A retrospective cross sectional study on clinical profile of neonatal seizures in a tertiary care government hospital, Western India

Qury Nagadia; Ghosha Pandav; Urja Nagadia; Nisha Prajapati; Nehal Patel; Rashmi Thanvi

doi:10.4103/cjhr.cjhr_24_22

ORIGINAL ARTICLE

Year : 2022 | Volume : 9 | Issue : 4 | Page : 231-236

A retrospective cross sectional study on clinical profile of neonatal seizures in a tertiary care government hospital, Western India

Qury Nagadia¹, Ghosha Pandav¹, Urja Nagadia², Nisha Prajapati³, Nehal Patel¹, Rashmi Thanvi¹
¹ Department of Pediatrics, GMERS Medical College and Sola Civil Hospital, Ahmedabad, Gujarat, India
² Department of Pediatrics, Pandit Dindayal Medical College, Rajkot, Gujarat, India
³ Department of Pediatrics, GMERS Medical College, Gandhinagar, Gujarat, India

Date of Submission	27-Feb-2022
Date of Decision	03-May-2022
Date of Acceptance	05-May-2022
Date of Web Publication	17-Mar-2023

Correspondence Address:
Nehal Patel
Department of Pediatrics, GMERS Medical College, Sola, Near Gujarat High Court, S. G. Highway, Sola, Ahmedabad - 380 016, Gujarat
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/cjhr.cjhr_24_22

Abstract

Background: Convulsion during the first few weeks of life in a newborn is a frequent problem. Such disturbances may have many causes contributing to their etiology and have prognostic significance as well. Objective: This study aimed to determine the etiology, effect of gestational age, onset, types, and mortality of neonatal convulsions. We also aimed to evaluate the clinical parameters, computed tomography (CT) brain scan, neurosonogram, metabolic profile, and cerebrospinal fluid analysis as well as the response of antiepileptic drugs and outcome in these babies. Materials and Methods: A retrospective cross-sectional study was done at the neonatal intensive care unit of a tertiary care teaching hospital. The study group comprised 358 neonates with neonatal seizures (163 inborn and 195 referred) admitted over 2 years. Data were entered in Microsoft Excel and analyzed in SPSS version 12 (Chicago, Illinois, USA). Results: Out of 10,232 live births, 163 had seizures in the neonatal period, giving an incidence of 15.9/1000 live births. The most common type of seizure was tonic accounting for 33.2%. The most common etiology was perinatal asphyxia – 50.8%, followed by central nervous system infection – 20.1%. One hundred and twenty-six out of 358 patients expired contributing to mortality of 35.1%. All the newborns with perinatal asphyxia had seizures within the first 7 days. Conclusions: Improvement in antenatal and perinatal care with early identification of high-risk mothers will reduce the incidence of birth asphyxia and thereby of neonatal convulsions. Subtle seizures are most common and should not be missed. CT brain scan and neurosonogram are useful in the early detection of cerebral edema, ischemic hypodensities, and hemorrhage which contributes to prognostic significance.

Keywords: Hypoxic-ischemic encephalopathy, neonatal seizures, neuroimaging

How to cite this article:
Nagadia Q, Pandav G, Nagadia U, Prajapati N, Patel N, Thanvi R. A retrospective cross sectional study on clinical profile of neonatal seizures in a tertiary care government hospital, Western India. CHRISMED J Health Res 2022;9:231-6

How to cite this URL:
Nagadia Q, Pandav G, Nagadia U, Prajapati N, Patel N, Thanvi R. A retrospective cross sectional study on clinical profile of neonatal seizures in a tertiary care government hospital, Western India. CHRISMED J Health Res [serial online] 2022 [cited 2023 Apr 1];9:231-6. Available from: https://www.cjhr.org/text.asp?2022/9/4/231/371936

Introduction

Seizures in neonates are relatively common with variable clinical manifestations. It is often the first sign of neurological dysfunction and is a powerful predictor of long-term cognitive and developmental impairment. Neonates are at risk for the development of seizures as metabolic, toxic, structural, and infectious diseases are more likely to be manifested during this period of life.

This study aims to find out the incidence of neonatal seizures in hospital-born babies and the probable etiology with clinical parameters including gestational age, age of seizure onset, and type of seizures within the available facilities.

Materials and Methods

A retrospective cross-sectional study was done at the neonatal intensive care unit (NICU) of a tertiary care teaching hospital, Gujarat, India. The study group comprised 358 neonates with neonatal seizures (163 inborn and 195 referred) admitted over 2 years.

