Observational Study Medicine ®

Neonatal seizures: Etiologies, clinical

characteristics, and radiological features
A cross-sectional study
Downloaded from http://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy

Mohammed Almuqbil, MDa,b,c,* , Yousof Alrumayyan, MDb, Shahad Alattas, MDb, Duaa Baarmah, MDb,
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 02/18/2024

Waleed AlTuwaijri, MDa,b, Ahmed AlRumayyan, MDa,b, Mohammed Tala AlRifai, MDa,b, Asma Al Madhi, MDd,
Hassan Al-shehri, MDe, Saif Alsaif, MDa,f

Abstract
Seizures are a common clinical indication of central nervous system damage or abnormality in neonates. We aimed to identify the
etiologies, clinical characteristics, and radiological features of neonatal seizures. This is a cross-sectional, retrospective, descriptive
study using data obtained from the neonatal intensive care unit in King Abdulaziz Medical City (KAMC), a governmental, academic
tertiary hospital in Riyadh, Saudi Arabia. The population of interest were neonates diagnosed with a neonatal seizure at KAMC
between April 2015 and March 2019. A total of 61 patients with neonatal seizures were included in the study. The most common
etiology was hypoxic-ischemic encephalopathy (43%). A total of 32 patients were full-term (52.5%). Around one-fifth of the study
sample (21.3%) had a family history of neonatal seizures. Around 43.0% of the patients had epilepsy episodes. More than half of
the patients (57.0%) were on one anti-seizure medication. Patients were followed up after 1 year, they had multiple comorbidities,
including developmental delay, epilepsy, and cerebral palsy. Developmental delay was identified in 62.3% of the patients. A total
of 19 patients have passed away (31%). Neonatal seizures are a common manifestation of neurologic disorders in neonates and
are associated with high morbidity and mortality. Therefore, early identification of seizure etiology and proper management may
help to improve the outcome.
Abbreviations: EEG = electroencephalography, HIE = hypoxic ischemic encephalopathy, IEM = inborn errors of metabolism,
KAMC = King Abdulaziz Medical City, MLPT = moderate and late preterm, SD = standard deviation.
Keywords: Apgar score, genetic seizure, metabolic seizure, neonatal neurological disorders, neonatal seizure

1. Introduction provide a massive challenge to physicians due to their poor

responsiveness to antiepileptic medicines.[4] In addition, elec-
Seizures are a common clinical indication of central nervous troencephalographic findings are not specific, and other tests,
system damage or abnormality in neonates.[1] The incidence of such as magnetic resonance imaging, may yield normal results,
clinical seizures in infants is about 1 to 3 per 1000.[2] According making it difficult to establish a proper diagnosis.[5] There
to a previous study, the majority of newborn convulsions are are several neurodevelopmental prognostic variables among
attributable to known causes and are seldom associated with term newborns with seizures. There is evidence that late-on-
neonatal-onset epilepsy.[3] Specific etiologies of seizure activ- set seizures are linked with improved outcomes.[6] Neonatal
ity, such as metabolic diseases, are difficult to detect and, as seizures were substantially related to an increased chance of
a result, are often overlooked or misunderstood. Seizures developing epilepsy, cerebral palsy, headaches, and intellectual
associated with inherited metabolic disorders, for instance, impairments.[7,8]

