Neonatal Seizures

Clinical Guideline

V1.0

September 2020
Summary

Possible Seizures
1. Admit to NNU
2. ABC
3. Measure glucose

Evaluate History and Examination

Use section 2 to evaluate seizures

Initial Treatment
1. ABC
2. IV cannulation
3. First line investigations
4. Give antibiotics +/- Aciclovir
5. Initiate CFM monitoring

Treat seizures if they are

 Over 3 minutes
 Greater than 3 seizures per hour
 Associated dysautonomia
 Consider treating electrical seizures
As per treatment algorithm

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 Treat underlying Symptomatic cause
Consider HIE, Hypoglycaemia, Metabolic, Sepsis, Drug withdrawal

Phenobarbitone CD
Intravenous: 20mg/kg
Loading dose over 20 minutes

Phenobarbitone CD
Intravenous: 10mg/kg
Aim to get Phenobarbitone level to ~40mcg/mL

If seizure continues If hypotensive/unstable/Concerns

about IV access

Phenytoin Levetiracetam
Intravenous: 20mg/kg Intravenous: 40mg/kg
Loading dose over 20 minutes Loading dose over 15 minutes

If seizure continues Inform PNTS

team

Midazolam CD
IV loading 150-200 microgram/kg
Then infusion 60 microgram/kg/hour adjusted according to response
(Beware can make seizures worse)

If seizure continues

Pyridoxine Trial
Intravenous 100mg
2 doses – 2 hours apart

Add Biotin (available as tablets that can be crushed. Order from pharmacy) and
Calcium folinate (IV available from pharmacy or emergency cupboard) after
d/w neurology / metabolic team

If seizure continues

Consider Lidocaine / Hypothermia / Phenobarbital coma

Valproate can be used if metabolic seizure disproven

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1. Aim/Purpose of this Guideline
Seizures are the commonest clinical manifestation of neurological dysfunction in
neonates. The estimated incidence is 1.5 - 5.5 per 1000 births in term infants;
however this is higher in preterm infants. ~85% of seizures in neonates are
symptomatic in origin occurring secondary to an identifiable aetiology. Prompt
diagnosis of the cause is important as this can help target the most appropriate
approach to management

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2. The Guidance
2.1. Aetiology

The commonest causes of ‘symptomatic’ seizures in neonates are; hypoxic

ischaemic encephalopathy, infarctions, intracranial infection, hypoglycaemia, inborn
errors of metabolism and structural malformations. The other 6-10% comprise of
the neonatal epilepsy syndromes such as early myoclonic encephalopathy and self-
limited neonatal seizures.

2.2. Recognition
Clinical diagnosis of neonatal seizures is difficult; paroxysmal events are
misdiagnosed as epileptic in ~50% of cases. A seizure is defined as a transient
occurrence of symptoms and / or signs due to abnormal excessive or synchronous
neuronal activity within the brain. Several different seizure types can exist in
neonates (See Table 1 on next page).

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Table 1. The ILAE classification of neonatal seizures types.

Type & frequency Clinical signs 12 lead EEG findings

Automatisms Coordinated motor activity mimicking a Variable correlation. Can require
voluntary movement. Typically oral with other more than one EEG. Easily
features. For example leg cycling. mistaken for non-seizure activity.

Tonic Sustained stiffening & posturing of Variable correlation. Generalised

limbs/trunk. Can include deviation of head or tonic posturing is rarely epileptic
eyes. in origin.

Clonic Rhythmic jerking at 1-4Hz. Can be unifocal or Correlation high, especially if

multifocal and symmetrical or asymmetrical. unifocal.

Myoclonic ‘Shock like’ jerking usually in the flexor Difficult to differentiate from non-
muscle groups. Can be single or multiple. epileptic myoclonus.

Epileptic Spasm Sudden flexion, extension or predominantly Can be difficult to differentiate

proximal and truncal muscle groups. between myoclonic seizures.

Autonomic A distinct alteration in autonomic nervous Can present at apnoea. Typically

system function. Can involve pupils / seen alongside other seizure
cardiovascular / gastrointestinal / vasomotor types.
and thermoregulation.

Behavioural arrest A sudden pause in activities. Freezing or May have other autonomic
immobilisation of movements. features.