Inclusion criteria

Patients with clinical history and observation of seizure activity and/or such activity during the hospital stay by parents or residents or the nursing staff
The onset of seizures within the first 4 weeks of life.

Exclusion criteria

Neonates with doubtful seizure, apnea, or jitteriness were not included in the study
Seizure due to neonatal tetanus was not included in the study.

Jitteriness was differentiated from seizures by the following characteristics:

The absence of an abnormality of gaze or eye movements
Its provocation by stimulation of the infant or by stretching a joint, in contrast to the spontaneous occurrence of seizures
The cessation of movement with passive flexion
The absence of fast and slow component characteristic of a clonic seizure.

Detailed history taking and careful physical and neurological examination were carried out on each study subject. Hypoxic-ischemic encephalopathy staging was done using Sarnat classification. Gestational age was estimated using New Ballard Scoring and modified Dubowitz scoring system. Blood samples were taken under strict aseptic conditions. Blood glucose, serum calcium, and magnesium were also analyzed by standard biochemical methods. Urine analysis for reducing substances and serum bilirubin estimation was done wherever required. Computed tomography (CT) scan brain was performed after stabilizing the baby. CT scan was done using a third-generation subsecond, single-slice, spiral CT machine, Toshiba Asteion, Japan. Slice thickness for the posterior fossa structures was 5 mm and for the rest of the brain was 10 mm. The smallest slice thickness was 0.67 mm. The whole procedure takes around 10 min to complete the scan.

Cerebrospinal fluid (CSF) analysis for total cell count, differential count, sugar, protein, globulin, and chlorides as well as culture and gram stain was performed. Neurosonogram was done as soon as the baby's condition was stabilized. X-ray chest, X-ray skull, and thyroid profile were done wherever indicated. The babies were treated with antiepileptic drugs, antibiotics, IV fluids, and oxygen therapy according to their clinical condition.^[1] Phototherapy was given wherever necessary.

Our criteria to define sepsis, hypoglycemia, and hypocalcemia were as follows:

Criterion for sepsis was as follows: the presence of two or more of the following:

(a) total cell count <5000/mm³, (b) band cell-to-mature neutrophil ratio more than 0.2, (c) C-reactive protein more than 10 mg/ml, (d) radiological evidence of pneumonia, and (e) isolation of pathogen either from blood or CSF by culture.

Criterion for hypoglycemia: blood glucose level <40 mg/dl.

Criterion for hypocalcemia: serum calcium level <7 mg/dl.

The study was approved by the institutional ethics committee.

Results

Three hundred and fifty-eight neonates were studied, out of which 163 were born in our hospital and 195 were referred from outside (outborn). During the study period of 2 years, 163 of total 10,232 live births had seizures in the neonatal period, giving an incidence of 15.9 per 1000 live births. Out of 358 cases, 183 were males and 175 were females.

[Figure 1] depicts that the highest incidence of neonatal seizures was in the term babies and lowest in postterm babies.

Figure 1: Number of newborns with different gestational age having seizures

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[Figure 2] shows the highest incidence of seizures found in patients delivered by forceps delivery and lowest in those who were normally delivered. On application of Chi-square test, the difference was statistically significant with P = 0.0039 (P < 0.01), indicating that the proportion of seizures among babies delivered by forceps delivery was significantly higher than among those delivered through other modes of delivery. No significant relation was found with the parity of mother. 53.9% of mothers were primipara and 46.1% were multipara.

Figure 2: Relationship of live born having seizure with the mode of delivery

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The most common type of seizure in our study was tonic accounting for 33.2%, followed by 32.3% of multifocal clonic and 15.2% of mixed. Other types of seizures were subtle, focal clonic, and myoclonic, with the frequency of 12.3%, 6.2%, and 1.1%, respectively.

Seizure incidence was highly associated with antenatal and perinatal risk factors. It was more common in babies of anemic mothers. Out of 358 cases, 241 (67.6%) had anemia; 53 (14.9%) had hypertension; approximately 9% of each mother had fever, premature rupture of membranes (PROM), and cephalopelvic disproportion; and only two (0.5%) mothers had diabetes.

