Neonatal seizures are the most common neurological emergency in the neonatal period and serve as an important indicator of underlying cerebral dysfunction¹. They are defined as sudden alterations in neurological function—sensory, motor, or autonomic—resulting from abnormal synchronous cortical neuronal discharge. The incidence ranges from 1.1–4 per 1,000 live births and is higher in preterm and low-birth-weight neonates due to neurological immaturity and increased susceptibility to perinatal complications². Neonatal seizures occur within the first 28 days of life and may present as clinical, subclinical, or electrographic-only events³. Unlike seizures in older children, neonatal seizures are often subtle and non-convulsive, making clinical recognition challenging⁴.

Identification of the underlying etiology is essential for appropriate management and prognostication. Hypoxic-ischemic encephalopathy (HIE) is the most common cause, particularly in term neonates, and typically presents within the first 24 hours of life⁴,⁵. Other significant causes include metabolic disturbances such as hypoglycemia, hypocalcemia, hypomagnesemia, and hyponatremia⁶. The timing of seizure onset often provides diagnostic clues: seizures within 24 hours are frequently associated with HIE or vascular events; those occurring between 24–72 hours are commonly related to metabolic abnormalities or infections; and seizures after 72 hours may be due to structural brain malformations, inborn errors of metabolism, or viral infections such as herpes simplex virus⁷,⁸.

Clinically, neonatal seizures are classified as subtle, tonic, clonic, or myoclonic according to Volpe’s classification, with subtle seizures being the most frequent⁹,¹⁰. Due to their often subtle presentation, electroencephalographic (EEG) monitoring plays a crucial role in accurate diagnosis¹¹. Immediate outcomes depend on etiology, timing, seizure burden, and response to treatment. While seizures secondary to transient metabolic disturbances generally have favorable outcomes, those associated with HIE or structural abnormalities carry higher risks of morbidity and adverse neurodevelopmental sequelae¹². Despite advancements in neonatal care, neonatal seizures continue to pose diagnostic and therapeutic challenges, particularly in low- and middle-income countries where regional data remain limited⁵,¹³.

The present study was undertaken to evaluate the clinical profile, etiological spectrum, and immediate outcomes of neonatal seizures in term neonates.

MATERIALS AND METHODS

This prospective observational study was conducted in the Neonatal Intensive Care Unit (NICU) of the Department of Pediatrics at a tertiary care hospital over a period of 24 months (June 2023–June 2025), after obtaining approval from the Institutional Ethics Committee. A total of 238 term neonates presenting with seizures within the first 28 days of life were enrolled after written informed consent from parents or legal guardians.

Preterm neonates, very low birth weight infants, neonates aged more than 28 days, those with inborn errors of metabolism, major congenital malformations, prior exposure to antiepileptic drugs, recurrent seizures, or lack of consent were excluded.

A detailed clinical evaluation was performed using a structured Case Record Form. Seizure characteristics, including timing of onset (<24 hours, 24–72 hours, >72 hours) and type (subtle, clonic, tonic, myoclonic, multifocal), were documented. Antenatal, perinatal, and birth histories were recorded. Relevant investigations included complete blood count, CRP, blood glucose, serum electrolytes (calcium, magnesium), CSF analysis, neurosonography, EEG, CT scan (if indicated), and metabolic screening. Immediate outcomes were assessed in terms of survival, response to antiepileptic therapy, and duration of hospital stay.

Data were entered in Microsoft Excel and analyzed using SPSS version 22.0. Continuous variables were expressed as mean ± SD and categorical variables as frequencies and percentages.

OBSERVATIONS AND RESULTS

Table 1: Perinatal and Birth Characteristics of Term Neonates with Seizures (n = 238)

Table 2: Clinical Profile of Seizures in Term Neonates (n = 238)

Table 3: Etiology vs. Time of Onset of Seizures

Figure 1: General Examination in Term Neonates with Seizures

Figure 2: Central Nervous System (CNS) Examination Findings

Figure 3: Study of neurosonogram abnormality in neonates with HIE

Table 4: Laboratory Investigations

Figure 4: Various biochemical abnormalities in study population (n=97)

Table 5: Distribution of various microorganisms implicated in neonatal seizures

Table 6: Response to AED/Treatment

Figure 5: Immediate Outcome of Neonatal Seizures

A total of 238 term neonates with seizures were included in the study. Normal vaginal delivery was the most common mode of delivery (55.0%), followed by lower segment cesarean section (41.6%). Nearly one-fourth (24.4%) required resuscitation at birth. Male neonates predominated (60.1%), and most had a birth weight between 2.5–3.5 kg (86.1%).

