The Neonatal Cardio-Renal-Brain Axis in Hypoxic-Ischemic Encephalopathy

Hypoxic-ischaemic encephalopathy (HIE) remains one of the leading causes of neonatal mortality and long-term neurodevelopmental disability worldwide despite major advances in neonatal intensive care and the widespread implementation of therapeutic hypothermia. Traditionally, HIE has been viewed predominantly as a cerebral disorder, with clinical management focused largely on neuroprotection and seizure control. However, growing evidence suggests that perinatal hypoxia-ischaemia induces a complex multisystem response involving profound interactions between cardiovascular dysfunction, acute kidney injury, cerebral autoregulatory failure, systemic inflammation, and metabolic disturbances. Myocardial injury may lead to reduced cardiac output and impaired cerebral perfusion, while renal dysfunction contributes to fluid imbalance, altered drug pharmacokinetics, and amplification of inflammatory pathways that further exacerbate secondary brain injury. Therapeutic hypothermia, although neuroprotective, introduces additional physiological alterations that influence myocardial performance, systemic vascular resistance, and renal blood flow. These interdependent mechanisms have led to increasing recognition of a neonatal cardio-renal-brain axis as a central determinant of neurological recovery following perinatal asphyxia. This review explores current understanding of organ crosstalk in HIE, examines emerging biomarkers and monitoring strategies, and discusses how multimodal haemodynamic assessment may facilitate a transition from protocol-driven treatment toward precision neurocritical care in the neonatal intensive care unit. Keywords: Hypoxic-ischaemic encephalopathy; neonatal haemodynamics; therapeutic hypothermia; acute kidney injury; precision neurocritical care