Acute symptomatic neonatal seizures, brain injury, and long-term outcome: The role of neuroprotective strategies

References

• Pisani F, Facini C, Bianchi E, et al. Incidence of neonatal seizures, perinatal risk factors for epilepsy and mortality after neonatal seizures in the province of Parma, Italy. Epilepsia. 2018;59(9):1764–1773.
   PubMed Web of Science ®Google Scholar
• Pisani F, Fusco C, Spagnoli C. Linking acute symptomatic neonatal seizures, brain injury and outcome in preterm infants. Epilepsy Behav. 2020;112:107406.
   PubMed Web of Science ®Google Scholar
• Vasudevan C, Levene M. Epidemiology and aetiology of neonatal seizures. Semin Fetal Neonatal Med. 2013;18(4):185–191.
   PubMed Web of Science ®Google Scholar
• Clancy RR, Legido A. The exact ictal and interictal duration of electroencephalographic neonatal seizures. Epilepsia. 1987;28(5):537–541.
   PubMed Web of Science ®Google Scholar
• Volpe JJ. Neonatal seizures: Current concepts and revised classification. Pediatrics. 1989;84:422–428.
   PubMed Web of Science ®Google Scholar
• Lombroso CT. Neonatal seizures: Historic note and present controversies. Epilepsia. 1996;37(s3):5–13.
   PubMedGoogle Scholar
• Mizrahi EM, Kellaway P. Characterization and classification of neonatal seizures. Neurology. 1987;37(12):1837–1844.
   PubMed Web of Science ®Google Scholar
• Nagarajan L, Palumbo L, Ghosh S. Classification of clinical semiology in epileptic seizures in neonates. Eur J Paediatr Neurol. 2012;16(2):118–125.
   PubMed Web of Science ®Google Scholar
• Pisani F, Pavlidis E. The role of electroencephalogram in neonatal seizure detection. Expert Rev Neurother. 2018;18:95-100.
   Google Scholar
• Rakshasbhuvankar A, Rao S, Palumbo L, et al. Amplitude integrated electroencephalography compared with conventional video eeg for neonatal seizure detection: A diagnostic accuracy study. J Child Neurol. 2017;32(9):815–822.
   PubMed Web of Science ®Google Scholar
• Nagarajan L, Ghosh S, Palumbo L. Ictal electroencephalograms in neonatal seizures: Characteristics and associations. Pediatr Neurol. 2011;45(1):11–16.
   PubMed Web of Science ®Google Scholar
• Murray DM, Boylan GB, Ali I, et al. Defining the gap between electrographic seizure burden, clinical expression and staff recognition of neonatal seizures. Arch Dis Child Fetal.Fetal Neonatal Ed. 2008;93:F187-91.
   Web of Science ®Google Scholar
• Malone A, Ryan CA, Fitzgerald A, et al. Interobserver agreement in neonatal seizure identification. Epilepsia. 2009;50(9):2097–2101.
   PubMed Web of Science ®Google Scholar
• McBride MC, Laroia N, Guillet R. Electrographic seizures in neonates correlate with poor neurodevelopmental outcome. Neurology. 2000;55(4):506–513.
   PubMed Web of Science ®Google Scholar
• Shellhaas RA, Chang T, Tsuchida T, et al. The american clinical neurophysiology society’s guideline on continuous electroencephalography monitoring in neonates. J Clin Neurophysiol. 2011;28(6):611–617.
   PubMed Web of Science ®Google Scholar
• Slaughter LA, Patel AD, Slaughter JL. Pharmacological treatment of neonatal seizures: a systematic review. J Child Neurol. 2013;28(3):351–364.
   PubMed Web of Science ®Google Scholar
• Sharpe C, Reiner GE, Davis SL, et al. NEOLEV2 INVESTIGATORS. LevetiracetamVersus Phenobarbital for Neonatal Seizures: A randomized controlled trial. Pediatrics. 2020;145(6):e20193182.
   PubMed Web of Science ®Google Scholar
• Painter MJ, Scher MS, Stein AD, et al. Phenobarbital compared with phenytoin for the treatment of neonatal seizures. N Engl J Med. 1999;341(7):485–489.
   PubMed Web of Science ®Google Scholar
• Spagnoli C, Seri S, Pavlidis E, et al. Phenobarbital for neonatal seizures: Response rate and predictors of refractoriness. Neuropediatrics. 2016;47(5):318–326.
   PubMedGoogle Scholar
• Glass HC, Shellhaas RA, Tsuchida TH, et al. Seizures in preterm neonates: A multicenterobservational cohort study. Pediatr Neurol. 2017;72(72):19–24.
   PubMedGoogle Scholar
• Boylan GB, Rennie JM, Pressler RM, et al. Phenobarbitone, neonatal seizures, and video- EEG. Arch Dis Child Fetal Neonatal Ed. 2002;86(3):F165–70.
   PubMed Web of Science ®Google Scholar
• Glass HC, Costarino AT, Stayer SA, et al. Outcomes for extremely premature infants. Anesth Analg. 2015;120(6):1337–1351.
   PubMed Web of Science ®Google Scholar
• Andreolli A, Turco EC, Pedrazzi G, et al. Incidence of epilepsy after neonatal seizures: Apopulation-based study. Neuroepidemiology. 2019;52(3–4):144–151.
   PubMed Web of Science ®Google Scholar
• Pisani F, Facini C, Pavlidis E, et al. Epilepsy after neonatal seizures: Literature review. Eur J Paediatr Neurol. 2015;19(1):6–14.
   PubMed Web of Science ®Google Scholar
• Pisani F, Barilli AM, Sisti L, et al. Preterm infants with video-EEG confirmed seizures: Outcome at 30 months of age. Brain Dev. 2008;30(1):20–30.
   PubMed Web of Science ®Google Scholar
• Pisani F, Copioli C, Di Gioia C, et al. Neonatal seizures: Relation of ictal videoelectroencephalography findings with neurodevelopmental outcome. J Child Neurol. 2008;23:394–398.
   PubMed Web of Science ®Google Scholar
• Pisani F, Facini C, Pelosi A, et al. Neonatal seizures in preterm newborns: A predictive model for outcome. Eur J Paediatr Neurol. 2016;20(2):243–251.
   PubMed Web of Science ®Google Scholar
• Dwivedi D, Lin N, Venkatesan C, et al. Clinical, neuroimaging, and electrographicpredictors of phenobarbital failure in newborns with hypoxic ischemic encephalopathy and seizures. J Child Neurol. 2019;34(8):458–463.
