ARTICLE

Neonatal Seizures
Emily S. Stieren, MD, PhD,* Catherine A. Rottkamp, MD, PhD,* Amy R. Brooks-Kayal, MD†
*Division of Neonatology, Department of Pediatrics, University of California, Davis, Sacramento, CA
†
Department of Neurology, University of California, Davis, Sacramento, CA

PRACTICE GAP
Seizures are common in neonates with underlying brain injury.
Neonatologists need to recognize which infants are at risk for seizures and
implement and interpret neuromonitoring for those infants.
Neonatologists should be familiar with the basic diagnostic evaluation for
neonatal seizures, including laboratory testing. Recently published research
studies, reviews, and expert consensus guidelines provide consistent
recommendations for the pharmacologic treatment of neonatal seizures.
Neonatologists should also be aware of the long-term outcomes of
patients with neonatal seizures so that they can properly counsel families.

AUTHOR DISCLOSURES Dr Brooks-Kayal

serves as a director on the American OBJECTIVES After completing this article, readers should be able to:
Board of Psychiatry and Neurology. She
has also participated on Data Safety
Monitoring Boards or Advisory Boards for 1. Be familiar with the common etiologies and diagnostic evaluation for
NINDS Epilepsy Therapy Screening
neonatal seizures.
Program, NINDS PREVeNT Trial, and
Annals of Neurology as an Associate 2. Describe the most recent recommendations regarding the treatment of
Editor. Drs Stieren and Rottkamp have
disclosed no financial relationships
acute symptomatic neonatal seizures with antiseizure medication.
relevant to this article. This commentary 3. Explain the most recent evidence regarding the duration of therapy for
does not contain a discussion of an
unapproved/investigative use of a acute symptomatic neonatal seizures.
commercial product/device.

ABBREVIATIONS
ABSTRACT
Neonatal seizures are common among patients with acute brain injury or
aEEG amplitude-integrated
electroencephalography critical illness and can be difficult to diagnose and treat. The most common
ASM antiseizure medication etiology of neonatal seizures is hypoxic-ischemic encephalopathy, with
cEEG continuous
other common causes including ischemic stroke and intracranial
electroencephalography
CSF cerebrospinal fluid hemorrhage. Neonatal clinicians can use a standardized approach to
EEG electroencephalography patients with suspected or confirmed neonatal seizures that entails
GABA c-aminobutyric acid
HIE hypoxic-ischemic
laboratory testing, neuromonitoring, and brain imaging. The primary goals
encephalopathy of management of neonatal seizures are to identify the underlying cause,
ICH intracranial hemorrhage correct it if possible, and prevent further brain injury. This article reviews
IEM inborn error(s) of metabolism
ILAE International League Against
recent evidence-based guidelines for the treatment of neonatal seizures
Epilepsy and discusses the long-term outcomes of patients with neonatal seizures.
KCC2 potassium-chloride
cotransporter 2
MR magnetic resonance
MRI magnetic resonance imaging INTRODUCTION
ND neurodevelopmental
NKCC1 sodium-potassium-chloride The highest incidence of seizures across the lifespan is during the neonatal pe-
cotransporter 1 riod. The estimated incidence of neonatal seizures is 1 to 3 per 1,000 live births

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 for term infants and is considerably higher for preterm in- Receptors for glutamate, the primary excitatory transmit-
fants. (1)(2) Most seizures that manifest in the neonatal pe- ter, are overexpressed in the developing brain compared to
riod are acute provoked seizures, that is, they are associated the adult brain, and developmental regulation of glutamate
with acute brain pathology or systemic illness. The most receptor subunits leads to slower signaling kinetics and
common cause of provoked seizures in neonates is hypoxic- lower responsiveness to endogenous inhibition by magne-
ischemic encephalopathy (HIE), followed by stroke and intra- sium. (5) In addition, the primary inhibitory neurotrans-
cranial hemorrhage (ICH). (3) mitter in the adult brain, g-aminobutyric acid (GABA), can
Neonatal seizures can be difficult to diagnose because exert an excitatory effect in the neonatal brain because of
the clinical manifestations differ significantly from those age-related differences in the expression of chloride co-
seen in older children and adults. The relative paucity of transporters in the postsynaptic membrane (Fig 1). De-
myelin in the neonatal brain makes generalized seizures creased expression of the neuronal potassium-chloride
uncommon, and often there are no or very subtle clinical cotransporter 2 (KCC2), a chloride extruder, leads to unop-
correlates of electrographic seizures. The connectivity and posed action of the sodium-potassium-chloride cotransporter 1
neurotransmitter profile of the neonatal brain make it par- (NKCC1), resulting in the accumulation of chloride ions in
ticularly vulnerable to seizures and resistant to currently the intracellular space. In this scenario, stimulation of postsyn-
available antiseizure medications (ASMs). (4) aptic GABAA receptors leads to chloride efflux (rather than
Research has shown an association between neonatal influx) and depolarization, rather than hyperpolarization. The
seizures and long-term outcomes, including epilepsy, cog- overabundance of synaptic connections combined with the
nitive impairment, and cerebral palsy. It has been difficult predominance of excitatory neurotransmission in the imma-
to dissect whether these outcomes are direct results of the ture brain maximizes responsiveness and plasticity and also
seizure activity or consequences of the underlying etiology creates a relatively hyperexcitable state and increased propen-
of the seizures. However, there is an emerging consensus sity for epileptogenesis. Any disease process that leads to a
that neonatal seizures have a direct impact on the develop- disruption of cellular homeostasis in the central nervous sys-
ing brain by causing cell death and altering neuronal cir- tem can trigger seizures, and the primary goal of patient man-
cuitry during a critical window of development. Thus, agement is to identify the underlying cause and restore
recent research has focused on optimizing treatment strat- homeostasis.
egies for neonatal seizures. HIE remains the most common etiology of neonatal seiz-
ures, with seizures occurring in 40% to 60% of HIE pa-
ETIOLOGY AND DIAGNOSTIC EVALUATION tients. (6) HIE can result from birth asphyxia or any other
There are several features of the immature human brain process or event that causes severe or prolonged hypoxemia
that puts the neonatal period at the highest risk for seiz- or reduction in cerebral blood flow. Other relatively common
ures across the lifespan. At term gestational age, synaptic etiologies of acute provoked seizures in neonates are stroke,
and dendritic spine density in the brain is at its highest. ICH (eg, subarachnoid hemorrhage and periventricular hem-
As the human brain matures, synaptic connections are orrhage), metabolic derangements, and infection. Infections
maintained and strengthened in a use-dependent manner. associated with seizures include bacterial sepsis/meningitis

Figure 1. In mature synapses (right panel), combined action of the KCC2 chloride transporter and the NKCC1 chloride importer leads to net extrusion of
chloride ions into the extracellular space. Stimulation of GABA receptors in this scenario leads to chloride influx and hyperpolarization of the postsynaptic
membrane (inhibition). In immature synapses (left panel), unopposed action of NKCC1 chloride transporters leads to the accumulation of intracellular
chloride. Stimulation of GABA receptors in this scenario leads to chloride efflux and subsequent depolarization (excitation). GABA5c-aminobutyric acid,
NKCC15sodium-potassium-chloride cotransporter 1, KCC25potassium-chloride cotransporter 2. (Image created with BioRender.com.)

