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Electrographic Seizures are associated with Brain Injury in Neonates undergoing Therapeutic Hypothermia after Perinatal Hypoxia-Ischaemia

Presented at the Neonatal Society 2013 Summer Meeting (programme).

Shah D1,2, Wusthoff CJ3, Clarke P4, Wyatt JS5, Ramaiah SM4, Dias RJ1, Becher J6, Kapellou O7, Boardman JP6,8

1 Royal London Hospital, London, UK
2 Barts and the London Medical School, London, UK
3 Stanford University School of Medicine, Palo Alto, California, USA
4 Norfolk and Norwich University Hospitals, Norfolk, UK
5 University College London, London, UK
6 Royal Infirmary of Edinburgh, Edinburgh, UK
7 Homerton University Hospital, London, UK
8 MRC / University of Edinburgh Centre for Reproductive Health, Edinburgh, UK

Background: Seizures are common among newborns with hypoxic-ischemic encephalopathy (HIE) but the relationship between seizure burden and severity of brain injury among neonates receiving therapeutic hypothermia (TH) for HIE is unclear. We tested the hypothesis that seizure burden is a risk factor for cerebral injury as seen on MRI in this group.

Methods: Term neonates undergoing 72 hours of TH at four centers were selected for study if they had continuous 2 channel EEG with amplitude-integrated EEG (aEEG) and MRI. aEEGs were independently analyzed for severity of background and seizure burden. MRIs were graded by the severity of injury using a system that has been shown to predictive of outcome in this group of infants (1). aEEGs and MRIs were rated independently and in a blinded fashion by two experts.

Results: Of 85 neonates, 52% had seizures on aEEG. Overall, 35% had high seizure burden, 49% had abnormal aEEG background in the first 24 hours and 36% had severe injury on MRI. Seizures were most common on the first day, with significant recurrence during and after rewarming. Factors associated with poor outcome on MRI were: high seizure burden, poor aEEG background in first 24 hours, poor aEEG background at 48 hours and 10-minute Apgar score. In multivariate logistic regression, high seizure burden was independently associated with poor MRI outcome (OR 5.00, 95% CI 1.47-17.05 p=0.01); neither aEEG background, nor 10 minute Apgar score were significant in the model.

Conclusion: Electrographic seizure burden is associated with severity of brain injury on MRI in newborns with HIE undergoing therapeutic hypothermia, independent of aEEG background. Seizures are common during cooling, particularly on day one, with a significant rebound on day four.

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1. Rutherford M et al. Lancet neurology. 2010;9(1):39-45

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