Objective To investigate the prognostic accuracy of longitudinal analysis of amplitude-integrated
electroencephalography (aEEG) background activity to predict long-term neurodevelopmental
outcome in neonates with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic
hypothermia.Study design This single-center observational study included 149 neonates
for derivation and 55 neonates for validation with moderate-severe HIE and of gestational
age 35 weeks at a tertiary neonatal intensive care unit. Single-channel aEEG background
pattern, sleep-wake cycling, and seizure activity were monitored over 84 hours during
therapeutic hypothermia and rewarming, then scored for each 6-hour interval. Neurodevelopmental
outcome was assessed using the Bayley Scales of Infant Development, Second Edition.
Favorable outcome was defined as having both a Mental Development Index (MDI) score
and Psychomotor Development Index (PDI) score >= 70, and adverse outcome was defined
as either an MDI or a PDI <70 or death. Regression modeling for longitudinal analysis
of repeatedly measured data was applied, and area under the receiver operating characteristic
curve (AUC) was calculated.Resuits Longitudinal aEEG background analysis combined
with sleep-wake cycling score had excellent predictive value (AUC, 0.90; 95% CI, 0.85-0.95),
better than single aEEG scores at any individual time point. The model performed well
in the independent validation cohort (AUC, 0.87; 95% CI, 0.62-1.00). The reclassification
rate of this model compared with the conventional analysis of aEEG background at 48
hours was 18% (24 patients); 14% (18 patients) were reclassified correctly. Our results
were used to develop a user-friendly online outcome prediction tool.Conclusions Longitudinal
analysis of aEEG background activity and sleep-wake cycling is a valuable and accurate
prognostic tool.