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Research Article | Volume 11 Issue 6 (June, 2025) | Pages 63 - 69
Study of Clinico-etiological cause of neonatal seizure and its outcome neonatal intensive care unit
 ,
 ,
 ,
1
Assistant professor, Department of paediatrics, Chalmeda Anand Rao Institute of Medical Sciences, Bommakal, Karimnagar, Telangana
2
Associate professor, Department of paediatrics, Chalmeda Anand Rao Institute of Medical Sciences, Bommakal, Karimnagar, Telangana
3
Professor & HOD, Department of paediatrics, Chalmeda Anand Rao Institute of Medical Sciences, Bommakal, Karimnagar, Telangana
Under a Creative Commons license
Open Access
Received
April 21, 2025
Revised
May 5, 2025
Accepted
May 20, 2025
Published
June 3, 2025
Abstract

Background: Neonatal seizures are critical indicators of underlying neurological dysfunction and are associated with high morbidity and mortality. Early identification of etiological factors is essential for timely management and better outcomes. Objectives: To study the clinico-etiological profile of neonatal seizures and evaluate their outcomes in neonates admitted to the neonatal intensive care unit (NICU). Methods: This prospective observational study was conducted in Department of Paediatrics, CAIMS, Karimnagar over 12 months in a tertiary care NICU and included 60 neonates presenting with seizures. Detailed clinical history, biochemical investigations, neuroimaging, and EEG (where available) were used to determine the etiology. Outcomes were assessed at discharge. Results: Of the 60 neonates, 60% were male and 46.7% had a birth weight <2.5 kg. Subtle seizures were the most common type (46.7%), followed by tonic (23.3%) and clonic seizures (16.7%). Hypoxic-ischemic encephalopathy (36.7%) was the leading cause, followed by metabolic (20%) and infectious (16.7%) etiologies. Biochemical abnormalities included hypoglycemia (30%) and hypocalcemia (16.7%). Ventilator and inotrope support were required in 30% and 23.3% of cases, respectively. At discharge, 53.3% had a favorable outcome, 16.7% had neurological sequelae, and 20% succumbed to illness. Conclusion: HIE and metabolic disturbances remain the predominant causes of neonatal seizures. Subtle seizures are the most frequent and often underdiagnosed, emphasizing the need for improved diagnostic vigilance. Early recognition and management can significantly improve outcomes.

Keywords
INTRODUCTION

Neonatal seizures are one of the most common neurological emergencies encountered in neonatal intensive care units (NICUs), with an estimated incidence of 1–3.5 per 1000 live births in term neonates and up to 57–132 per 1000 live births in preterm infants [1,2]. They often indicate serious underlying cerebral pathology and are associated with increased morbidity and mortality if not promptly recognized and managed [3]. The neonatal brain differs significantly from that of older children in terms of excitability and seizure thresholds, due to its ongoing developmental plasticity, immature inhibitory neurotransmitter systems, and high density of excitatory NMDA receptors [4]. This physiological predisposition increases vulnerability to various insults, both structural and metabolic, leading to seizures during the neonatal period.

 

The etiology of neonatal seizures is diverse and can be broadly categorized into structural, metabolic, infectious, genetic, and idiopathic causes [5]. Hypoxic-ischemic encephalopathy (HIE) remains the leading cause in term neonates, particularly in resource-limited settings, followed by metabolic disturbances like hypoglycemia and hypocalcemia, and infections such as meningitis and sepsis [6,7]. In preterm infants, intraventricular hemorrhage and periventricular leukomalacia are more frequent causes [8]. Clinically, seizures in neonates are often subtle and difficult to recognize due to the immaturity of the nervous system. They may present as lip smacking, ocular movements, apnea, or bicycling movements rather than the classic tonic-clonic activity seen in older children [9]. The use of electroencephalography (EEG), especially amplitude-integrated EEG (aEEG), has become a valuable tool for diagnosis and monitoring [10].