[Table 1] shows the most common etiology of seizure as perinatal asphyxia (50.8%) followed by central nervous system (CNS) infection (20.1%). This was followed by hypocalcemia (10%), hypoglycemia, and intracranial hemorrhage. We were not able to trace any significant etiological factors in about 17% of patients. We observed that the perinatal asphyxia was more common in the inborn babies of our hospital (P = 0.0026), while CNS infection was more common in outborn babies. This observation is most probably due to the immediate treatment given to the outborn babies in other centers postdelivery in the early neonatal period, while the newborn with CNS infection may have approached our institute after being symptomatic postdischarge.

Table 1: Etiology of seizures for babies born inside and outside the study hospital

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[Table 2] shows the correlation between occurrences of seizure to the days of life. In perinatal asphyxia, most of the seizures occur in the first 3 days. In the next few days, seizures are likely due to the secondary complications of perinatal asphyxia such as hypocalcemia and hemorrhage. Seizures due to CNS infection mostly occur after the 1^st week of life.

Table 2: Relationship of etiology to age at onset of seizures

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It is evident from [Table 3] that perinatal asphyxia was most commonly associated with tonic and focal clonic types of seizures, while intracranial hemorrhage and hypoglycemia presented with tonic type predominantly. Hypocalcemia had predilection toward multifocal clonic and focal clonic types of seizures, and CNS infection was associated mainly with multifocal clonic and tonic types.

Table 3: Relationship of etiology to the type of seizures

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[Figure 3] shows the relationship between the ages at seizure onset with the mortality. No significant difference was found between mortality among the children having seizure onset during the first 7 days and among the children having seizure onset after 7 days (P = 0.6009).

Figure 3: Relationship between the age of life at onset of seizures and mortality

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Most of the neonatal seizures were controlled by monotherapy of anticonvulsant drugs (70.9%). We have used phenobarbitone as the first-line anticonvulsant drug for all our newborns. Only 70 patients (19.5%) required more than one and 12 (3.4%) patients required more than two drugs to control them; nine (2.5%) patients had refractory seizures.

Mortality data showed that death due to perinatal asphyxia was 84 of 181 (46.4%), to intracranial hemorrhage was 9 of 11 (81.8%), to hypoglycemia was 3 of 23 (13%), to hypocalcemia was 1 of 38 (2.6%), and to CNS infection was 35 of 70 (50%). This means the prognosis of hypocalcemia was good and intracranial hemorrhage was worst of all.

Discussion

Convulsive disorders are fairly frequent problems during the first few weeks of life. Such disturbances may have many causes contributing to their etiology. Due to the immature nervous system of the newborn, convulsions can occur even following a minor insult. Keeping this in view, the present study was carried out to find out the causes of neonatal seizures.

The incidence of neonatal seizures in our hospital was 15.9/1000 live births. Other previous studies also confirm the incidence as high as 57.5/1000 in infants with birth weights lower than 1500 g but only 2.8/1000 for infants with birth weights of 2500–3999 g.^{[2],[3],[4],[5]} Our hospital being a referral center resulted in more deliveries of high-risk mothers having antenatal and natal complications, hence the higher incidence of seizures.

The most common maternal risk factor associated with neonatal seizures was anemia in the present study, whereas infants of women who were 40 and older; with diabetes mellitus, intrapartum fever, or infection; or who delivered ≥42 weeks had an increased risk of seizures as per Glass et al.^[6]

Relation to sex

Holden et al. and Painter et al. have described a slight male preponderance.^[7],[8] There was no statistical significance of sex predominance in our study.

Relation to the type of delivery and parity

Our study indicates that forceps and cesarean section were at higher risk of having neonatal seizures. There was no significant difference in intraventricular hemorrhage, subdural hemorrhage, seizure, or sepsis between the cesarean delivery and vaginal delivery groups in other studies.^[9] No significant association was found between neonatal seizures and mother's age, parity, or multiple births by Saliba et al. as also in our study.^[10]

Relationship to gestational age maturity

One hundred and thirty-one (37%) were preterm, 214 (60%) were term, and 11 (3%) were postterm. In contrast to our study, Scher et al., Mizrahi and Kellaway, and Singhal et al. have the incidence of neonatal seizures higher in preterm than in term babies.^{[11],[12],[13]}

This can be due to birth asphyxia which is the most common cause of seizures in full-term babies and is associated with perinatal complications such as prolonged second stage of labor.