   PubMed Web of Science ®Google Scholar
• Pisani F, Sisti L, Seri S. A scoring system for early prognostic assessment after neonatal seizures. Pediatrics. 2009;124(4):580–587.
   PubMed Web of Science ®Google Scholar
• Garfinkle J, Shevell MI. Prognostic factors and development of a scoring system for outcome of neonatal seizures in term infants. Eur J Paediatr Neurol. 2011;15(3):222–229.
   PubMed Web of Science ®Google Scholar
• Johnston MV, Fatemi A, Wilson MA, et al. Treatment advances in neonatal neuroprotection and neurointensive care. Lancet Neurol. 2011;10(4):372–382.
   PubMed Web of Science ®Google Scholar
• Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33(10):696–705.
   PubMedGoogle Scholar
• Hope PL, Costello AM, Cady EB, et al. Cerebral energy metabolism studied with phosphorus NMR spectroscopy in normal and birth-asphyxiated infants. Lancet. 1984;2(8399):366–370.
   PubMed Web of Science ®Google Scholar
• Hope PL, Reynolds EO. Investigation of cerebral energy metabolism in newborn infants by phosphorus nuclear magnetic resonance spectroscopy. Clin Perinatol. 1985;12:261–275.
   PubMed Web of Science ®Google Scholar
• Ferriero DM. Neonatal brain injury. N Engl J Med. 2004;351(19):1985–1995.
   PubMed Web of Science ®Google Scholar
• Johnston MV. Excitotoxicity in perinatal brain injury. Brain Pathol. 2005;15(3):234–240.
   PubMed Web of Science ®Google Scholar
• Johnston MV, Trescher WH, Ishida A, et al. Neurobiology of hypoxic-ischemic injury in the developing brain. Pediatric Res. 2001;49(6):735–741.
   PubMed Web of Science ®Google Scholar
• Ben-Ari Y, Holmes GL. Effects of seizures on developmental processes in the immature brain. Lancet Neurol. 2006;5(12):1055–1063.
   PubMed Web of Science ®Google Scholar
• Jensen FE. The role of glutamate receptor maturation in perinatal seizures and brain injury. Int J Dev Neurosci. 2002;20(3–5):339–347.
   PubMed Web of Science ®Google Scholar
• Volpe JJ. Brain injury in premature infants: A complex amalgam of destructive and developmental disturbances. Lancet Neurol. 2009;8(1):110–124.
   PubMed Web of Science ®Google Scholar
• Kidokoro H, Anderson PJ, Doyle LW, et al. Brain injury and altered brain growth in preterm infants: Predictors and prognosis. Pediatrics. 2014;134(2):e444–53.
   PubMed Web of Science ®Google Scholar
• Vesoulis ZA, Mathur AM, Autoregulation C, et al. the Transitioning Premature Infant. Front Pediatr. 2017;5:64.
   PubMed Web of Science ®Google Scholar
• Lein ES, Finney EM, McQuillen PS, et al. Subplate neuron ablation alters neurotrophin expression and ocular dominance column formation. Proc Natl Acad Sci USA. 1999;96(23):13491–13495.
   PubMed Web of Science ®Google Scholar
• McQuillen PS, Sheldon RA, Shatz CJ, et al. Selective vulnerability of subplate neurons after early neonatal hypoxiaischemia. J Neurosci. 2003;23(8):3308–3315.
   PubMed Web of Science ®Google Scholar
• Fleiss B, Tann CJ, Degos V, et al. Inflammation-induced sensitization of the brain in term infants. Dev Med Child Neurol. 2015;57:17–28.
   PubMed Web of Science ®Google Scholar
• Pisani F, Cerminara C, Fusco C, et al. Neonatal status epilepticus vs recurrent neonatal seizures: Clinical findings and outcome. Neurology. 2007;69:2177–2185.
   PubMed Web of Science ®Google Scholar
• Nunes ML, Yozawitz EG, Zuberi S, et al. Neonatal seizures: Is there a relationship between ictal electroclinical features and etiology? A critical appraisal based on a systematic literature review. Epilepsia Open. 2019;4(1):10–29.
   PubMedGoogle Scholar
• Glass HC, Shellhaas RA, Wusthoff CJ, et al. Contemporary profile of seizures in neonates: A prospective cohort study. J Pediatr. 2016;174:98–103.
   PubMed Web of Science ®Google Scholar
• Pavlidis E, Spagnoli C, Pelosi A, et al. Neonatal status epilepticus: Differences between preterm and term newborns. Eur J Paediatr Neurol. 2015;19(3):314–319.
   PubMed Web of Science ®Google Scholar
• Herman ST. Epilepsy after brain insult: Targeting epileptogenesis. Neurology. 2002;59(Issue 9, Supplement 5):S21–26.
   PubMed Web of Science ®Google Scholar
• Harris ML, Malloy KM, Lawson SN, et al. Standardized treatment of neonatal status epilepticus improves outcome. J Child Neurol. 2016;31(14):1546–1554.
   PubMed Web of Science ®Google Scholar
• De Haan TR, Langeslag J, van der Lee JH, et al. A systematic review comparing neurodevelopmental outcome in term infants with hypoxic and vascular brain injury with and without seizures. BMC Pediatr. 2018;18(1):147.
   PubMedGoogle Scholar
• Kharoshankaya L, Stevenson NJ, Livingstone V, et al. Seizure burden and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy. Dev Med Child Neurol. 2016;58(12):1242–1248.
   PubMed Web of Science ®Google Scholar
• Fox CK, Mackay MT, Dowling MM, et al. Prolonged or recurrent acute seizures after pediatric arterial ischemic stroke are associated with increasing epilepsy risk. Dev Med Child Neurol. 2017;59(1):38–44.
   PubMed Web of Science ®Google Scholar
• van Rooij LG, Toet MC, van Huffelen AC, et al. Effect of treatment of subclinical neonatal seizures detected with aEEG: Randomized, controlled trial. Pediatrics. 2010;125(2):e358–66.
   PubMed Web of Science ®Google Scholar
• Glass HC, Glidden D, Jeremy RJ, et al. Clinical neonatal seizures are independently associated with outcome in infants at risk for hypoxic-ischemic brain injury. J Pediatr. 2009;155(3):318–323.
   PubMed Web of Science ®Google Scholar
• Ramantani G, Schmitt B, Plecko B, et al. Neonatal Seizures-Are We there Yet? Neuropediatrics. 2019;50(5):280–293 .
