麻豆传媒

Treating both clinical and electrographic seizures in newborns did not lead to better survival or neurodevelopmental outcomes at 2 years compared with treating only clinically detected seizures, a showed.

Odds of death or severe disability were not significantly different between the electrographic seizure group -- in which seizures detected on electroencephalography (EEG) were treated in addition to clinical seizures -- compared with the clinical seizure group, in which only seizures detected clinically were treated (OR 1.83, 95% CI 0.96-3.49, P=0.14), reported Rod Hunt, PhD, of Monash University in Australia, and co-authors in .

Contrary to what the researchers hypothesized, the clinical seizure group had better cognitive scores at 2 years.

"This is the largest study to date exploring whether or not we should treat all electrographic seizures in newborns, and the result is unexpectedly inconclusive," Hunt told 麻豆传媒.

"We need to be careful treating all seizures with currently employed anticonvulsant drugs, as we may not be improving the outcomes for these vulnerable infants," he said.

Neonatal seizures indicate the presence of acute brain injury such as hypoxic-ischemic encephalopathy (HIE) or stroke, congenital brain malformations, or genetic epileptic syndromes, observed Martin Offringa, MD, PhD, and Brian Kalish, MD, both of the Hospital for Sick Children in Toronto, in an .

"Given concerns about the risk that ongoing seizures drive intensification of seizure activity and may cause additional injury to the brain, neonatal seizures are often treated aggressively with anticonvulsant medications," Offringa and Kalish wrote.

"Most neonatal seizures are subclinical, i.e., EEG epileptogenic discharges occur without any temporally related clinical motor or autonomic symptoms, and, moreover, the diagnosis of clinical seizures in neonates is highly unreliable," they added. "Therefore, neuromonitoring with amplitude-integrated EEG (aEEG) or continuous EEG (cEEG) has become the standard of care among tertiary NICUs [neonatal intensive care units]."

The trial evaluated term or near-term neonates (at least 35 weeks' gestation) with encephalopathy who were younger than 48 hours old. They were recruited from 2012 to 2016 from tertiary NICUs and randomized into two groups.

The researchers aimed to enroll 300 newborns in each group. However, recruitment ended prematurely with 212 neonates because of slow progress and loss of equipoise when a suggesting treating all electrographic seizures was beneficial.

Over 2 years, 20 infants in each group were lost to follow-up or had incomplete data, leaving 86 in the electrographic seizure group and 86 in the clinical seizure group for the primary analysis. Both groups underwent aEEG, but electrographic seizures in the clinical group were not revealed to the treating physician.

In both arms of the study, clinically apparent seizures were treated. In the electrographic group, EEG-detected seizures fulfilling diagnostic criteria were treated if they lasted more than 2 minutes or occurred more than twice in 24 hours.

The primary outcome was death or severe disability at 2 years. Severe disability was defined as scores in any developmental domain more than 2 standard deviations below the Australian mean on the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), or the presence of cerebral palsy, blindness, or deafness.

Of the 212 neonates, mean gestational age was 39.2 weeks and 58% were male. Most newborns (72%) had moderate to severe HIE, and 84% had electrographic seizures. In the electrographic group, 86% of neonates were treated with anticonvulsant drugs, as were 69% in the clinical group.

A total of 38 infants (44%) in the electrographic group and 27 (31%) in the clinical group met the primary outcome. Ten neonates in the electrographic group and four in the clinical group died before the 2-year assessment.

At 2 years, cognitive domain outcomes on the BSID-III were worse in the electrographic group (mean scores 97.4) than the clinical group (mean scores 103.8; mean difference -6.5, 95% CI -1.2 to -11.8, P=0.01). Secondary outcomes, including time to suck feeds, seizure burden, and MRI brain injury scores, were similar between groups.

With recruitment closing early, the trial was underpowered for its primary and secondary outcomes, the researchers acknowledged. "Further analysis is underway interrogating the direct impact of our commonly employed anticonvulsants," Hunt said. "Urgent research is required to find more effective anticonvulsants that are also neuroprotective."

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