 

The outcome of neonatal seizures depends largely on the underlying etiology, severity, and timeliness of intervention. Studies suggest that seizures due to metabolic causes generally have a favorable prognosis if treated early, whereas those resulting from HIE or structural brain abnormalities may lead to long-term neurodevelopmental impairments such as cerebral palsy, epilepsy, and cognitive deficits [11, 12]. Given the complex etiology and significant implications for long-term outcomes, early identification of the clinico-etiological factors and timely management are essential. This study aims to evaluate the clinical presentations, underlying etiologies, and outcomes of neonates presenting with seizures in a NICU setting. It is anticipated that the findings will contribute to a better understanding of local epidemiology and support the development of region-specific management protocols.

MATERIALS AND METHODS

This was a prospective observational study conducted in the Neonatal Intensive Care Unit (NICU) of a tertiary care hospital, over a period of 12 months. The study was conducted in the NICU of the Department of Pediatrics at Chalmeda Anand Rao Institute of Medical Sciences, a tertiary care teaching hospital located in Karimnagar, Telangana.

 

Study Population

All neonates admitted to the NICU with clinically diagnosed seizures during the study period were included.

 

Inclusion Criteria

  • Neonates (0 to 28 days of life) of either sex.
  • Neonates presenting with clinically evident seizures during NICU stay.
  • Parents/guardians who provided written informed consent.

 

Exclusion Criteria

  • Neonates with seizures secondary to known congenital metabolic disorders diagnosed antenatally.
  • Neonates with major congenital malformations incompatible with life.
  • Neonates with incomplete clinical records or whose parents declined consent.

 

Sample Size

A total of 60 neonates who fulfilled the inclusion criteria were enrolled during the study period. The sample size was determined based on the average number of neonatal seizures admitted in the past two years and using standard prevalence estimates from previous regional studies.

 

Data Collection Procedure

Data was collected using a pretested structured proforma, which included the following components:

  1. Demographic details: Age, sex, birth weight, gestational age, mode of delivery.
  2. Clinical characteristics: Type and timing of seizure, associated signs and symptoms.
  3. Antenatal and perinatal history: Maternal illnesses, antenatal care, complications during delivery, birth asphyxia.
  4. Etiological classification: The cause of seizure was classified based on clinical, laboratory, and radiological findings into categories such as hypoxic-ischemic encephalopathy (HIE), metabolic, infective, structural, and idiopathic.
  5. Outcome: Assessed at discharge in terms of:
    •  
    • Neurological status at discharge (normal/mild deficit/severe deficit).
    • Duration of NICU stay.

 

Statistical Analysis

Data were compiled using Microsoft Excel and analyzed using SPSS version 25. Descriptive statistics were used for demographic data and clinical features. Categorical variables were expressed as frequencies and percentages. Continuous variables were expressed as mean ± standard deviation (SD). Associations between etiological factors and outcomes were tested using the Chi-square test or Fisher’s exact test. A p-value of <0.05 was considered statistically significant.

 

RESULTS

Table 1: Distribution of demographic profile among study population

Parameter

Frequency

Percentage

Gender

Male

36

60

Female

24

40

Birth Weight

< 2.5 kg

28

46.7

2.5–4.0 kg

30

50

> 4.0 kg

2

3.3

Mode of Delivery

Vaginal

35

58.3

Caesarean

25

41.7

Place of Delivery

Hospital

52

86.7

Home

8

13.3

This table outlines the basic demographic characteristics of the 60 neonates enrolled in the study. A male predominance was observed (60%), with most neonates having a birth weight in the normal range of 2.5–4.0 kg (50%). Nearly half the neonates were of low birth weight (<2.5 kg), suggesting a potential association with neurological complications. Vaginal delivery was more common (58.3%) than cesarean section (41.7%), and the majority of deliveries occurred in hospital settings (86.7%), highlighting institutional healthcare accessibility in most cases.

