Evaluation of the efficacy and safety of levetiracetam treatment for neonatal seizures in extremely preterm infants



Levetiracetam, Neonatal seizures, Preterm


Aim: Levetiracetam (LEV) is increasingly being used to treat seizures in the neonatal period. Data about using LEV in extremely preterm infants with seizures is insufficient and limited with only a handful studies. This study aimed to evaluate the efficacy and safety of LEV in the treatment of seizures in extremely preterm infants.
Methods: This retrospective cohort study was conducted on extremely premature newborns, those who were born ≤28 weeks of gestational age, and took their first intravenous dose of levetiracetam due to neonatal seizure before their 44th gestational week between September 2017-February 2019. Loading and maintenance dosage of LEV, previously used antiepileptic medications, response to treatment and side effects of LEV were recorded.
Results: Twenty extremely preterm neonates (9 males and 11 females) who received LEV were evaluated. Gestational ages ranged from 23 to 28 weeks, with a median of 26.5 weeks. Birth weights ranged from 520-1210 gr and 15 infants (75%) had extremely low birth weights. For the treatment of seizures, 12 patients (60 %) were initially started on levetiracetam as first-line therapy and eight patients (40%) were administered levetiracetam as a second or third-line antiepileptic drug. The efficiency of seizure control with LEV was 60 % (12/20) in all patients. The median LEV dose at the time seizure control was achieved was 40 mg/kg. No side effects were observed due to LEV treatment.
Conclusion: This study shows that LEV can be efficient and safe for seizure management in extremely preterm infants. Seizure control was better achieved when LEV was given as the first-line antiepileptic medication in extremely preterm infants.


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Ahrens S, Ream MA, Slaughter LA. Status Epilepticus in the Neonate: Updates in Treatment Strategies. Curr Treat Options Neurol. 2019;2:8-22.

Khan O, Cipriani C, Wright C, Crisp E, Kirmani B. Role of intravenous levetiracetam for acute seizure management in preterm neonates. Pediatr Neurol. 2013;49:340-3.

Booth D, Evans DJ. Anticonvulsants for neonates with seizures. Cochrane Database Syst Rev. 2004(4):CD004218.

Kurtom W, Courchia B, Pensirikul A, Sosenko I, Del-Moral T. Lack of response to treatment with levetiracetam in extreme preterm infants with seizures. J Perinatol. 2019;39:1480-4.

Ghosh S, Cabassa Miskimen AC, Brady J, Robinson MA, Zou B, Weiss M, et al. Neurodevelopmental outcomes at 9-14 months gestational age after treatment of neonatal seizures due to brain injury. Childs Nerv Syst. 2019;35:1571-8.

Ben-Ari Y, Holmes GL. Effects of seizures on developmental processes in the immature brain. Lancet Neurol. 2006;5:1055-63.

Pisani F, Facini C, Pelosi A, Mazzotta S, Spagnoli C, Pavlidis E. Neonatal seizures in preterm newborns: A predictive model for outcome. Eur J Paediatr Neurol. 2016;20:243-51.

Kohelet D, Shochat R, Lusky A, Reichman B, Israel Neonatal N. Risk factors for neonatal seizures in very low birthweight infants: population-based survey. J Child Neurol. 2004;19:123-8.

Han JY, Moon CJ, Youn YA, Sung IK, Lee IG. Efficacy of levetiracetam for neonatal seizures in preterm infants. BMC Pediatr. 2018;18:13-6.

Bittigau P, Sifringer M, Genz K, Reith E, Pospischil D, Govindarajalu S, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A. 2002;99:15089-94.

Spagnoli C, Seri S, Pavlidis E, Mazzotta S, Pelosi A, Pisani F. Phenobarbital for Neonatal Seizures: Response Rate and Predictors of Refractoriness. Neuropediatrics. 2016;47:318-26.

Kilicdag H, Daglioglu K, Erdogan S, Guzel A, Sencar L, Polat S, et al. The effect of levetiracetam on neuronal apoptosis in neonatal rat model of hypoxic ischemic brain injury. Early Hum Dev. 2013;89:355-60.

Falsaperla R, Vitaliti G, Mauceri L, Romano C, Pavone P, Motamed-Gorji N, et al. Levetiracetam in Neonatal Seizures as First-line Treatment: A Prospective Study. J Pediatr Neurosci. 2017;12:24-8.

Kreimer AM, Littrell RA, Gibson JB, Leung NR. Effectiveness of Levetiracetam as a First-Line Anticonvulsant for Neonatal Seizures. J Pediatr Pharmacol Ther. 2019;24:320-6.

Ozalkaya E, Topcuoglu S, Karatepe H, Tuten A, Gokmen T, Karatekin G. Efficacy of levetiracetam in premature infants: our experience and review of the literature. J Matern Fetal Neonatal Med. 2019;32:4093-6.

Favrais G, Ursino M, Mouchel C, Boivin E, Jullien V, Zohar S, et al. Levetiracetam optimal dose-finding as first-line treatment for neonatal seizures occurring in the con[ of hypoxic-ischaemic encephalopathy (LEVNEONAT-1): study protocol of a phase II trial. BMJ Open. 2019;9(1):e022739. doi: 10.1136/bmjopen-2018-022739.

Sharpe CM, Capparelli EV, Mower A, Farrell MJ, Soldin SJ, Haas RH. A seven-day study of the pharmacokinetics of intravenous levetiracetam in neonates: marked changes in pharmacokinetics occur during the first week of life. Pediatr Res. 2012;72:43-9.

Khan O, Chang E, Cipriani C, Wright C, Crisp E, Kirmani B. Use of intravenous levetiracetam for management of acute seizures in neonates. Pediatr Neurol. 2011;44:265-9.






Research Article

How to Cite

Mert MK, Tekin Orgun L. Evaluation of the efficacy and safety of levetiracetam treatment for neonatal seizures in extremely preterm infants. J Surg Med [Internet]. 2020 May 1 [cited 2023 Feb. 6];4(5):394-9. Available from: https://jsurgmed.com/article/view/724986