   PubMed Web of Science ®Google Scholar
• Pisani F, Pavlidis E. What is new: Talk about status epilepticus in the neonatal period. Eur J Paediatr Neurol. 2018;22:757-762..
   Web of Science ®Google Scholar
• Perlman JM, Volpe JJ. Seizures in the preterm infant: Effects on cerebral blood flow velocity, intracranial pressure, and arterial blood pressure. J Pediatr. 1983;102(2):288‐93.
   PubMed Web of Science ®Google Scholar
• Boylan GB, Panerai RB, Rennie JM, et al. Cerebral blood flow velocity during neonatal seizures. Arch Dis Child Fetal Neonatal Ed. 1999;80(2):F105‐F110.
   PubMed Web of Science ®Google Scholar
• Shuhaiber H, Bolton S, Alfonso I, et al. Cerebral regional oxygen fluctuations and decline during clinically silent focal electroencephalographic seizures in a neonate. J Child Neurol. 2004;19:539‐540.
   Web of Science ®Google Scholar
• Boylan GB, Young K, Panerai RB, et al. Dynamic cerebral autoregulation in sick newborn infants. Pediatr Res. 2000;48(1):12‐7.
   PubMed Web of Science ®Google Scholar
• Pourcyrous M, Basuroy S, Tcheranova D, et al. Brain-derived circulating endothelial cells in peripheral blood of newborn infants with seizures: A potential biomarker for cerebrovascular injury. Physiol Rep. 2015;3(3):e12345.
   PubMed Web of Science ®Google Scholar
• Murray DM, Boylan GB, Fitzgerald AP, et al. Persistent lactic acidosis in neonatal hypoxic-ischaemic encephalopathy correlates with EEG grade and electrographic seizure burden. Arch Dis Child Fetal Neonatal Ed. 2008;93(3):F183–6.
   PubMed Web of Science ®Google Scholar
• Fernandez F, Verdu A, Quero J, et al. Cerebrospinal fluid lactate levels in term infants with perinatal hypoxia. Pediatr Neurol. 1986;2(1):39–42.
   PubMedGoogle Scholar
• Hanrahan JD, Cox IJ, Azzopardi D, et al. Relation between proton magnetic resonance spectroscopy within 18 hours of birth asphyxia and neurodevelopment at 1 year of age. Dev Med Child Neurol. 1999;41(2):76–82.
   PubMed Web of Science ®Google Scholar
• Hanrahan JD, Cox IJ, Edwards AD, et al. Persistent increases in cerebral lactate concentration after birth asphyxia. Pediatr Res. 1998;44(3):304–311.
   PubMed Web of Science ®Google Scholar
• Zimmermann A, Domoki F, Bari F. Seizure-induced alterations in cerebrovascular function in the neonate. Dev Neurosci. 2008;30(5):293‐305.
   PubMed Web of Science ®Google Scholar
• Miller SP, Weiss J, Barnwell A, et al. Seizure- associated brain injury in term newborns with perinatal asphyxia. Neurology. 2002;58(4):542–548.
   PubMed Web of Science ®Google Scholar
• Wirrell EC. Neonatal seizures: To treat or not to treat? Semin Pediatr Neurol. 2005;12(2):97–105.
   PubMedGoogle Scholar
• Ikeda T, Murata Y, Quilligan EJ, et al. Foetal heart rate patterns in post-asphyxiated foetal lambs with brain damage. Am J Obstet Gynecol. 1998;179(5):1330–1337.
   Google Scholar
• Yager JY, Armstrong EA, Mujashita H, et al. Prolonged neonatal seizures exacerbate hypoxic-ischaemic brain damage: Correlation with cerebral energy metabolism and excitatory amino acid release. Dev Neurosci. 2002;24(5):367–381.
   PubMed Web of Science ®Google Scholar
• Zhang G, Raol YH, Hsu FC, et al. Effects of status epilepticus on hippocampal GABAA receptors are age-dependent. Neuroscience. 2004;125(2):299–303.
   PubMed Web of Science ®Google Scholar
• Zhang G, Raol YS, Hsu FC, et al. Long-term alterations in glutamate receptor and transporter expression following early-life seizures are associated with increased seizure susceptibility. J Neurochem. 2004;88(1):91–101.
   PubMed Web of Science ®Google Scholar
• McCabe BK, Silveira DC, Cilio MR, et al. Reduced neurogenesis after neonatal seizures. J Neurosci. 2001;21(6):2094–2103.
   PubMed Web of Science ®Google Scholar
• Liu Z, Yang Y, Silveira DC, et al. Consequences of recurrent seizures during early brain development. Neuroscience. 1999;92(4):1443–1454.
   PubMed Web of Science ®Google Scholar
• Holmes GL, Gairsa JL, Chevassus-Au-Louis N, et al. Consequences of neonatal seizures in the rat: morphological and behavioral eff ects. Ann Neurol. 1998;44(6):845–857.
   PubMed Web of Science ®Google Scholar
• Holmes GL, Sarkisian M, Ben-Ari Y, et al. Mossy fiber sprouting after recurrent seizures during early development in rats. J Comp Neurol. 1999;404:537–553.
   PubMed Web of Science ®Google Scholar
• Bickler PE, Gallego SM, Hansen BM. Developmental changes in intracellular calcium regulation in rat cerebral cortex during hypoxia. J Cereb Blood Flow Metab. 1993;13(5):811–819.
   PubMed Web of Science ®Google Scholar
• Marks JD, Friedman JE, Haddad GG. Vulnerability of CA1 neurons to glutamate is developmentally regulated. Brain Res Dev Brain Res. 1996;97(2):194–206.
   PubMedGoogle Scholar
• Patel M, Li QY. Age dependence of seizure-induced oxidative stress. Neuroscience. 2003;118(2):431–437.
   PubMed Web of Science ®Google Scholar
• Stafstrom CE. Mother’s milk protects the immature brain from seizure-induced cell death. Epilepsy Curr. 2003;3(4):144–145.
   PubMedGoogle Scholar
• Parfenova H, Leffler CW, Basuroy S, et al. Antioxidant roles of heme oxygenase, carbon monoxide, and bilirubin in cerebral circulation during seizures. J Cereb Blood Flow Metab. 2012;32(6):1024–1034.
   PubMed Web of Science ®Google Scholar
• Volpe JJ. Dysmaturation of premature brain: Importance, cellular mechanisms, and potential interventions. Pediatr Neurol. 2019;95:42–66.