Unclassified Unusual clinical features or inadequate Poor EEG correlation.

description.

2.3. Evaluation - (Resuscitation if needed should always be the priority)

2.3.1. History

Take a thorough birth history to include:

 Gestational age
 Pregnancy complications (Gestational diabetes / infection / Growth
restriction)
 Maternal drug use including recreational.
 Risk factors for infection (See infection guideline)
 Labour + delivery (?Instrumentation / trauma)
 Does baby meet criteria A for therapeutic cooling?

Is there a family history of seizures or metabolic conditions?

2.3.2. Seizure description

It is important that a description (semiology) of the paroxysmal event is

documented in the notes by the witness.

This should include: the type of movement seen and limbs involved, the onset
and offset of movements, frequency + symmetry of movements, duration of
movements, any eye or head deviation (versive) movements and association
of movements with sleep.
Neonatal Seizures Clinical Guideline V1.0
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 An attempt to hold the limb and the response to this action should be
documented. This is because seizures are highly unlikely to modify or stop
with simple restraint.

2.3.3. Examination

Observations should be performed including: Temperature / BP / HR /

Saturations / RR.

A thorough examination should be completed of all systems but to include the

following key areas:

Examination area Specific diagnostic signs and considerations

Macrocephaly - Hydrocephalus / megalencephaly
Head Microcephaly - Congenital CNS infections / Cerebral malformations
Circumference Sutures and anterior fontanelle -Hydrocephalus and
meningoencephalitis

Vesicular lesions - Consider HSV infection / Incontinentia pigmenti

Ash leaf macule - Tuberous sclerosis (Use Woods lamp)
Skin
Port wine stain - Consider Sturge-Weber syndrome
Blueberry Muffin skin - Consider congenital Rubella

Ophthalmology Absent red reflex - Retinoblastoma or Cataracts

Coloboma - Associated with absent Corpus Callosum

Mid facial hypoplasia (Cleft palate, Hypotelorism) Cerebral dysgenesis

Dysmorphology
Multiple congenital abnormalities - Consider genetic diagnosis

Neurological Hypotonia / Jittery / Poor suck / reduced neonatal reflexes - HIE

status Reduced response + other concerning features - Severe systemic
disease

2.3.4. Investigations

A set of first line investigations are required to try to understand the underlying
seizure aetiology. Supplementary investigations may be requested based on
results from the first line investigations or at the discretion of the consultant
neonatologist / paediatric neurologist.

Investigation type First line investigations Supplemental investigations.

U+E, Lab Glucose, Blood gas,
Ammonia, TORCH screen,
Bone profile, Magnesium, Liver
Acylcarnitines, Amino acids,
Blood function tests, Lab lactate, FBC,
Biotinidase, Carbohydrate deficient
Coagulation screen, Blood
transferrin, Carnitine profile.
culture, Blood Herpes PCR
Organic acids, 5-Alpha aminoadipic
Urine Consider a toxicology screen
semialdehyde (5-AASA)
Cerebrospinal fluid
Glucose, Protein, Microscopy + Lactate, Amino acids,
(When safe to
Culture, Viral PCR Neurotransmitters.
undertake)
Neuroimaging Cranial ultrasound Cranial MRI
Cerebral function monitor +
Neurophysiology Departmental EEG
Consider departmental EEG
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 2.3.5. Monitoring of seizure

2.3.5.1. Clinical monitoring

Nursing staff and medical staff should document any abnormal

movements or concerns about autonomic features on the neonatal
seizure record sheet (See Appendix 3)

2.3.5.2. Cerebral function monitor (CFM; also known as Amplitude

integrated EEG (aEEG))

aEEG should be started if a seizure disorder is suspected; this is

especially so in the paralysed infant as clinical seizures will be
supressed.

Seizures normally present as an abrupt transient rise in the lower

margin. Often accompanied by a smaller rise in the upper margin;
hence narrowing of the bandwidth.

Due to limited electrode channels it is not possible to identify the locus

of abnormal electrical activity as well as frequency and duration of
seizures. Focal or brief seizures may also not be identified on CFM.

