A Study of a Blood Marker in Newborns With Brain Injury Caused by Lack of Oxygen at Birth

Hypoxic-ischemic encephalopathy (HIE) is a critical clinical condition arising from perinatal asphyxia, leading to acute-phase mortality and significant long-term neurological morbidity during the neonatal period. In recent years, therapeutic hypothermia has become the standard treatment approach for HIE, with proven effectiveness in reducing both mortality and severe neurodevelopmental sequelae. However, its therapeutic benefit is not consistent across all cases, and some newborns may still develop permanent neurological damage and developmental impairments despite receiving treatment. This highlights the need for reliable biomarkers that can reveal the extent of central nervous system injury in the early period, predict prognosis, and objectively assess treatment response.

Neurofilament light chain (NfL), a myelinated axon-specific structural protein released into the bloodstream following central nervous system injury, has gained increasing attention as a potential biomarker. Neurofilaments are abundant within axons and play a crucial role in radial growth during development, maintenance of axon caliber, and electrical signal conduction. They are intermediate filaments with a diameter of approximately 10 nm and are composed of four major subunits within the central nervous system: heavy, medium, and light neurofilament polypeptides, along with α-internexin.

In various pathological conditions, neurofilaments may accumulate in large quantities within neuronal cell bodies and proximal axons. Such accumulations are characteristic lesions in several neurological disorders, including motor neuron diseases, hereditary neuropathies, neurofilament inclusion disorders, giant axonal neuropathies, metabolic neuropathies, and degenerative motor neuron conditions. Although NfL levels are typically higher in cerebrospinal fluid than in blood, serum or plasma measurements are clinically advantageous due to their minimally invasive nature, reproducibility, and practical applicability. Accordingly, NfL has been widely investigated as a biomarker in both cerebrospinal fluid and blood for a range of neurodegenerative and neurological diseases.

In the neonatal population, clinical investigations have largely focused on HIE, where serum and plasma NfL levels have been associated with disease severity and long-term neurodevelopmental outcomes. Beyond HIE, NfL also shows potential prognostic value in preterm-related morbidities such as intraventricular hemorrhage, periventricular leukomalacia, and diffuse white matter injury. Moreover, its use is being explored as a biochemical indicator of perioperative neurological injury in infants undergoing cardiopulmonary bypass for congenital heart disease, as well as in neonatal sepsis and sepsis-associated encephalopathy.

Recent research has demonstrated significant associations between NfL levels and both magnetic resonance imaging findings and long-term neurodevelopmental outcomes in newborns with HIE treated with therapeutic hypothermia. These observations support the potential of NfL as a biomarker reflecting axonal injury and as a prognostic indicator. However, the number of studies that systematically compare NfL levels at different sampling time points remains limited, emphasizing the need to determine the optimal timing of measurement and to standardize its use in clinical practice.

The primary objective of this study is to measure NfL levels in blood samples obtained at defined time intervals after birth in order to assess the timing and extent of brain involvement. This will support early prognostic evaluation and contribute to the development of future diagnostic algorithms. The secondary objective is to compare infants diagnosed with HIE to a control group, thereby clarifying the extent of brain injury associated with HIE in the neonatal period.