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 (especially early onset) and meningoencephalitis because of However, ultrasonography is not sensitive enough to de-
toxoplasmosis, others (syphilis, hepatitis B), rubella, cytomeg- tect hypoxic-ischemic brain injury or subtle cortical mal-
alovirus, herpes simplex infections, and enteroviruses. Less formations. Therefore, high-resolution brain imaging with
often, neonatal seizures are due to neonatal-onset epilepsy, magnetic resonance imaging (MRI) should be performed
which can be associated with structural brain anomalies, for all patients with neonatal seizures to aid in diagnosis
inborn errors of metabolism (IEMs), or genetic disorders. and prognostication. (12) Diffusion-weighted imaging and
(7)(8) magnetic resonance (MR) spectroscopy also provide diag-
nostic and predictive value regarding hypoxic-ischemic in-
Laboratory Evaluation jury. (13)
When seizures are suspected or confirmed, the initial eval-
uation should include a thorough history and physical ex- Electroencephalography
amination, as well as laboratory testing to identify any A large proportion of neonatal seizures do not have observ-
correctable or treatable causes, such as hypoglycemia, elec- able clinical manifestations, especially in neonates who are
trolyte derangements (eg, hyponatremia, hypocalcemia, or critically ill or have been treated with ASMs, which increases
hypomagnesemia), or infection. A complete blood cell the incidence of electroclinical uncoupling. (3)(14)(15)(16)(17)
count with differential should be obtained, and a coagula- Newborns are less likely to display motor correlates because
tion panel should be considered if there is concern for of the immaturity of motor tracts and the relative lack of
hemorrhage. Infectious evaluation should include blood myelination at this stage in development. Newborns may
and cerebrospinal fluid (CSF) cultures and CSF testing also display nonepileptic paroxysmal movements, such as jit-
for glucose, protein, cell counts, and herpes simplex virus teriness or sleep myoclonus, which can be falsely categorized
polymerase chain reaction. Placental pathology may re- as seizures and treated unnecessarily. Evidence indicates that
veal evidence of infection. If there is a concern for peri- diagnostic accuracy is poor if based solely on clinical signs
natal asphyxia, laboratory evaluation should include tests and symptoms. (18)(19)(20)(21) Because of this, the Interna-
of end organ function, including liver function tests and tional League Against Epilepsy (ILAE) Task Force on Neona-
serum creatinine. tal Seizures has emphasized that electroencephalography
Further evaluation for IEM may also be warranted, espe- (EEG) is necessary for the diagnosis of seizures in neonates.
cially if the history and initial evaluation are unrevealing or if (22)(23) Video recording of suspected seizure activity can
seizures are unremitting. IEMs associated with neonatal seiz- aid in diagnostic accuracy, and continuous video record-
ures include neurotransmitter metabolism disorders, energy ing should accompany EEG monitoring of neonates, if avail-
metabolism disorders, and disorders of intracellular biosyn- able. (22)(24)
thetic pathways. (9) Consultation with genomic medicine is In centers where continuous video EEG monitoring or
recommended to guide the evaluation. Some initial tests to neurology support is not available, practitioners in the NICU
consider include serum ammonia, lactate, amino acid pro- can use amplitude-integrated EEG (aEEG). When compared
file, very-long-chain fatty acids, and urine organic acids. Al- with clinical observation alone, aEEG monitoring has been
though rare, neonatal-onset epilepsy may also be considered, shown to reduce total seizure duration because of earlier de-
especially if seizures are unprovoked or refractory to treat- tection. (25) aEEG presents time-compressed and filtered
ment. Epilepsy gene panels are available and have good diag- EEG data that can be displayed at the bedside and does not
nostic yield for patients with early-onset seizures (37% in a require formal training in neurology or neurophysiology to
recent review). (10) Whole exome sequencing has also been interpret the results. For seizure detection in neonates, aEEG
shown to have good diagnostic yield and may be a more has lower sensitivity compared to full montage EEG. (26)(27)
cost-effective option than chromosomal microarray; however, Specifically, aEEG can fail to detect seizures that are brief or
turnaround time is currently longer than that of gene panel arise from brain areas other than the centrotemporal region.
testing or chromosomal microarray. (11) On the other hand, the specificity of aEEG for seizure detec-
tion is relatively high, and false-positive identifications can
Imaging be minimized if the tracing is accompanied by video moni-
Head ultrasonography, which is accessible in most set- toring or by notating events that might cause artifacts on the
tings and noninvasive, can identify hydrocephalus, large tracing, such as patting or rocking the infant. (28) When
space-occupying lesions such as hematomas or arteriove- used in conjunction with continuous EEG (cEEG), aEEG can
nous malformations, and some structural brain anomalies. facilitate real-time recognition of potential seizure activity