Informed consent was obtained from all subjects involved in the study. neurology, Genetics and Metabolism, Department of Pediatrics, King Abdullah
The authors have no funding and conflicts of interest to disclose. specialized Children’s Hospital (KASCH), King Abdulaziz Medical city (KAMC),
Ministry of national guard health affairs (MNG-HA), Prince Mutib Ibn Abdullah Ibn
All data generated or analyzed during this study are included in this published Abdulaziz, AR Rimayah, P.O. Box 22490, MC 1940, Riyadh 11426, Saudi Arabia
article [and its supplementary information files]. (e-mail: [email protected], [email protected]).
This study was approved by the institutional review board at King Abdullah Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.
International Research Center in Riyadh, Saudi Arabia. This is an open-access article distributed under the terms of the Creative
a
College of Medicine, King Saud bin Abdulaziz University for Health Sciences Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is
(KSAU-HS), Riyadh, Saudi Arabia, b Department of Pediatrics, King Abdullah permissible to download, share, remix, transform, and buildup the work provided
Specialist Children Hospital (KASCH), National Guard Health Affairs (NGHA), it is properly cited. The work cannot be used commercially without permission
Riyadh, Saudi Arabia, c King Abdullah International Medical Research Center from the journal.
(KAIMRC), Ministry of National Guard, Riyadh, Saudi Arabia, d Department of How to cite this article: Almuqbil M, Alrumayyan Y, Alattas S, Baarmah D,
Pediatric Neurology, National Neuroscience Institute, King Fahad Medical City, AlTuwaijri W, AlRumayyan A, AlRifai MT, Al Madhi A, Al-shehri H, Alsaif S.
Riyadh, Saudi Arabia, e Department of Pediatrics, College of Medicine, Imam Neonatal seizures: Etiologies, clinical characteristics, and radiological features: A
Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia, f Department of cross-sectional study. Medicine 2023;102:37(e35185).
Neonatology, King Abdulaziz Medical City (KAMC), National Guard Health Affairs
(NGHA), Riyadh, Saudi Arabia. Received: 1 April 2023 / Received in final form: 26 July 2023 / Accepted: 21
August 2023
*Correspondence: Mohammed Almuqbil, College of medicine, King Saud
bin Abdulaziz University for health Sciences (KSAU-HS), Consultant Pediatric http://dx.doi.org/10.1097/MD.0000000000035185

1
 Almuqbil et al. • Medicine (2023) 102:37Medicine

Neonatal electroencephalography (EEG) is very important 2.3. Data collection

for the diagnosis of neonatal seizures since the majority of neo- The etiologies, clinical characteristics, and radiological fea-
natal seizures are not noticeable.[9] Previous literature reported tures of the patients were collected from the electronic med-
that in epilepsy, EEG sensitivity ranges from 25% to 56%, ical records of the patients. The neonatal seizure in this study
which is relatively low.[10] Some individuals experience symp- was diagnosed as per Volpe classification schema. It is a widely
toms resembling those of an epileptic seizure, but without any used classification tool for classifying seizures. Volpe classifi-
abnormal electrical activity in the brain.[10,11] These are clinical cation schema is based on the paroxysmal clinical phenom-
manifestations that resemble seizures but are typically not epi- ena documented in medical records by consulting pediatric
leptic in nature. These seizures, which are caused by mental
Downloaded from http://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy

neurologists, attending neurologists, house staff, or neonatal

duress or a physical condition, could be termed non-epilep- nursing staff.[23] In our study, the seizure types were catego-
tic.[10,11] For this reason, EEG background patterns have been rized according to Volpe classification schema, meaning that
used in the etiological categorization of newborns, particularly
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 02/18/2024

