Etiology and Short Term Outcome of Neonatal Convulsion in NICU at Benghazi Children Hospital

Background: Neonatal seizures are the most prominent feature of neurological dysfunction during neonatal period, which are abnormal electrical dis-charges in the central nervous system of neonates, usually manifest as stereotyped muscular activity or autonomic changes, occurring in approximately 1.8 - 3.5/1000 live birth. Objective: The aims of study are to determine pre-valence rate, natural history, time of onset, etiological factors, clinical types and the short term outcome of neonatal convulsion. Settings: This study conducted in Neonatal Department at Benghazi Children Hospital—Libya. Patients and Methods: Descriptive cross sectional study, included all neonates who developing clinically identifiable seizures, admitted from 1 st of March 2013 to 1 st of March 2014. The data collected by using a designed perform including; gender, nationality, residence, place of transfer, gestational age, time of onset, mode of delivery, and history of maternal diseases, family history of neonatal seizures in previous siblings or death, jaundice and ex-change transfusion were taken. Details examination include dysmorphic fea-tures, weight, head circumference were recorded. Types of seizures were diagnosed by clinical observations, and the etiology of neonatal seizures had been identified from imaging study and from initial relevant investigations which include blood glucose levels, arterial blood gases, serum calcium, elec-trolytes, phosphate and cerebrospinal fluid examination for evidence of infection. In addition to treatments received, as well as causes of deaths. Results: Among babies with birth asphyxia, 76% delivered vaginally. 43/150 mothers presented with different medical problems, 32% of them had preeclampsia followed by diabetes in 28%. 127 (85%) babies had normal birth weight and 128 (86%) lie within normal range of head circumference. The most common type of seizure was subtle (48%) followed by clonic (36%). Cranial ultrasound performed to 110 (73%), among them, 16 babies MRI or CT scan were done. The most common cause of seizure was birth asphyxia (30%) followed by infection (16%), hypocalcemia (14%). Phenobarbitone was the most common drug used in treatment (60%), followed by phenytoin (40%) and resistant cases for treatment received pyridoxine (2%). 77 (52%) improved and discharged home without treatment. Mortality rate was 15%; among them 44% from IEM, followed by birth asphyxia 22%. There is strong association between main causes and the outcome with p = 0.005. Conclusion: The majority of neonates in our study were full term and male. The most common etiology of seizures is birth asphyxia. Hypocalcemia is the most common biochemical abnormality. Subtle represents the commonest type of seizure. Phenobarbitone is still the most commonly prescribed anticonvulsant. Inborn error of metabolism carries a higher mortality rate. Statically analysis showed there is significant association between main causes of neonatal convulsions and the outcome with p = 0.005.


Introduction
A seizure or convulsion is a paroxysmal, time-limited change in motor activity and/or behavior that results from abnormal electrical activity in the brain.
Neonatal seizures by definition occur within the first 4 weeks of life in a full-term infant and up to 44 weeks from conception for premature infants (4 weeks after term) and are most frequent during the first 10 days of life [1].
Seizures are more common in the neonatal period than in any other stage and affect approximately 1% of all neonates, with greater frequency in premature or low birth weight babies as compared to term babies. In the neonatal intensive care units, the incidence goes as high as 10% to 25% out of which about 15% will die and 35% to 40% will have major neurological squeal [2]. Seizures represent the brain's final common response to insult. The initial injury may be brief, but membrane damage releases excitotoxic substances such as glutamate which triggers further epileptic activity. Magnetic resonance imaging of the brain has shown markedly reduced myelination in children who had suffered from neonatal convulsions [3].
The newborn brain is particularly vulnerable to seizures which are associated with poor neuro developmental outcome. This vulnerability is thought to be due to a combination of enhanced excitability, and low levels of the inhibitory neurotransmitter gamma aminobutyric acid (GABA). That's lead to adverse effect on neurodevelopment and may predispose to cognitive, behavioral or epileptic complication later in life [4] [5].
This study was conducted in neonatal department at Benghazi Children Hospital; it is a referral hospital for all eastern parts of Libya. The department capacity is around 40 incubators, and it is staffed by a highly skilled team from both doctors and nurses. Therefore, the aims of this study were to determine the prevalence rate, the natural history, time of onset, etiological factors, clinical types and to evaluate the short term outcome of neonatal convulsions.  The data interpreted in tables and figures, the numerical data were shown as percent, minimum and maximum, median, mean ± SD.

Patients and Methods
Appropriate statistical test of significance like chi-sq test was used as necessary to find the significance of observed difference between the studied variables, and p value < 0.05 was taken as level of significance.
Limitations: There were limitations in some diagnostic investigations in the hospital like investigations for IEM as well as EEG services.

Results
Among the 2842 neonates admitted to neonatal care unit during the study period with different medical problems, 150 (5.2%) neonates (term and preterm) developed clinically identifiable seizures and were found eligible for the study.

Residence and Place of Transfer
• The vast majority of the babies 114 (76%) were from Benghazi; forty eight babies (42%) admitted directly from their homes through hospital neonatal OPD. Other 66 babies transferred from other hospitals including 45 babies from governmental hospitals and 21 babies from private hospitals. • All babies referred from outside Benghazi were delivered in governmental hospitals and were as follow (10 from Al Bayda, 7 from Ajdabiya, 6 from Al Marj, 5 from Darnah, 2 from Sabha, 2 from Tobruk, 2 from Al Abyar, 1 from Kufra, 1 from Sirt).