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 that can subsequently be confirmed by neurophysiologists. Infants undergoing therapeutic hypothermia for moderate-
In addition, aEEG can provide information about back- to-severe HIE should have continuous video EEG monitor-
ground electrical activity, which allows for the assessment of ing. If the background EEG pattern is normal for the first
severity of encephalopathy and may have diagnostic utility. 24 hours, it is reasonable to discontinue the EEG for the re-
mainder of the cooling period, as evidence suggests that in-
SEIZURE DETECTION AND CLASSIFICATION fants with a normal background EEG tracing for the first
The ILAE recently convened a task force to update the 24 hours are unlikely to go on to have seizures. (30) Re-
warming is associated with an increased risk of seizures,
ILAE Classification of Seizures and Epilepsies to include a
even in infants who have not had any previous seizures;
classification framework specifically for neonatal seizures.
thus, practitioners should consider continuing EEG moni-
(23) According to this classification, the historical categori-
toring during the rewarming period. (31) Given that seiz-
zation of seizures as focal or generalized onset is not rele-
ures provoked by acute acquired brain injury are unlikely to
vant to the neonatal population because all seizures that
recur after initial resolution, cEEG is not required when
arise in the newborn period are considered to have focal
weaning from ASMs. If electrographic seizures are detected
onset, although they may migrate to other parts of the
at any point, the American Clinical Neurophysiology Society
brain or progress to become generalized.
recommends continuing EEG monitoring until 24 hours of
Neonatal seizures are broadly categorized as electro-
seizure freedom.
clinical or electrographic-only (also referred to as subclinical).
Electroclinical seizures, or seizures with both electrographic
MANAGEMENT
and clinical components, can be further characterized by the
Supportive Care
predominant clinical manifestation, which might be motor,
Because seizures in neonates are often a sign of underly-
such as tonic posturing or myoclonus, or nonmotor, such as
ing brain pathology or injury, suspected or confirmed seiz-
autonomic alterations or behavioral arrest. The clinical char-
ures should be treated as medical emergencies. The
acteristics, or semiology, of neonatal seizures may suggest
primary goals of patient management are to identify the
a particular etiology. For example, motor clonic seizures are
cause of the seizures, control the seizures when possible,
typical in cases of focal ischemia or cerebral hemorrhage,
and prevent or mitigate further brain injury. Care should
whereas myoclonic seizures are associated with IEM.
be taken to maintain normothermia (unless undergoing
KCNQ2-related seizures typically present with a particular
therapeutic hypothermia for presumed HIE), normal ven-
sequence beginning with a motor tonic phase followed by
tilation (with strict avoidance of hypocarbia) and oxygena-
a myoclonic or clonic phase. Acute vital sign changes in
tion, normal blood pressure, normoglycemia, and normal
the absence of other clinical signs rarely represent seiz-
serum electrolyte levels.
ures in neonates. (29)
Therapeutic hypothermia is now the standard of care
Given the high risk for subclinical seizures in the neonatal
for presumed HIE in neonates. Few studies have specifi-
population, it is appropriate to monitor high-risk infants with
cally addressed the effect of therapeutic hypothermia on
cEEG even when they do not demonstrate overt signs of sei- seizure occurrence or seizure burden in patients with
zure activity. According to published guidelines from the HIE, and it is no longer possible to study this directly be-
American Clinical Neurophysiology Society, cEEG monitoring cause therapeutic hypothermia has been adopted as the
should be considered for infants who are at high risk of hav- standard of care. Based on limited evidence, including
ing seizures, including those with acute encephalopathy, sig- comparisons to historical controls, most experts agree that
nificant cardiopulmonary compromise (including infants who therapeutic hypothermia may reduce overall seizure bur-
require extracorporeal membrane oxygenation or cardiopul- den in HIE patients. (32)(33)(34)
monary bypass), perinatal stroke, suspected or confirmed cen-
tral nervous system infection, central nervous system trauma, Antiseizure Medication
abnormal neuroimaging findings, or microcephaly. Continu- By definition, acute symptomatic seizures are generally
ous EEG should also be considered for preterm infants with self-limited and tend to abate as the patient recovers and
acute high-grade intraventricular hemorrhage. (22) Particular brain function is restored. Therefore, there has been some
attention should be paid to infants who are receiving signifi- debate regarding the necessity of treating with ASMs.
cant sedation and/or neuromuscular blockade that would pre- While there are reports of associations between high
clude meaningful neurologic examination. seizure burden and adverse long-term outcomes, a direct

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 causal relationship is difficult to establish. (35)(36)(37)(38) population. (41)(42)(43)(44) The poor response rate to phe-
However, there is general consensus among experts that a nobarbital in neonates might be related to the immaturity
higher seizure burden is associated with worse outcomes of GABAergic networks and more specifically to the pre-
and that treatment of acute provoked seizures with ASMs dominance of the NKCC1 cotransporter in developing neu-
may lead to improved outcomes. (32) There is also evi- rons, which alters the chloride electrochemical gradient
dence that neonatal seizures become less responsive to that is necessary for phenobarbital to exert its effects.
ASM treatment over time, and, thus, prompt identification (45)(46)(47) Also of concern is that preclinical studies in
and treatment of neonatal seizures should be a priority. rodents have provided evidence that phenobarbital exerts
(39) Ideally, there has been confirmation of seizure activity toxic effects on the developing brain, and results of clinical
with EEG before giving ASMs; however, the recent ILAE studies have also suggested that long-term ASM therapy
guidelines suggest that the Brighton criteria can be used may be associated with adverse neurodevelopmental (ND)
to make decisions about whether to start treatment for outcomes, including cerebral palsy and lower IQ scores.
clinical seizurelike activity when cEEG is not available. (48)(49)(50)(51)(52) This has led to increased interest in
(18)(23) Evidence suggests that adoption of a NICU seizure newer ASMs in this population, particularly levetiracetam,
treatment guideline or pathway can lead to reductions in sei- which displays more favorable pharmacokinetics, does not
zure burden, risk of progression to status epilepticus, and appear to increase neuronal apoptosis in animal models,
length of hospital stay (Fig 2). (32)(40) and does not rely on GABAergic signaling pathways to ex-
Phenobarbital remains the most commonly used ASM ert its effects. (49)(53) In clinical studies, however, the re-
in the NICU despite its limited efficacy in the neonatal sponse rate to levetiracetam is similar to or lower than

Concern for seizure

Place on connuous vEEG

(or aEEG, if EEG not available)

Check blood glucose

Confirmed electrographic seizure
and electrolytes

If family history of
Phenobarbital load
Correct any abnormalies channelopathy, consider
(20 mg/kg)
sodium channel blocker early

Phenobarbital load
(20 mg/kg)

Leveracetam load Fosphenytoin load

(60 mg/kg)
OR (20 mg/kg)

If unclear eology and/or

Midazolam infusion failed control with two ASMs,
consider trial of pyridoxine

Figure 2. Example of seizure treatment pathway based on current evidence and expert consensus recommendations. aEEG5amplitude-integrated
electroencephalography, ASM5antiseizure medication, vEEG=video EEG.