   PubMed Web of Science ®Google Scholar
• Ghosh S. Development of the neonatal cerebral cortex. In: Nagarajan L, editor. Neonatal seizures. Current management and future challenges. Mc Keith Press; 2016:1-11.
   Google Scholar
• Wyckoff MH, Aziz K, Escobedo MB, et al. Part 13: Neonatal resuscitation: 2015 American heart association guidelines update for cardiopulmonary resuscitation and emergency cardiovascular care. Circulation. 2015;132(18 suppl 2):S543–S560.
   PubMed Web of Science ®Google Scholar
• Azzopardi D, Strohm B, Marlow N, et al. TOBY Study Group. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med. 2014;371:140–149.
   PubMed Web of Science ®Google Scholar
• Guillet R, Edwards AD, Thoresen M, et al. Seven- to eight-year follow-up of the CoolCap trial of head cooling for neonatal encephalopathy. Pediatr Res. 2012;71(2):205–209.
   PubMed Web of Science ®Google Scholar
• Edwards AD, Brocklehurst P, Gunn AJ, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: Synthesis and meta-analysis of trial data. BMJ. 2010;340(feb09 3):c363.
   PubMedGoogle Scholar
• Liu X, Jary S, Cowan F, et al. Reduced infancy and childhood epilepsy following hypothermia-treated neonatal encephalopathy. Epilepsia. 2017;58(11):1902.
   PubMed Web of Science ®Google Scholar
• Gunn AJ, Thoresen M. Hypothermic neuroprotection. NeuroRx. 2006;3(2):154–169.
   PubMedGoogle Scholar
• Jacobs SE, Berg M, Hunt R, et al. Cooling for newborns with hypoxic-ischemic encephalopathy. Cochrane Database Syst Rev. 2013;1:CD003311.
   PubMed Web of Science ®Google Scholar
• Shah PS. Hypothermia: A systematic review and meta-analysis of clinical trials. Semin Fetal Neonatal Med. 2010;15:238-46..
   PubMed Web of Science ®Google Scholar
• Low E, Boylan GB, Mathieson SR, et al. Cooling and seizure burden in term neonates: An observational study. Arch Dis Child Fetal Neonatal Ed. 2012;97(4):F267–F272.
   PubMed Web of Science ®Google Scholar
• Srinivasakumar P, Zempel J, Wallendorf M, et al. Therapeutic hypothermia in neonatal hypoxic ischemic encephalopathy: Electrographic seizures and magnetic resonance imaging evidence of injury. J Pediatr. 2013;163(2):465–470.
   PubMed Web of Science ®Google Scholar
• Harbert MJ, Tam EW, Glass HC, et al. Hypothermia is correlated with seizure absence in perinatal stroke. J Child Neurol. 2011;26(9):1126–1130.
   PubMed Web of Science ®Google Scholar
• Orbach SA, Bonifacio SL, Kuzniewicz MW, et al. Lower incidence of seizure among neonates treated with therapeutic hypothermia. J Child Neurol. 2014;29(11):1502–1507.
   PubMed Web of Science ®Google Scholar
• Thoresen M, Satas S, Løberg EM, et al. Twenty-four hours of mild hypothermia in unsedated newborn pigs starting after a severe global hypoxicischemic insult is not neuroprotective. Pediatr Res. 2001;50(3):405–411.
   PubMed Web of Science ®Google Scholar
• Roelfsema V, Bennet L, George S, et al. Window of opportunity of cerebral hypothermia for post-ischemic white matter injury in the near-term fetal sheep. J Cereb Blood Flow Metab. 2004;24(8):877–886.
   PubMed Web of Science ®Google Scholar
• Hammerman C, Kaplan M. Ischemia and reperfusion injury. The ultimate pathophysiologic paradox. Clin Perinatol. 1998;25(3):757–777.
   PubMed Web of Science ®Google Scholar
• Smit E, Liu X, Jary S, et al. Cooling neonates who do not fulfil the standard cooling criteria - short- and longterm outcomes. Acta Paediatr. 2015;104(2):138–145.
   PubMed Web of Science ®Google Scholar
• Herrera TI, Edwards L, Malcolm WF, et al. Outcomes of preterm infants treated with hypothermia for hypoxic-ischemic encephalopathy. Early Hum Dev. 2018;125:1–7.
   PubMed Web of Science ®Google Scholar
• Rao R, Trivedi S, Vesoulis Z, et al. Safety and short-term outcomes of therapeutic hypothermia in preterm neonates 34-35 weeks gestational age with hypoxic-ischemic encephalopathy. J Pediatr. 2017;183:37–42.
   PubMed Web of Science ®Google Scholar
• Lee JK, Poretti A, Perin J, et al. Optimizing cerebral autoregulation may decrease neonatal regional hypoxic-ischemic brain injury. Dev Neurosci. 2017;39(1–4):248–256.
   PubMed Web of Science ®Google Scholar
• Solevåg AL, Schmölzer GM, Cheung PY. Novel interventions to reduce oxidative- stress related brain injury in neonatal asphyxia. Free Radic Biol Med. 2019;142:113–122.
   PubMed Web of Science ®Google Scholar
• Palmer C, Towfighi J, Roberts RL, et al. Allopurinol administered after inducing hypoxia-ischemia reduces brain injury in 7-day-old rats. Pediatr Res. 1993;33:405–411.
   PubMed Web of Science ®Google Scholar
• Van Bel F, Shadid M, Moison RM, et al. Effect of allopurinol on postasphyxial free radical formation, cerebral hemodynamics, and electrical brain activity. Pediatrics. 1998;101(2):185.
   PubMed Web of Science ®Google Scholar
• Gunes T, Ozturk MA, Koklu E, et al. Effect of allopurinol supplementation on nitric oxide levels in asphyxiated newborns. Pediatr Neurol. 2007;36(1):17–24.
   PubMed Web of Science ®Google Scholar
• Kaandorp JJ, Van Bel F, Veen S, et al. Long-term neuroprotective effects of allopurinol after moderate perinatal asphyxia: Follow-up of two randomised controlled trials. Arch Dis Child Fetal Neonatal Ed. 2012;97:F162-6.
   PubMed Web of Science ®Google Scholar
• Klumper J, Kaandorp JJ, Schuit E, et al. Behavioral and neurodevelopmental outcome of children after maternal allopurinol administration during suspected fetal hypoxia: 5-Year follow up of the ALLO-trial. PLoS One. 2018;13(8):e0201063.
