Antiseizure medication at discharge in infants with hypoxic-ischaemic encephalopathy: an observational study

Abstract

ObjectivesTo assess variability in continuation of antiseizure medication (ASM) at discharge and to evaluate if continuation of ASM at discharge is associated with death or disability among infants with hypoxic-ischaemic encephalopathy (HIE) and seizures.DesignRetrospective study of infants enrolled in three National Institute of Child Health and Human Development Neonatal Research Network Trials of therapeutic hypothermia.Setting22 US centres.PatientsInfants with HIE who survived to discharge and had clinical or electrographic seizures treated with ASM.ExposuresASM continued or discontinued at discharge.OutcomesDeath or moderate-to-severe disability at 18–22 months, using trial definitions. Multivariable logistic regression evaluated the association between continuation of ASM at discharge and the primary outcome, adjusting for severity of HIE, hypothermia trial treatment arm, use of electroencephalogram, discharge on gavage feeds, Apgar Score at 5 min, birth year and centre.ResultsOf 302 infants included, 61% were continued on ASMs at discharge (range 13%–100% among 22 centres). Electroencephalogram use occurred in 92% of the cohort. Infants with severe HIE comprised 24% and 22% of those discharged with and without ASM, respectively. The risk of death or moderate-to-severe disability was greater for infants continued on ASM at discharge, compared with those infants discharged without ASM (44% vs 28%, adjusted OR 2.14; 95% CI 1.13 to 4.05).ConclusionsIn infants with HIE and seizures, continuation of ASM at discharge varies substantially among centres and may be associated with a higher risk of death or disability at 18–22 months of age.

Reducing the Percent of Surviving Infants with Acute Symptomatic Seizures Discharged on Anti-Seizure Medication

“…Previous studies have shown variation by center in the percent of infants with acute symptomatic seizures discharged on ASM. (10,17,18) Historically our academic provider group working in three local hospitals, or has had a high proportion of infants with seizures discharged on ASM. This was compounded by challenges in obtaining neurology follow-up in a timely manner after discharge, resulting in infants being exposed to prolonged duration of ASM.…”

“…(4-9) Continuation of ASM at discharge may be associated with increased neurodevelopmental impairment. (10) While higher than the average population, epilepsy risk in neonates following acute symptomatic seizures remains relatively low and seizures often do not present until months to years after discharge. (11)(12)(13) Continuation of ASM after discharge does not decrease the risk of epilepsy.…”

Neonatal seizures. Treat! But when, with what and for how long?

“…Sewell et al , on behalf of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, provide more evidence on the enormous variation in practice that exists for these infants, with an observational study on antiseizure medication (ASM) use after discharge for infants with hypoxic-ischaemic encephalopathy (HIE) 1. The data were collected on infants who had been enrolled into various cooling trials over the preceding 15 years.…”

“…The conclusion was that discontinuation of ASM at hospital discharge was safe. Of course, the results of this study could not have influenced the results of Sewell et al ,1 as their data were retrieved from randomised controlled trials (RCTs) conducted over the previous decade. While no data were available on which ASM was employed, it would be reasonable to conclude that this was phenobarbital for the majority, as was the case in the previous study 2.…”

“…The pathway to novel drug development is also long and challenging, but recent recommendations for phenobarbital as first-line therapy exist in part because evidence for something safer and more efficacious is lacking. Sewell et al 1 conclude that ‘more studies are needed on the efficacy and long-term effects of ASM treatment’…they absolutely are. In the treatment of neonatal seizures, we have to continue to strive to do better.…”