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 that of phenobarbital for treating neonatal seizures. were also considerations but have been associated with hypo-
(44)(54)(55) Recent reports also suggest that, similar to tension and oversedation, respectively.
other ASMs such as phenobarbital, levetiracetam is linked to the Treatment of neonatal seizures remains an active area
rare but serious side effect Drug Reaction with Eosinophilia of research. The diuretic bumetanide, which inhibits
and Systemic Symptoms (DRESS) syndrome in both adults NKCC1 channels, has been studied as a second-line or ad-
and children. (56) junct ASM for neonatal seizures; however, there is limited
Recently, the ILAE published a guideline for the treat- evidence regarding efficacy and some evidence that it may
ment of seizures in neonates that included the evidence- increase the risk of hearing impairment. (61)(62) An on-
based recommendation for phenobarbital as the first-line going phase 2 clinical trial (NCT04519645) is being con-
ASM in neonates with acute provoked seizures, regardless of ducted to evaluate the efficacy and safety of lacosamide as
etiology. (32) In cases with a family history of or clinical fea- a second-line ASM for neonatal seizures.
tures suggestive of a channelopathy (eg, KCNQ2-related seiz- Because of the lack of rigorous randomized controlled
ures), first-line treatment with a sodium channel blocker, trials that address the efficacy and long-term impacts of
such as phenytoin or carbamazepine, is reasonable. Authors ASMs in the neonatal population, there remains a great
of a 2023 Cochrane review also concluded that, based on deal of practice variation across practitioners and institu-
available evidence, phenobarbital is “probably more effective tions. A 2021 descriptive analysis of treatment pathways
than levetiracetam in achieving seizure control.” (57) This from 11 level IV NICUs indicated that while there was
conclusion was largely based on the results of a randomized agreement with respect to EEG monitoring and first-line
controlled trial, and the authors were unable to draw any treatment with intravenous phenobarbital 20 mg/kg, there
conclusions regarding the impact of phenobarbital versus was considerable variability in second- and third-line
levetiracetam on other short-term outcomes, such as in- ASMs, with most pathways including either phenytoin or
hospital mortality or need for mechanical ventilation, or on levetiracetam as the preferred second-line agent. (42)
long-term ND outcomes based on the available evidence. (55)
Only 1 included trial reported on the efficacy of phenobarbi- Duration of Therapy
tal versus phenytoin as first-line ASM for control of EEG- Another consideration is the duration of ASM therapy after
confirmed seizures and did not provide sufficient evidence successful treatment of acute provoked seizures. One con-
to support the use of either medication over the other. (58) cern is that discontinuation of ASM before NICU discharge
Based on evidence from 2 trials that reported on the efficacy may put patients at risk for recurrent seizures or develop-
of phenobarbital versus phenytoin as first-line treatment ment of epilepsy. On the other hand, there are also concerns
of clinical seizures, the authors of the Cochrane review that long-term treatment, particularly with phenobarbital,
concluded that phenobarbital “may result in better seizure may have negative ND consequences. Results of retrospective
control after the first loading dose … when compared to studies have suggested that ASM discontinuation before
phenytoin.” (59)(60) Based on the available literature, the NICU discharge does not increase the risk of subsequent
authors were unable to make any firm conclusions regard- seizures or ND impairment. (63)(64) In 2011, the World
ing preferred second-line agent(s) or the impact of ASM Health Organization issued a recommendation that clini-
maintenance therapy following initial seizure control on cians consider discontinuation of ASM after 72 hours of sei-
seizure burden, mortality, or long-term ND outcomes. The zure freedom in neonates with normal EEG and neurologic
authors graded the quality of available evidence for pheno- examination. (24) A more recent multicenter prospective
barbital versus levetiracetam as first-line ASM for seizure study showed no differences in functional neurodevelopment
control as having moderate-certainty, and all other avail- or risk for epilepsy between patients who were continued on
able evidence to support the use of other ASM for seizure ASM therapy after hospital discharge and those who were
control or any ASM for any of the other outcomes (mortal- not. (65) The authors suggest that the new findings support
ity, development of epilepsy, ND impairment) was graded discontinuation of ASM before discharge for all newborns
as having low-certainty or very low-certainty. The authors after successful treatment (defined as 24 hours of seizure
of the 2023 ILAE guidelines concluded that there was not freedom) of acute symptomatic seizures even in the setting
enough evidence to recommend a particular second-line of abnormal EEG background or examination findings at
ASM for acute symptomatic neonatal seizures but stated discharge. (65) However, some experts suggest that clini-
that phenytoin or levetiracetam were preferred second-line cians carefully consider patient-specific factors, such as un-
agents, based on expert consensus. Lidocaine and midazolam derlying etiology of seizures and extent of brain injury,

