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Epilepsy and the need for drug treatment in infancy and early school years after perinatal asphyxia and therapeutic hypothermia

Presented at the Neonatal Society 2017 Autumn Meeting.

Liu X1, Jary S1, Cowan F1, Thoresen M1,2,3

1 Department of Neonatal Neuroscience, School of Clinical Sciences, University of Bristol, UK
2 Neonatal Intensive Care Unit, St. Michaels Hospital, Bristol Childrens Hospital, Bristol, UK
3 Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

Background: In infants who underwent therapeutic hypothermia (TH) for perinatal asphyxia in trials before 2006, the epilepsy rate at 2 years defined as needing regular antiepileptic drugs (AEDs), was 10-16% in both cooled and non-cooled children. We sought to determine the epilepsy rate and regular AED usage in a cohort of children who had perinatal asphyxia from 2007-2013 for whom cooling was the standard of care.

Methods: 151 cooled infants ≥36 weeks gestation who fulfilled Bristol modified TOBY cooling criteria (1) were included and data collected prospectively. All infants had amplitude integrated EEG (aEEG) continuously recorded from pre-cooling till after rewarming; clinical and non-clinical seizures were treated. Background aEEG pattern was severity classified <6 hours from birth, time in hours to recovery of the aEEG pattern was noted as was seizure type and duration and the use of AEDs. Infants underwent MRI scanning on median day 9 (IQR 6-11) and injury severity (2) was scored from 0-11. Survivors had a neurological assessment and Bayley- III exam at 18-24 months. Post-neonatal seizure occurrence and AED usage were collected in all survivors at 2 years and in a subset from 4-8 years. Epilepsy according to the ILEA definition was also assessed (3).

Results: aEEG confirmed seizures occurred pre-cooling in 77/151(57%) of infants, 48% seized during and/or after cooling and received AEDs. Only one infant went home on AEDs. At 18-24 months, 34% of children had adverse outcomes including 11% mortality. At 2 years, of 134 survivors, only 2% were on AEDs though 7% had ILEA defined epilepsy. In the 103 4-8 year olds, the number on AEDs had risen to 7% and 13% had ILEA defined epilepsy. Those on AEDs had higher MRI scores than those not on AEDs, median (IQR) 9(8-11) vs. 2(0-4)) and poorer outcomes. Nine of 14 children with ILEA defined epilepsy had CP (64%) compared to 13/120(11%) without epilepsy. The number of different AEDs given for neonatal seizures, the severity of onset aEEG pattern and the severity of MRI scores predicted poor outcome and epilepsy in this cohort.

Conclusion: We report, in a regional cohort of 151 infants cooled for perinatal asphyxia, 2% on AEDs at 2 years rising to 7% on AEDs at early school age. These AED rates are much lower than reported in the cooling trials even adjusting for our cohort´s milder asphyxia. Using the ILEA definition 7% had epilepsy at 2 years and 13% at 4-8 years. Long-term follow-up is needed to document final epilepsy and AED usage rates.

Corresponding author: marianne.thoresen@bristol.ac.uk

References
1. Smit E, Liu X, Jary S, Cowan F, Thoresen M – Cooling neonates who do not fulfil the standard cooling criteria – short- and long-term outcomes. Acta Paediatrica 2015;104(2):138-145
2. Rutherford MA, Ramenghi L, Edwards AD et al. Lancet Neurology 2010;9(1):38ö45
3. Fisher RS, Acevedo C, Arzimanoglou A, Bogacz A, Cross JH, Elger CE, et al. ILAE official report: a practical clinical definition of epilepsy. Epilepsia. 2014;55(4):475-82

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