the paroxysmal clinical phenomena documented in medical

term neonates with seizures. Multiple studies have indicated records (by consulting pediatric neurologists, attending neu-
that frequent electrographic seizures in newborns are substan- rologists, house staff, or neonatal nursing staff) were used to
tially associated with severe brain damage and major develop- classify the seizure types based on the schema. Only the most
mental delay.[12,13] prominent seizure type was considered for the study in cases
Acute provoked seizures and early-onset epilepsies are dis- where there were several seizure types. Electroencephalogram,
tinct seizure types with distinct underlying causes, clinical mani- electrolyte, and brain imaging examinations were performed
festations, and prognoses. Acute provoked seizures are triggered on infants who had seizures if their clinical situation allowed
by specific factors (such as head trauma, fever, metabolic it. All of the enrolled neonates had follow-up by phone call,
imbalances, and infections, or an isolated event such as brain during which developmental and seizure histories were gath-
injury).[14,15] They occur in response to the imminent presence ered. The National Guard seizure protocol was used as the
of the provocateur and are typically isolated occurrences of any standard protocol for the management and investigation of
age. Once the triggering factor is treated or eliminated, these neonatal seizures.
seizures typically cease.[15] EEG findings may be normal or may
reveal abnormalities related to the underlying cause.[15] Early-
onset epilepsies, on the other hand, are a group of epileptic
disorders that typically manifest in infancy or early childhood. 2.4. Ethical approval
Typically, developmental or genetic factors abnormalities. Early- This study was approved by the institutional review board at
onset epilepsies may manifest as recurrent seizures that occur King Abdullah International Research Center in Riyadh, Saudi
over a prolonged period and commence in childhood (typically Arabia.
before the age of 3).[14,16,17] In early-onset epilepsies, EEG record-
ings frequently reveal aberrant brain activity (including spikes,
sharp waves, and other epileptiform discharges, even between 2.5. Data analysis
seizures).[16,17]
Inborn errors of metabolism (IEM) are an uncommon cause Summary statistics were presented as the mean (SD, standard
of newborn seizures compared to other causes.[18] Due to an deviation) for continuous variables and as frequencies and per-
increased demand for glucose and oxygen, metabolic diseases centages for the categorical data. The data analysis was com-
have been related to brain changes such as cerebral hyperperfu- pleted using SPSS Statistics Version 27.
sion.[19] In the newborn era, the diagnosis of IEM remains prob-
lematic. Not all IEMs are screened for in newborns. Neonatal
convulsions resistant to medication should raise the possibility 3. Results
of IEMs.[20] According to studies, inherited metabolic disorders
3.1. Patients’ baseline characteristics
are often linked with a bad prognosis.[2]
Previous literature has demonstrated that the APGAR score Table 1 below presents the baseline characteristics of the
is useful for defining the birth status of newborns and predicting patients. A total of 61 patients fit the inclusion criteria and were
their outcomes has been validated by research.[21] In addition, included in the study. Almost half of the patients (57.4%; n =
it has been established that an APGAR score of less than 3 at 5 35) were males, and 32 were term births (52.5%). The median
minutes of life is predictive of poor neurologic outcomes.[22] This gestational age was 38 weeks (interquartile range (IQR): 23–39).
research aims to characterize the etiology, clinical features, and The remaining 48.0% of the patients were preterm births
radiological characteristics of neonatal seizures. (24.6% late preterm, 23.0% extreme preterm). The median
birth weight was 2.75 kg (IQR: 0.5–3.1), and the median birth
head circumference was 34.0 cm (IQR: 20.5–35.0). The average
2. Methods APGAR score at 5 minutes was 4 (SD: 2.6). More than half of
the births (62.3%) were by cesarean section, and 36.1% were
2.1. Study design spontaneous vaginal births.
This is a cross-sectional, retrospective study that was conducted The most common etiologies for the patients were hypox-
at the neonatal intensive care unit in King Abdulaziz Medical ic-ischemic encephalopathy, and intracranial hemorrhage,
City (KAMC). KAMC is a governmental, academic tertiary hos- accounting for 42.6% and 19.7%, respectively (Fig. 1).
pital in Riyadh, Saudi Arabia. The data were extracted for the Almost one-fifth of the patients (21.3%) had a family
period between April 2015 and March 2019. history of seizure. At birth, more than half of the patients
(54.1%) needed intubation, and 23.0% needed positive pres-
sure ventilation (PPV). Fetal declaration was reported for 7
patients. Almost one-quarter of the patients (23.0%) were
2.2. Study population
diagnosed with congenital anomalies. A similar proportion
Study subjects were recruited from the neonatal intensive care of the patients (21.3%) were diagnosed with dysmorphism.
unit in KAMC. The population of interest in this particular Figure 2 presents the etiology and associated gestational age
study was the newborn children diagnosed with a neonatal sei- comorbidities. The head size was normal for most of the
zure. The exclusion criterion was if the seizure occurred after 29 patients (73.8%). The EEG background was normal for only
days of life. 39.3% of the patients. EEG epileptiform discharges were

2
 Almuqbil et al. • Medicine (2023) 102:37www.md-journal.com

Table 1
Patients’ baseline characteristics.
Variable Category Frequency Percentage

Etiology (gestational age comorbidities) Hypoxic-ischemic encephalopathy 26 42.6

Intracranial hemorrhage 12 19.7
Genetic syndromes 10 16.4
Brain malformation 2 3.3
Downloaded from http://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy

Inborn errors of metabolism 1 1.6

Others/unknown 10 16.4
Gestational age group
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 02/18/2024

