Neonatal seizures

What is a neonatal seizure?

A neonatal seizure is an abnormal, paroxysmal, electrographically-confirmed event in a baby in the first 28 days of life (extended to 44 weeks corrected gestational age for infants born preterm). The newborn brain is uniquely seizure-prone: excitatory glutamate circuits mature before inhibitory GABA circuits, and at this stage GABA itself is paradoxically excitatory — which both predisposes to seizures and partly explains why standard antiseizure medicines work less well than in older children.

Clinically, neonatal seizures often look very different from seizures in older children. The most common types are subtle (oral-buccal-lingual movements, autonomic changes, eye deviation, repetitive cycling or rowing movements), focal clonic (rhythmic jerking of a limb or one side), and tonic. Generalised tonic-clonic seizures are extremely rare in newborns — when they appear to occur, they are usually a sequence of multifocal events.

Crucially, most neonatal seizures are 'electrographic-only' — the EEG shows clear seizure activity but the baby looks calm. Conversely, many movements that look like seizures (jitteriness, benign neonatal sleep myoclonus, normal motor automatisms) are not seizures at all. This is why the 2021 ILAE framework makes EEG confirmation central.

The current ILAE framework (2021 + 2022, confirmed in the 2025 update)

The classification of neonatal seizures lives in two complementary documents — and the 2025 ILAE update explicitly preserves both for the neonatal age group, only modernising the wider classification used for older children and adults. So 'what does ILAE say in 2026?' is answered by reading these two papers together:

Pressler RM et al. (2021) — the dedicated neonatal seizure classification, which replaced the older Volpe and adult-style frameworks.

Zuberi SM et al. (2022) — the position statement on epilepsy syndromes with onset in neonates and infants (up to 2 years), grouping these into self-limited epilepsies, developmental and epileptic encephalopathies, and aetiology-specific syndromes.

Beniczky S et al. (Lancet Neurology, April 2025) — updates the 2017 ILAE seizure classification for older children, adolescents and adults (six main changes, including a move from 'awareness' to 'consciousness' as a classifier). The 2025 update states explicitly that neonatal seizures continue to be classified under the 2021 Pressler framework.

• Seizures are diagnosed on the basis of EEG (full video-EEG, or amplitude-integrated EEG / aEEG when conventional EEG is unavailable). A seizure is defined electrographically as a sudden, abnormal EEG event lasting ≥10 seconds with a clear beginning, middle and end.
• Each EEG seizure is then classified by its predominant clinical correlate: motor (clonic, tonic, myoclonic, spasms, sequential, automatisms), non-motor (autonomic, behavioural arrest), or electrographic-only.
• Events that look like seizures clinically but have no EEG correlate are categorised as 'clinical-only suspected seizures' rather than counted as confirmed seizures. This avoids both over- and under-treatment.
• Status epilepticus in the neonate is defined as the sum of seizure activity exceeding 50% of any 1-hour epoch — a definition specific to this age group.
• The classification is etiology-aware: every diagnosis is expected to be linked to a suspected cause (acute symptomatic vs. a defined neonatal-onset epilepsy syndrome under the 2022 framework).

Neonatal-onset epilepsy syndromes (2022 ILAE syndromes paper)

When seizures are not purely acute-symptomatic but reflect an underlying epilepsy syndrome that begins in the newborn period, the 2022 Zuberi paper provides the agreed definitions. These syndromes are grouped into three categories:

• Self-limited neonatal epilepsies — most importantly self-limited familial neonatal epilepsy (KCNQ2 or, less often, KCNQ3 loss-of-function) and self-limited non-familial neonatal epilepsy. Seizures usually begin in the first week of life, the baby develops normally, and seizures remit within weeks to months.
• Developmental and epileptic encephalopathies (DEEs) with neonatal onset — including KCNQ2-DEE (severe gain- or loss-of-function variants), early infantile DEE (Ohtahara syndrome with burst-suppression EEG), and epilepsy of infancy with migrating focal seizures (EIMFS, often KCNT1).
• Aetiology-specific neonatal syndromes — including SCN2A-, STXBP1-, CDKL5-, GNAO1- and pyridoxine-dependent (ALDH7A1) presentations, where the cause directly drives both the seizure pattern and the choice of treatment (sodium-channel blockers for KCNQ2 and gain-of-function SCN2A; vitamin B6 for pyridoxine-dependent epilepsy; ganaxolone trials for CDKL5).

Why babies have seizures: aetiology

Most neonatal seizures are acute symptomatic — that is, a sign of an underlying brain insult, not of a chronic epilepsy. The relative proportions vary slightly between cohorts but commonly include:

