with neonatal encephalopathy, regardless of gestational age, severity, or underlying cause.

Lead author, Dr Aoife Branagan, who conducted the research while at Trinity’s School of Medicine and is now completing a neonatal fellowship at McGill University, Montreal, said: “For decades there has been debate over how to define neonatal encephalopathy. Reaching international agreement is a crucial first step towards improving diagnosis, developing new treatments, and ensuring that families receive clearer explanations about their child’s condition and prognosis.”

A notable feature of the project was the involvement of parents and caregivers alongside clinicians and scientists. Family representatives participated throughout the process, helping to shape both the wording and the priorities of the final definition. The researchers believe that adopting a single, internationally recognised definition will improve the design of clinical trials and facilitate more accurate investigations into the causes of newborn brain injury. The DEFiNE team’s next objective is to establish internationally agreed diagnostic criteria and further refine the terminology surrounding related conditions such as HIE and perinatal asphyxia.

The researchers were helped by the Newborn Brain Society, which is a global, professional medical society made up of neonatologists, neurologists, researchers, and allied healthcare professionals. They were also helped by global patient and family support organisation Hope for HIE and UK-based charity PEEPS for HIE which is dedicated entirely to supporting those affected by HIE. 

Authors