Table 2: Distribution of type of seizures among study population

Type of Seizures

Frequency

Percentage

Subtle

28

46.7

Tonic

14

23.3

Clonic

10

16.7

Myoclonic

5

8.3

Mixed

3

5

This table categorizes the seizure types observed among the neonates. Subtle seizures were the most frequently encountered (46.7%), followed by tonic (23.3%) and clonic (16.7%) seizures. Myoclonic (8.3%) and mixed types (5%) were less commonly observed. This distribution reflects the diagnostic challenge of identifying seizures in neonates, where subtle presentations often dominate.

 

Table 3: Distribution of aetiologies among study population

Etiology

Frequency

Percentage

HIE

22

36.7

Metabolic

12

20

Infectious

10

16.7

Structural

6

10

Idiopathic

7

11.7

Genetic/metabolic syndrome

3

5

The table lists the various underlying causes of neonatal seizures. Hypoxic-ischemic encephalopathy (HIE) was the leading cause, accounting for 36.7% of cases, followed by metabolic disturbances (20%) and infectious etiologies (16.7%). Structural abnormalities and idiopathic causes accounted for 10% and 11.7%, respectively, while genetic/metabolic syndromes were noted in 5%. This etiological spectrum underscores the need for early perinatal monitoring and metabolic screening.

Table 4: Distribution of Outcomes and other related parameters

Parameters

Frequency

Percentage

Hospital stay

< 7 days

15

25

7–14 days

28

46.7

> 14 days

17

28.3

Enteral Feeding Started

Day 1–2

20

33.3

Day 3–5

26

43.3

> Day 5

14

23.3

Ventilator Support

Required

18

30

Not Required

42

70

Ventilator Support

Required

14

23.3

Not Required

46

76.7

Outcome

Discharged (normal)

32

53.3

Discharged (with sequelae)

10

16.7

Mortality

12

20

DAMA

6

10

This comprehensive table presents clinical management variables and outcomes. Most neonates had a hospital stay between 7–14 days (46.7%), with enteral feeding initiated within 3–5 days in 43.3% of cases. Around 30% required ventilatory support and 23.3% required inotropic support. Regarding outcomes, 53.3% were discharged with no neurological deficits, 16.7% had sequelae, 20% died, and 10% were discharged against medical advice (DAMA). These findings reflect the severity of underlying conditions and the need for timely NICU interventions.

Table 5: Distribution of biochemical abnormalities

Biochemical Abnormalities

Frequency

Percentage

Hypoglycemia

18

30

Hypocalcemia

10

16.7

Hyponatremia

5

8.3

Hyperbilirubinemia

7

11.7

Metabolic acidosis

9

15

This table highlights key metabolic abnormalities associated with neonatal seizures. Hypoglycemia was the most prevalent (30%), followed by hypocalcemia (16.7%) and metabolic acidosis (15%). Hyponatremia (8.3%) and hyperbilirubinemia (11.7%) were also noted. These results emphasize the critical role of biochemical evaluation in the early detection and management of neonatal seizures.

DISCUSSION

Neonatal seizures represent a significant neurological emergency and are often the first sign of underlying cerebral dysfunction. In this study involving 60 neonates, we observed important trends in demographics, seizure types, etiologies, clinical course, and outcomes.

 

In the present study A male preponderance (60%) was observed, consistent with studies by Kumar et al. and Sood et al., which also reported a higher incidence in male neonates, likely due to sex-related vulnerability of the male brain to hypoxic insults and metabolic stressors [13,14]. In our cohort, low birth weight (<2.5 kg) was seen in 46.7% of cases, which aligns with the findings by Amudhan et al., who reported low birth weight in 40–50% of neonates with seizures, emphasizing its role as a significant risk factor [15]. Most neonates in this study were delivered in hospitals (86.7%), suggesting increased institutional access, which contrasts with older rural-based studies that reported a higher proportion of home births [16]. The predominance of vaginal deliveries (58.3%) over cesarean sections (41.7%) differs from some tertiary care studies where cesarean deliveries were more common, possibly due to referral bias [17].

