Treatment of seizures in the neonate: Guidelines and consensus-based recommendations-Special report from the ILAE Task Force on Neonatal Seizures


Ronit M. Pressler, Clinical Neuroscience, UCL-Great Ormond Street Institute of Child Health, London, UK.
Nicholas S. Abend, Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Stéphan Auvin, Department Medico-Universitaire Innovation Robert-Debré, Robert Debré Hospital, Public Hospital Network of Paris, Pediatric Neurology, University of Paris, Paris, France.
Geraldine Boylan, INFANT Research Centre, University College Cork, Cork, Ireland.
Francesco Brigo, Department of Neurology, Hospital of Merano (SABES-ASDAA), Merano, Italy.
Maria Roberta Cilio, Division of Pediatric Neurology, Saint-Luc University Hospital, and Institute of Neuroscience, Université Catholique de Louvain, Brussels, Belgium.
Linda S. De Vries, Department of Neonatology, University Medical Center, Utrecht, the Netherlands.
Maurizio Elia, Unit of Neurology and Clinical Neurophysiopathology, Oasi Research Institute-IRCCS, Troina, Italy.
Alberto Espeche, Department of Neurology, Hospital Materno Infantil, Salta, Argentina.
Cecil D. Hahn, Department of Pediatrics, Division of Neurology, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
Terrie Inder, Department of Pediatrics, Newborn Medicine, Children's Hospital of Orange County, University of California, Irvine, Irvine, California, USA.
Nathalie Jette, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Angelina Kakooza-Mwesige, Department of Pediatrics and Child Health, Makerere University College of Health Sciences, Kampala, Uganda.
Silke Mader, Scientific Affairs, European Foundation for the Care of Newborn Infants, Munich, Germany.
Eli M. Mizrahi, Departments of Neurology and Pediatrics, Baylor College of Medicine, Houston, Texas, USA.
Solomon L. Moshé, Isabelle Rapin Division of Child Neurology, Saul R. Korey Department of Neurology, Montefiore Medical Center, Bronx, New York, USA.
Lakshmi Nagarajan, Children's Neuroscience Service, Department of Neurology, Perth Children's Hospital and University of Western Australia, Nedlands, Western Australia, Australia.
Iris Noyman, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Magda L. Nunes, Pontifícia Universidade Católica do Rio Grande do Sul-PUCRS School of Medicine and the Brain Institute, Porto Alegre, Brazil.
Pauline Samia, Departments of Pediatrics and Child Health, Aga Khan University, Nairobi, Kenya.
Eilon Shany, Department of Neonatology, Soroka Medical Center, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.
Renée A. Shellhaas, Department of Neurology, Washington University, St. Louis, Missouri, USA.
Ann Subota, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Chahnez Charfi Triki, Child Neurology Department, Hedi Chaker Hospital, Sfax Medical School, University of Sfax, Sfax, Tunisia.
Tammy Tsuchida, Departments of Neurology and Pediatrics, Children's National Health System, George Washington University School of Medicine, Washington, District of Columbia, USA.
Kollencheri Puthenveettil Vinayan, Department of Pediatric Neurology, Amrita Institute of Medical Sciences, Cochin, India.
Jo M. Wilmshurst, Department of Paediatric Neurology, Red Cross War Memorial Children's Hospital, Neuroscience Institute, University of Cape Town, Cape Town, South Africa.
Elissa G. Yozawitz, Isabelle Rapin Division of Child Neurology, Saul R. Korey Department of Neurology, Montefiore Medical Center, Bronx, New York, USA.
Hans Hartmann, Clinic for Pediatric Kidney, Liver, and Metabolic Diseases, Hannover Medical School, Hannover, Germany.

Document Type

Journal Article

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Delphi; antiseizure medication; epilepsy; evidence-based guideline; neonate; provoked seizures


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.