Short-Term Neurodevelopmental Outcome in Term Neonates Treated with Phenobarbital versus Levetiracetam: A Single-Center Experience

BACKGROUND: Phenobarbital (PB) has been traditionally used as the first-line treatment for neonatal seizures. More recently, levetiracetam (LEV) has been increasingly used as a promising newer antiepileptic medication for treatment of seizures in neonates. OBJECTIVES: The aim of our study was to compare the effect of PB vs. LEV on short-term neurodevelopmental outcome in infants treated for neonatal seizures. METHOD: This randomized, one-blind prospective study was conducted on term neonates admitted to the Neonatal Intensive Care Unit of S. Bambino Hospital, University Hospital "Policlinico-Vittorio Emanuele," Catania, Italy, from February 2016 to February 2018. Thirty term neonates with seizures were randomized to receive PB or LEV; the Hammersmith Neonatal Neurological Examination (HNNE) was used at baseline (T0) and again one month after the initial treatment (T1). RESULTS: We found a significantly positive HNNE score for the developmental outcomes, specifically tone and posture, in neonates treated with LEV. There was no significant improvement in the HNNE score at T1 in the neonates treated with PB. CONCLUSION: This study suggests a positive effect of levetiracetam on tone and posture in term newborns treated for neonatal seizures. If future randomized-controlled studies also show better efficacy of LEV in the treatment of neonatal seizures, LEV might potentially be considered as the first-line anticonvulsant in this age grou

Symptomatic seizures in preterm newborns: a review on clinical features and prognosis

Neonatal seizures are the most common neurological event in newborns, showing higher prevalence in preterm than in full-term infants. In the majority of cases they represent acute symptomatic phenomena, the main etiologies being intraventricular haemorrhage, hypoxic-ischemic encephalopathy, central nervous system infections and transient metabolic derangements.Current definition of neonatal seizures requires detection of paroxysmal EEG-changes, and in preterm newborns the incidence of electrographic-only seizures seems to be particularly high, further stressing the crucial role of electroencephalogram monitoring in this population. Imaging work-up includes an integration of serial cranial ultrasound and brain magnetic resonance at term-equivalent age. Unfavourable outcomes following seizures in preterm infants include death, neurodevelopmental impairment, epilepsy, cerebral palsy, hearing and visual impairment. As experimental evidence suggests a detrimental role of seizures per se in determining subsequent outcome, they should be promptly treated with the aim to reduce seizure burden and long-term disabilities. However, neonatal seizures show low response to conventional anticonvulsant drugs, and this is even more evident in preterm newborns, due to intrinsic developmental factors. As a consequence, as literature does not provide any specific guidelines, due to the lack of robust evidence, off-label medications are often administered in clinical practice

Neonatal Seizure;A Review

The occurrence of neonatal seizures may be the first and perhaps, the only clinical sign of a central nervous system (CNS) disorder in the newborn infant. Identifying the etiology for the neonatal seizures is/critical to prognosis and treatment. The most common etiology for neonatal seizures is hypoxic-ischemic encephalopathy. Seizures may indicate the presence of a potentially treatable etiology and should prompt an immediate evaluation to determine the precise cause and institute etiology-specific therapy.In this review article, we will discuss the etiology, classification, clinical features, diagnosis and the approaches to treatment of neonatal seizures. Key words: Neonate,Seizure,CNS, Anti-Epileptic drugs(AED'S

Neonatal seizures

In childhood, the risk for seizures is greatest in the neonatal period. Currently used therapies have limited efficacy. Although the treatment of neonatal seizures has not significantly changed in the past several decades, there has been substantial progress in understanding developmental mechanisms that influence seizure generation and responsiveness to anticonvulsants. This review includes an overview of current approaches to the diagnosis and treatment of neonatal seizures, identifies some of the critical factors that have limited progress, and highlights recent insights about the pathophysiology of neonatal seizures that may provide the foundation for better treatment. Ann Neurol 2007Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/57360/1/21167_ftp.pd

A survey of relative frequency of etiologies, time of onset, efficacy of drug therapy and risk factors for clinical neonatal seizures

Introduction: Seizure is a common condition in neonatal period and may become first feature of neurologic dysfunction. In most cases, diagnosis of neonatal seizure and its different etiologies are based on history, clinical manifestations and identification of risk factors. I conducted this study to evaluate relative frequency of etiologies, time of onset, efficacy of drug therapy and risk factors for clinical neonatal seizures. Methods and materials: Between March 2002 and March 2003, a cohort of 4632 live born neonates in Alavi hospital of Ardabil, Iran were assessed as a retrospective cross-sectional study. 79 of these infants have been diagnosed with clinical neonatal seizures which only 70 included in the study because of inadequate or low reliability of information in medical records. In first step, a descriptive study of relative frequency of neonatal seizures was performed, followed an analytical study of time of onset, efficacy of drug therapy and risk factors. Results: Hypoxic-ischemic encephalopathy was the most common etiology of neonatal seizures. Infections, acute metabolic disorders and intracranial hemorrhage were the next three important etiologies. The average time of onset in preterm infants was second day of life compared with term infants that was first day of life (P=0.021). In comparison with female infants, male infants were more affected with seizures and in light of efficacy of drug therapy, clinical seizures were mainly controlled with two antiepileptic drugs in preterms compared with terms whose clinical seizures were mainly controlled with one drug (P=0.005). Multivariate analysis using logistic regression showed that, birth weight less than 1500 gr (P<0.001) and male gender (P=0.012) were two significant risk factors for preterm infants. For term infants, significant risk factors included small birth weight for gestational age (P=0.001), birth by cesarean section (P=0.005), primiparity (P=0.01) and male gender (P=0.017). Conclusion and suggestion: This study confirmed relatively high frequency of HIE among different etiologies and the effect of low birth weight on the risk of clinical neonatal seizures in preterm and term infants. Because of high incidence of seizure in this hospital and increased risk of seizure among infants born by cesarean section and to primiparous mothers, further evaluation for assessing the role of these two factors is needed