 

Types of Seizures

Subtle seizures were the most common type (46.7%), consistent with the literature, where subtle seizures remain underdiagnosed due to their atypical presentations [18]. Studies by Mizrahi and Kellaway have emphasized that subtle motor phenomena like eye deviation, sucking, and bicycling movements are often missed without EEG confirmation [19].

 

Etiological Profile

Hypoxic-ischemic encephalopathy (HIE) was the most frequent cause (36.7%), followed by metabolic abnormalities (20%), infections (16.7%), and structural causes (10%). This is in agreement with several Indian studies, such as that by Malik et al., where HIE accounted for nearly 40% of neonatal seizures in term neonates [20]. Internationally, Glass et al. also reported HIE as the leading etiology in their prospective cohort [1]. The presence of idiopathic cases (11.7%) is similar to the 10–15% rate reported in other observational studies where advanced diagnostics were not uniformly available [12].

 

Notably, metabolic disturbances like hypoglycemia and hypocalcemia were significant contributors, accounting for 30% and 16.7% respectively. This was similar to findings by Kumar et al. and Pisani et al., where hypoglycemia was a leading reversible cause, particularly in neonates with feeding difficulties or intrauterine growth retardation [13, 11].

 

Biochemical Abnormalities

The presence of hypoglycemia (30%) and metabolic acidosis (15%) highlights the importance of early metabolic screening. These findings are consistent with those of Sreenivasan et al., who emphasized metabolic causes as reversible with timely intervention [21].

 

Clinical Course and Outcome

The hospital stay ranged from <7 days (25%) to >14 days (28.3%), depending on etiology and need for supportive care. Enteral feeding was delayed (>5 days) in 23.3%, particularly among neonates with severe HIE or requiring ventilation.

 

Ventilator support was required in 30% and inotropes in 23.3%, reflecting the severity of systemic involvement. Similar ventilatory support rates (25–35%) were reported in neonates with severe HIE in international studies such as those by Glass et al. and Boylan et al. [1,22].

 

Mortality was observed in 20% of neonates, which is slightly lower than that reported by Ronen et al. (24%) and Malik et al. (22.5%) but still highlights the high risk associated with neonatal seizures [23,20]. Favorable neurological outcome (discharge without sequelae) was observed in 53.3%, comparable to other Indian studies but lower than some high-resource settings where early EEG and targeted therapy are more accessible [24].

 

 

Table 6: Comparison summary of present study with other studies

Parameter

Present Study

Comparable Study

Findings

Male predominance

60%

Kumar et al. (65%) [1]

Similar

HIE as leading cause

36.70%

Malik et al. (40%) [8]

Similar

Subtle seizures common

46.70%

Mizrahi et al. (50%) [7]

Similar

Hypoglycemia

30%

Pisani et al. (28%) [12]

Comparable

Mortality

20%

Ronen et al. (24%) [15]

Slightly lower

CONCLUSION

This study highlights that hypoxic-ischemic encephalopathy remains the leading cause of neonatal seizures, followed by metabolic and infectious etiologies. Subtle seizures were the most common clinical presentation, often posing diagnostic challenges in the NICU. Biochemical abnormalities such as hypoglycemia and hypocalcemia were frequently observed, reinforcing the importance of early metabolic screening. Despite the availability of intensive care, the mortality rate was 20%, and 16.7% of neonates were discharged with neurological sequelae, underlining the significant morbidity associated with neonatal seizures. Early identification of etiological factors, prompt intervention, and supportive care are crucial for improving outcomes, and the findings emphasize the need for strengthening neonatal screening, perinatal care, and NICU protocols to reduce seizure-related morbidity and mortality.

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