International Journal of Contemporary Pediatrics

Yadav S et al. Int J Contemp Pediatr. 2023 Sep;10(9):1406-1411

http://www.ijpediatrics.com pISSN 2349-3283 | eISSN 2349-3291

DOI: https://dx.doi.org/10.18203/2349-3291.ijcp20232585
Original Research Article

Study of etiological factors and immediate outcomes of

neonatal seizure among preterm and term neonate in a tertiary health
centre of Northern India
Surbhi Yadav1*, Payal Agrawal1, Vinod K. Sharma2, Rekha2, Sunder Lal Yadav3

1
Department of Pediatrics, SGT Medical College Hospital and Research Institute, Budhera, Gurugram, Haryana, India
2
Department of Pediatrics, Deen Dayal Upadhyay Hospital, Hari Nagar, New Delhi, India
3
Medical Officer, Kanina, Haryana, India

Received: 04 July 2023

Revised: 25 July 2023
Accepted: 02 August 2023

*Correspondence:
Dr. Surbhi Yadav,
E-mail: [email protected]

Copyright: © the author(s), publisher and licensee Medip Academy. This is an open-access article distributed under
the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial
use, distribution, and reproduction in any medium, provided the original work is properly cited.

ABSTRACT

Background: Neonatal seizures result due to altered neurological functions like motor, behavioural and autonomic
function. We conducted this study to assess the incidence, etiological factors, and immediate outcomes of neonatal
seizures in term and preterm neonates.
Methods: This prospective observational study included all neonates delivered in a tertiary health centre of New Delhi
from Nov 2015 to Oct 2016 and admitted in Neonatal Intensive Care Unit with clinically identified seizures up to 28
days of postnatal age.
Results: Out of 11,109 live births during the study period, 302 developed neonatal seizures with overall incidence of
2.71%. The early preterm (12.05%), very low birth weight babies (56.30%), and neonates in first 24 hrs of life (68.9%)
had the highest incidence of neonatal seizures. The commonest seizure type was subtle seizures (52.3%). In early
preterm commonest etiology was infection (31.3%) while in late preterm and term neonates most common etiology was
Hypoxic ischaemic encephalopathy 59% and 72% respectively. Overall, HIE was the most common etiology (57%).
Out of 302 cases, 81 (26.8%) cases have died. HIE was found to be the most common cause for mortality. Mortality
was highest in early preterms (49.3%) and very low birth weight neonates (52.3%). Also, mortality was maximum
among neonates having subtle seizures (29.1%) and seizures occurring within 24 hrs of life (30.8%).
Conclusions: Persistently high incidence of neonatal seizures requires further strengthening of antenatal, natal, and
post-natal health services. Early identification of neonatal seizures and timely intervention are very important for better
outcomes.

Keywords: Neonatal seizures, Incidence, Neonate, Term preterm, Etiology, Subtle, Hypoxic ischaemic
encephalopathy

INTRODUCTION (Gamma-amino butyric acid: GABA) makes the immature

central nervous system susceptible for seizures.3 Unlike
Neonatal seizures result due to altered neurological seizures in children or adults, generalized tonic-clonic
functions like motor, behavioural and autonomic function convulsions do not occur in neonatal period due to
and can affect neonate of any gestational age.1,2 Enhanced incomplete myelination and arborization of axons and
excitability and low levels of inhibitory neurotransmitters dendritic processes.4 The incidence of seizures varies

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 Yadav S et al. Int J Contemp Pediatr. 2023 Sep;10(9):1406-1411