Progeny, December 2003, Vol. 19, no. 4

This newsletter from The Department of Public Health about perinatal health care and statistics

A randomized controlled trial on comparison of phenobarbitone and levetiracetam for the treatment of neonatal seizures: pilot study

Background: Phenobarbitone is the most commonly used drug for treatment of neonatal seizures, irrespective of the cause of the seizures. However, there is concern about its adverse effects on brain, resulting in impairment of cognition and behaviour, and liver. So there is an urgent need for an alternative antiepileptic drug for treatment of neonatal seizures. Levetiracetam is a relatively new anticonvulsant. There are no randomized controlled trials about its use in neonates. This trial was designed with the objective to compare the efficacy of levetiracetam and phenobarbitone in the treatment of clinically apparent neonatal seizures in term and late preterm neonates.Methods: The study was designed as an open label randomized controlled trial. Study population included babies of >2 kg admitted in Neonatal Intensive Care Unit within 48 hours of birth with neonatal seizures due to perinatal asphyxia. If seizures persisted even after correction of hypoglycemia and hypocalcaemia, babies were randomized for intervention to either levetiracetam or phenobarbitone.Results: Clinically apparent seizures were controlled in only 23.3% neonates assigned to receive levetiracetam  as compared to 86.7% neonates assigned to receive phenobarbitone  (p<0.001).Conclusions: Present study demonstrated that levetiracetam is not as good as phenobarbitone in controlling neonatal seizures due to perinatal asphyxia in term and near term neonates. Also, it takes longer time than phenobarbitone in controlling clinical seizures. Superiority of phenobarbitone was observed both when given as a first line drug and after cross over.

Early changes in pro-inflammatory cytokine levels in neonates with encephalopathy are associated with remote epilepsy.

BackgroundNeonatal seizures are associated with adverse neurologic sequelae including epilepsy in childhood. Here we aim to determine whether levels of cytokines in neonates with brain injury are associated with acute symptomatic seizures or remote epilepsy.MethodsThis is a cohort study of term newborns with encephalopathy at UCSF between 10/1993 and 1/2000 who had dried blood spots. Maternal, perinatal/postnatal, neuroimaging, and epilepsy variables were abstracted by chart review. Logistic regression was used to compare levels of cytokines with acute seizures and the development of epilepsy.ResultsIn a cohort of 26 newborns with neonatal encephalopathy at risk for hypoxic ischemic encephalopathy with blood spots for analysis, diffuse alterations in both pro- and anti-inflammatory cytokine levels were observed between those with (11/28, 39%) and without acute symptomatic seizures. Seventeen of the 26 (63%) patients had &gt;2 years of follow-up and 4/17 (24%) developed epilepsy. Higher levels of pro-inflammatory cytokines IL-6 and TNF-α within the IL-1β pathway were significantly associated with epilepsy.ConclusionsElevations in pro-inflammatory cytokines in the IL-1β pathway were associated with later onset of epilepsy. Larger cohort studies are needed to confirm the predictive value of these circulating biomarkers

FAKTOR PROGNOSTIK MUNCULNYA PALSI SEREBRAL PADA ANAK DENGAN RIWAYAT KEJANG NEONATAL

Latar Belakang: Bayi dengan riwayat kejang ada kemungkinan untuk mengalami kerusakan otak. Kerusakan ini biasanya terjadi pada sistem limbik yang terdiri dari hipokampus, hipotalamus, girus cinguli, amygdala dan ganglia basalis serta daerah sekitar sistem limbik yaitu thalamus dan serebelum. Sehingga akan memicu terjadinya palsi serebral yang mengakibatkan keterbatasan aktivitas. Tujuan: Mengetahui faktor prognostik yang mempengaruhi kejadian palsi serebral pada dua tahun pertama kehidupan anak dengan riwayat kejang neonatus dan mengetahui free survival rate-nya saat usia 2 tahun. Metode: Penelitian ini menggunakan desain kohort retrospektif dengan menggunakan data dari rekam medik. Subjek penelitian dipilih dengan metode consecutive sampling yaitu bayi yang mengalami kejang neonatus periode Januari 2006 sampai Januari 2012 , setelah 2 tahun dilihat mengalami palsi serebral atau tidak. Analisis dengan uji Chi-square,uji Fisher exact, independent t-test, dan kaplann meier. Hasil: Didapatkan hasil faktor prognostik yang bermakna adalah lama persalinan (p : 0,024¥ ; OR: 9,625; 95%CI :2,136-43,364). Setelah dilakukan uji kaplann meier didapatkan hasil bahwa dari 50 neonatus yang mengalami kejang, 4% mengalami palsi serebral pada usia 24 bulan, 4% pada usia 25 bulan, 6% pada usia 26 bulan, 4% pada usia 28 bulan, 2% pada usia 29 bulan dan 2% pada usia 31 bulan. Kesimpulan: Lama persalinan merupakan faktor prognostik kejadian palsi serebral pada anak dengan riwayat kejang neonatus sedangkan usia gestasi, preeklamsi, jenis kelamin, skor apgar dan berat bayi lahir tidak. Free survival rate anak dengan riwayat kejang neonatus yang mengalamipalsiserebralsaatusia 2 tahunadalah 96%. Kata Kunci palsi serebral, kejang neonatus, lama persalinan, faktor prognostik