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

Abstract

IMPORTANCE 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.OBJECTIVE 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. DESIGN, SETTING, AND PARTICIPANTSThis 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.EXPOSURES 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 P Յ .10 in a joint model except cause, which was included for face validity). MAIN OUTCOMES AND MEASURESFunctional 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.RESULTS 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]; P = .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%; P = .49), with a propensity-adjusted odds ratio of 1.5 (95% CI, 0.7-3.4; P = .32). CONCLUSIONS AND RELEVANCEIn 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 wit...

Parent Mental Health and Family Coping over Two Years after the Birth of a Child with Acute Neonatal Seizures

“…Longitudinal examination of the well-being of families was a pre-specified secondary aim of a comparative effectiveness study examining the safety of early discontinuation of antiseizure medication after acute symptomatic neonatal seizures [ 9 ]. Families were enrolled at one of nine United States (US) children’s hospitals.…”

“…Excluded were neonates with transient cause for seizures (e.g., hyponatremia, hypocalcemia, hypoglycemia without brain injury) or neonatal onset genetic epilepsy syndromes. Characteristics of these infants, along with analyses related to neonatal seizure treatment and developmental outcomes, have been reported [ 9 ].…”

Neonatal seizures: stepping outside the comfort zone

“…The duration of drug continuation after seizure resolution remains variable 50) but accumulating evidence supports their earlier discontinuation before hospital discharge, although exact timing has not been reported 42) if acute symptomatology is con firmed, as it will not be associated with the risk of child hood epilepsy or worse neurodevelopmental outcomes. 51) Interesting ly, Vegda et al 52) designed an algorithm for medication disconti nuation based on the risk of recurrence and availability of EEG/ aEEG; therefore, seizures that are controlled with one drug and resolved within 2-3 days, it is reasonable to withdraw and stop the medication prior to discharge. If the seizures exceed 7 days, require more than 2 drugs for control, or are confirmed as epilepsy, it is reasonable to maintain the baby on 1 or 2 drugs at discharge and refer them for following by a neurologist to decide when to wean the medication.…”

Neonatal seizures—diagnostic options and treatment recommendations

“…Discontinuation of ASM prior to hospital discharge has not been related to a higher risk of post-neonatal epilepsy or less favorable neurodevelopmental outcomes at the 2-year follow-up. Therefore, while the World Health Organization recommends withdrawing ASM after 72 h of seizure freedom in those with normal EEG and neurological examination [29], others suggest expanding this recommendation to neonates with abnormal EEG and neurological examination [10]. However, if seizures are uncontrolled or neonatalonset epilepsy has been diagnosed [14], ASM should be maintained and neonates should be referred to specialized neuropediatric clinics for further management.…”