• Hypoxic-ischaemic encephalopathy (HIE) — by far the commonest cause, accounting for around 40–50% of seizures in term babies. Therapeutic hypothermia is now standard for moderate-to-severe HIE in term and late-preterm infants and reduces both seizure burden and adverse outcome.
• Acute ischaemic stroke (perinatal arterial ischaemic stroke) — typically presents in a previously well baby in the first 72 hours of life with focal clonic seizures of one limb; MRI confirms a territorial infarct, usually in the left middle cerebral artery distribution.
• Intracranial haemorrhage — intraventricular haemorrhage in preterm infants; subdural, subarachnoid or parenchymal bleeds in term babies after difficult deliveries.
• Central-nervous-system infection — bacterial or viral meningitis/encephalitis, including TORCH infections (cytomegalovirus, toxoplasmosis, herpes) and increasingly Group B Streptococcus, E. coli and Listeria.
• Metabolic disturbances — hypoglycaemia, hypocalcaemia, hyponatraemia, and inborn errors of metabolism (urea cycle disorders, mitochondrial disease, non-ketotic hyperglycinaemia, sulphite oxidase deficiency).
• Vitamin-responsive epilepsies — pyridoxine-dependent epilepsy (PDE-ALDH7A1), pyridoxal phosphate-dependent epilepsy, biotinidase deficiency, folinic-acid-responsive seizures. These are uncommon but critical to recognise because targeted vitamin treatment is curative for seizures and can prevent severe disability.
• Brain malformations — cortical dysplasia, polymicrogyria, schizencephaly, holoprosencephaly, lissencephaly and tuberous sclerosis lesions.
• Genetic neonatal-onset epilepsies — KCNQ2 (self-limited familial neonatal epilepsy and developmental-and-epileptic encephalopathy), KCNQ3, SCN2A (gain-of-function neonatal-onset), STXBP1, CDKL5, KCNT1, and others. These often present with sequential or migrating focal seizures and a striking EEG.
• Withdrawal from in-utero exposure (maternal opioid use), neonatal abstinence syndrome, or local-anaesthetic toxicity from inadvertent intrapartum fetal scalp injection.

Treatment

Treatment of neonatal seizures is urgent — prolonged seizures and high seizure burden are independently associated with worse neurodevelopment. However, every antiseizure medicine used in the newborn period also has potential adverse effects on the developing brain, so the principle is: confirm seizures electrographically, treat promptly with the most evidence-based agent at the right dose, and identify and treat the underlying cause in parallel.

• Phenobarbital — the worldwide first-line drug. Loading dose 20 mg/kg IV, with further 10 mg/kg doses up to 40 mg/kg total. Stops seizures in roughly 40–60% of acute-symptomatic cases; effectiveness is lower in HIE and after multiple loading doses. Tested head-to-head against levetiracetam in NEOLEV2 (2020): phenobarbital achieved seizure freedom in 80% vs. 28% for levetiracetam — but at the cost of more sedation and respiratory compromise.
• Levetiracetam — increasingly used as first-line in many NICUs because of a more favourable side-effect profile, easier monitoring (no need for blood levels), and possible neuroprotective profile in animal models, despite the lower efficacy shown in NEOLEV2. Loading 40–60 mg/kg IV.
• Midazolam (or other benzodiazepines) — second- or third-line continuous infusion when phenobarbital and levetiracetam fail; effective but causes hypotension and sedation.
• Lidocaine — used in some European centres (especially Scandinavia) as second-line after phenobarbital; effective for refractory seizures, though cardiac arrhythmia is a risk and it must not follow recent phenytoin.
• Phenytoin / fosphenytoin — historically used as second-line; less preferred now because of unpredictable pharmacokinetics in the newborn, cardiac monitoring needs and infusion-site reactions.
• Pyridoxine, pyridoxal phosphate, biotin and folinic acid — should be tried empirically in any baby with refractory neonatal seizures of unclear cause: pyridoxine 100 mg IV under EEG observation, biotin 10 mg, folinic acid 5 mg twice daily. These are diagnostic and therapeutic for the vitamin-responsive epilepsies.
• Targeted treatment of the underlying cause: cooling for moderate-to-severe HIE, antibiotics and aciclovir for suspected infection, correction of glucose/calcium/sodium, surgery for very rare expanding haemorrhage, ketogenic diet for certain refractory presentations.

Stopping antiseizure medication and the question of duration

A major shift in the last decade has been towards stopping antiseizure medication early — often before the baby is discharged from the NICU — in babies with acute-symptomatic seizures whose underlying cause has resolved and who are otherwise well. The 2021 ILAE consensus and several observational studies show that, once EEG seizures stop, the great majority of babies with HIE or perinatal stroke remain seizure-free if their first medication is stopped within days, even though they may carry a small ongoing risk of later epilepsy.

Babies with a defined neonatal-onset genetic epilepsy or a structural brain malformation usually need ongoing treatment beyond the NICU stay; the diagnosis is made on genetics and imaging, and choice of medication is then guided by the syndrome (for example, sodium-channel blockers such as carbamazepine and phenytoin for KCNQ2 and gain-of-function SCN2A).

Prognosis

Outcome after neonatal seizures depends overwhelmingly on the underlying cause and on the seizure burden, not on the seizures themselves. Babies with acute-symptomatic seizures from mild HIE or transient hypoglycaemia who become quickly seizure-free often have good neurodevelopmental outcomes, while those with severe HIE, large infarcts, brain malformations or severe genetic epileptic encephalopathies face a higher risk of cerebral palsy, epilepsy, learning disability and autism spectrum disorder. About 10–30% of survivors of any neonatal seizure go on to develop epilepsy in childhood — the figure is much higher after severe HIE or genetic causes.

Modern long-term follow-up programmes (combining infant developmental assessment, EEG monitoring at key ages and serial imaging) help identify children who will benefit from early intervention.

How an educational review can help

After a NICU stay involving seizures, families are often handed a great deal of complex information at once — EEG reports, MRI findings, a list of medications, and uncertain prognostic statements. An educational review can translate these into plain language, place the findings against current ILAE guidance, and help you prepare focused questions for your treating team about medication duration, follow-up, developmental support and the chance of later epilepsy.

It is an educational second opinion — not a diagnosis, treatment or prescription — and it does not replace the care of your child's own clinicians.