Gestational Age
According to WHO, preterm is defined as baby born alive before 37 weeks of pregnancy are completed. Term baby, between the complete 37 and 42 weeks while post term baby, after 42 weeks.

Age at Presentation
• Their age at presentation ranged from birth to 28 days with median 6 days and mean of (8.2 ± 7.1SD). • We classified the neonatal seizures by age of onset into early onset < 3 days and late onset after 3 days of age.  Table 3.   (6%) were assisted deliveries; 8 by vacuum and 2 by forceps. • Cesarean sections were done in 49 (33%) mothers, 39 as elective and 10 emergency.
• Among 45 babies with birth asphyxia, nearly three quarters (76%) delivered vaginally and (24%) by C/S. Table 4 and Figure 4 below illustrate mode of delivery and its correlation to birth asphyxia.

Maternal Diseases
• Among 43 mothers with different medical problems, 14 (32%) mothers had preeclampsia. Followed by diabetes in 12 (28%) mothers including; diabetes mellitus type I and II as well as gestational diabetes, 2 babies of these mothers had hypoglycemia while hypocalcemia found in third one.
• Three (7%) mothers had epilepsy; the causes of convulsions in their babies were one with hypocalcemia, the second one with hyponatremia and the third one with ICH. As shown in Table 5.

Birth Weight
According to baby growth chart published by WHO; Normal birth weight ranged from 2.5 -4.5 kg, and low birth weight (LBW) between 1.5 -<2.5 kg.

Head Circumference
According to WHO, normal range of head circumference in term newborn is 35 ± 2 cm.
• The vast majority of the babies 128 (86%) lie within normal range.

Types of Convulsions
• Nearly half of the babies 72 (48%) had subtle convulsion.

Imaging Done
• For the most of babies, 110 (73%) cranial ultrasound was performed, additional imaging CT or MRI was done to 16/110 as guided according to history, physical examination and investigations, which reviled 5 babies with ICH and 20 babies with brain edema. As shown in Table 9.    -Hypoglycemia in 12 (14%) babies; among them congenital heart disease and IDM 2 babies each.

Main Causes of Neonatal Convulsions
• Inborn error of metabolism 15 (10%) babies; four of them diagnosed as maple syrup urine disease and one as organic acidaemia. The others 10 just diagnosed clinically as well as from family history and from course of the disease.
• CNS structural defects 9 (5%) babies; 6 with hydrocephalus (two edwards syndrome and one robinow syndrome), one with operated encephalocele, one patau syndrome with holoprosencephaly, and other one with operated meningiocele.
• Four (3%) babies had kernicterus; their total serum bilirubin were as follow: 26.2, 28.7, 37, 38.2 mg/dl. one of them had hypocalcemia. Table 10 and Table 11 below illustrate main causes of convulsion and coexistence biochemical abnormalities with the main causes.
• 50/150 (33%) babies discharged on anticonvulsant treatment; the vast majority of them (88%) discharged with one drug only. Six (12%) babies with two drugs; 4 babies with (oral Luminal and calcium gluconate), others 2 with (oral Luminal and Clonazepam). Table 12 and Table 13 below show the medications used during admissions and after discharge.

The outcome
• Seventy seven (52%) babies improved and discharged home without treatment in satisfactory condition.

Correlation between Babies's Gender and the Outcome
• Half of babies in both gender discharged without treatments.
• Death rate was nearly the same in both gender with 15% in male and 16% in female. As shown in Table 14.
• There is no significance association between baby's gender and the outcome with p = 0.960.

Correlation between Babies's Residence and the Outcome
• According to residence, there is no difference in both group of babies regarding to treatments at discharge or in death rate. See Table 15.

Correlation between Gestational Age and the Outcome
• One third of preterm babies were discharged without treatments versus 53% in term babies. • In spite of that preterm babies had a higher rate 40% of treatments needed at discharged as well as higher death rate with 27% versus 33%, 14% respectively in term babies, there is no significance association between gestational age and the outcome with p = 0.455. As shown in Table 16.        • Among babies with CNS structural defects three (13%) died; two edwards and one patau syndrome. • While one baby died from kernicterus as well as one from infection. As shown in Table 20.

Conclusions
• The majority of neonates who developed seizures were male and full term.
• The most common etiology of seizures is birth asphyxia.
• Hypocalcemia is most common biochemical abnormality.
• Subtle represents the commonest type of seizure.
• Phenobarbitone is still the most commonly prescribed anticonvulsant.
• Inborn error of metabolism carries a higher mortality rate.
• Statically analysis showed there is significant association between main causes of neonatal convulsions and the outcome with p = 0.005.

Recommendations
Regular updating of the data is recommended with increasing attention to save the data electronically. Improvement of antenatal services and obstetrical care with regular monitoring of fetal heart rate to ensure safe delivery and appropriate neonatal resuscitation to avoid birth asphyxia; Improvement of the laboratory services and the availability of investigations and other advanced procedures to detect and diagnose an inborn error of metabolism. EEG services are strongly needed in the unit. Quick assessment, timely diagnosis and aggressive management according to the etiology are necessary to prevent the morbidity and mortality associated with neonatal seizures. Future studies should include large sample size and should include other hospitals in our locality; in addition we recommend prospective studies which focus on the long term neurological and developmental outcome following neonatal seizures.

Conflicts of Interest
The authors declare no conflicts of interest regarding the publication of this paper.