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Seizures are common in neonates, but there is substantial management variability. The Neonatal Task Force of the International League Against Epilepsy (ILAE) developed evidence‐based recommendations about antiseizure medication (ASM) management in neonates in accordance with ILAE standards. Six priority questions were formulated, a systematic literature review and meta‐analysis were performed, and results were reported following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) 2020 standards. Bias was evaluated using the Cochrane tool and risk of Bias in non‐randomised studies ‐ of interventions (ROBINS‐I), and quality of evidence was evaluated using grading of recommendations, assessment, development and evaluation (GRADE). If insufficient evidence was available, then expert opinion was sought using Delphi consensus methodology. The strength of recommendations was defined according to the ILAE Clinical Practice Guidelines development tool. There were six main recommendations. First, phenobarbital should be the first‐line ASM (evidence‐based recommendation) regardless of etiology (expert agreement), unless channelopathy is likely the cause for seizures (e.g., due to family history), in which case phenytoin or carbamazepine should be used. Second, among neonates with seizures not responding to first‐line ASM, phenytoin, levetiracetam, midazolam, or lidocaine may be used as a second‐line ASM (expert agreement). In neonates with cardiac disorders, levetiracetam may be the preferred second‐line ASM (expert agreement). Third, following cessation of acute provoked seizures without evidence for neonatal‐onset epilepsy, ASMs should be discontinued before discharge home, regardless of magnetic resonance imaging or electroencephalographic findings (expert agreement). Fourth, therapeutic hypothermia may reduce seizure burden in neonates with hypoxic–ischemic encephalopathy (evidence‐based recommendation). Fifth, treating neonatal seizures (including electrographic‐only seizures) to achieve a lower seizure burden may be associated with improved outcome (expert agreement). Sixth, a trial of pyridoxine may be attempted in neonates presenting with clinical features of vitamin B6‐dependent epilepsy and seizures unresponsive to second‐line ASM (expert agreement). Additional considerations include a standardized pathway for the management of neonatal seizures in each neonatal unit and informing parents/guardians about the diagnosis of seizures and initial treatment options. [ABSTRACT FROM AUTHOR]

Today, in NICUs all over the world, seizure treatment is started only when there is a strong clinical suspicion of seizures and/or there is confirmatory aEEG/cEEG evidence. Keywords: clinical trials; drug development; hypoxic-ischemic encephalopathy; seizures in newborns; treatment EN clinical trials drug development hypoxic-ischemic encephalopathy seizures in newborns treatment 1874 1879 6 07/15/22 20220701 NES 220701 INTRODUCTION Seizures present both diagnostic and therapeutic challenges in neonates who are admitted to neonatal intensive care units (NICUs) worldwide. Of course there is variability, as seizure onset depends on the time of occurrence of the primary injury.18 Seizures in HIE have a typical evolution, with a peak in seizure burden within the first 30 hours. Amplitude integrated EEG (aEEG) is more widely available for clinical management, but 20%-40% of seizures will be missed, in addition to a significant risk of false-positive detections.12 aEEG is not recommended for clinical trials of neonatal seizure treatment.13 WHAT DO WE KNOW ABOUT SEIZURES IN HIE?. [Extracted from the article]

Neonatal seizures are the most prevalent and distinctive sign of neurologic dysfunction in early life and pose an immense challenge for clinicians. Improvements in neonatal care have increased the survival rate of extremely premature infants, considerably changing the spectrum of underlying etiologies, and instigating a gradual shift from mortality to morbidity. Recognizing neonatal seizures can be challenging due to variability in presentation but clinical features can often provide valuable clues about etiology. Yet, the majority of neonatal seizures are subclinical. Even though conventional electroencephalography (EEG) with simultaneous video detection of seizures still represents the diagnostic gold standard, continuous monitoring using a one- to two-channel amplitude-integrated EEG with concurrent unprocessed EEG can be crucial for early recognition and intervention. Furthermore, tremendous progress has been made in neuroimaging, and all infants with seizures should have a magnetic resonance imaging (MRI) to help identify the underlying etiology. While the majority of neonatal seizures are caused by hypoxic-ischemic events, stroke, hemorrhage, or infection, approximately 15% of patients will require more sophisticated algorithms for diagnostic workup, including metabolic and genetic screening. These recent developments have led to renew interest in the classification of neonatal seizures, which aim to help identify etiology and guide appropriate therapeutic and prognostic decisions. In this review, we outline recent progress made in the etiology, diagnosis, and treatment of neonatal seizures and highlight areas that deserve further research. [ABSTRACT FROM AUTHOR]