Prognostic Neurobiomarkers in Neonatal Encephalopathy

Therapeutic hypothermia (TH) is now a standard treatment for infants with moderate-to-severe neonatal encephalopathy (NE), and improves brain damage on neuroimaging and neurodevelopmental outcomes. Critically, for effective neuroprotection, hypothermia should be started within 6 h from birth. There is compelling evidence to suggest that a proportion of infants with mild NE have material risk of developing brain damage and poor outcomes. This cohort is increasingly being offered TH, despite lack of trial evidence for its benefit. In current practice, infants need to be diagnosed within 6 h of birth for therapeutic treatment, compared to retrospective NE grading in the pre-hypothermia era. This presents challenges as NE is a dynamic brain disorder that can worsen or resolve over time. Neurological symptoms of NE can be difficult to discern in the first few hours after birth, and confounded by analgesics and anesthetic treatment. Using current enrolment criteria, a significant number of infants with NE that would benefit from hypothermia are not treated, and vice versa, some infants receive hypothermia when its benefit will be limited. Better biomarkers are needed to further improve management and treatment of these neonates. In the present review, we examine the latest research, and highlight a central limitation of most current biomarkers: that their predictive value is consistently greatest after most neuroprotective therapies are no longer effective.