Prognostic value of neonatal EEG following therapeutic hypothermia in survivors of hypoxic-ischemic encephalopathy

Tuomas Koskela,Giles S Kendall,Sara Memon,Magdalena Sokolska,Thalitha Mabuza,Angela Huertas-Ceballos,Subhabrata Mitra,Nicola J Robertson,Judith Meek,Kimberley Whitehead

doi:10.1016/j.clinph.2021.05.031

Abstract

ObjectiveEarly prediction of neurological deficits following neonatal hypoxic-ischemic encephalopathy (HIE) may help to target support. Neonatal animal models suggest that recovery following hypoxia-ischemia depends upon cortical bursting. To test whether this holds in human neonates, we correlated the magnitude of cortical bursting during recovery (≥postnatal day 3) with neurodevelopmental outcomes. MethodsWe identified 41 surviving infants who received therapeutic hypothermia for HIE (classification at hospital discharge: 19 mild, 18 moderate, 4 severe) and had 9-channel electroencephalography (EEG) recordings as part of their routine care. We correlated burst power with Bayley-III cognitive, motor and language scores at median 24 months. To examine whether EEG offered additional prognostic information, we controlled for structural MRI findings. ResultsHigher power of central and occipital cortical bursts predicted worse cognitive and language outcomes, and higher power of central cortical bursts predicted worse motor outcome, all independently of structural MRI findings. ConclusionsClinical EEG after postnatal day 3 may provide additional prognostic information by indexing persistent active mechanisms that either support recovery or exacerbate brain damage, especially in infants with less severe encephalopathy. SignificanceThese findings could allow for the effect of clinical interventions in the neonatal period to be studied instantaneously in the future.

Highlights

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of acquired neonatal brain injury (Gale et al, 2018)
At University College London Hospitals (UCLH), infants who undergo 72 hours of therapeutic hypothermia for HIE are continuously monitored with 9channel EEG for at least 3 days (Azzopardi et al, 2008)
EEG features on postnatal day 3 have been reported to predict neurodevelopmental outcome (Cainelli et al, 2018; Li et al, 2013), with greater accuracy than earlier EEG findings (Hamelin et al, 2011)

Summary

Introduction

Hypoxic-ischemic encephalopathy (HIE) is the most common cause of acquired neonatal brain injury (Gale et al, 2018). The magnitude of cortical bursts and its dependence on sleep state can be assessed using electroencephalography (EEG). At University College London Hospitals (UCLH), infants who undergo 72 hours of therapeutic hypothermia for HIE are continuously monitored with 9channel EEG for at least 3 days (Azzopardi et al, 2008). Given that abnormality of EEG is associated with extent of structural brain injury on magnetic resonance imaging (MRI) (Iyer et al, 2014; Rutherford et al, 2010), we sought to determine whether EEG provided additional prognostic information to structural MRI, which is a known predictor (Lally et al, 2019; MartinezBiarge et al, 2010; Sánchez Fernández et al, 2017)

Methods

Results

Conclusion