Term 32 52.5
Late preterm 15 24.6
Extreme preterm 14 23.0
Gender
Male 35 57.4
Female 26 42.6
Family history
Yes 13 21.3
No 41 67.2
Pregnancy
Eventful 40 65.6
Uneventful 20 32.8
Unknown 1 1.6
Birth history
Spontaneous vaginal delivery 22 36.1
Cesarean section 38 62.3
Unknown 1 1.6
Resuscitation history at birth
Oxygenation and bagging 7 11.5
Positive pressure ventilation 14 23.0
Intubation 33 54.1
Unknown 7 11.5
Fetal deceleration 7 14.9
Congenital anomalies 14 23.0
Dysmorphism 13 21.3
Head size
Normal 45 73.8
Microcephaly 5 8.2
Macrocephaly 4 6.6
EEG background
Normal 24 39.3
Abnormal 29 47.5
Not Done 8 13.1
EEG epileptiform discharges 20 32.8
EEG burst suppression 9 14.8
Treated with cooling 20 32.8
Continuous variables Mean/median Standard Deviation/interquartile range
Gestational age (wk) (Median) 38.0 23–39
Apgar score at 5 min (Mean) (n = 60) 4.0 2.6
Cord pH (Mean) (n = 22) 6.9 0.1
Cord CO2 (Median) (n = 22) 76 0–88.8
Cord deficit (Mean) (n = 17) −11.8 5.7
Blood gas pH (Mean) (n = 52) 7.1 0.2
Blood gas CO2 (Median) (n = 52) 49 23–55.25
Gas base deficit (Median) (n = 52) −8.9 −27.0 to 4.38
Seizure onset (d) (Median) (n = 58) 1.0 1–5.25
Birth weight (kg) (Median) (n = 60) 2.75 0.5–3.1
Birth head circumference (cm) (Median) (n = 59) 34.0 20.5–35
Expired after (d) (Median) (n = 19) 5 1–16.5
Head circumference at follow-up (cm) (Mean) (n = 36) 43.75 23.5–47
Age at follow-up (Median) (n = 38) 13 1–23
Current age (mo) (Median) (n = 41) 31.0 14–37
EEG = electroencephalography.

identified in 32.8% of the patients, and 9 of them had EEG 1–5.25). For the number of seizures before treatment,
burst suppression. 45.9% of the patients had 1 seizure, 24.6% had 2 to 4
seizures, 16.4% had 5 to 10 seizures, and 3 patients had
more than 10 seizures. The main type of seizure was focal
3.2. Seizure history tonic (36.1%), followed by clonic (23.0%), lip smacking/
Table 2 below presents seizure profiles among the patients. other (19.7%), myoclonic (seven patients), and subtle (two
The overall mean time for seizure onset was 1.0 days (IQR: patients).

3
 Almuqbil et al. • Medicine (2023) 102:37Medicine

Figure 3 presents seizure types in each etiology category. The for patients who survived the neonatal period. Developmental
seizure tone was identified as normal for 37.7% of the patients, delay was identified in 62.3% of the patients. Around 43.0%
42.6% as hypotonic, and only 1 patient as hypertonic. of the patients had epilepsy episodes. Concerning cerebral palsy,
at follow-up, 39.3% of the patients were diagnosed as spastic
3.3. One year follow up and outcomes quadriplegic. Nineteen patients died (31.0%): 4 due to hypoxic
ischemic encephalopathy (HIE), 4 due to genetic/metabolic
Figure 4 presents the developmental outcome in each etiology cat- causes, 2 with brain malformations, 1 with intracranial hemor-
egory. The median follow-up age was 13.0 months (IQR: 1–23) rhage, and 7 from unknown causes. Ten deaths occurred during
the first month of life, and the remaining 9 in the first year of
Downloaded from http://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy

life. Table 3 below presents the patients outcomes after 1 year

of follow-up.
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 02/18/2024

3.4. Acute anti-seizure medication

In total, 57% of the patients received 1 drug, 28% 2 drugs,
9 patients 3 and more. Phenobarbital was administered to 60
patients (98.4%), phenytoin to 19 (31.1%), levetiracetam to
13 (21.3%), midazolam to 3, and clonazepam to one. In all,
31 patients were discharged on maintenance therapy, while 15
patients did not need maintenance therapy.

