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Study of Etiology, Onset and Clinical Manifestations of Neonatal Seizures in a Tertiary Care Centre

1,2 M.D. Pediatrics, Associate Professor, Department of Pediatrics, Grant Govt Medical College, Mumbai 3,4 Junior Resident, M.D. Pediatrics, Department of Pediatrics, Grant Govt Medical College, Mumbai *Corresponding Author Shaista Parween Junior Resident, M.D. Pediatrics, Department of Pediatrics, Grant Govt Medical College, Mumbai Postal Address: H.no.2, Cross Rd 4B, Barinagar, Telco , Jsr-831004 Abstract Background: The most vulnerable period of life to develop seizures is the neonatal period. These events very often signify serious damage or malfunction of the immature developing central nervous system. Neonatal seizures may arise as a result of diverse etiologies and can have varied presentations. Aims and Objective: Our study was aimed to find etiological factors, time of onset, clinical manifestations and various outcomes of neonatal seizures. Methods: There were 110 neonates admitted in the NICU of a tertiary care centre in metropolitian city, with history of convulsions during the study period of 24 months from November 2016 to October 2018. Detailed antenatal history and baseline characteristics of convulsing neonate were recorded at admission. Clinical details of each seizure episode reported by the mother and subsequently observed by the resident doctors on duty were recorded. Venous blood was collected as soon as possible and blood glucose, total serum calcium levels, Na+, K+, Mg and P-levels were done immediately after baby had seizures and before instituting any treatment. Data was described as mean ± SE and %age. SPSS 22.0 and MS Excel software were used for data analysis. Results: Hypoxic ischemic encephalopathy was the commonest etiology of neonatal seizures followed by neonatal meningitis. Majority of Hypoxic ischemic encephalopathy patients presented with seizures in the first 72 hrs. of life. Subtle seizures were the commonest seizure types encountered. Hypoglycaemia was the commonest biochemical abnormality in primary metabolic seizures. Hypocalcaemia was the next commonest abnormality and most common outcome was Residual neurological abnormality followed by Epilepsy. Conclusions: Hypoxic ischemic encephalopathy was the commonest etiology with subtle seizures being the commonest clinical types encountered. Hypoglycaemia was the most frequent biochemical abnormality found and most common outcome was residual neurological abnormality.


Introduction
Seizures are the most common and most important manifestation of neurologic dysfunction in neonates and carry a high risk for mortality and adverse long-term outcomes. 57.5 per 1000 neonates with birth weight <1.5 gm and 2.8 per 1000 neonates weight between 2.5 and 3.99 kg have seizures. The occurrence of neonatal seizures per se has been positively correlated with structural brain damage http://jmscr.igmpublication.org/home/ ISSN (e)-2347-176x ISSN (p) 2455-0450 DOI: https://dx.doi.org/10.18535/jmscr/v7i8.70 and its consequent sequels at later stages in life. Seizures are a sign of an underlying cerebral pathology, the most common of which is Hypoxic-Ischaemic Encephalopathy (HIE) in term neonates (78%) followed by Septicaemia, Hypoglycaemia and Meningitis in order of frequency. The commonest type of seizures is subtle seizure (45.5%) followed by tonic, clonic, spasm and myoclonic seizures. Hypoxic-ischemia is considered the most common cause of neonatal seizures. Metabolic disorders and Meningitis are the second most common cause of neonatal seizures occurring in full term small for gestational age neonates. Intracranial hemorrhage is implicated in 10% to 15% of seizures. Hypomagnesaemia with serum <1.5 mg/dl can occasionally manifest with tetany and seizures at 2-4 weeks of age. Hyponatraemia as a result of fluid overload, renal compromise and SIADH (syndrome of inappropriate ADH secretion) can be a frequent complication of birth asphyxia and could complicate the management of seizures in this condition. Subtle seizures are the most frequent seizure type, which may consist of only horizontal deviation and or jerking of the eyes, repetitive blinking or fluttering of eyelids, drooling, suckling or other oro-buccal movements. Neonates with seizures are at risk of death, whereas survivors are at risk of neurological sequelae, developmental delay, later epilepsy and cognitive impairment. So, we need to initiate an early diagnostic workup to determine the causes. Early recognition and treatment of biochemical disturbances are essential for the optimal management and satisfactory outcome. There is a strong correlation of time of onset of neonatal seizures with the etiology and prognosis. For example, birth asphyxia usually presents in the first three days of life whereas meningitis usually presents after first week. If baby convulse within hours of delivery, it signifies poor prognosis and brain damage.

Materials and methods
This study of etiology, onset and clinical manifestations and outcome of neonatal seizures was conducted in the Neonatal Intensive Care Units (NICU) of a tertiary care centre in the metropolitian city over a period of 24 months. Proper history, clinical examination was performed on all the admitted neonates with seizures. The study population was selected according to inclusion criteria. The structured proforma included antenatal history, natal history, post natal history, family history, immunisation history, general and systemic examination, relevant laboratory findings. Proper maternal and neonatal histories were taken from reliable person, clinical examinations were done using aseptic precautions. Rectal/Axillary temperature was measured using clinical thermometer. Pupillary response was examined using a pen torch. Arterial and venous blood was drawn using aseptic precautions for required biochemical and haematological investigations. Lumbar puncture was done in all neonates with convulsions after taking proper consent. Multichannel non-invasive monitor was used to monitor heart rate, saturation of oxygen and carbon dioxide. Statistical analysis: Data was described as mean ± SE and %age. Software used for data analysis was SPSS 22.0 (statistical package for social sciences) and MS Excel. Complete Blood Count, continuous Electroencephalography was essential for the diagnosis of seizures in neonates due to their subtle clinical expression, non-specific neurological presentation and a high frequency of electro-clinical uncoupling in the neonatal period. Blood sugar, serum electrolytes such as sodium, potassium, serum calcium, magnesium and urea nitrogen level, Lumbar puncture, Metabolic workup, USG Skull, CT Brain, MRI Brain and genetic testing were done.

