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A seizure may be the first sign of neurological dysfunction and serious systemic disease. The potential etiologies are diverse and range from very serious brain injury to benign, age-limited genetic conditions. Because the underlying cause of the seizures may be an acute, potentially harmful, and treatable metabolic derangement (eg, hypoglycemia) or infection, early recognition, evaluation, and treatment are important.


Seizures occur more often during the first week of life than at any other time.1 The reported incidence ranges from 1 to 5 per 1000 newborns in developed countries.2, 3, and 4 The incidence is much higher in developing countries.5 Premature and low birth weight infants also have a higher incidence of seizures than term and normal weight newborns.4,6,7

Etiology of Seizures in the Neonate

The most common etiology of seizures in the neonate is a hypoxic-ischemic insult as a result of conditions such as perinatal asphyxia, cardiac disease, and respiratory distress. Other common causes include infections, cerebral dysgenesis, and stroke. Less-common etiologies are the benign epilepsy syndromes that present in the neonatal period. A large variety of rare genetic and metabolic conditions are associated with severe seizures and a poor long-term prognosis, although some are treatable. The most severe seizure disorders in neonates are caused by early infantile epileptic encephalopathy (EIEE; Otahara syndrome) and early myoclonic epilepsy (EME).8,9

Hypoxic-Ischemic Encephalopathy

Hypoxic-ischemic encephalopathy is the most common etiology of neonatal seizures. Approximately two-thirds of all neonatal seizures are a result of this cause.10 Both animal studies and human case studies showed that the frequency and severity of neonatal seizures in the setting of hypoxic-ischemic encephalopathy usually parallel that of the encephalopathy.11,12

Seizures caused by hypoxic encephalopathy usually manifest in the first 2 days of life.13 They are often persistent and difficult to control acutely. When they do come under control from a clinical perspective, they frequently persist on electroencephalogram (EEG). Seizures caused by an acute hypoxic insult are often transient, so seizure medication may only be needed in the short term. However, there is an independent long-term risk of epilepsy later in life. Approximately one-third of these infants will develop epilepsy.14



The organisms most commonly responsible for neonatal seizures during the first few days of life are β-hemolytic group B streptococci (GBS), Escherichia coli, and other gram-negative organisms reflecting maternal flora. Later-onset meningitis may be the result of community exposure as well.15 Seizures are among the common presenting signs of meningitis in the neonate, along with irritability, lethargy, poor feeding, poor tone, and apnea.16 Furthermore, seizures in the setting of neonatal meningitis are a concerning prognostic sign ...

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