Study of Clinical Pro ile of Neonatal seizures in a NICU of Rural Central India

Seizures are common neonatal illness amongst neurological disorders. The study was conducted to determine the clinical pro ile of neonatal seizures. A hospital based prospective observational study was undertaken in the NICU of a rural set up in central India. A total of 82 neonates admitted with seizures or who developed seizures later during the stay in NICU were subject population of the study. Of 82 neonates with seizures, the overall mean for duration of stay was 14.34 (±10.41) days and the interquartile range was 1-32 days and male predominance. Majority of neonates included were extramural deliveries (62.19%). The distribution of neonates in the study according to their gestational age, birth weight, route of delivery & MSAF was found to be statistically insigni icant (p Value >0.05). The vaginal route of delivery was more common than the caesarean section amongneonateswith seizures in the study. The overallmortality ratewas 17.07%(14/82) .Inmost of the cases, the causes of neonatal seizures were present. Birth asphyxia was the main etiology identi ied. The antenatal services and intrapartum monitoring is important.


INTRODUCTION
The neonatal period, unquestionably is the most hazardous period of life, never again in life individual is confronted with more dramatic changes than in transition from dependent intrauterine existence to independent post natal life. The new born brain responds in the form of convulsion even to minor insult, because of the immaturity of the nervous system. The presentation of a newborn with seizures represents a true emergency (Scher and Painter, 1989) and frequently indicates signi icant neurological dysfunction or damage to the immature nervous system (Holden and Freeman, 1975).
Seizures during the neonatal period are relatively common, occurring in approximately 1.8 to 3.5 per 1000 live births, with greater frequency in premature or low birth weight babies as compared to term babies (Mizrahi, 2001). The highest incidence of neonatal seizures occurs during the irst 48 hours of life (Garg, 1972).
In the Neonatal Intensive Care Unit, the incidence goes as high as 10 to 25% out of which about 15% will die and 35 to 40% will have major neurological sequelae. (David et al., 2002) The major causes of neonatal seizures are Hypoxic-Ischemic Encephalopathy (HIE), which represents about 50% of the causes of neonatal seizures. Metabolic abnormalities, infection, intracranial hemorrhage, developmental anomalies are the other important causes (Sabzehei et al., 2014;Marzoki, 2010). Inborn errors of metabolism are amongst the rare causes of neonatal seizures.
The causes of seizures in preterm neonates is different from that seen in term neonates, where the HIE is the most frequent cause in term neonates, followed by cerebral malformations and metabolic disturbances, while in preterm neonates intraventricular hemorrhage and infections are the most frequent causes. (Vasudevan and Levene, 2013) Neonates can have subtle seizures or tonic, focal, multifocal and myoclonic types of convulsions.
There is increasing evidence that neonatal seizures have an adverse effect on neurodevelopment and may predispose to cognitive, behavioural or epileptic complication later in life. (Levene, 2002) Therefore, the aim of the study was to determine the clinical pro ile of neonatal seizures.

MATERIALS AND METHODS
This was a prospective, observational study conducted over two years on the neonates with seizures admitted in NICU of a rural set up in central India.

Inclusion Criteria
All newborns of upto age </= 28 days brought to NICU during the study period with clinically identi ied seizures, de ined as-sudden abnormal repetitive, rhythmic movement of any part of the body with or without deviation of angle of eyes and frothing from mouth which were not suppressed by physical pressure alone or subtle convulsion.

Exclusion Criteria
1. Neonates with known congenital malformation of the CNS.

Sample size
All babies ful illing the inclusion criteria who were brought for hospitalization during the study period were consecutively recruited. There were thus neonates included in the study.

Study Method
Ethical clearance was obtained for this study from the Institutional Ethics Committee. Babies who were reported with clinical seizures identi ied on history or observation by the neonatal intesivist at the time of hospitalization were included after obtaining written consent from parents. At the time of recruitment, a detailed history was recorded. Their mothers' previous obstetric history, family history, antenatal, natal and post natal risk factors which includes maternal drug addiction / withdrawal, maternal chronic disease, prolonged rupture of membranes, bleeding, pregnancy induced hypertension drugs taken during pregnancy, gestational age assessment by LMP, small for date, low birth weight baby, perinatal asphyxia, traumatic delivery, septicemia, meningitis, intracranial bleed and hyperbilirubinemia, The detailed history about age of occurrence of irst seizure, duration of seizure, number of seizures, type of seizure. Clinical examination indings were noted including anthropometry. The course of illness was recorded and outcome noted. During hospitalization any relevant investigations done and treatment given as per protocol of NICU and was recorded in a prevalidated case record form.