depending on the case definition, method of ascertainment, serology, serum parathyroid hormone, and metabolic
and definition of the neonatal period.5 The incidence of profile for inborn errors of metabolism. Radiological
neonatal seizures varies from 1.1 to 8.5 per 1000 live investigations (chest X-ray, cranial ultrasonography,
births. The wide range is because of variable incidence in computed tomography, and magnetic resonance imaging
different gestational ages, where preterm and very low of the brain) and EEG were performed if necessary. All the
birth weight neonates have the highest incidence. It may neonates were managed as per the standard treatment
affect up-to 3.4% of neonates getting admitted in neonatal protocols.
intensive care unit.6
Statistical analysis
Focal or multifocal, clonic, tonic, myoclonic, and subtle
seizures are commonly seen in neonates with subtle Statistical analysis was conducted using SPSS 20.0 system
seizure being the most common presentation.7 The primary version. The qualitative parameters were compared using
cause of neonatal seizures is Hypoxic-Ischemic the chi-square test/ Fisher’s exact test, whichever is
Encephalopathy (HIE), which accounts for approximately applicable, p value less than 0.05 was considered
50% of cases, followed by metabolic abnormalities, significant.
infection, intracranial hemorrhage, developmental
anomalies, and inborn errors of metabolism.8-10 The latter RESULTS
being rare but their detection permits specific treatment (if
available) and genetic counselling. Etiology of seizure Out of 11,109 livebirths during the study period, 302
depends on gestational age of the neonate. HIE is the most developed neonatal seizures. The incidence of neonatal
common cause in term neonates while intracranial seizures was found to be 2.71% in our hospital. However,
hemorrhage and infections are more common in preterm the incidence in preterms was 5 times more (8.70%) than
neonates.11 Electroencephalograph (EEG) is an important term (1.66%) and incidence in early preterms was 7 times
tool and can be used for detection as well as diagnosis of more (12.05%) than term (1.66%) as shown in (Table 1).
neonatal seizures, also it gives an estimate of perinatal
brain damage. The variability of normal maturation of Table 1: Incidence of neonatal seizures according to
brain can influence its interpretation, also the restricted gestational age.
availability of equipment are its limitations.12 The risk of
mortality and associated morbidities like developmental No. of No. Incidence
delay, focal neurological deficits, and cognitive Gestational age
Neonates of of NDS
impairment, makes this clinical entity a matter of concern (weeks)
Delivered NDS* (%)
for clinicians. Early detection and timely intervention can Term (≥ 37) 9443 157 1.66%
reduce the morbidity profile.12 This study was conducted Preterm (≤ 37) 1666 145 8.70%
to determine the incidence rate, etiology, and short-term <34
outcome of clinically recognizable neonatal seizures. (Early 556 67 12.05%
preterm)
METHODS Preterm
34-36.6
(Late 1110 78 7.02%
This prospective observational study was conducted at the preterm)
department of pediatrics, Deen Dayal Upadhyay Hospital, Total 11,109 302 2.71%
New Delhi, over the course of one year, from November *Neonates Developed Seizures- NDS
2015 to October 2016, following approval from the
institutional ethical committee and written consent from Neonatal seizures were found to be more common in male
parents/guardians. The study included all neonates neonates (57%) and in low birthweight babies (56.30%).
delivered in our hospital and admitted to the Neonatal Un-booked cases (86.4%) and neonates delivered by
Intensive Care Unit (NICU) with clinically identified normal vaginal delivery (NVD) (57.9%) were more
seizures up to 28 days of postnatal age, excluding preterm affected. Seizures were more common in first 24 hrs of life
neonates less than 28 weeks of gestational age, neonates (68.9%) and subtle seizures were found to be the most
with obvious congenital malformations, and those whose common type of seizures (52.3%) as shown in table 2. Out
parents did not give consent. of 302 cases, 152 (50.4%) cases had associated maternal
factors while 150 cases (49.60%) had no associated
A detailed history of the seizure episode including its maternal factors. Amongst them pregnancy induced
onset, duration, type, number, and antenatal, natal, and hypertension (PIH) was the most common (19.8%)
postnatal risk factors were obtained for each case, followed by premature rupture of membrane (PROM)
followed by detailed clinical examination. Essential (16.5%) as depicted in (Table 2).
laboratory investigations were conducted, such as blood
gas, blood glucose, serum calcium, sodium, magnesium, Hypoxic ischaemic encephalopathy (HIE) was found to be
sepsis screen, serum bilirubin levels, serum urea and the most common etiological factor (57%) followed by
creatinine, blood culture, and CSF examination were done infection (18.5%) (sepsis 9.6% and meningitis 8.9%),
as required. Additional investigations included TORCH

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metabolic causes (14.9%) and intra-cranial haemorrhage metabolic disturbances and kernicterus as shown in (Table
as depicted in table 3 and (Figure 1). 4).

