Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures

Abstract

<div class="section"> <a class="named-anchor" id="ab-noi210025-1"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e521">Question</h5> <p id="d9485095e523">Is discontinuation of antiseizure medication (ASM) after resolution of acute symptomatic neonatal seizures and prior to discharge from the hospital associated with functional neurodevelopment or epilepsy at 24 months? </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-2"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e526">Findings</h5> <p id="d9485095e528">In this comparative effectiveness study of 303 children with neonatal seizures from 9 centers, 64% had ASM maintained at hospital discharge. No difference was found between ASM maintenance and discontinuation groups in functional neurodevelopment or epilepsy; 13% of children developed epilepsy, including more than one-third with infantile spasms. </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-3"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e531">Meaning</h5> <p id="d9485095e533">These results support discontinuing ASMs for most neonates with acute symptomatic seizures prior to discharge from the hospital, an approach that may represent an evidence-based change in practice for many clinicians. </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-4"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e537">Importance</h5> <p id="d9485095e539">Antiseizure medication (ASM) treatment duration for acute symptomatic neonatal seizures is variable. A randomized clinical trial of phenobarbital compared with placebo after resolution of acute symptomatic seizures closed early owing to low enrollment. </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-5"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e542">Objective</h5> <p id="d9485095e544">To assess whether ASM discontinuation after resolution of acute symptomatic neonatal seizures and before hospital discharge is associated with functional neurodevelopment or risk of epilepsy at age 24 months. </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-6"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e547">Design, Setting, and Participants</h5> <p id="d9485095e549">This comparative effectiveness study included 303 neonates with acute symptomatic seizures (282 with follow-up data and 270 with the primary outcome measure) from 9 US Neonatal Seizure Registry centers, born from July 2015 to March 2018. The centers all had level IV neonatal intensive care units and comprehensive pediatric epilepsy programs. Data were analyzed from June 2020 to February 2021. </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-7"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e552">Exposures</h5> <p id="d9485095e554">The primary exposure was duration of ASM treatment dichotomized as ASM discontinued vs ASM maintained at the time of discharge from the neonatal seizure admission. To enhance causal association, each outcome risk was adjusted for propensity to receive ASM at discharge. Propensity for ASM maintenance was defined by a logistic regression model including seizure cause, gestational age, therapeutic hypothermia, worst electroencephalogram background, days of electroencephalogram seizures, and discharge examination (all <i>P</i> ≤ .10 in a joint model except cause, which was included for face validity). </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-8"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e560">Main Outcomes and Measures</h5> <p id="d9485095e562">Functional neurodevelopment was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS) at 24 months powered for propensity-adjusted noninferiority of early ASM discontinuation. Postneonatal epilepsy, a prespecified secondary outcome, was defined per International League Against Epilepsy criteria, determined by parent interview, and corroborated by medical records. </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-9"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e565">Results</h5> <p id="d9485095e567">Most neonates (194 of 303 [64%]) had ASM maintained at the time of hospital discharge. Among 270 children evaluated at 24 months (mean [SD], 23.8 [0.7] months; 147 [54%] were male), the WIDEA-FS score was similar for the infants whose ASMs were discontinued (101 of 270 [37%]) compared with the infants with ASMs maintained (169 of 270 [63%]) at discharge (median score, 165 [interquartile range, 150-175] vs 161 [interquartile range, 129-174]; <i>P</i> = .09). The propensity-adjusted average difference was 4 points (90% CI, −3 to 11 points), which met the a priori noninferiority limit of −12 points. The epilepsy risk was similar (11% vs 14%; <i>P</i> = .49), with a propensity-adjusted odds ratio of 1.5 (95% CI, 0.7-3.4; <i>P</i> = .32). </p> </div><div class="section"> <a class="named-anchor" id="ab-noi210025-10"> <!-- named anchor --> </a> <h5 class="section-title" id="d9485095e579">Conclusions and Relevance</h5> <p id="d9485095e581">In this comparative effectiveness study, no difference was found in functional neurodevelopment or epilepsy at age 24 months among children whose ASM was discontinued vs maintained at hospital discharge after resolution of acute symptomatic neonatal seizures. These results support discontinuation of ASM prior to hospital discharge for most infants with acute symptomatic neonatal seizures. </p> </div><p class="first" id="d9485095e584">This comparative effectiveness study assesses whether discontinuation of antiseizure medication prior to discharge from the hospital after resolution of acute symptomatic neonatal seizures is associated with impaired functional neurodevelopment or the risk of epilepsy at 24 months. </p>