Data Management and Statistical Analysis
Statistical analysis was performed using percentage. The analysis of Student's t-test was used for comparisons. Categorical variables were compared using Chi square test and Fischer's exact test. A p-value 0.05 was considered signi icant.  (1) and Multiple sclerosis (1) while one mother suffered from gestational diabetes mellitus. A Neonatal sepsis was common co-morbidity in the study as 45 (54.87%) neonates had a positive blood culture report among all neonates. The overall mortality rate was 17.07% (14/82) while survival rate was 82.92% (68/82) in the present study.

Out
In the present study many patterns of seizures were found with relation to patient characteristics, types of seizures, its causes and associations with the maternal and neonatal factors.

DISCUSSION
In the study carried out by Perveen et al. (2016), there were 41(68.33%) males with female: male ratio of 1:2.15.
In another study conducted by Gowda et al. (2019) there was male preponderance as well with 56 (56%) male neonates and 44(44%) female neonates with female to male ratio of 1:1.27.
In yet another study by Rao et al. (2018), there was again male preponderance among neonates with seizures. In another study conducted in the NICU of a tertiary care hospital in Nasik 156 , out of the 127 neonates studied, 118(92.91%) neonates were full term while 7(5.51%) were preterm. Among the neonates studied by Gowda et al. (2019), the mean birth weight values were 2.56(±0.64)Kg. Holden and Freeman (1975) found that the incidence of neonatal seizure were 63% in normal weight and 37% in less than 2.5 kg. Shah and Singh (2008) in his study of neonatal seizures Clinico-biochemical pro ile of Neonatal Seizures studied 90 babies , found that the percentage of neonatal seizure was more in normal weight babies 66% than the babies whose weight was less than 2.5 kg. i.e. 33%. Similar results were found in our study.
In another study conducted by Patil et al. (2018), onset of seizures was found to be within irst 3 days of life in 101(79.5%) neonates while after 3 days of life, only 26 (20.5%) neonates developed seizures. It was also concluded that, onset of seizures within irst 3 days of life of had statistically signi icant correlation with birth asphyxia being the causative factor with p<0.001 In the study done by Amudhadevi and Kanchana (2018), the onset of seizures on the irst two days of life was seen in 62 (59.6%) neonates, In the study conducted by Arpino et al. (2001), there was a strong association between preeclampsia, chronic hypertension and PIH with neonatal seizures.
In the study undertaken for analysis of antenatal risk factors for seizures in term newborns by Glass et al. (2009) unadjusted analysis showed maternal hypertension was associated with seizures; however, in the adjusted analysis, which included all antenatal, intrapartum, and infant covariates, the risk of maternal hypertension was no longer significant. Each of the variables was evaluated individually in a regression with hypertension and found that no single variable had a signi icant effect. Although the p value was not signi icant in this study for maternal diseases but a signi icant percentage of neonates had mothers with pre Eclampsia. This could be attributed to the fact that preeclampsia/eclampsia leads to decreased utero-placental perfusion. Pathak et al. (2013), 78.89%(86/109) newborn had seizures accountable for perinatal insult while CNS infections was accountable for 16.51%(18/108) of cases. thus leading to adverse neonatal neurological outcome including seizures. Brunquell et al. (2002), most common type of seizures were subtle (51%) followed by focal clonic(42%), multifocal clonic(30%) and generalized tonic (23%) In another study, evaluating the safety & ef icacy of LEV in neonatal seizures, Ramantani et al. (2011) found subtle seizures to be the most common type (42.10%) Kher et al. (2017) having 18.35% (35/109) neonates who died , and our study had got near similar(17.07%) percentage of died neonates. that is 65(26%) can be due to the severity of the etiological factors in newborns with neonatal seizures.
But when compared with the study done by Nunes et al. (2008) found that 24.7% of the cases died in the neonatal period; higher than the current study. Study in same setup by Kher et al. (2017) showed mortality of 26%. It can be due to the severity of the maternal risk factors in newborns with neonatal seizures.
The study was not without limitations, irst the neurodevelopmental outcome of neonates could not be done at later stages of life for assessment of long term effect of seizures on CNS development. Another shortcoming was EEG could not be done because of infrastructural limitations in the hospital. EEG monitoring is important to identify nonconvulsive seizures and non obvious seizures in predisposed neonates.

CONCLUSION
The distribution of neonates in the study according to their gender, gestational age, birth weight, route of delivery, place of delivery, meconium stain of amniotic luid, age of presentation, duration of stay, maternal factors and cause of seizure was found to be statistically insigni icant. The most common cause of seizures and death was birth asphyxia. In the present study, multifocal seizures were most common type of neonatal seizures was observed.