2.3.5.3. Departmental EEG

An EEG can be useful in confirming seizures and looking at the

background cortical activity. Video EEG’s are useful when neurological
signs are subtle and in neonates who are sedated. They can aid with
locating the origin of the seizure. Their sensitivity is higher than aEEG
but they may still miss seizures originating from deeper structures.

The neurophysiology scientists are an excellent resource if there are

any questions about suitability for EEG.

2.4. Treatment

2.4.1. Inform the on-call consultant of the possibility of seizures.

2.4.2. It is important to firstly consider and treat underlying aetiologies which cause
symptomatic seizures.

1. Correct blood glucose (See hypoglycaemia guideline).

2. Give antibiotics and consider anti-virals if meningoencephalitis is

likely.

3. Correct underlying metabolic / electrolyte abnormalities.

2.4.3. The infant should be nursed in an environment that minimises all sensory
stimulation.

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 2.4.4. There is no consensus on when to initiate treatment for seizures. Consider
treatment in the following scenarios.

1. A single seizure lasting > 3 mins or greater than 3 seizures per

hour.
2. Treat if signs of dysautonomia are present e.g cardiovascular
compromise.
3. Consider treating electrographic seizures only to reduce seizure
burden.

2.4.5. Be prepared to give respiratory support when initiating anticonvulsant

therapy.

2.4.6. Treatment algorithm

See summary sheet for treatment algorithm

2.5. Antiepileptic choice + monitoring

 Phenobarbitone (also known as phenobarbital):- Is the most studied anti-

epileptic in neonates. It has a more predictable metabolism and is more
cardiovascularly stable than Phenytoin 7. Phenobarbitone can be sedating and
therefore cause electroclinical dissociation (Clinical seizure reduces but
continues electrographically). Measure levels after 12 hours and aim for a level
of ~40mg/l.

 Phenytoin:- Phenytoin is used as a second line and should be used if the child
has a stable cardiovascular system. Due to its variable metabolism phenytoin
should not be used for a prolonged period. Measure a level after 12 hours;
levels should be 8-16mg/l. Levels are likely to be higher in therapeutically
cooled infants and therefore maintenance doses are best avoided.

 Levetiracetam:- Limited data but case series have not identified major adverse
side effects. 7,8

 Lidocaine:- In the only randomised controlled trial of Lidocaine in neonatal

seizures it had a response rate of 70%. There is a narrow therapeutic window
and in therapeutic hypothermia a dose modification is required. It should also
not be used after Phenytoin to reduce chances of arrhythmias. The dosage
schedule changes depending if the infant is preterm of term. The dosing
schedule is found in the neonatal formulary.

 Midazolam:- Benzodiazepines act on the GABA receptors. It is understood that

the developing brain may have an excitatory response to benzodiazepines
rather than the preferred inhibition. Because of this effect doctors should be
aware of the potential of Midazolam making seizures worse and therefore
preferential consideration of Lidocaine infusion should be thought about early.
Some evidence suggests that midazolam can work synergistically with
Lidocaine.

 Sodium Valproate:- Sodium valproate has some restrictions to its use due to
the potential to cause severe hepatotoxicity in unrecognised metabolic disorders
e.g mitochondropathies. Other side effects can include pancreatitis /
Neonatal Seizures Clinical Guideline V1.0
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 thrombocytopenia / neutropenia. Therefore experience in the neonatal period is
highly limited 5. However, it is useful in the term neonate with generalised
refractory seizures where a metabolic cause is highly unlikely or disproven.
Therefore, sodium valproate should be reserved for after a discussion with a
paediatric neurologist.

2.6. Discontinuation of anti-epileptics

The majority of seizures in the neonatal population are symptomatic in origin. Seizure
burden is highest around the time of insult and usually has a finite and short period of
activity.

In the context of acute symptomatic seizures discontinuing the anti-epileptics quickly

when the seizures have stopped should be considered. If it is likely that there is an
underlying neurometabolic syndrome precipitating the seizures then advice from the
local Consultant with interest in epilepsy or Bristol Paediatric Neurology team should
be sought.

2.7. Vitamin responsive seizures

Where a vitamin responsive seizure is suspected advice from the paediatric neurology
team should be sought.
They have a wide variability in the presentation but 40% of pyridoxine dependent
seizures occur within the first 24 hours9.
Nearly 40% of these infants present with evidence of hypoxic ischaemic
encephalopathy, low Apgar scores and cord acidosis.
They are irritable, often have low tone and have treatment refractory seizures with
conventional anti-epileptics.