4. Discussion
Seizures are the most conspicuous manifestation of neurologic
dysfunction in the newborn era. It is crucial to determine the
underlying cause of newborn seizures. Etiology dictates prog-
nosis and outcome and directs therapy techniques.[23] Accurate
diagnosis may lead to etiology-specific treatment and may pre-
vent central nervous system impairment that might otherwise
arise if the underlying illness were left untreated. It may be
important to treat the underlying cause of seizures in order to
manage the seizures themselves.[24] In our study, HIE was the
most common seizure etiology among late preterm and term
neonates (42.6%), whereas intracranial hemorrhage was more
common among extremely preterm neonates (19.7%), which is
similar to other internationally reported studies.[3] HIE is a form
of brain dysfunction caused by a reduction in oxygen or blood
supply to the brain. HIE may develop before, during, or after
Figure 1. Etiologies of neonatal seizure. labor and delivery.[25,26] The length of time the brain is deprived
of oxygen or blood flow may affect the severity of a brain

Figure 2. Etiology and associated gestational age comorbidities of the group (1: full term, 2: late preterm, 3: extreme preterm).

4
 Almuqbil et al. • Medicine (2023) 102:37www.md-journal.com

injury. Children with HIE may have no long-term repercussions. abnormalities) do, in fact, have a genetic basis, despite the fact
Some may have mild to moderate impairments as a result of that it is not always simple to identify the underlying pathogenic
HIE, while others may be severely disabled. A HIE-related brain mutation. Decoupling the etiologies may consequently be diffi-
injury may result in developmental delay, cognitive disability, cult or perhaps inappropriate.[27] Regarding this, the most recent
cerebral palsy, or epilepsy. As a baby matures, the symptoms of International League Against Epilepsy Task Force on Neonatal
HIE may become increasingly apparent.[25,26] Seizures advocated a reorganized, less restrictive, and nonhierar-
In our study, genetic and metabolic causes accounted for chical diagnostic categorization.[28] Multiple categories (genetic,
16.4% of all causes of neonatal seizures, and these were primar- metabolic, structural, immunological, and unknown) that are
ily among preterm neonates. It is usually challenging to discern a no longer regarded as mutually exclusive may be used to clas-
Downloaded from http://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy

significant etiological difference between genetic, metabolic, and sify epilepsy. Since genetic, metabolic, and structural factors
structural forms. Metabolic diseases and deformities (structural account for 10 to 15% of all newborn seizures, this technique is
important for giving an accurate diagnostic evaluation, enabling
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 02/18/2024

a sufficient and early treatment start, and reducing adverse

outcomes.[1,16,29,30]
Table 2
In our study, individuals with HIE, cerebral bleeding, and met-
Patients seizure profile. abolic/genetic factors were more likely to have poor outcomes,
Variable Category Frequency Percentage comparable to the results published by Baudou in 2019.[31] A
total of 36.8% of the deceased had HIE, 5.3% had cerebral
Number of seizures before treatment hemorrhage, 36.8% had genetic syndromes, 10.5% had brain
1 28 45.9 malformations, and 5.3% had inherited metabolic disorders.
2–4 15 24.6 Despite the fact that 73.1% of those with HIE and 91.7%
5–10 10 16.4 of those with cerebral hemorrhage survived, we observed the
>10 3 4.9
opposite tendency, with 70% of those with genetic disorders
Unknown 1 1.6
Seizure type and 100% of those with IEM (n = 1) and brain malformations
Tonic 22 36.1 (n = 2) passing away.
Clonic 14 23.0 In terms of gestational age, 69.2% of patients with HIE were
Myoclonic 7 11.5 full-term, 75% of patients with cerebral hemorrhage were very
Subtle 2 3.3 preterm, and 50% of patients with genetic disorders were full-
Other 12 19.7 term; and 30% were late preterm neonates. The 2 individuals
Encephalopathy with brain malformations were a term baby and a late preterm
None 12 19.7 infant. A late preterm infant had an inherited metabolic dis-
Mild 18 29.5 order. A previous study in Russia examined the psychomotor
Moderate 16 26.2 development of newborns with neonatal seizures (NS) born at
Severe 8 13.1
various gestational ages.[32] This study included 52 infants with
Tone
Normal tone 23 37.7
neonatal seizures who were born at various gestational ages.
Hypotonia 26 42.6 Only 32.7% of the infants evaluated had no developmental
Hypertonia 1 1.6 delay on any of the 5 Bayley-III scores. On at least 1 measure,
62.3% of patients had a significant developmental delay (score

Figure 3. Seizure types in each etiology category.

