Abstracts

Rationale: Hypoxic-ischemic encephalopathy (HIE) is the most common cause of long term CNS injury in neonates, occurring in 2 to 5 of 1,000 live term births. Selective hypothermia has been found to improve neurodevelopmental outcome. HIE is the most common cause of neonatal seizures and often used as predictors of death and disability. However, seizures may be underestimated given continuous EEG (cEEG) is not routinely used with selective hypothermia. We hypothesize that by using continuous EEG monitoring throughout the duration of cooling we can detect 1) electrographic seizures and 2) persistent background abnormalities that may be associated with significant neurodevelopmental impairment and mortality. Methods: Simultaneous cEEG and amplitude-integrated EEG (aiEEG) recordings from 45 neonates undergoing hypothermia for moderate to severe HIE (gestational age >36wks, age <6 hr, 10 minute Apgar <5, pH<7, base deficit > -11, with moderate to severe HIE by neurological exam and EEG) were collected prospectively. Fifteen of the 34 surviving infants returned for follow up and were assessed with Bayley III developmental scales at 6, 12, and 18 months of age. All data are presented as mean ±SD. Results: Thirty-four neonates survived and 11 expired (n=45). There was no significant association between birth resuscitation, APGAR scores, baseline PH, and baseline base excess with death. Electrographic seizures were present in 64% (29 of 45), and did not show any association with outcome (p=0.55). Prolonged interburst interval (IBI) (25.1±21.4 vs 47 ±15.5 sec) was associated with mortality on day 1 of cooling, after rewarming (14.1±11.5 vs 44.5± 23.6 sec) and on the last day of recording (9.5 ±11 vs 41.3 ±26 sec) (p<0.05 for all). Depressed amplitude on day 1 of cooling (10.2± 7.7 vs 4.1 ±2.5μv) was associated with non-survival (p<0.001). Similarly, aiEEG, with persistent abnormality of background during cooling and after rewarming was associated with non-survival (p<0.04). At the 18 month follow-up Bayley III exam, a longer IBI on day 1 of cooling correlated with worse cognitive and motor developmental scores (r=-0.55, p<0.07 and r=-0.64, p<0.04), and longer IBI after rewarming correlated with worse cognitive (r= -0.76, p<006), language (r= -0.62, p<0.04) and motor development scores (r= -0.84, p<0.001). Conclusions: Seizures are common in HIE infants undergoing hypothermia and often missed by clinical assessment alone, however, do not have a significant impact on outcome. Excessive discontinuity throughout monitoring and decreased amplitude on the first day of cooling are indicators of poor survival in infants with HIE, as well as markers for neurodevelopmental outcome in surviving HIE infants. Infants with HIE undergoing therapeutic hypothermia should therefore concurrently be monitored on continuous EEG to help guide treatment as well as assist in prognostication.