Investigations for vitamin responsive seizures and a therapeutic trial of vitamins

should be given for refractory seizures.

A CFM or EEG should be in place before giving the vitamins as the electrographic
seizures may quickly improve.

2.7.1. Pyridoxine:- 100mg Intravenous trial dose. Dose can be repeated after 2
hours 10.
Can be given intravenously but be aware can cause apnoea and cerebral
depression. Pyridoxine can also cause a transient drop in blood pressure
so monitoring should be in place.
Send a urine for 5- Alpha Amino Adipic Semialdehyde (5-AASA) which is
commonly elevated in pyridoxine seizures.

2.7.2. Biotin:- Discuss with paediatric neurology team for dosage schedule.

2.7.3. Calcium Folinate (Follinic acid):- Discuss with paediatric neurology

team for dosage schedule.

Neonatal Seizures Clinical Guideline V1.0

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3. Monitoring compliance and effectiveness
Element to be Compliance with policy/Key changes to practice
monitored
Lead Dr Christopher Bell (Consultant Paediatrician and Neonatal
Governance lead)
Tool Audit and review tool using WORD or Excel template
Frequency Annual
Reporting Consultant led neonatal clinical guidelines group
arrangements
Acting on Dr Chris Warren Consultant Paediatrician and Neonatologist
recommendations
and Lead(s)
Change in practice Required changes to practice will be identified and actioned within
and lessons to be 3 months, immediately if required. A lead member of the team will
shared be identified to take each change forward where appropriate.
Lessons will be shared with all the relevant staff/stakeholders

4. Equality and Diversity

4.1. This document complies with the Royal Cornwall Hospitals NHS Trust
service Equality and Diversity statement which can be found in the
'Equality, Inclusion & Human Rights Policy' or the Equality and Diversity
website.

4.2. Equality Impact Assessment

The Initial Equality Impact Assessment Screening Form is at Appendix 2.

Neonatal Seizures Clinical Guideline V1.0

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Appendix 1. Governance Information
Document Title
This document replaces (exact
title of previous version):
Date Issued/Approved:
Date Valid From:
Date Valid To:
Directorate / Department
responsible (author/owner):
Contact details:
Brief summary of contents
Suggested Keywords:
Target Audience
Executive Director responsible
for Policy:
Approval route for consultation
and ratification:
General Manager confirming
approval processes
Name of Governance Lead
confirming approval by specialty
and care group management
meetings
Links to key external standards
Related Documents:
Neonatal Seizures Clinical Guideline V1.0
Neonatal Seizures Clinical Guideline V1.0
New Document
July 2020
September 2020
September 2023
Dr Christopher Butler (Consultant Paediatrician
with Expertise in Epilepsy and Neurology Lead)
01872 252667
This guideline is designed to provide guidance to
neonatal staff on the treatment of seizures in the
neonatal period
Neonatal, Epilepsy
RCHT CFT KCCG

Medical Director
Neonatal Guidelines Group
Mary Baulch
Caroline Amukusana
None required
1. Management of seizures in neonates.
Nottingham university Neonatal unit guideline.
2. ILAE classification of seizures and the
epilepsies. Epilepsia; Pressler et al.
3. Shellhaas RA. Clinical features, evaluation, and
diagnosis of neonatal seizures. Uptodate.
4. El-Dib M, Chang T, Tsuchida TN, et al. Amplitude-
integrated electroencephalography in neonates.
Pediatr Neurol 2009
5. Ainsworth SB. Neonatal Formulary: Drug Use in
Pregnancy and the First Year of Life.
6. Slaughter LA, Patel AD, Slaughter JL.
Pharmacological treatment of neonatal seizures: a
systematic review. J Child Neurol 2013
7. Ramantani G, Ikonomidou C, Walter B, et al.
Levetiracetam: safety and efficacy in neonatal
Page 11 of 15
 seizures. Eur J Paediatr Neurol 2011;
8. Fürwentsches A, Bussmann C, Ramantani G, et al.
Levetiracetam in the treatment of neonatal
seizures: a pilot study. Seizure.
9. Baxter P. Pyridoxine-dependent and pyridoxine-
responsive seizures. Dev Med Child Neurol 2001
10. Evalina London Paediatric Formulary, Online
http://cms.ubqo.com/public/d2595446-ce3c-47ff-
9dcc-63167d9f4b80#
11. Plymouth Neonatal Intensive Care neonatal
seizure guideline.