Etiology of neonatal seizures

In accordance with our study, Scher et al., Mizarhi et al., Sheth et al., and Nelson also had the most common cause of neonatal seizure as hypoxic-ischemic encephalopathy.^{[2],[4],[5],[14]}

[Table 4] demonstrates the comparison of different studies with our study results. We had a little higher incidence of seizures with undetermined etiology. There were 61 (17%) neonates on whom the definite etiology was not established in the present study. Whereas Painter et al. reported a 5% incidence, Volpe reported a 10% incidence, and Mizrahi and Kellaway noted a 10% incidence.^[5],[8],[15] This wide variation in detection of neonatal seizures was due to the following reasons:

Table 4: Comparison of different studies

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Unavailability of certain facilities: real-time gray-scale portable sector ultrasonography is required for the precise diagnosis of intracranial hemorrhage, cerebral malformations, etc., Electroencephalogram is helpful, especially in the diagnosis of apneic seizures and enzyme studies for specific diagnosis of inborn error of metabolism. We were unable to perform these investigations due to the financial constraint we had for the further required diagnostic workup
The criteria adopted for labeling the cause of seizure. For instance, what certain authors label “5^th-day seizure” is labeled idiopathic by some.

Relation to the type of seizure

In our study, the most common type of seizure was tonic, followed by multifocal clonic, while subtle seizures were most common in neonates, followed by clonic, tonic, and myoclonic seizures as per Volpe.^[16] The reason behind the difference observed was due to the lower socioeconomic status and substandard educational level of the parents of our subjects leading to missed or delayed recognition of subtle seizures as well as due to the unavailability of video electroencephalography (EEG) for early detection of subtle seizures at our center.

Relation to the time of onset of seizures

The time of onset of seizures depends upon the etiology. Sixty percent of seizures due to hypoxic-ischemic encephalopathy have seizures within the first 12 h.^{[2],[3],[17],[18]} Seizure due to CNS infection generally occurs after 7 days. In our study, 79% of seizures due to hypoxic-ischemic encephalopathy occurred during the first 3 days, and the remaining 21% were maybe because of secondary causes due to hypoxic-ischemic encephalopathy such as hypocalcemia and intraventricular hemorrhage. Seventy-four percent of CNS infection has onset of seizures after 8 days of life.

Relation of antiepileptic drug given

In our study, total 87.4% of patients required anticonvulsants. In other newborns (12.6%), seizures were controlled by giving dextrose or calcium and were attributed due to metabolic causes alleviating administration of any anticonvulsants. By giving phenobarbital, 20 mg per kg 40% cessation was achieved. Phenobarbitone 40 mg/kg achieved 70% cessation, phenytoin 20 mg/kg led to 85% cessation, and lorazepam – 0.05–0.1 mg/kg led to 95% cessation of convulsions. Painter et al. also showed that both of the two most commonly used anticonvulsants (phenobarbital and phenytoin) were similarly effective controlling seizures in < 50% of infants, but they did not report mortality or neurodevelopmental outcome of it.^[8]

Mortality

The risk of neonatal mortality due to seizures has decreased in recent years due to early detection, better drug availability, and management. Mortality is related to the etiology, type, and gestational age at presentation. Cerebral malformations and severe hypoxia-ischemia are associated with poor outcome.^{[1],[2],[19],[20],[21]} In our study, mortality was 35.1% as ours is a tertiary care referral center.

Conclusions

Improvement in antenatal and perinatal care with early identification of high-risk mothers will reduce the incidence of birth asphyxia and thereby of neonatal convulsions. Prompt treatment of maternal infections, maternal screening for bacterial and TORCH infections as well as strict aseptic precaution should be taken in labor and neonatal wards to prevent neonatal sepsis. Initiation of early and adequate feeding should be established to prevent hypoglycemic and hypocalcemic seizures. Continuous EEG monitoring and bedside neuroimaging facilities can aid in early diagnosis of nonclinical and subtle seizures and CNS abnormalities, respectively.

Limitation

Our study has a major limitation of the unavailability of video EEG monitoring for the neonatal seizure. The Task Force of Neonatal Seizures 2017 has emphasized the role of EEG in diagnosing neonatal seizures.^[21] Seizures can be overt motor and can be only electrographic and nonmotor which can be easily missed if continuous EEG is not done. Video EEG can have added benefits for neonatal seizures which may be controlled clinically but may continue as nonmotor seizures and require EEG monitoring for a further 24 h.

Patient consent

Parent's/legally authorized representative's written informed consent was taken for the NICU admission of their newborns.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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