麻豆传媒

Keeping newborns on antiseizure medication after acute neonatal seizures stopped did not change development outcomes or prevent epilepsy, a comparative effectiveness study showed.

No difference was seen in functional neurodevelopment at age 24 months in children whose antiseizure medication was discontinued versus maintained after acute symptomatic neonatal seizures resolved, reported Hannah Glass, MDCM, MAS, of the University of California San Francisco, and co-authors, in .

Overall, 13% of children developed epilepsy, which was not associated with treatment duration. Median age at epilepsy onset was 7 months.

"More than 16,000 babies in the U.S. have seizures each year due to a variety of causes, most commonly brain injury around the time of birth," Glass said. "Many of these children have lifelong disabilities and medical conditions like cerebral palsy and epilepsy," she told 麻豆传媒.

"Although the seizures usually subside within 3 or 4 days, children are often treated with antiseizure medications for several months" -- an approach developed before the advent of continuous video-electroencephalogram (EEG) to diagnose seizure onset and resolution, or MRI and genetic testing to determine the cause of seizures, she added.

Long-term antiseizure drugs can expose children to potentially neurotoxic effects with prolonged use, Glass pointed out.

"This study supports the findings from smaller studies that stopping the antiseizure medicine before a child goes home from the hospital leads to many fewer days of treatment with potentially harmful antiseizure medications like phenobarbital, and that there is no increased risk of epilepsy or developmental issues when the medicine is stopped early," she said.

"For children who have neonatal seizures due to an early brain injury and whose treating physician has confirmed that the seizures have stopped for at least 24 hours of EEG monitoring, the antiseizure medications can safely be discontinued," she continued. "This approach will be a change in practice for many clinicians."

While neonatal care clinicians seek to avoid unnecessary harm to their patients' developing brains, what constitutes unnecessary harm often is unclear, observed Eric Payne, MD, MPH, of the University of Calgary in Alberta, Canada, and Elaine Wirrell, MD, of the Mayo Clinic in Rochester, Minnesota, in an .

"In the field of epilepsy treatment, we are often caught between the proverbial rock and hard place: our seizure medications can cause harm but so can seizures," they noted.

A comparing phenobarbital with placebo showed children with febrile seizures in the phenobarbital cohort had a significantly lower IQ after 2 years of treatment, Payne and Wirrell observed.

"Glass and colleagues have provided clarity through data that support the 2011 to consider stopping antiseizure medications without a taper after 72 hours of seizure freedom for neonates with normal findings on neurological examination and/or EEG," they wrote. "The current study suggests this recommendation should include all neonates with acute symptomatic seizures, even in the setting of an abnormal EEG and neurological examination results."

In , Glass and co-authors evaluated 303 neonates with acute symptomatic seizures at nine U.S. centers. Children were born from July 2015 to March 2018. Those with transient reversible seizure causes or neonatal-onset epilepsy syndromes were excluded.

In total, 282 children had follow-up data and 270 had the primary outcome measure of functional neurodevelopment at 24 months. A little more than half (54%) of the children evaluated at 24 months were boys.

Seizure cause was hypoxic-ischemic encephalopathy in 43% of infants, ischemic stroke in 26%, intracranial hemorrhage in 18%, or other acute brain injury in 13%. Phenobarbital was the first loading anti-seizure medication for 90% of neonates.

Researchers used the Warner Initial Developmental Evaluation of Adaptive and Functional Skills () to determine functional neurodevelopment. They defined post-neonatal epilepsy, a secondary outcome, by , determined by parent interview and medical records.

Most neonates (64%) continued antiseizure medication after hospital discharge. Median treatment duration for these children was 4 months, compared with 6 days for children whose medication was stopped.

At 24 months, median WIDEA-FS scores were similar in each group (165 in children who discontinued vs 161 in those who maintained treatment, P=0.09). The propensity-adjusted average difference was 4 points (90% CI -3 to 11 points), which met the a priori noninferiority limit of -12 points.

Epilepsy risk also was similar (11% in children who discontinued vs 14% in those who maintained treatment, P=0.49) with a propensity-adjusted odds ratio of 1.5 (95% CI 0.7-3.4, P=0.32).

Subgroup analyses showed that of infants born prematurely, the estimated WIDEA-FS score difference was 14 points higher in those who stopped taking antiseizure drugs at discharge. Among children with hypoxic-ischemic encephalopathy as seizure cause, the estimated WIDEA-FS score difference was 10 points higher in those who stopped.

While the study was powered to determine noninferiority for the primary outcome of 24-month functional neurodevelopment, larger and longer-term studies are needed for other outcomes including epilepsy, the researchers acknowledged. The group will follow this cohort of children into school age to further assess learning and development.

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