Table 3: Distribution of neonates as per etiology

60 (n=302).
50
40 Etiology N %
30 HIE (Hypoxic ischaemic
20 172 57
encephalopathy)
10
Sepsis 29 9.6
0
Meningitis 27 8.9
Hypoglycemia 26 8.6
Hypocalcemia 19 6.3
ICH (Intra-cranial haemorrhage) 19 6.3
Kernicterus 4 1.3
Figure 1: Distribution of neonates as per etiology.
Unknown 6 2
Total 302 100
As per the gestational age, most common etiology in early
preterm neonates was infection (31.3%) while in late
preterm and term neonates, the most common etiology was The association of gestational age (GA), birth weight and
HIE 59% and 72 % respectively. outcome with etiology came out to be statistically
significant with p value of 0.001. Comparison of mortality
Table 2: Neonatal characteristics (n=302). with other parameters showed that mortality was highest
in early preterms (49.3%) and very low birth weight babies
Neonatal characteristics N % (52.3%). Also, mortality was more in babies in whom 1st
Male 172 57.0 seizure developed within 24 hrs of age (30.8%) and in
Gender neonates with subtle seizures than clonic, tonic, and
Female 130 43.0
myoclonic seizures as shown in (Table 5).
<1.5 65 21.5
Birth Weight
1.5-2.499 105 34.8
(Grams) DISCUSSION
>2.5 132 43.7
Ante natal Booked 41 13.6
A seizure is defined as a paroxysmal involuntary
registration Un-booked 261 86.4 disturbance of brain function. The various presentations of
LSCS 127 42.05 neonatal seizures are impairment in consciousness,
Mode of Delivery
NVD 175 57.9 abnormal motor, or behavioural activity, and sensory or
0-24 208 68.9 autonomic disturbances.1 Neonatal seizures can adversely
Onset of Seizures
25-48 42 13.9 affect neurodevelopment and may result in cognitive,
according to age
49-72 25 8.3 behavioural, and epileptic complications in later life. As
(Hrs)
>72 27 8.9 this could be the sole presentation of underlying CNS
Subtle 158 52.3 disorder, early recognition is very important.
Clonic 104 34.4
Type of seizure
Tonic 38 12.6 In our study the overall incidence of neonatal seizures was
Myoclonic 2 0.7 2.7% which is lower than the studies done by Sabzehei et
PIH 60 19.8 al and Sahana et al while higher than the study done by
PROM 50 16.5 Venkatesh et al which can be due to tertiary care status of
Placenta previa 14 4.63 our hospital where high risk and complicated deliveries are
Multiple referred and most of them are un-booked deliveries
12 3.97 (86.4%).1,4,8,13 The incidence of neonatal seizures was 1.6
pregnancy
Maternal risk % in term neonates and 8.70% in preterm, among preterm
Oligo-
factors 6 1.98 neonates early preterm had 12.05% and late preterm had
hydramnios
Chronic 7.02%. So total preterm (early and late) had a higher (5
maternal 6 1.98 times) incidence than term and among preterm early
diseases preterm had a higher incidence. These findings are
GDM 4 1.32 consistent with other studies done by Tekgul et al and
Kumar et al.14,15 The overall incidence of prematurity in
HIE was found to be the most common cause of seizures the current study was 15%. Preterm babies may have
among all weight groups. Outcomes of study showed that multifactorial etiology for neonatal seizures. Low birth
out of 302 cases, 81 (26.8%) cases were died and 221 weight, maternal illnesses, and metabolic causes could be
(73.20%) were discharged. The most common cause of the contributing factors. We found male predominance in
mortality was HIE while no mortality was noted in our study which is consistent with other studies, we do not
have any plausible mechanism behind that.

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Table 4: Association of gestational age (GA), birth weight and outcome with etiology.