5
 Almuqbil et al. • Medicine (2023) 102:37Medicine
Downloaded from http://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 02/18/2024

Figure 4. Developmental outcome in each etiology category.

The majority of seizures recorded in premature infants are caused

Table 3 by intraventricular hemorrhage and infections.[34]
Patients outcomes at 1 yr of follow-up. In our study, the mean APGAR score was 2.19 (SD: 1.98)
Variable Category Frequency Percentage for HIE, 5.17 (SD: 2.04) for intracranial hemorrhage, 5.20 (SD:
2.53) for genetic syndromes, and 6.0 for both cases of brain
Developmental delay in 1 yr malformation, and the single case of IEM. The mean gestational
None 23 37.7 ages were between 36 and 38 weeks for all etiologies except
Mild 11 18.0 intracranial hemorrhage, which was 28.1 weeks (6.5 SD). The
Moderate 14 23.0 relationship between Apgar score and gestational age has been
Severe 13 21.3 shown in prior research. Apgar scores are correlated with the
Expired 19 31.1 maturity level of newborn infants.[35,36] The 1- and 5-minute
Epilepsy 26 42.6
Apgar scores correlated closely with gestational age. Respiratory
Cerebral palsy No 20 32.8
Spastic quadriplegic 24 39.3
efforts, muscular tone, and reflex were the primary predictors of
Hemiplegic 9 14.8 a diminishing Apgar score as gestational age decreased.[35]
Diplegic 8 13.1 Multiple studies recommend a scoring system for prognostic
evaluation following newborn convulsions. One of the scores is
dependent on birth weight, status epilepticus, the Apgar score,
the neurologic examination at seizure start, cerebral ultrasonog-
composite >= 70).[32] Another study compared neurodevelop- raphy, and the success of anticonvulsant medication.[16] Another
ment and social-emotional development between moderate and study found a correlation between gestational age, seizures,
late preterm (MLPT) infants and term-born control infants at abnormal EEG, underlying etiology, and the quantity of med-
age 2 years.[33] Compared with term-born infants, MLPT chil- icines used to manage the seizure.[37]
dren showed lower cognitive, linguistic, and motor development This research has a number of limitations that need attention.
at age 2 years. Compared to term-born infants, MLPT infants First, the sample size of the research was quite small. Second,
had increased risks of developmental delay, with adjusted odds some patients were born outside of the hospital, and incomplete
ratios of 1.8 (95% CI, 1.1–3.0) for cognitive delay, 3.1 (95% information was acquired. Lastly, several individuals passed
CI, 1.8–5.2) for linguistic delay, and 2.4 (95% CI, 1.3–4.5) for away before the cause of their newborn convulsions was iden-
motor delay.[33] tified. Therefore, it is advised to conduct prospective research
In our study, congenital abnormalities were found among 16% with more regular genetic testing and longer follow-up periods.
of HIE patients, 27.3% among intracranial hemorrhage patients,
75% among genetic syndromes, and 50% among brain malfor-
mations, but were not evident in the 1 patient with IEM. Similarly,
dysmorphism was evident in only 8.7% HIE cases, none with 5. Conclusion
intracranial hemorrhage, 70% among genetic syndromes, 1 (50%) This research explored the causes, clinical manifestations, and
with brain malformations, and none among IEM. Preterm new- radiological manifestations of newborn seizures. Seizures in
borns have a distinct etiological profile than full-term infants.[34] infants may be indicative of serious underlying medical con-
Hypoxic-ischemic encephalopathy is the most common cause of ditions requiring immediate treatment. It indicated that sei-
newborn convulsions in full-term infants, followed by localized zures are a frequent symptom of neurologic abnormalities in
ischemia (stroke), brain abnormalities, and metabolic disorders. newborns and are linked with significant morbidity and death.