   PubMed Web of Science ®Google Scholar
• Azzopardi D, Robertson NJ, Kapetanakis A, et al. Anticonvulsant effect of xenon on neonatal asphyxial seizures. Arch Dis Child Fetal Neonatal Ed. 2013;98(5):F437–9.
   PubMed Web of Science ®Google Scholar
• Goldenberg RL, Rouse DJ. Preterm birth, cerebral palsy and magnesium. Nat Med. 1997;3(2):146–147.
   PubMed Web of Science ®Google Scholar
• Nowak L, Bregestovski P, Ascher P. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984;307(5950):462–465.
   PubMed Web of Science ®Google Scholar
• Bhat MA, Charoo BA, Bhat JI, et al. Magnesium sulfate in severe perinatal asphyxia: A randomized, placebo-controlled trial. Pediatrics. 2009;123(5):e764–9.
   PubMed Web of Science ®Google Scholar
• Khashaba MT, Shouman BO, Shaltout AA, et al. Excitatory amino acids and magnesium sulfate in neonatal asphyxia. Brain Dev. 2006;28(6):375–379.
   PubMed Web of Science ®Google Scholar
• Ichiba H, Yokoi T, Tamai H, et al. Neurodevelopmental outcome of infants with birth asphyxia treated with magnesium sulfate. Pediatr Int. 2006;48(1):70–75.
   PubMed Web of Science ®Google Scholar
• Gathwala G, Khera A, Singh J, et al. Magnesium for neuroprotection in birth asphyxia.
   Google Scholar
• Groenendaal F, Rademaker CM, Toet MC, et al. Effects of magnesium sulphate on amplitude-integrated continuous EEG in asphyxiated term neonates. Acta Paediatr. 2002;91(10):1073–1077.
   PubMed Web of Science ®Google Scholar
• Tagin M, Shah PS, Lee KS. Magnesium for newborns with hypoxic-ischemic encephalopathy: A systematic review and meta-analysis. J Perinatol. 2013;33(9):663–669.
   PubMed Web of Science ®Google Scholar
• Jung EJ, Byun JM, Kim YN, et al. Antenatal magnesium sulfate for both tocolysis and fetal neuroprotection in premature rupture of the membranes before 32 weeks’ gestation. J Matern Fetal Neonatal Med. 2018;31(11):1431–1441.
   PubMed Web of Science ®Google Scholar
• Alonso-Alconada D, Alvarez A, Arteaga O, et al. Neuroprotective effect of melatonin: a novel therapy against perinatal hypoxia-ischemia. Int J Mol Sci. 2013;14(5):9379–9395.
   PubMed Web of Science ®Google Scholar
• Reiter RJ, Tan DX, Osuna C, et al. Actions of melatonin in the reduction of oxidative stress: A review. J Biomed Sci. 2000;7:444–458.
   PubMed Web of Science ®Google Scholar
• Fulia F, Gitto E, Cuzzocrea S, et al. Increased levels of malondialdehyde and nitrite/nitrate in the blood of asphyxiated newborns: Reduction by melatonin. J Pineal Res. 2001;31(4):343–349.
   PubMed Web of Science ®Google Scholar
• Radogna F, Diederich M, Ghibelli L. Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol. 2010;80(12):1844–1852.
   PubMed Web of Science ®Google Scholar
• Mayo JC, Sainz RM, Tan DX, et al. Antiinflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5- methoxykynuramine (AFMK) and N1-acetyl-5- methoxykynuramine (AMK), in macrophages. J Neuroimmunol. 2005;165(1–2):139–149.
   PubMed Web of Science ®Google Scholar
• Kaur C, Sivakumar V, Lu J, et al. Melatonin attenuates hypoxia-induced ultrastructural changes and increased vascular permeability in the developing hippocampus. Brain Pathol. 2008;18:533–547.
   PubMed Web of Science ®Google Scholar
• Aly H, Elmahdy H, El-Dib M, et al. Melatonin use for neuroprotection in perinatal asphyxia: A randomized controlled pilot study. J Perinatol. 2015;35(3):186–191.
   PubMed Web of Science ®Google Scholar
• Jantzie LL, Miller RH, Robinson S. Erythropoietin signaling promotes oligodendrocyte development following prenatal systemic hypoxic-ischemic brain injury. Pediatr Res. 2013;74(6):658–667.
   PubMed Web of Science ®Google Scholar
• Felderhoff-Mueser U, Bittigau P, Sifringer M, et al. causes cell death in the developing brain. Neurobiol Dis. 2004;17(2):273–282.
   PubMed Web of Science ®Google Scholar
• Brehmer F, Bendix I, Prager S, et al. Interaction of inflammation and hyperoxia in a rat model of neonatal white matter damage. PLoS One. 2012;7:1–13.
   Web of Science ®Google Scholar
• Gerstner B, DeSilva TM, Genz K, et al. Hyperoxia causes maturation-dependent cell death in the developing white matter. J Neurosci. 2008;28(5):1236–1245.
   PubMed Web of Science ®Google Scholar
• Serdar M, Herz J, Kempe K, et al. Fingolimod protects against neonatal white matter damage and long-term cognitive deficits caused by hyperoxia. Brain Behav Immun. 2016;52:106–119.
   PubMed Web of Science ®Google Scholar
• Hoeber D, Sifringer M, van de Looij Y, et al. Erythropoietin Restores Long-Term.
   Google Scholar
• Juul SE, McPherson RJ, Bauer LA, et al. A phase I/II trial of high-dose erythropoietin in extremely low birth weight infants: pharmacokinetics and safety. Pediatrics. 2008;122(2):383–391.
   PubMed Web of Science ®Google Scholar
• Fauchère J-C, Dame C, Vonthein R, et al. An approach to using recombinant erythropoietin for neuroprotection in very preterm infants. Pediatrics. 2008;122(2):375–382.
   PubMed Web of Science ®Google Scholar
• Rogers EE, Bonifacio SL, Glass HC, et al. Erythropoietin and hypothermia for hypoxic-ischemic encephalopathy. Pediatr Neurol. 2014;51(5):657–662.
   PubMed Web of Science ®Google Scholar
• McAdams RM, McPherson RJ, Mayock DE, et al. Outcomes of extremely low birth weight infants given early high-dose erythropoietin. J Perinatol. 2013;33(3):226–230.
   PubMed Web of Science ®Google Scholar
• Leuchter RH, Gui L, Poncet A, et al., Association between early administration of high-dose erythropoietin in preterm infants and brain MRI abnormality at term-equivalent age. JAMA. 312(8): 817–824. 2014.
