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Published on: June 11, 2020
Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy
Xun Liu1, Sally Jary1, Frances Cowan1
1Neonatal Neuroscience, Translational Health Sciences, Bristol Medical School, University of Bristol, Bristol, United Kingdom.
Insights
Neonatal encephalopathy treated with cooling therapy can lead to epilepsy in children. This study found 13% of children developed epilepsy by early school age, with 7% requiring medication.
Area of Science:
- Neonatal neurology
- Pediatric epilepsy
- Therapeutic hypothermia
Background:
- Neonatal encephalopathy (NE) is a serious condition in newborns.
- Therapeutic hypothermia (cooling) is a standard treatment for NE following perinatal asphyxia.
- Epilepsy is a common long-term complication of NE.
Purpose of the Study:
- To determine the proportion of infants treated with therapeutic hypothermia for NE who develop epilepsy.
- To assess epilepsy rates and antiepileptic drug (AED) use up to 8 years of age.
- To identify predictors of epilepsy in this cohort.
Main Methods:
- A regional cohort of 151 infants with NE underwent 72-hour cooling.
- Clinical and amplitude-integrated electroencephalography (aEEG) monitored seizures.
- Brain MRI, neurodevelopmental outcomes, and epilepsy diagnoses (ILAE criteria) were assessed up to 8 years.
- Predictors of epilepsy, including aEEG severity and MRI scores, were analyzed.
Main Results:
- Seizures occurred in 57% before cooling and 48% during/after cooling.
- At 2 years, 6% had epilepsy (2% on AEDs); by 4-8 years, 13% had epilepsy (7% on AEDs).
- Higher MRI scores and more AEDs for neonatal seizures predicted childhood epilepsy.
- Children with epilepsy had significantly poorer neurodevelopmental outcomes and higher rates of cerebral palsy.
Conclusions:
- Epilepsy develops in a significant proportion of infants treated for NE with cooling, persisting into early school age.
- AED requirements in this cohort were lower than in previous cooling trials.
- Neonatal seizure characteristics, aEEG severity, and MRI findings are important predictors of long-term epilepsy risk.
Objective:
To investigate what proportion of a regional cohort of cooled infants with neonatal encephalopathy develop epilepsy (determined by the International League Against Epilepsy [ILAE] definition and the number of antiepileptic drugs [AEDs]) up to 8 years of age.
Methods:
From 2006-2013, 151 infants with perinatal asphyxia underwent 72 h cooling. Clinical and amplitude-integrated electroencepalography (aEEG) with single-channel EEG-verified neonatal seizures were treated with AEDs. Brain magnetic resonance imaging (MRI) was assessed using a 0-11 severity score. Postneonatal seizures, epilepsy rates, and AED treatments were documented. One hundred thirty-four 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 precooling in 77 (57%) 151 of neonates; 48% had seizures during and/or after cooling and received AEDs. Only one infant was discharged on AEDs. At 18-24 months, one third of infants had an adverse outcome including 11% mortality. At 2 years, 8 (6%) infants had an epilepsy diagnosis (ILAE definition), of whom 3 (2%) received AEDs. Of the 103 4- to 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 [interquartile range] 9 [8-11] vs. 2 [0-4]) and poorer outcomes. Nine (64%) of 14 children with epilepsy had cerebral palsy compared to 13 (11%) of 120 without epilepsy, and 10 (71%) of 14 children with epilepsy had adverse outcomes versus 23 (19%) of 120 survivors without epilepsy. The number of different AEDs given to control neonatal seizures, aEEG severity precooling, 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 those reported in the cooling trials, even with adjusting for our cohort's milder asphyxia. Long-term follow-up is needed to document final epilepsy rates.
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