Cause of neonatal seizures (Etiology), N (%) Total no. of

Variable
HIE Infection Metabolic ICH Kernicterus Unknown neonates
13 17
28-33.6 21 (31.3) 15 (22.4) 01 (1.5) 00 (0.0) 67
(19.4) (25.4)
GA 46 01
34-36.6 18 (23.1) 12 (15.4) 01 (1.3) 00 (0.0) 78
(weeks) (59.0) (1.3)
01
>37 113 (72) 17 (10.8) 18 (11.5) 02 (1.3) 06 (3.8) 157
(0.6)
24 09
<1.5 19 (29.2) 11 (16.9) 01 (1.53) 01 (1.53) 65
(36.9) (13.8)
Birth 54 09
1.5-2.499 22 (20.9) 19 (18.0) 01 (0.95) 00 (0.0) 105
weight (51.4) (8.5)
94 01
>2.5 15 (11.3) 15 (11.3) 02 (1.51) 05 (3.7) 132
(71.2) (0.75)
114 08
Discharge 44 (19.9) 45 (20.4) 04 (1.8) 06 (2.7) 221
(51.6) (3.6)
Outcome
58 11
Expired 12 (14.8) 00 (0.0) 00 (0.0) 00 (0.0) 81
(71.6) (13.6)

Table 5: Relationship of outcome of neonatal seizures with GA, birth weight, age at onset of seizures and type of
seizures.

Outcome N (%)
Variable Total P value
Discharge Expired
28-33.6 34 (50.7) 33 (49.3) 67
GA (weeks) 34-36.6 60 (76.9) 18 (23.1) 78 0.001
>37 127 (80.9) 30 (19.1) 157
<1.5 31 (47.7) 34 (52.3) 65
Birth weight 1.5-2.499 79 (75.2) 26 (24.8) 105 0.001
>2.5 111 (84.1) 21 (15.9) 132
0-24 144 (69.2) 64 (30.8) 208
25-48 33 (78.6) 09 (21.4) 42
Onset of Seizure 0.001
49-72 20 (80) 05 (20.0) 25
>72 24 (88.9) 03 (11.1) 27
Clonic 76 (73.1) 28 (26.9) 104
Myoclonic 02 (100) 00 (0.0) 02
Type of Seizure 0.001
Subtle 112 (70.9) 46 (29.1) 158
Tonic 31 (81.6) 07 (18.4) 38

Neonatal seizures were more common in low birthweight which PIH was the major cause found in 19.8% of cases
babies (56.30%) as compared to normal birthweight babies followed by PROM in 16.50%. The association of
(43.70%) which is comparable with the study conducted maternal factors with neonatal seizures was comparatively
by Shah et al.4,13,16,17 Low birth weight has many higher than the other studies, this could be because o the
predisposing common factors for neonatal seizures namely fact that most of the neonates who had seizures were
maternal illnesses, neonatal infections, decreased delivered through un-booked pregnancies (85.6%) and our
metabolic stores, etc. We found seizures were more hospital is a tertiary care one and many high-risk delivery
common in vaginally delivered babies. It may be assumed cases were being referred to the institute for the further
that vaginal delivery if difficult may cause asphyxia and management.19,20 The overall most common etiology of
subsequent complications and asphyxia remained the neonatal seizure was HIE (57%) and second most common
leading cause of seizures in our study. Most of the cases was infection (18.5%) and the least one was kernicterus
i.e., 82.8% had seizures during the first 48 hrs of life which (1.3%). Various studies reported the percentage of HIE
is like the previous studies.13,16,18 The most common varies from 38% to 66% which is similar to the present
seizure type was subtle (52.3%), this is consistence with study.13,18 In early preterms, infection (31.3%) and ICH
the Chesti et al study.16 Many underlying maternal risk (25.4%) were found to be common causes while in late
factors have been described as important predisposing preterms and terms, HIE and metabolic disturbances were
factors for neonatal seizures. Out of 302 cases, 152 more common. Previous studies show that the most
(50.4%) cases had associated maternal factors, amongst common cause of seizures in preterm was ICH followed

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 Yadav S et al. Int J Contemp Pediatr. 2023 Sep;10(9):1406-1411

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