Seizures in Preterm Neonates: A Multicenter Observational Cohort Study

Abstract

BACKGROUND The purpose of this study was to characterize seizures among preterm neonates enrolled in the Neonatal Seizure Registry, a prospective cohort of consecutive neonates with seizures at seven pediatric centers that follow the American Clinical Neurophysiology Society’s neonatal electroencephalography monitoring guideline. STUDY DESIGN Of 611 enrolled neonates with seizures, 92 (15%) were born preterm. Seizure characteristics were evaluated by gestational age at birth for extremely preterm (<28 weeks, N = 18), very preterm (28 to <32 weeks, N = 18), and moderate to late preterm (32 to <37 weeks, N = 56) and compared with term neonates. RESULTS Hypoxic-ischemic encephalopathy (33%) and intracranial hemorrhage (27%) accounted for the etiology in more than half of preterm neonates. Hypothermia therapy was utilized in 15 moderate to late preterm subjects with encephalopathy. The presence of subclinical seizures, monotherapy treatment failure, and distribution of seizure burden (including status epilepticus) was similar in preterm and term neonates. However, exclusively subclinical seizures occurred more often in preterm than term neonates (24% vs 14%). Phenobarbital was the most common initial medication for all gestational age groups, and failure to respond to an initial loading dose was 63% in both preterm and term neonates. Mortality was similar among the three preterm gestational age groups; however, preterm mortality was more than twice that of term infants (35% vs 15%). CONCLUSIONS Subclinical seizures were more common and mortality was higher for preterm than term neonates. These data underscore the importance of electroencephalographic monitoring and the potential for improved management in preterm neonates.

Response to antiseizure medications in neonates with acute symptomatic seizures

“…Neonates from the initial NSR cohort were previously reported. 2,3,5 Neonates were included if they received a loading dose of an ASM and adequate documentation regarding response to the loading dose was available. Neonates with events that were determined not to be seizures based on history, semiology, or cEEG were not enrolled.…”

“…1 Little is known about additional characteristics associated with initial treatment failure, although we previously showed that preterm and term neonates were equally likely to have persistent seizures after a loading dose of phenobarbital 2 and there was no difference in treatment response to initial doses of phenobarbital, phenytoin, or levetiracetam as the first-line ASM. In the 1999 clinical trial of phenobarbital versus phenytoin, seizures recurred in >50% of neonates following the first loading dose of either medication, and neonates with higher seizure burden were less likely to respond.…”

“…In the 1999 clinical trial of phenobarbital versus phenytoin, seizures recurred in >50% of neonates following the first loading dose of either medication, and neonates with higher seizure burden were less likely to respond. 1 Little is known about additional characteristics associated with initial treatment failure, although we previously showed that preterm and term neonates were equally likely to have persistent seizures after a loading dose of phenobarbital 2 and there was no difference in treatment response to initial doses of phenobarbital, phenytoin, or levetiracetam as the first-line ASM. 3 We hypothesized that treatment response to ASMs would not differ by seizure etiology and that treatment response would be dose dependent.…”

The probability of seizures during continuous EEG monitoring in high‐risk neonates

“…Current consensus guidelines 13 aim to balance the need to identify seizures in critically ill neonates with the substantial personnel and equipment resources required to support cEEG, 14 but are based on limited neonatal data. 26,27 In addition, younger age 28,29 and EEG background abnormalities 22,[30][31][32][33] are associated with increased seizure incidence; however, the impact of early EEG features on the time course of seizure presentation in high-risk neonates is unknown. [15][16][17][18][19][20] Delayed seizure onset beyond 24 hours has been reported in acute neonatal encephalopathy [21][22][23][24][25] and congenital cardiac disease cohorts.…”

“…[15][16][17][18][19][20] Delayed seizure onset beyond 24 hours has been reported in acute neonatal encephalopathy [21][22][23][24][25] and congenital cardiac disease cohorts. 26,27 In addition, younger age 28,29 and EEG background abnormalities 22,[30][31][32][33] are associated with increased seizure incidence; however, the impact of early EEG features on the time course of seizure presentation in high-risk neonates is unknown.…”