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 when discontinuing ASMs, particularly in conditions asso- The review included 9 studies (570 infants total) that re-
ciated with a high risk for subsequent epilepsy, such as is- ported on outcomes in infants with seizures related to
chemic stroke. (66) Larger and more long-term studies are stroke (4 studies), HIE (4 studies), and ICH (1 study). The
needed to further elucidate the risks and benefits of discon- pooled risk ratio for adverse ND outcome (CP or develop-
tinuing ASMs before hospital discharge for acute symptom- mental score of at least 2 standard deviations below the
atic seizures with a range of etiologies. reference mean) was 8.41 (95% confidence interval [CI],
4.07–17.39) for infants with seizures due to HIE and 4.95
PROGNOSIS AND OUTCOMES (95% CI, 1.07–23.0) for those with seizures due to stroke.
Acute symptomatic neonatal seizures are associated with (36) In a retrospective analysis of term neonates with
mortality, epilepsy, and ND impairment. (67) The long- aEEG-diagnosed status epilepticus, researchers found that
term outcome of neonatal seizures is most closely related 75% of infants had a poor outcome (death or severe ND
to the underlying etiology. In a cohort of 89 patients with impairment). (71) Most of the deaths were due to elective
clinical neonatal seizures, 35% had poor long-term out- cessation of life-sustaining measures after it was deter-
comes (death or cognitive impairment). (68) In this cohort, mined that the prognosis was poor. (71) In the overall cohort,
cerebral dysgenesis and global hypoxia-ischemia were the duration of status epilepticus did not predict outcome, which
etiologies most associated with poor outcomes. (68) Con- is consistent with the results of previous studies. (71) How-
versely, a normal neurologic examination in the neonatal pe- ever, infants with a poor outcome were more likely to have a
riod or early infancy was associated with favorable outcomes. nonreassuring aEEG background pattern (flat tracing, contin-
Most studies aimed at determining long-term outcomes fol- uous low voltage, or burst suppression) before the onset of
lowing neonatal seizures have focused on neonates with status epilepticus compared to infants with a good outcome.
HIE, which makes it difficult to separate the contribution of (71) This suggests that the severity of the underlying brain
the underlying injury and the seizure burden to subsequent injury is the most important predictor of outcome.
ND outcomes. However, there is evidence from preclinical Overall, the risk of epilepsy after neonatal seizure is esti-
and clinical studies that seizures are independently associated mated to be 25%, with the greatest risk being in the first
with adverse long-term outcomes, particularly in the setting of year of age. (67) In a single-center retrospective study of
HIE. In several landmark studies, it was demonstrated that 87 patients with acute symptomatic neonatal seizures who
seizures are independently associated with MRI findings of were admitted to a specialized neonatal neurocritical care
brain injury. Glass and colleagues looked at a cohort of service, 9% of survivors were diagnosed with epilepsy by age
77 term neonates with HIE and found that even after control- 5 years. (72) Seizure etiology was related to the frequency of
ling for the severity of hypoxic-ischemic brain injury on MRI, epilepsy diagnosis, but the frequency of seizures and EEG
patients with seizures had lower full-scale IQ scores at 4 years background pattern were not associated with the develop-
of age and that those with higher seizure burden were more ment of epilepsy. The lower epilepsy rate observed in this co-
affected. (38) In another study of neonatal HIE patients, it was hort might be related to high mortality during the neonatal
demonstrated that after controlling for the structural changes period. Data from the Neonatal Seizure Registry of infants
on MRI and the amount of resuscitation required at birth, sei- with acute neonatal seizures demonstrated that the risk of
zure burden was associated with indicators of brain injury on epilepsy by 24 months of age was 13%. (73) In this same
MR spectroscopy. (69) study, severely abnormal EEG background, high number of
Trowbridge and colleagues recently evaluated the ND days with EEG-confirmed seizures, higher seizure burden,
outcomes at 18 to 22 months of neonates prospectively en- need for more than 1 ASM, and abnormal neurologic find-
rolled in a randomized controlled trial of bumetanide as ings at discharge were associated with the development of
an add-on therapy for infants with seizures refractory to epilepsy. (73) The development of epilepsy was associated
phenobarbital. (70) They found that there was a significant with a threefold increase in ND impairment. In cases of in-
correlation between seizure burden and lower develop- fantile and early childhood epileptic encephalopathies, evi-
mental scores across all domains. (70) Interestingly, the dence has shown that earlier control of seizures is associated
authors demonstrated that this association was stronger in with improved ND outcomes. (74) In summary, multiple
infants with HIE and stroke than with ICH. (70) In 2018, studies have demonstrated that in neonates with brain in-
De Haan and colleagues published a systematic review of jury, seizure activity increases the risk of poor outcomes;
studies of term neonates with EEG-confirmed seizures however, further studies are required to establish if this is
who had ND follow-up until at least 18 months of age. correlative or causative.

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 KEY POINTS
• Most seizures that occur during the neonatal period are • Understand the differential diagnosis and
acute provoked seizures associated with brain injury or evaluation of neonatal seizures.
systemic illness. • Understand the management of neonatal seizures,
• HIE remains the most common cause of neonatal seizures. including the role of neurophysiologic monitoring.
Ischemic stroke and ICH are also common causes.
• A large proportion of neonatal seizures do not have clinical
manifestations, and neonates display paroxysmal move-
ments that might be incorrectly classified as seizures. EEG
References
is necessary to definitively diagnose seizures in neonates.
• aEEG is a bedside tool that can be used in conjunction 1. Glass HC, Pham TN, Danielsen B, Towner D, Glidden D, Wu YW.
Antenatal and intrapartum risk factors for seizures in term
with conventional EEG or in settings where conven- newborns: a population-based study, California 1998-2002. J Pediatr.
tional EEG is not available. Advantages of aEEG are that 2009;154(1):24–28
it does not require specialized training to interpret, has 2. Vasudevan C, Levene M. Epidemiology and aetiology of neonatal
a high specificity for seizure detection, and provides seizures. Semin Fetal Neonatal Med. 2013;18(4):185–191
information about background electrical activity. The 3. Glass HC, Shellhaas RA, Wusthoff CJ, et al; Neonatal Seizure
primary disadvantage of aEEG is that it has a lower sen- Registry Study Group. Contemporary profile of seizures in neonates:
a prospective cohort study. J Pediatr. 2016;174:98–103
sitivity than conventional EEG for seizure detection.
4. Jensen FE. Neonatal seizures: an update on mechanisms and
• The primary goals in the treatment of patients with neonatal management. Clin Perinatol. 2009;36(4):881–900, vii [vii]
seizures are to identify the underlying cause, correct it 5. Rakhade SN, Jensen FE. Epileptogenesis in the immature brain:
when possible, and prevent or mitigate further brain injury. emerging mechanisms. Nat Rev Neurol. 2009;5(7):380–391
• Phenobarbital remains the most commonly used ASM in 6. Shankaran S, Laptook AR, Ehrenkranz RA, et al; National Institute
neonates despite its limited efficacy. Recent evidence sug- of Child Health and Human Development Neonatal Research
gests that phenobarbital is more efficacious than levetirace- Network. Whole-body hypothermia for neonates with hypoxic-
ischemic encephalopathy. N Engl J Med. 2005;353(15):1574–1584
tam or phenytoin, and the ILAE has recently published
7. Glass HC. Neonatal seizures: advances in mechanisms and
recommendations that include phenobarbital as the pre- management. Clin Perinatol. 2014;41(1):177–190
ferred first-line ASM for neonatal seizures. (32)(57) 8. Shellhaas RA, Wusthoff CJ, Tsuchida TN, et al; Neonatal Seizure
• For most patients with acute symptomatic neonatal seiz- Registry. Profile of neonatal epilepsies: characteristics of a
ures, it is probably safe to discontinue ASMs before prospective US cohort. Neurology. 2017;89(9):893–899
NICU discharge. However, practitioners may consider 9. Van Hove JL, Lohr NJ. Metabolic and monogenic causes of seizures
continuing maintenance ASM therapy after discharge in in neonates and young infants. Mol Genet Metab. 2011;104(3):214–230