6
 Almuqbil et al. • Medicine (2023) 102:37www.md-journal.com

Investigating the causes and symptoms can aid in the identifi- [13] Srinivasakumar P, Zempel J, Trivedi S, et al. Treating EEG seizures
cation of these conditions, guiding the healthcare team in the in hypoxic ischemic encephalopathy: a randomized controlled trial.
development of a comprehensive treatment and management Pediatrics. 2015;136:e1302–9.
[14] Cornet MC, Morabito V, Lederer D, et al. Neonatal presentation of
strategy. Therefore, early diagnosis of the seizure cause and
genetic epilepsies: early differentiation from acute provoked seizures.
appropriate care may contribute to an improved prognosis. Epilepsia. 2021;62:1907–20.
[15] Moosavi R, Swisher CB. Acute provoked seizures-work-up and man-
agement in adults. Semin Neurol. 2020;40:595–605.
Acknowledgments [16] Pisani F, Percesepe A, Spagnoli C. Genetic diagnosis in neonatal-onset
King Abdullah International Medical Research Center epilepsies: back to the future. Eur J Paediatr Neurol. 2018;22:354–7.
Downloaded from http://journals.lww.com/md-journal by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCy

(KAIMRC), Ministry of National Guard, Riyadh, Saudi Arabia. [17] Pisani F, Spagnoli C, Falsaperla R, et al. Seizures in the neonate: a
review of etiologies and outcomes. Seizure. 2021;85:48–56.
[18] Loman AM, ter Horst HJ, Lambrechtsen FA, et al. Neonatal seizures:
wCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8K2+Ya6H515kE= on 02/18/2024

Author contributions aetiology by means of a standardized work-up. Eur J Paediatr Neurol.

