Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy

Objective To investigate what proportion of a regional cohort of cooled infants with neonatal encephalopathy, develop epilepsy (ILAE-definition and AED) up to 8 years of age.

Methods From 2006-2013, 151 infants, with perinatal asphyxia underwent 72 hours cooling. Clinical and aEEG with single-channel EEG verified neonatal seizures were treated with anti-epileptic drugs (AEDs). Brain MRI was assessed using a 0-11 severity score. Post-neonatal seizures, epilepsy-rates and AED treatments were documented. 134 survivors were assessed at 18-24 months; adverse outcome was defined as death or Bayley-III composite Cognition/Language or Motor scores <85 and/or severe cerebral palsy or severely reduced vision/hearing. Epilepsy-rates in 103 children age 4-8 years were also documented.

Results aEEG confirmed seizures occurred pre-cooling in 77/151(57%) neonates; 48% seized during and/or after cooling and received AEDs. Only one infant was discharged on AEDs. At 18-24 months one-third of infants had adverse outcome including 11% mortality. At 2 years, 8(6%) infants had an epilepsy diagnosis (ILEA definition), of whom 3(2%) received AEDs. Of the 103 4-8 year olds, 14(13%) had developed epilepsy, with 7(7%) receiving AEDs. Infants/children 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 epilepsy had CP(64%) compared to 13/120(11%) without epilepsy and 10/14(71%) children with epilepsy had adverse outcomes versus 23/120(19%) survivors without epilepsy. The number of different AEDs given to control neonatal seizures, aEEG severity pre-cooling and MRI scores predicted childhood epilepsy.

Significance We report, in a regional cohort of infants cooled for perinatal asphyxia, 6% with epilepsy at 2 years (2% on AEDs) increasing to 13%(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. Long-term follow-up is needed to document final epilepsy-rates.