certain patients at high risk for seizure recurrence, such 10. Stefanski A, Calle-L
opez Y, Leu C, P
erez-Palma E, Pestana-Knight E,
Lal D. Clinical sequencing yield in epilepsy, autism spectrum
as those with ischemic stroke. disorder, and intellectual disability: a systematic review and meta-
• Neonatal seizures are associated with adverse long-term analysis. Epilepsia. 2021;62(1):143–151
outcomes, including ND impairment and epilepsy. Seizure 11. S
anchez Fern
andez I, Loddenkemper T, Ga
ınza-Lein M, Sheidley
etiology is a major predictor of outcomes. It is difficult to BR, Poduri A. Diagnostic yield of genetic tests in epilepsy: a
determine if the presence of seizures is an independent meta-analysis and cost-effectiveness study. Neurology. 2019;
92(5):e418–e428
risk factor for adverse outcomes or if seizures merely re-
12. Weeke LC, Van Rooij LG, Toet MC, Groenendaal F, de Vries LS.
flect the severity of underlying brain injury. In HIE, how- Neuroimaging in neonatal seizures. Epileptic Disord. 2015;17(1):1–11,
ever, there is evidence that seizures do lead to more severe quiz 11
brain injury and worse long-term outcomes. 13. Cheong JL, Coleman L, Hunt RW, et al; Infant Cooling Evaluation
Collaboration. Prognostic utility of magnetic resonance imaging in
neonatal hypoxic-ischemic encephalopathy: substudy of a
randomized trial. Arch Pediatr Adolesc Med. 2012;166(7):634–640
American Board of Pediatrics 14. Nash KB, Bonifacio SL, Glass HC, et al. Video-EEG monitoring in
Neonatal-Perinatal Content newborns with hypoxic-ischemic encephalopathy treated with
Specifications hypothermia. Neurology. 2011;76(6):556–562
15. Clancy RR. Prolonged electroencephalogram monitoring for seizures
• Understand the spectrum of seizures in the
and their treatment. Clin Perinatol. 2006;33(3):649–665, vi
newborn infant.
16. Hahn CD, Riviello JJ Jr. Neonatal seizures and EEG: electroclinical
dissociation and uncoupling. NeoReviews. 2004;5(8):e350–e355

Vol. 25 No. 6 J U N E 2 0 2 4 e345

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by HINARI BAND 1 user
 17. Scher MS, Alvin J, Gaus L, Minnigh B, Painter MJ. Uncoupling of 33. Low E, Boylan GB, Mathieson SR, et al. Cooling and seizure burden
EEG-clinical neonatal seizures after antiepileptic drug use. Pediatr in term neonates: an observational study. Arch Dis Child Fetal
Neurol. 2003;28(4):277–280 Neonatal Ed. 2012;97(4):F267–F272
18. Pellegrin S, Munoz FM, Padula M, et al; Brighton Collaboration 34. Srinivasakumar P, Zempel J, Wallendorf M, Lawrence R, Inder T,
Neonatal Seizures Working Group. Neonatal seizures: case Mathur A. Therapeutic hypothermia in neonatal hypoxic ischemic
definition & guidelines for data collection, analysis, and presentation encephalopathy: electrographic seizures and magnetic resonance
of immunization safety data. Vaccine. 2019;37(52):7596–7609 imaging evidence of injury. J Pediatr. 2013;163(2):465–470
19. Soul JS, Pressler R, Allen M, et al; International Neonatal 35. Kharoshankaya L, Stevenson NJ, Livingstone V, et al. Seizure
Consortium. Recommendations for the design of therapeutic trials burden and neurodevelopmental outcome in neonates with hypoxic-
for neonatal seizures. Pediatr Res. 2019;85(7):943–954 ischemic encephalopathy. Dev Med Child Neurol. 2016;58(12):
20. Murray DM, Boylan GB, Ali I, Ryan CA, Murphy BP, Connolly S. 1242–1248
Defining the gap between electrographic seizure burden, clinical 36. De Haan TR, Langeslag J, van der Lee JH, van Kaam AH. A
expression and staff recognition of neonatal seizures. Arch Dis Child systematic review comparing neurodevelopmental outcome in term
Fetal Neonatal Ed. 2008;93(3):F187–F191 infants with hypoxic and vascular brain injury with and without
21. Malone A, Ryan CA, Fitzgerald A, Burgoyne L, Connolly S, Boylan seizures. BMC Pediatr. 2018;18(1):147
GB. Interobserver agreement in neonatal seizure identification. 37. Shah DK, Wusthoff CJ, Clarke P, et al. Electrographic seizures are
Epilepsia. 2009;50(9):2097–2101 associated with brain injury in newborns undergoing therapeutic
22. Shellhaas RA, Chang T, Tsuchida T, et al. The American Clinical hypothermia. Arch Dis Child Fetal Neonatal Ed. 2014;99(3):F219–F224
Neurophysiology Society’s Guideline on Continuous 38. Glass HC, Glidden D, Jeremy RJ, Barkovich AJ, Ferriero DM, Miller
Electroencephalography Monitoring in Neonates. J Clin Neurophysiol. SP. Clinical neonatal seizures are independently associated with
2011;28(6):611–617 outcome in infants at risk for hypoxic-ischemic brain injury.
23. Pressler RM, Cilio MR, Mizrahi EM, et al. The ILAE classification of J Pediatr. 2009;155(3):318–323
seizures and the epilepsies: modification for seizures in the neonate. 39. Pavel AM, Rennie JM, de Vries LS, et al. Neonatal seizure
Position paper by the ILAE Task Force on Neonatal Seizures. management: is the timing of treatment critical? J Pediatr.
Epilepsia. 2021;62(3):615–628 2022;243:61–68.e2
24. World Health Organization. Guidelines on Neonatal Seizures. Geneva, 40. Harris ML, Malloy KM, Lawson SN, Rose RS, Buss WF, Mietzsch
Switzerland: World Health Organization; 2011 U. Standardized treatment of neonatal status epilepticus improves
25. van Rooij LG, Toet MC, van Huffelen AC, et al. Effect of treatment outcome. J Child Neurol. 2016;31(14):1546–1554
of subclinical neonatal seizures detected with aEEG: randomized, 41. Bartha AI, Shen J, Katz KH, et al. Neonatal seizures: multicenter
controlled trial. Pediatrics. 2010;125(2):e358–e366
variability in current treatment practices. Pediatr Neurol. 2007;37(2):85–90
26. Shellhaas RA, Soaita AI, Clancy RR. Sensitivity of amplitude-
42. Keene JC, Morgan LA, Abend NS, et al. Treatment of neonatal
integrated electroencephalography for neonatal seizure detection.
seizures: comparison of treatment pathways from 11 neonatal
Pediatrics. 2007;120(4):770–777
intensive care units. Pediatr Neurol. 2022;128:67–74
27. Toet MC, van der Meij W, de Vries LS, Uiterwaal CS, van Huffelen
43. Falsaperla R, Scalia B, Giugno A, et al. Treating the symptom or
KC. Comparison between simultaneously recorded amplitude
treating the disease in neonatal seizures: a systematic review of the
integrated electroencephalogram (cerebral function monitor) and
literature. Ital J Pediatr. 2021;47(1):85
standard electroencephalogram in neonates. Pediatrics.
2002;109(5):772–779 44. Qiao MY, Cui HT, Zhao LZ, Miao JK, Chen QX. Efficacy and safety
of levetiracetam vs. phenobarbital for neonatal seizures: a systematic
28. Glass HC, Wusthoff CJ, Shellhaas RA. Amplitude-integrated electro-
review and meta-analysis. Front Neurol. 2021;12:747745
encephalography: the child neurologist’s perspective. J Child Neurol.
2013;28(10):1342–1350 45. Dzhala VI, Talos DM, Sdrulla DA, et al. NKCC1 transporter
facilitates seizures in the developing brain. Nat Med.
29. Dang LT, Shellhaas RA. Diagnostic yield of continuous video
2005;11(11):1205–1213
electroencephalography for paroxysmal vital sign changes in
pediatric patients. Epilepsia. 2016;57(2):272–278 46. Brooks-Kayal AR, Jin H, Price M, Dichter MA. Developmental
expression of GABA(A) receptor subunit mRNAs in individual
30. Benedetti GM, Vartanian RJ, McCaffery H, Shellhaas RA. Early
hippocampal neurons in vitro and in vivo. J Neurochem.
electroencephalogram background could guide tailored duration of
1998;70(3):1017–1028
monitoring for neonatal encephalopathy treated with therapeutic
hypothermia. J Pediatr. 2020;221:81–87.e1 47. Brooks-Kayal AR, Shumate MD, Jin H, Rikhter TY, Kelly ME,
Coulter DA. Gamma-aminobutyric acid(A) receptor subunit
31. Chalak LF, Pappas A, Tan S, et al; Eunice Kennedy Shriver National
expression predicts functional changes in hippocampal dentate
Institute of Child Health and Human Development Neonatal
granule cells during postnatal development. J Neurochem.
Research Network. Association between increased seizures during
rewarming after hypothermia for neonatal hypoxic ischemic 2001;77(5):1266–1278
encephalopathy and abnormal neurodevelopmental outcomes at 48. Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse
2-year follow-up: a nested multisite cohort study. JAMA Neurol. neurodevelopmental outcomes after exposure to phenobarbital and
2021;78(12):1484–1493 levetiracetam for the treatment of neonatal seizures. J Perinatol.
32. Pressler RM, Abend NS, Auvin S, et al. Treatment of seizures in the 2013;33(11):841–846
neonate: guidelines and consensus-based recommendations-Special 49. Forcelli PA, Janssen MJ, Vicini S, Gale K. Neonatal exposure to
report from the ILAE Task Force on Neonatal Seizures. Epilepsia. antiepileptic drugs disrupts striatal synaptic development. Ann
2023;64(10):2550–2570 Neurol. 2012;72(3):363–372