   PubMed Web of Science ®Google Scholar
• Jakab A, Ruegger C, Bucher HU, et al. Swiss EPO neuroprotection trial group. network based statistics reveals trophic and neuroprotective effect of early high dose erythropoetin on brain connectivity in very preterm infants. Neuroimage Clin. 2019;22:101806.
   PubMed Web of Science ®Google Scholar
• Juul SE, Comstock BA, Wadhawan R, et al. PENUT trial consortium. a randomized trial of erythropoietin for neuroprotection in preterm infants. N Engl J Med. 2020;382:233–243.
   PubMed Web of Science ®Google Scholar
• Shingo T, Sorokan ST, Shimazaki T, et al. Erythropoietin regulates the in vitro and in vivo production of neuronal progenitors by mammalian forebrain neural stem cells. J Neurosci. 2001;21:9733–9743.
   PubMed Web of Science ®Google Scholar
• Osredkar D, Sall JW, Bickler PE, et al. Erythropoietin promotes hippocampal neurogenesis in in vitro models of neonatal stroke. Neurobiol Dis. 2010;38(2):259–265.
   PubMed Web of Science ®Google Scholar
• Gonzalez FF, McQuillen P, Mu D, et al. Erythropoietin enhances long-term neuroprotection and neurogenesis in neonatal stroke. Dev Neurosci. 2007;29(4–5):321–330.
   PubMed Web of Science ®Google Scholar
• Sola A, Wen T-C, Hamrick SEG, et al. Potential for protection and repair following injury to the developing brain: a role for erythropoietin? Pediatr Res. 2005;57:110R–7R.
   PubMed Web of Science ®Google Scholar
• Wang L, Zhang Z, Wang Y, et al. Treatment of stroke with erythropoietin enhances neurogenesis and angiogenesis and improves neurological function in rats. Stroke. 2004;35(7):1732–1737.
   PubMed Web of Science ®Google Scholar
• Gonzalez FF, Abel R, Almli CR, et al. Erythropoietin sustains cognitive function and brain volume after neonatal stroke. Dev Neurosci. 2009;31(5):403–411.
   PubMed Web of Science ®Google Scholar
• Larpthaveesarp A, Georgevits M, Ferriero DM, et al. Delayed erythropoietin therapy improves histological and behavioral outcomes after transient neonatal stroke. Neurobiol Dis. 2016;93:57–63.
   PubMed Web of Science ®Google Scholar
• Brion LP, Bell EF, Raghuveer TS. Vitamin E supplementation for prevention of morbidity and mortality in preterm infants. Cochrane Database Syst Rev. 2003;16(4):CD003665.
   Google Scholar
• Mathew OP. Apnea of prematurity: pathogenesis and management strategies. J Perinatol. 2011;31:302–310.
   PubMed Web of Science ®Google Scholar
• Rivkees SA, Wendler CC. Adverse and protective influences of adenosine on the newborn and embryo: Implications for preterm white matter injury and embryo protection. Pediatr Res. 2011;69:271-8.
   PubMed Web of Science ®Google Scholar
• Silva CG, Métin C, Fazeli W, et al. Adenosine receptor antagonists including caffeine alter fetal brain development in mice. Sci Transl Med. 2013;5(197):197ra104.
   PubMed Web of Science ®Google Scholar
• Fleiss B, Tann CJ, Degos V, et al. Inflammation-induced sensitization of the brain in term infants. Dev Med Child Neurol. 2015;57(Suppl 3):17–28.
   PubMedGoogle Scholar
• Fazeli W, Zappettini S, Marguet SL, et al. Early-life exposure to caffeine affects the construction and activity of cortical networks in mice. Exp Neurol. 2017;295:88–103.
   PubMed Web of Science ®Google Scholar
• Vesoulis ZA, McPherson C, Neil JJ, et al. Early high-dose caffeine increases seizure burden in extremely preterm neonates: A preliminary study. J Caffeine Res. 2016;6:101–107.
   PubMedGoogle Scholar
• Dix LML, van Bel F, Baerts W, et al. Effects of caffeine on the preterm brain: An observational study. Early Hum Dev. 2018;120:17–20.
   PubMed Web of Science ®Google Scholar
• Hoecker C, Nelle M, Poeschl J, et al. Caffeine impairs cerebral and intestinal blood flow velocity in preterm infants. Pediatrics. 2002;109(5):784–787.
   PubMed Web of Science ®Google Scholar
• Endesfelder S, Weichelt U, Schiller C, et al. Caffeine protects against anticonvulsant induced impaired neurogenesis in the developing rat brain. Neurotox Res. 2018;34:173–187.
   PubMed Web of Science ®Google Scholar
• Wagenaar N, de Theije CGM, de Vries LS, et al. Promoting neuroregeneration after perinatal arterial ischemic stroke: neurotrophic factors and mesenchymal stem cells. Pediatr Res. 2018;83(1–2):372–384.
   PubMed Web of Science ®Google Scholar
• Wei ZZ, Gu X, Ferdinand A, et al. Intranasal delivery of bone marrow mesenchymal stem cells improved neurovascular regeneration and rescued neuropsychiatric deficits after neonatal stroke in rats. Cell Transplant. 2015;;24:391-402.
   Web of Science ®Google Scholar
• Van Velthoven CTJ, Kavelaars A, van Bel F, et al. Mesenchymal stem cell transplantation changes the gene expression profile of the neonatal ischemic brain. Brain Behav Immun. 2011;25(7):1342–1348.
   PubMed Web of Science ®Google Scholar
• Stanne TM, Aberg ND, Nilsson S, et al. Low circulating acute brain-derived neurotrophic factor levels are associated with poor long-term functional outcome after ischemic stroke. Stroke. 2016;47(7):1943–1945.
   PubMed Web of Science ®Google Scholar
• El Shimi MS, Hassanein SMA, Mohamed MH, et al. Predictive value of vascular endothelial growth factor in preterm neonates with intraventricular haemorrhage. J Matern Fetal Neonatal Med. 2012;25(9):1586–1590.
   PubMed Web of Science ®Google Scholar
• Koehne P, Hochhaus F, Felderhoff-Mueser U, et al. Vascular endothelial growth factor and erythropoietin concentrations in cerebrospinal fluid of children with hydrocephalus. Childs Nerv Syst. 2002;18(3–4):137–141.