Seizures most frequently occurred between 24–72 hours of life (50.0%), followed by >72 hours (25.63%) and <24 hours (24.36%). Subtle seizures were the predominant type (56.72%), followed by focal clonic (19.74%), tonic (11.76%), and multifocal seizures (10.92%); myoclonic seizures were rare (0.84%).

Metabolic disturbances were the leading etiology (40.75%), followed by sepsis/meningitis (33.19%) and hypoxic-ischemic encephalopathy (24.36%). HIE was the major cause of seizures within the first 24 hours, whereas metabolic and infectious causes predominated after 24 hours.

Abnormal neurosonogram findings were observed in 21.85% of neonates, most commonly diffuse parenchymal echoes. Laboratory evaluation revealed elevated CRP levels and biochemical abnormalities suggestive of metabolic derangements. Among metabolic causes, hypoglycemia (31.95%) and hypocalcemia (29.89%) were most frequent.

Among culture-positive cases, Escherichia coli (36.70%) was the most commonly isolated organism. Phenobarbitone monotherapy controlled seizures in 71.0% of neonates. Overall survival was 90.75%, with a mortality rate of 9.24%. Most neonates required hospitalization for 11–15 days.

DISCUSSION

Neonatal seizures remain the most frequent neurological emergency in the neonatal period and are important indicators of underlying cerebral dysfunction¹–⁴. In the present study, normal vaginal delivery was the most common mode of delivery, and nearly one-fourth of neonates required resuscitation at birth, suggesting a significant contribution of perinatal asphyxia. Similar findings have been reported in previous studies¹⁴–¹⁶. Male predominance observed in our study is also consistent with earlier reports¹⁴–¹⁷.

Most seizures occurred within the first 72 hours of life, particularly between 24–72 hours, emphasizing the vulnerability of the early neonatal period. Subtle seizures were the most common type, reflecting the known difficulty in clinical recognition of neonatal seizures⁹,¹⁰. Metabolic disturbances emerged as the leading etiology, followed by sepsis/meningitis and hypoxic-ischemic encephalopathy (HIE), comparable to findings reported by Chaudhary et al¹⁴, Paul et al¹⁵, Patel and Mehta¹⁶, and Nair et al¹⁷. HIE was the predominant cause of seizures within the first 24 hours, while metabolic and infectious causes were more common after 24 hours, in agreement with other studies¹⁸,¹⁹.

Clinical examination revealed abnormalities in tone and reflexes in a significant proportion of neonates, indicating varying degrees of neurological dysfunction. Similar observations have been documented by Soul et al²⁰, Tekgul et al²¹, Kumar et al²², and Sahana et al²³. Abnormal neurosonogram findings in approximately one-fifth of neonates further supported structural or hypoxic brain injury, consistent with previous literature¹⁷,²².

Laboratory findings highlighted the major role of metabolic abnormalities. Hypoglycemia and hypocalcemia were the most common biochemical disturbances, aligning with earlier studies¹⁴,¹⁶,²²,²⁵. Elevated CRP levels supported an infectious etiology in a substantial subset, similar to findings by Bhatt et al²⁴. Among culture-positive cases, E. coli was the most common organism isolated, consistent with previous reports²⁵.

Phenobarbitone was effective as first-line therapy in the majority of neonates, confirming its continued role as the drug of choice for neonatal seizures⁸,²⁶. Combination therapy was required in refractory cases, indicating higher seizure burden or severe underlying pathology. The overall survival rate of 90.75% in the present study is comparable with earlier studies¹⁴,¹⁷, though variations in mortality across studies may reflect differences in case severity and availability of neonatal intensive care facilities¹⁶.

Despite improvements in neonatal care, neonatal seizures remain associated with significant morbidity and mortality. Early identification of etiology, prompt correction of metabolic derangements, and timely initiation of appropriate antiepileptic therapy are crucial to improving immediate outcomes and preventing long-term neurological sequelae¹¹–¹³.

CONCLUSION

In conclusion, present study demonstrates that metabolic abnormalities, particularly hypoglycemia and hypocalcemia, were the most common causes of neonatal seizures, followed by sepsis or meningitis. Seizures most frequently occurred between 24–72 hours of life, showed a male predominance, and were predominantly subtle in nature, emphasizing the need for careful clinical observation. E. coli was the most commonly isolated pathogen in culture-positive cases, and neurosonography proved to be a valuable tool in assessing neurological involvement and predicting outcomes. Phenobarbitone monotherapy was effective in most neonates, though some required combination therapy or correction of underlying metabolic disturbances. Despite advances in neonatal care, seizures were associated with significant morbidity, prolonged hospitalization, and a mortality rate of 9.2%. Early detection, prompt correction of biochemical abnormalities, and etiology-specific management are essential to improve outcomes and reduce long-term neurological sequelae, highlighting the need for continuous video-EEG monitoring and larger, long-term studies for more definitive conclusions.

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