e346 NeoReviews

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by HINARI BAND 1 user
 50. Torolira D, Suchomelova L, Wasterlain CG, Niquet J. Phenobarbital treatment of seizures in newborn babies with hypoxic ischaemic
and midazolam increase neonatal seizure-associated neuronal injury. encephalopathy (NEMO): an open-label, dose finding, and feasibility
Ann Neurol. 2017;82(1):115–120 phase 1/2 trial. Lancet Neurol. 2015;14(5):469–477
51. Bittigau P, Sifringer M, Genz K, et al. Antiepileptic drugs and 63. Guillet R, Kwon J. Seizure recurrence and developmental disabilities
apoptotic neurodegeneration in the developing brain. Proc Natl Acad after neonatal seizures: outcomes are unrelated to use of
Sci USA. 2002;99(23):15089–15094 phenobarbital prophylaxis. J Child Neurol. 2007;22(4):389–395
52. Farwell JR, Lee YJ, Hirtz DG, Sulzbacher SI, Ellenberg JH, Nelson 64. Fitzgerald MP, Kessler SK, Abend NS. Early discontinuation of
KB. Phenobarbital for febrile seizures–effects on intelligence and on antiseizure medications in neonates with hypoxic-ischemic
seizure recurrence. N Engl J Med. 1990;322(6):364–369 encephalopathy. Epilepsia. 2017;58(6):1047–1053
53. Manthey D, Asimiadou S, Stefovska V, et al. Sulthiame but not 65. Glass HC, Soul JS, Chang T, et al. Safety of early discontinuation of
levetiracetam exerts neurotoxic effect in the developing rat brain. antiseizure medication after acute symptomatic neonatal seizures.
Exp Neurol. 2005;193(2):497–503 JAMA Neurol. 2021;78(7):817–825
54. B€attig L, D€
unner C, Cserpan D, et al. Levetiracetam versus 66.Volpe JJ. Commentary - Early discontinuation of antiseizure
phenobarbital for neonatal seizures: a retrospective cohort study. medication in neonatal seizures - Proceed with caution. J Neonatal
Pediatr Neurol. 2023;138:62–70 Perinatal Med. 2022;15(2):203–207
55. Sharpe C, Reiner GE, Davis SL, et al; NEOLEV2 Investigators. 67. Glass HC, Grinspan ZM, Shellhaas RA. Outcomes after acute
Levetiracetam versus phenobarbital for neonatal seizures: a symptomatic seizures in neonates. Semin Fetal Neonatal Med.
randomized controlled trial. Pediatrics. 2020;145(6):e20193182 2018;23(3):218–222
56. US Food and Drug Administration. FDA warns of rare but serious 68. Tekgul H, Gauvreau K, Soul J, et al. The current etiologic profile
drug reaction to the antiseizure medicines levetiracetam (Keppra, and neurodevelopmental outcome of seizures in term newborn
Keppra XR, Elepsia XR, Spritam) and clobazam (Onfi, Sympazan). infants. Pediatrics. 2006;117(4):1270–1280
https://www.fda.gov/drugs/drug-safety-and-availability/fda-warns- 69.Miller SP, Weiss J, Barnwell A, et al. Seizure-associated brain
rare-serious-drug-reaction-antiseizure-medicines-levetiracetam- injury in term newborns with perinatal asphyxia. Neurology.
keppra-keppra-xr-elepsia-xr Accessed January 2, 2024 2002;58(4):542–548
57. Abiramalatha T, Thanigainathan S, Ramaswamy VV, Pressler R, 70. Trowbridge SK, Condie LO, Landers JR, et al; Boston Bumetanide
Brigo F, Hartmann H. Anti-seizure medications for neonates with Trial Group. Effect of neonatal seizure burden and etiology on the
seizures. Cochrane Database Syst Rev. 2023;10(10):CD014967 long-term outcome: data from a randomized, controlled trial. Ann
58. Painter MJ, Scher MS, Stein AD, et al. Phenobarbital compared with Child Neurol Soc. 2023;1(1):53–65
phenytoin for the treatment of neonatal seizures. N Engl J Med. 71. van Rooij LG, de Vries LS, Handryastuti S, et al. Neurodevelopmental
1999;341(7):485–489 outcome in term infants with status epilepticus detected with
59. Solanki DI, Gohil JR, Patel AP. Comparative efficacy of phenobarbital, amplitude-integrated electroencephalography. Pediatrics. 2007;
phenytoin and lorazepam for the treatment of neonatal seizures: a 120(2):e354–e363
randomized trial. J Clin Neonatol. 2015;4(4):232–236 72. Glass HC, Numis AL, Gano D, Bali V, Rogers EE. Outcomes after
60.Pathak G, Upadhyay A, Pathak U, Chawla D, Goel SP. Phenobarbitone acute symptomatic seizures in children admitted to a neonatal
versus phenytoin for treatment of neonatal seizures: an open-label neurocritical care service. Pediatr Neurol. 2018;84:39–45
randomized controlled trial. Indian Pediatr. 2013;50(8):753–757 73. Shellhaas RA, Wusthoff CJ, Numis AL, et al. Early-life epilepsy after
61. Soul JS, Bergin AM, Stopp C, et al; Boston Bumetanide Trial Group. acute symptomatic neonatal seizures: a prospective multicenter
A pilot randomized, controlled, double-blind trial of bumetanide to study. Epilepsia. 2021;62(8):1871–1882
treat neonatal seizures. Ann Neurol. 2021;89(2):327–340 74. Jehi L, Wyllie E, Devinsky O. Epileptic encephalopathies: optimizing
62. Pressler RM, Boylan GB, Marlow N, et al; NEonatal seizure treatment seizure control and developmental outcome. Epilepsia. 2015;56(10):
with Medication Off-patent (NEMO) consortium. Bumetanide for the 1486–1489