   PubMed Web of Science ®Google Scholar
• Imam SS, Gad GI, Atef SH, et al. Cord blood brain derived neurotrophic factor: Diagnostic and prognostic marker in full-term newborns with perinatal asphyxia. Pak J Biol Sci. 2009;12(23):1498–1504.
   PubMedGoogle Scholar
• Cotten CM, Murtha AP, Goldberg RN, et al. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr. 2014;164(973):e1–9.e1.
   Google Scholar
• Shimotake J, Derugin N, Wendland M, et al. Vascular endothelial growth factor receptor-2 inhibition promotes cell death and limits endothelial cell proliferation in a neonatal rodent model of stroke. Stroke. 2010;41(2):343–349.
   PubMed Web of Science ®Google Scholar
• Kim ES, Ahn SY, Im GH, et al. Human umbilical cord blood-derived mesenchymal stem cell transplantation attenuates severe brain injury by permanent middle cerebral artery occlusion in newborn rats. Pediatr Res. 2012;72(3):277–284.
   PubMed Web of Science ®Google Scholar
• Scafidi J, Hammond TR, Scafidi S, et al., Intranasal epidermal growth factor treatment rescues neonatal brain injury. Nature. 2014; 506(7487): 230e234.
   Web of Science ®Google Scholar
• Wood TL, Loladze V, Altieri S, et al. Delayed IGF-1 administration rescues oligodendrocyte progenitors from glutamate-induced cell death and hypoxic-ischemic brain damage. Dev Neurosci. 2007;29(4–5):302e310.
   Web of Science ®Google Scholar
• Zhong J, Zhao L, Du Y, et al. Delayed IGF-1 treatment reduced long-term hypoxia-ischemia- induced brain damage and improved behavior recovery of immature rats. Neurol Res. 2009;31(5):483e89.
   Web of Science ®Google Scholar
• Oppliger B, Joerger-Messerli M, Mueller M, et al. Intranasal delivery of umbilical cord-derived mesenchymal stem cells preserves myelination in perinatal brain damage. Stem Cells Dev. 2016;25:1234-42.
   PubMed Web of Science ®Google Scholar
• Chen LX, Ma SM, Zhang P, et al. Neuroprotective effects of oligodendrocyte progenitor cell transplantation in premature rat brain following hypoxic-ischemic injury. PLoS One. 2015;10(3):e0115997.
   PubMed Web of Science ®Google Scholar
• El-Dib M, Soul JS. The use of phenobarbital and other anti-seizure drugs in newborns. Semin Fetal Neonatal Med. 2017;22(5):321–327.
   PubMed Web of Science ®Google Scholar
• Van Den Broek MPH, Groenendaal F, Toet MC, et al. Pharmacokinetics and clinical efficacy of phenobarbital in asphyxiated newborns treated with hypothermia: A thermopharmacological approach. Clin Pharmacokinet. 2012;51(10):671e9.
   Web of Science ®Google Scholar
• Shellhaas RA, Ng CM, Dillon CH, et al. Population pharmacokinetics of phenobarbital in infants with neonatal encephalopathy treated with therapeutic hypothermia. Pediatr Crit Care Med. 2013;14(2):194e202.
   Web of Science ®Google Scholar
• Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Nat Acad Sci U S A. 2002;99:15089e94.
   Web of Science ®Google Scholar
• Forcelli PA, Kim J, Kondratyev A, et al. Pattern of antiepileptic drug-induced cell death in limbic regions of the neonatal rat brain. Epilepsia. 2011;52(12):E207e11.
   Web of Science ®Google Scholar
• Kaushal S, Tamer Z, Opoku F, et al. Anticonvulsant drug-induced cell death in the developing white matter of the rodent brain. Epilepsia. 2016;57(5):727e34.
   Web of Science ®Google Scholar
• Hellstrom-Westas L, Boylan G, Agren J. Systematic review of neonatal seizure management strategies provides guidance on anti-epileptic treatment. Acta Paediatr. 2015;104(2):123e9.
   Web of Science ®Google Scholar
• Sarkar S, Barks JD, Bapuraj JR, et al. Does phenobarbital improve the effectiveness of therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy? J Perinatol. 2012;32(1):15e20.
   Web of Science ®Google Scholar
• Young L, Berg M, Soll R. Prophylactic barbiturate use for the prevention of morbidity and mortality following perinatal asphyxia. Cochrane Database Syst Rev. 2016;5:CD001240.
   Google Scholar
• Strasser K, Lueckemann L, Kluever V, et al. Dose-dependent effects of levetiracetam after hypoxia and hypothermia in the neonatal mouse brain. Brain Res. 2016;1646:116–124.
   PubMed Web of Science ®Google Scholar
• Arican P, Olgac Dundar N, Mete Atasever N, et al. Comparison of the neurocognitive outcomes in term infants treated with levetiracetam and phenobarbital monotherapy for neonatal clinical seizures. Seizure. 2020;80:71–77.
   PubMed Web of Science ®Google Scholar
• Rennie JM, de Vries LS, Blennow M, et al. Characterisation of neonatal seizures and their treatment using continuous EEG monitoring: A multicentre experience. Arch Dis Child Fetal Neonatal Ed. 2019;104(5):F493–F501.
   PubMed Web of Science ®Google Scholar
• Dzhala VI, Kuchibhotla KV, Glykys JC, et al. Progressive NKCC1-dependent neuronal chloride accumulation during neonatal seizures. J Neurosci. 2010;30(35):11745‐61.
   PubMed Web of Science ®Google Scholar
• Nardou R, Yamamoto S, Chazal G, et al. Neuronal chloride accumulation and excitatory GABA underlie aggravation of neonatal epileptiform activities by phenobarbital. Brain. 2011;134(4):987–1002.
   PubMedGoogle Scholar
• Fitzgerald MP, Kessler SK, Abend NS. Early discontinuation of antiseizure medications in neonates with hypoxic-ischemic encephalopathy. Epilepsia. 2017;58(6):1047–1053.
   PubMed Web of Science ®Google Scholar
• Guillet R, Kwon J. Seizure recurrence and developmental disabilities after neonatal seizures: outcomes are unrelated to use of phenobarbital prophylaxis. J Child Neurol. 2007;22(4):389–395.
   PubMed Web of Science ®Google Scholar
• Guillet R, Kwon JM. Prophylactic phenobarbital administration after resolution of neonatal seizures: survey of current practice. Pediatrics. 2008;122(4):731–735.
   PubMed Web of Science ®Google Scholar
• Dixon BJ, Reis C, Ho WM, et al. Neuroprotective strategies after neonatal hypoxic ischemic encephalopathy. Int J Mol Sci. 2015;16(9):22368–22401.