Training Need Identified? Yes

Publication Location (refer to
Policy on Policies – Approvals Internet & Intranet  Intranet Only
and Ratification):
Document Library Folder/Sub
Clinical / Neonatal
Folder

Version Control Table

Version Changes Made by

Date Summary of Changes
No (Name and Job Title)
Dr Christopher Butler
(Consultant
July 2020 V1.0 Initial version Paediatrician with
Expertise in Epilepsy
and Neurology Lead)

All or part of this document can be released under the Freedom of Information
Act 2000

This document is to be retained for 10 years from the date of expiry.

This document is only valid on the day of printing

Controlled Document
This document has been created following the Royal Cornwall Hospitals NHS Trust
Policy for the Development and Management of Knowledge, Procedural and Web
Documents (The Policy on Policies). It should not be altered in any way without the
express permission of the author or their Line Manager.

Neonatal Seizures Clinical Guideline V1.0

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 Appendix 2. Initial Equality Impact Assessment
Section 1: Equality Impact Assessment Form
Name of the strategy / policy /proposal / service function to be assessed
Neonatal Seizures Clinical Guideline V1.0
Directorate and service area: Is this a new or existing Policy?
Child Health, Neonatal New
Name of individual/group completing EIA Contact details:
Dr Christopher Butler 01872 252667

1. Policy Aim
Who is the
strategy / policy / The guideline is aimed at hospital staff responsible for the
proposal / service assessment and treatment of seizures on the neonatal unit.
function aimed at?

2. Policy Objectives As above

3. Policy Intended
Outcomes
To improve the well-being of patients by offering the appropriate
management of epilepsy

4. How will
you measure
See section 3 above (Monitoring compliance and effectiveness)
the outcome?

5. Who is intended
to benefit from the Patients, parents/carers and staff
policy?
6a). Who did you Local External
Workforce Patients Other
consult with? groups organisations
x

b). Please list any

groups who have Neonatal Guidelines group
been consulted
about this procedure.
c). What was the
outcome of the Approved
consultation?

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7. The Impact
Please complete the following table. If you are unsure/don’t know if there is a negative impact
you need to repeat the consultation step.
Are there concerns that the policy could have a positive/negative impact on:
Protected
Yes No Unsure Rationale for Assessment / Existing Evidence
Characteristic
Age
X
Sex (male, female
non-binary, asexual X
etc.)

Gender
reassignment X

Race/ethnic
Any information provided should be in an accessible format
communities X for the parent/carer’s needs – i.e. available in different
/groups languages if required/access to an interpreter if required
Disability
(learning disability,
physical disability, Those parent/carers with any identified additional needs will
be referred for additional support as appropriate - i.e to the
sensory impairment,
X Liaison team or for specialised equipment.
mental health Written information will be provided in a format to meet the
problems and some family’s needs e.g. easy read, audio etc
long term health
conditions)
Religion/
other beliefs X

Marriage and civil

partnership X

Pregnancy and
maternity X

Sexual orientation
(bisexual, gay, X
heterosexual, lesbian)
If all characteristics are ticked ‘no’, and this is not a major working or service
change, you can end the assessment here as long as you have a robust rationale
in place.
I am confident that section 2 of this EIA does not need completing as there are no highlighted
risks of negative impact occurring because of this policy.

Name of person confirming result of initial

Neonatal Guidelines Group
impact assessment:
If you have ticked ‘yes’ to any characteristic above OR this is a major working or
service change, you will need to complete section 2 of the EIA form available here:
Section 2. Full Equality Analysis

For guidance please refer to the Equality Impact Assessments Policy (available
from the document library) or contact the Human Rights, Equality and Inclusion
Lead debby.lewis@nhs.net

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Appendix 3. Neonatal Seizure Chart (Pilot Form)

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