2014;18:360–7.
Conceptualization: Mohammed Almuqbil. [19] Saudubray J-M, Baumgartner MR, Walter J. Inborn Metabolic Diseases:
Data curation: Mohammed Almuqbil. Diagnosis and Treatment. Berlin, Heidelberg: Springer; 2006.
Formal analysis: Mohammed Almuqbil. [20] Falsaperla R, Sciuto L, La Spina L, et al. Neonatal seizures as onset of
Funding acquisition: Mohammed Almuqbil. Inborn Errors of Metabolism (IEMs): from diagnosis to treatment. A
Investigation: Mohammed Almuqbil, Yousof Alrumayyan, systematic review. Metab Brain Dis. 2021;36:2195–203.
Shahad Alattas, Duaa Baarmah, Waleed AlTuwaijri, Ahmed [21] Casey BM, McIntire DD, Leveno KJ. The continuing value of the
AlRumayyan, Mohammed Tala AlRifai, Asma Al Madhi, Apgar score for the assessment of newborn infants. N Engl J Med.
2001;344:467–71.
Hassan Al-shehri, Saif Alsaif.
[22] Moster D, Lie RT, Irgens LM, et al. The association of Apgar score with
Methodology: Mohammed Almuqbil. subsequent death and cerebral palsy: a population-based study in term
Project administration: Mohammed Almuqbil. infants. J Pediatr. 2001;138:798–803.
Resources: Mohammed Almuqbil. [23] Volpe J. Hypoxic-ischemic encephalopathy: biochemical and physio-
Software: Mohammed Almuqbil. logical aspects. In: Neurology of the Newborn. 2008:247–324.
Supervision: Mohammed Almuqbil. [24] UptoDate. Etiology and prognosis of neonatal seizures. 2022. Available
Validation: Mohammed Almuqbil. at: https://www.uptodate.com/contents/etiology-and-prognosis-of-neo-
Visualization: Mohammed Almuqbil. natal-seizures [access date February 15, 2023].
Writing – original draft: Mohammed Almuqbil. [25] Mass General for Children. Hypoxic Ischemic Encephalopathy: Causes
and symptoms. 2022. Available at: https://www.massgeneral.org/
Writing – review & editing: Mohammed Almuqbil, Yousof
children/hypoxic-ischemic-encephalopathy [access date February 15,
Alrumayyan, Shahad Alattas, Duaa Baarmah, Waleed 2023].
AlTuwaijri, Ahmed AlRumayyan, Mohammed Tala AlRifai, [26] Gunn AJ, Thoresen M. Neonatal encephalopathy and hypoxic-ischemic
Asma Al Madhi, Hassan Al-shehri, Saif Alsaif. encephalopathy. Handb Clin Neurol. 2019;162:217–37.
[27] Okumura A. Electroencephalography in neonatal epilepsies. Pediatr
Int. 2020;62:1019–28.
References [28] Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and con-
[1] Shellhaas RA. Seizure classification, etiology, and management. Handb cepts for organization of seizures and epilepsies: report of the ILAE
Clin Neurol. 2019;162:347–61. commission on classification and terminology, 2005-2009. Epilepsia.
[2] Uria-Avellanal C, Marlow N, Rennie JM. Outcome following neonatal 2010;51:676–85.
seizures. Semin Fetal Neonatal Med. 2013;18:224–32. [29] Pressler RM, Cilio MR, Mizrahi EM, et al. The ILAE classification of
[3] Shellhaas RA, Wusthoff CJ, Tsuchida TN, et al. Profile of neona- seizures and the epilepsies: modification for seizures in the neonate.
tal epilepsies: characteristics of a prospective US cohort. Neurology. Position paper by the ILAE task force on neonatal seizures. Epilepsia.
2017;89:893–9. 2021;62:615–28.
[4] Ficicioglu C, Bearden D. Isolated neonatal seizures: when to suspect [30] Spagnoli C, Fusco C, Percesepe A, et al. Genetic neonatal-onset epi-
inborn errors of metabolism. Pediatr Neurol. 2011;45:283–91. lepsies and developmental/epileptic encephalopathies with movement
[5] Lai YH, Ho CS, Chiu NC, et al. Prognostic factors of developmen- disorders: a systematic review. Int J Mol Sci. 2021;22:4202–16.
tal outcome in neonatal seizures in term infants. Pediatr Neonatol. [31] Baudou E, Cances C, Dimeglio C, et al. Etiology of neonatal seizures
2013;54:166–72. and maintenance therapy use: a 10-year retrospective study at Toulouse
[6] Tekgul H, Gauvreau K, Soul J, et al. The current etiologic profile and Children’s hospital. BMC Pediatr. 2019;19:1–9.
neurodevelopmental outcome of seizures in term newborn infants. [32] Zavadenko AN, Medvedev MI, Degtyareva MG. Otsenka nerv-
Pediatrics. 2006;117:1270–80. no-psikhicheskogo razvitiia deteĭ razlichnogo gestatsionnogo vozrasta
[7] Garfinkle J, Shevell MI. Cerebral palsy, developmental delay, and epi- s neonatal’nymi sudorogami [Assessment of neurodevelopment in chil-
lepsy after neonatal seizures. Pediatr Neurol. 2011;44:88–96. dren of different gestational age with neonatal seizures]. Zh Nevrol
[8] Oh A, Thurman DJ, Kim H. Independent role of neonatal seizures in Psikhiatr Im S S Korsakova. 2018;118:35–42.
subsequent neurological outcomes: a population-based study. Dev Med [33] Cheong JL, Doyle LW, Burnett AC, et al. Association between moder-
Child Neurol. 2019;61:661–6. ate and late preterm birth and neurodevelopment and social-emotional
[9] Murray DM, Boylan GB, Ali I, et al. Defining the gap between development at age 2 years. JAMA Pediatr. 2017;171:e164805–7.
electrographic seizure burden, clinical expression and staff rec- [34] Vasudevan C, Levene M. Epidemiology and aetiology of neonatal sei-
ognition of neonatal seizures. Arch Dis Child Fetal Neonatal Ed. zures. Semin Fetal Neonatal Med. 2013;18:185–91.
2008;93:F187–91. [35] Catlin EA, Carpenter MW, Brann BS 4th, et al. The Apgar score revis-
[10] Smith SJ. EEG in the diagnosis, classification, and management of ited: influence of gestational age. J Pediatr. 1986;109:865–8.
patients with epilepsy. J Neurol Neurosurg Psychiatry. 2005;76:ii2–7. [36] Zaigham M, Källén K, Olofsson P. Gestational age-related refer-
[11] Cedars Sinai. Non-Epileptic seizures. 2022. Available at: https://www. ence values for Apgar score and umbilical cord arterial and venous
cedars-sinai.org/health-library/diseases-and-conditions/n/non-epilep- pH in preterm and term newborns. Acta Obstet Gynecol Scand.
tic-seizures.html [access date July 19, 2023]. 2019;98:1618–23.
[12] van Rooij LG, Toet MC, van Huffelen AC, et al. Effect of treatment [37] Ronen GM, Buckley D, Penney S, et al. Long-term prognosis in chil-
of subclinical neonatal seizures detected with aEEG: randomized, con- dren with neonatal seizures: a population-based study. Neurology.
trolled trial. Pediatrics. 2010;125:e358–66. 2007;69:1816–22.