Circadian rhythms in pediatric neurocritical care: interfaces and opportunities.

Neurological disorders represent a disproportionate fraction of pediatric intensive care unit (PICU) admissions, accounting for approximately one quarter of all critically ill children. These conditions-including traumatic brain injury, hypoxic-ischemic encephalopathy, stroke, infectious and inflammatory disorders, epilepsy, and disorders of consciousness-are frequently accompanied by profound disruption of circadian rhythms. The circadian timekeeper is a fundamental biological system that coordinates physiology across scales, from molecular and cellular processes to systemic functions such as metabolism, immunity, thermoregulation, endocrine signaling, vascular regulation, synaptic physiology, and sleep-wake cycling. In the PICU and neonatal ICU (NICU) environments, multiple factors-including continuous or irregular lighting, noise, frequent clinical interventions, sedation, altered feeding schedules, and the pathophysiology of neurological injury itself-conspire to destabilize circadian organization. We summarize these contributing factors into pathways of critical care circadian desynchrony (C3D). This review examines the intersection between circadian biology and pediatric neurocritical care. We first summarize the molecular and systems-level architecture of the circadian system and distinguish circadian rhythms from sleep-wake state regulation. We then outline the development of sleep and circadian rhythms in the fetus, neonate, infant and child, emphasizing that pediatric circadian biology cannot be treated as a simple extension of adult neurology and chronobiology. We consider how the PICU and NICU environments disrupt circadian biology and discuss how circadian dysregulation manifests across common neurological conditions encountered in pediatric critical care including hypoxic-ischemic encephalopathy (HIE), traumatic brain injury (TBI), stroke, infection and autoimmune encephalitides, epilepsy, delirium, and status dystonicus. Emerging literature suggests that disturbances of circadian outputs-including hormone secretion, metabolism, immune signaling, thermoregulation, sleep-wake cycling, autonomic regulation, and gene expression-may influence neurological injury progression, recovery trajectories, and long-term neurodevelopmental outcomes. We review current methods used to measure sleep and circadian rhythms in critically ill children, including polysomnography, electroencephalography, actigraphy, biomarker-based approaches, and emerging physiological metrics derived from continuous monitoring. Finally, we discuss potential clinical strategies aimed at restoring circadian alignment in the PICU environment, including environmental modification, sedation-aware care, pharmacologic chronobiotics, time-structured nutrition, and chronotherapy. Together, we offer a conceptual framework that centralizes circadian desynchronization in pediatric neurocritical care as an under-explored, potentially targetable modifier of neurological injury and recovery in pediatric critical illness. Integrating circadian biology into pediatric neurocritical care may provide new opportunities for biomarker development, therapeutic intervention, prognostication, and personalized chronomedicine.