Results and observation
There were 110 neonates admitted in the NICU of a tertiary care centre in metropolitian city, with history of convulsions during the study period of 24 months from October 2016 to November 2018. JMSCR Vol||07||Issue||08||Page 408-413||August 2019 were normal. 13 neonates (11.8%) had hypoglycaemic seizures, of which 3 neonates (23.1%) developed residual neurological abnormality, 3 neonates (23.1%) died due to septicaemia. Hypocalcaemic seizures were found in 11 neonates (10%) of which 1 neonate (9.1%) developed epilepsy with abnormal EEG report, rest all were normally. 6 neonates (5.4%) had electrolytes imbalance, most common being hyponatraemia and hypernatraemia due to SIADH and severe dehydration. 2 neonates (2/6-33.3%) expired due to severe acidosis and CNS infection. 3 neonates (2.7%) had metabolic disorders as a cause of seizures, all died due to respiratory and liver pathology. 3 neonates (2.7%) had IVH and all neonates died due to respiratory failure and septicaemia. 4 neonates (3.6%) had genetic disorders as a cause of seizures and all neonates developed epilepsy. Chi sqare test of neonatal seizures etiology and neurodevelopmental outcome= 98.052 p=<0.001 (very highly significant). Hence from this study, there was a strong correlation between etiology of neonatal seizures and neurodevelopmental outcome.

Discussion
Neonatal seizures had slight predominance of male to female neonates. Male to Female ratio was 1.4:1. Seizures due to Birth asphyxia (39%) was seen more commonly in term appropriate for gestational age and all post term neonates and associated with perinatal factors like meconium stained liquor whereas seizures due to Hypoglycaemia (11.8%) was more common in low birth weight neonates. Most of neonatal seizures occured in the first week of life (85.4%), more so within first 3 days of life (54.5%). Highest number was seen on second day of life. The most common type of seizures was Subtle seizures (40.9%), followed by generalized tonic (29.1%), multifocal clonic (11.8%), focal clonic type (8.2%) and mixed type of seizures (10%). The commonest cause of neonatal seizures was Hypoxic Ischaemic Encephalopathy (39%) followed by Neonatal Meningitis (17.3%). Seizures due to Birth asphyxia had onset within first 3 days of life (97.6%) more so during second day (58.1%) with statistically significant correlation between etiology and onset of seizures (p<0.001). Majority of Hypoglycaemic seizures occured during, third and fourth day (92.3%). Seizures due to neonatal meningitis had onset at the end of first week and early second week. Hypocalcaemic seizures had 2 peaks, one on second day and the other after first week of life. Neonatal meningitis in this study was the second most common cause of seizures (17.2%). Organisms causing meningitis were mostly MRCONS and Klebsiella pneumonie which is community acquired or nosocomial acquired. This could be prevented by proper hand washing technique and hygienic delivery. Hypoglycaemia was the third most common cause of neonatal seizures (11.8%) and had adverse effect on brain therefore early detection and treatment of hypoglycaemia prevent brain injury and poor neurodevelopmental outcome. Most common neurological sequel was Residual neurological abnormality (27.3%) followed by Epilepsy (10%). Birth asphyxia was mainly responsible for development of Residual neurological abnormality. Mortality in this study was 16.4% (18/110) and Birth asphyxia was the leading cause of death. Morbidity rate was 37.2% (41/110). Birth asphyxia had poor neurodevelopmental outcome in the form of residual neurological abnormality (most common) and epilepsy. All patients with genetic causes developed epilepsy. Early detection of etiology of neonatal seizures is helpful with respect to prognosis and treatment. Subtle seizures were the commonest type of clinical seizures, which was difficult to identify, therefore careful observation of at risk newborns is necessary. The occurrence of seizures may be the first indication of neurological disorder and the time of onset of seizures has a correlation with the etiology of seizures and prognosis.

Conclusion and Recommendations
The most common etiology of neonatal seizures is Hypoxic-Ischemic Encephalopathy due to Birth asphyxia (39%) followed by Metabolic disorders (27.2%), CNS infection (24.5%) commonest being Neonatal Meningitis and Intracranial Hemorrhage (2.7%). Perinatal complications like MSAF, PIH, prolonged second stage of labour and unsafe home deliveries are frequently associated with HIE. Hence these can be prevented by proper antenatal and perinatal care to the mother. Most of the seizures occur in first 3 days of life and mainly due to Birth asphyxia (42/43-97.6%), hence the time of onset of neonatal seizures is significantly associated with the etiology. Subtle seizures are commonest type (40.9%) of clinical seizure and seen mainly in neonates with Birth asphyxia. Most common neurodevelopmental abnormality is Residual neurological abnormality (27.3%) followed by Epilepsy (10%) and most common etiology being Birth asphyxia. Mortality rate is 16.4% and Morbidity rate is 37.2%. Hence from outcome, it is found that mortality rate has decreased significantly due to improved neonatal intensive care in NICU of a tertiary care centre but morbidity is same. Most of the neonatal seizures are associated with perinatal complications, continued advances in perinatal and neonatal medicine may reduce seizure incidence in the future and prevent the neurologic, cognitive and epileptic consequences of neonatal seizures.