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 NEOREVIEWS QUIZ

NEO
QUIZ
1. Seizures are more common in neonates than any other age group, occurring
in 1 to 3 per 1,000 live births of term infants and at much higher rates in
preterm infants. Multiple developmental processes characteristic of the
immature human brain underlie this increased risk for seizures. Which of the
following mechanisms represents a mechanism of increased seizure risk in
neonates?
A. Increased expression of the neuronal potassium-chloride cotransporter 2.
B. Decreased sodium-potassium-chloride cotransporter1 activity.
C. Increased responsiveness of glutamate receptors to magnesium.
D. Excitatory effect of c-aminobutyric acid.
E. Decreased intracellular chloride ions.
REQUIREMENTS: Learners can
2. Most seizures in the neonate are acute symptomatic seizures, with hypoxic- take NeoReviews quizzes and
ischemic encephalopathy representing the most common cause of neonatal claim credit online only at:
seizures. Which of these other etiologies does NOT represent a cause of https://publications.aap.org/
acute provoked seizures? neoreviews.

A. Inborn error of metabolism. To successfully complete 2024

B. Stroke. NeoReviews articles for AMA PRA
C. Toxoplasmosis. Category 1 Credit™, learners
must demonstrate a minimum
D. Subarachnoid hemorrhage. performance level of 60% or
E. Enterovirus infection. higher on this assessment. If
you score less than 60% on the
3. The International League Against Epilepsy recently updated the classification
assessment, you will be given
of neonatal seizures. In this classification, seizures are categorized as additional opportunities to
electroclinical or electrographic-only. Seizures with a clinical component are answer questions until an
then further characterized as motor or nonmotor, based on the predominant overall 60% or greater score is
clinical manifestation. Which of the following seizure phenotypes is most achieved.

consistent with focal ischemia or cerebral hemorrhage?

This journal-based CME activity
A. Seizure with a motor tonic phase followed by a myoclonic phase. is available through Dec. 31,
B. Motor myoclonic seizure. 2026, however, credit will be
recorded in the year in which
C. Motor clonic seizure. the learner completes the quiz.
D. Nonmotor seizure with behavioral arrest.
E. Nonmotor seizure with autonomic changes.
4. A neonate born at 39 weeks’ gestation is admitted to your NICU for the
evaluation of seizures. The pregnancy and delivery were uncomplicated. He
was noted to be vigorous at birth with Apgar scores of 9 and 9 at 5 and
10 minutes, respectively. At 18 hours after birth, he was noted to have 2024 NeoReviews is approved
for a total of 30 Maintenance of
stiffening of his right upper extremity followed by rhythmic jerking that
Certification (MOC) Part 2
could not be suppressed. Upon further investigation, you discover a family credits by the American Board
history of seizures and you suspect a channelopathy. Which of the following of Pediatrics (ABP) through the
antiseizure medications represent the BEST first-line agent to treat this AAP MOC Portfolio Program.
infant’s seizures? NeoReviews subscribers can
claim up to 30 ABP MOC Part 2
A. Phenobarbital. points upon passing 30 quizzes
B. Levetiracetam. (and claiming full credit for
each quiz) per year. Subscribers
C. Lidocaine.
can start claiming MOC credits
D. Vigabatrin. as early as October 2024. To
E. Phenytoin. learn how to claim MOC points,
go to: https://publications.aap.
org/journals/pages/moc-credit.

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 5. Children with a history of neonatal seizures are at increased risk of
neurodevelopmental impairment and later development of epilepsy.
What is the overall risk of epilepsy after neonatal seizures?
A. 15%.
B. 25%.
C. 35%.
D. 45%.
E. 55%.

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