AimTo examine the relationship between electrographic seizures and long‐term outcome in neonates with hypoxic–ischemic encephalopathy (HIE).MethodFull‐term neonates with HIE born in Cork University Maternity Hospital from 2003 to 2006 (pre‐hypothermia era) and 2009 to 2012 (hypothermia era) were included in this observational study. All had early continuous electroencephalography monitoring. All electrographic seizures were annotated. The total seizure burden and hourly seizure burden were calculated. Outcome (normal/abnormal) was assessed at 24 to 48 months in surviving neonates using either the Bayley Scales of Infant and Toddler Development, Third Edition or the Griffiths Mental Development Scales; a diagnosis of cerebral palsy or epilepsy was also considered an abnormal outcome.ResultsContinuous electroencephalography was recorded for a median of 57.1 hours (interquartile range 33.5–80.5h) in 47 neonates (31 males, 16 females); 29 out of 47 (62%) had electrographic seizures and 25 out of 47 (53%) had an abnormal outcome. The presence of seizures per se was not associated with abnormal outcome (p=0.126); however, the odds of an abnormal outcome increased over ninefold (odds ratio [OR] 9.56; 95% confidence interval [95% CI] 2.43–37.67) if a neonate had a total seizure burden of more than 40 minutes (p=0.001), and eightfold (OR: 8.00; 95% CI: 2.06–31.07) if a neonate had a maximum hourly seizure burden of more than 13 minutes per hour (p=0.003). Controlling for electrographic HIE grade or treatment with hypothermia did not change the direction of the relationship between seizure burden and outcome.InterpretationIn HIE, a high electrographic seizure burden is significantly associated with abnormal outcome, independent of HIE severity or treatment with hypothermia.

Type of publicationArticle ( Embargo information Access to this article is restricted until 12 months after publication by the request of the publisher. Embargo lift date Antiepileptic Drugs: Efficacy, Safety and Tolerability 182The most frequently used AEDs in both term and preterm babies include phenobarbital, It is known that morphine clearance is decreased during hypothermia, resulting in an increased 358 concentration of morphine in both cerebrospinal fluid and plasma [127, 128]. In terms of 359 pharmacodynamic considerations, the affinity of morphine for its receptor appears reduced in 360 hypothermia, but the incidence of hypotension is increased [127, 129] (Table 1). Furthermore, there is a need to observe long-term 464 neurodevelopmental outcomes following each of the proposed treatments, and to define the 465 optimal length of time to continue with AED therapy given the concern regarding their effect 466 on long-term brain development [16, 150]. 467There is a paucity of data on the pharmacokinetics and efficacy of many AEDs used in

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