   PubMed Web of Science ®Google Scholar
• Follet PL, Deng W, Dai W, et al. Glutamate receptor-mediated oligodendrocyte toxicity in periventricular leukomalacia: A protective role for topiramate. J Neurosci. 2004;24:4412e20.
   Web of Science ®Google Scholar
• Schubert S, Brandl U, Brodhun M, et al. Neuroprotective effects of topiramate after hypoxia ischemia in newborn piglets. Brain Res. 2005;1058(1–2):129e36.
   Web of Science ®Google Scholar
• Liu Y, Barks JD, Xu G, et al. Topiramate extends the therapeutic window for hypothermia mediated neuroprotection after stroke in neonatal rats. Stroke. 2004;35(6):1460e5.
   Web of Science ®Google Scholar
• Filippi L, Fiorini P, Catarzi S, et al. Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI): A feasibility study. J Matern Fetal Neonatal Med. 2018;31(8):973–980.
   PubMed Web of Science ®Google Scholar
• Nuñez-Ramiro A, Benavente-Fernández I, Valverde E, et al. On behalf of the hypotop study group. topiramate plus cooling for hypoxic-ischemic encephalopathy: A randomized, controlled, multicenter, double-blinded trial. Neonatology. 2019;116:76–84.
   PubMed Web of Science ®Google Scholar
• Dzhala VI, Brumback AC, Staley KJ. Bumetanide enhances phenobarbital efficacy in a neonatal seizure model. Ann Neurol. 2008;63(2):222–235.
   PubMed Web of Science ®Google Scholar
• Cleary RT, Sun H, Huynh T, et al. Bumetanide enhances phenobarbital efficacy in a rat model of hypoxic neonatal seizures. PLoS One. 2013;8(3):e57148.
   PubMed Web of Science ®Google Scholar
• Pressler RM, Boylan GB, Marlow N, et al. Bumetanide for the treatment of seizures in newborn babies with hypoxic ischaemic encephalopathy (NEMO): an open-label, dose finding, and feasibility phase 1/2 trial. Lancet Neurol. 2015;14(5):469–477.
   PubMed Web of Science ®Google Scholar
• Brandt C, Seja P, Töllner K, et al. Bumepamine, a brain-permeant benzylamine derivative of bumetanide, does not inhibit NKCC1 but is more potent to enhance phenobarbital’s anti-seizure efficacy. Neuropharmacology. 2018;143:186–204.
   PubMed Web of Science ®Google Scholar
• Raol YH, Lapides DA, Keating JG, et al. A KCNQ channel opener for experimental neonatal seizures and status epilepticus. Ann Neurol. 2009;65(3):326–336.
   PubMed Web of Science ®Google Scholar
• Sampath D, Shmueli D, White AM, et al. Flupirtine effectively prevents development of acute neonatal seizures in an animal model of global hypoxia. Neurosci Lett. 2015;607:46–51.
   PubMed Web of Science ®Google Scholar
• Kristensen LV, Sandager-Nielsen K, Hansen HH. Kv7 (KCNQ) channel openers induce hypothermia in the mouse. Neurosci Lett. 2011;488(2):178–182.
   PubMed Web of Science ®Google Scholar
• Bouyssi-Kobar M, Du Plessis AJ, McCarter R, et al. Third trimester brain growth in preterm infants compared with in utero healthy fetuses. Pediatrics. 2016;138:e20161640.
   PubMed Web of Science ®Google Scholar
• Lasky RE, Williams AL. Noise and light exposures for extremely low birth weight newborns during their stay in the neonatal intensive care unit. Pediatrics. 2009;123(2):540–546.
   PubMed Web of Science ®Google Scholar
• Pineda RG, Neil J, Dierker D, et al. Alterations in brain structure and neurodevelopmental outcome in preterm infants hospitalized in different neonatal intensive care unit environments. J Pediatr. 2014;164(52–60.e2):52–60.e2.
   PubMedGoogle Scholar
• Schneider J, Duerden EG, Guo T, et al. Procedural pain and oral glucose in preterm neonates: brain development and sex-specific effects. Pain. 2018;159(3):515e525.
   Web of Science ®Google Scholar
• Kamino D, Studholme C, Liu M, et al. Postnatal polyunsaturated fatty acids associated with larger preterm brain tissue volumes and better outcomes. Pediatr Res. 2018;83(1):93e101.
   Web of Science ®Google Scholar
• Tam EW, Chau V, Barkovich AJ, et al. Early postnatal docosahexaenoic acid levels and improved preterm brain development. Pediatr Res. 2016;79:723e730.
   Web of Science ®Google Scholar
• Rose AL, Lombroso CT. A study of clinical, pathological, and electroencephalographic features in 137 full-term babies with a long-term follow-up. Pediatrics. 1970;45:404–425.
   PubMed Web of Science ®Google Scholar
• Pressler RM.From Channels to commissioning: a practical guide to epilepsy:Neonatal seizures;www.epilepsysociety.org.uk/sites/default/files/attachments/Chapter06Pressler2015.pdf.
   Google Scholar
• Castro Conde JR, Hernández Borges AA, Doménech Martínez E, et al. Midazolam in neonatal seizures with no response to phenobarbital. Neurology. 2005;64(5):876–879.
   PubMed Web of Science ®Google Scholar
• van Leuven K, Groenendaal F, Toet MC, et al. Midazolam and amplitude-integrated EEG in asphyxiated full-term neonates. Acta Paediatr. 2004;93(9):1221–1227.
   PubMed Web of Science ®Google Scholar
• Abend NS, Gutierrez-Colina AM, Monk HM, et al. Levetiracetam for treatment of neonatal seizures. J Child Neurol. 2011;26:465–470.
   PubMed Web of Science ®Google Scholar
• Weeke LC, Toet MC, van Rooij LG, et al. Lidocaine response rate in aEEG-confirmed neonatal seizures: Retrospective study of 413 full-term and preterm infants. Epilepsia. 2016;57(2):233–242.
   PubMed Web of Science ®Google Scholar
• Glass HC, Poulin C, Shevell MI. Topiramate for the treatment of neonatal seizures. Pediatr Neurol. 2011;44(6):439–442.
   PubMed Web of Science ®Google Scholar
• Riesgo R, Winckler MI, Ohlweiler L, et al. Treatment of refractory neonatal seizures with topiramate. Neuropediatrics. 2012;43(6):353–356.
   PubMed Web of Science ®Google Scholar