Neonatal seizures: A complex phenotype representing past, present and future risks for brain injury

Background: Neonatal seizures result due to altered neurological functions like motor, behavioural and autonomic function. We conducted this study to assess the incidence, etiological factors, and immediate outcomes of neonatal seizures in term and preterm neonates. Methods: This prospective observational study included all neonates delivered in a tertiary health centre of New Delhi from Nov 2015 to Oct 2016 and admitted in Neonatal Intensive Care Unit with clinically identified seizures up to 28 days of postnatal age. Results: Out of 11,109 live births during the study period, 302 developed neonatal seizures with overall incidence of 2.71%. The early preterm (12.05%), very low birth weight babies (56.30%), and neonates in first 24 hrs of life (68.9%) had the highest incidence of neonatal seizures. The commonest seizure type was subtle seizures (52.3%). In early preterm commonest etiology was infection (31.3%) while in late preterm and term neonates most common etiology was Hypoxic ischaemic encephalopathy 59% and 72% respectively. Overall, HIE was the most common etiology (57%). Out of 302 cases, 81 (26.8%) cases have died. HIE was found to be the most common cause for mortality. Mortality was highest in early preterms (49.3%) and very low birth weight neonates (52.3%). Also, mortality was maximum among neonates having subtle seizures (29.1%) and seizures occurring within 24 hrs of life (30.8%). Conclusions: Persistently high incidence of neonatal seizures requires further strengthening of antenatal, natal, and post-natal health services. Early identification of neonatal seizures and timely intervention are very important for better outcomes.

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. Biochemical abnormalities are commonly observed in neonates who are admitted in neonatal intensive care unit with seizures. Early recognition and treatment of biochemical disturbances is essential for optimal management and satisfactory long-term outcome.
 Objective: To assess clinical types and importance of biochemical abnormalities in neonatal seizures and to evaluate clinical type & time of onset of seizures in term and preterm neonates.
 Methods: A prospective observational study, where 100 neonates presenting with seizures admitted to neonatal intensive care unit of Jagadguru Jayadeva Murugarajendra Medical College, Davangere, from September 2015 to August 2017 were enrolled in the study. The detailed history along with clinical examination, 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. The relevant biochemical investigations were done immediately after baby had seizures and before instituting any specific treatment. The descriptive statistics such as mean and standard deviation (SD) for continuous variables, frequencies and percentages were calculated for categorical variables. The association between gestational age and other categorical variables were analyzed using chi-square test of independence. The comparison of mean of various quantitative variables was analyzed using ANOVA test. Etiology of neonatal seizures and associated biochemical abnormalities were diagnosed.
 Results: In the present study, out of 100 neonates studied, 64 were full term of which 49(76.5%) were appropriate for gestational age and 15(23.5%) were small gestational age, whereas 36 cases were preterm. Most neonatal seizures occur in first 3 days of life, i.e. 59%. Most of them occurred on first day of life (34%). Birth asphyxia was the cause of neonatal seizures in 82.35% neonates who developed seizures on day-1 of life. Birth asphyxia and septicemia are common cause of neonatal seizures in our study (38 cases each), followed by pure metabolic disturbances 19%. In pure metabolic seizures, hypoglycemia (47.8%) is most common more in preterm babies (55%) followed by hypocalcemia. In cases of non- metabolic seizures, which showed associated biochemical abnormalities, hypoglycemia was most common abnormality 23 of 52 cases (44.2%). 12 cases (52.1%) are associated with birth asphyxia and 11 cases (47.9%) are associated with septicemia. Subtle seizures were most common type of seizures in our study, followed by focal clonic, multifocal clonic, generalized tonic, subtle with GTC and subtle with clonic.
 Conclusion: Biochemical abnormalities are common in neonatal seizures and often go unorganized. These abnormalities may significantly contribute to seizure activity correction of these abnormalities work up is necessary for all cases of neonatal seizures.

Clinical value of a set of neuropeptides in term and preterm neonates with seizures: Brain derived neurotrophic factor, galanin and neuropeptide Y

Background: Neonatal seizures are the most prominent feature of neurological dysfunction during neonatal period. Neonatal seizures occur within the first 4 weeks of life in a full-term infant and up to 44 weeks from conception for premature infant. Neonatal seizures are occurring in approximately 1.8 – 3.5 / 1000 live birth.Objectives: To study clinical types, time of onset and to determine the etiology of neonatal seizures.Methods: Out of eighty eight full term and preterm neonates with seizure at neonatal care unit and general wards of Babylon Gynecology and Pediatrics teaching hospital were studied prospectively in regard to clinco-biochemical profile of neonatal seizures from period 1st of May 2009 to 1st of December 2009.Results: Eighty eight full term and preterm neonates, (95.4%) of them were term and (4.6%) were preterm. The most common cause of neonatal convulsion was metabolic disturbances collectively constitute (47.7%).The other causes were asphyxia (15.4%),meningitis (6.6%),structural abnormalities (4.4%) and unknown cause (27.2%). Tonic type occurred in (100%) of preterm patients while in term patients, (31.8℅) of them were subtle type ,followed by tonic type (24.3℅) , focal clonic (16.2℅),generalized tonic clonic (11.3℅) and multi focal clonic type(11.3℅). 80℅ of hypoglycemia occurred in male patients.Conclusions: The commonest cause of seizure was metabolic abnormalities. Subtle seizures were the commonest type of seizure observed in term babies and tonic seizures were the most commonest type in preterm babies in this studyRecommendations: Metabolic abnormalities should be excluded in every case of neonatal seizure. Improving of thelaboratory services and the availability of other investigations must be available. Proper fetal monitoring during labor is recommended to avoid birth asphyxia .

Seizures in the neonatal period are associated with increased mortality and morbidity. Bedside amplitude-integrated electroencephalography (aEEG) has facilitated the detection of electrographic seizures; however, whether these seizures should be treated remains uncertain. To determine if the active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improves survival free of severe disability at 2 years of age compared with only treating clinically detected seizures. This randomized clinical trial was conducted in tertiary newborn intensive care units recruited from 2012 to 2016 and followed up until 2 years of age. Participants included neonates with encephalopathy at 35 weeks' gestation or more and younger than 48 hours old. Data analysis was completed in April 2021. Randomization was to an electrographic seizure group (ESG) in which seizures detected on aEEG were treated in addition to clinical seizures or a clinical seizure group (CSG) in which only seizures detected clinically were treated. Primary outcome was death or severe disability at 2 years, defined as scores in any developmental domain more than 2 SD below the Australian mean assessed with Bayley Scales of Neonate and Toddler Development, 3rd ed (BSID-III), or the presence of cerebral palsy, blindness, or deafness. Secondary outcomes included magnetic resonance imaging brain injury score at 5 to 14 days, time to full suck feeds, and individual domain scores on BSID-III at 2 years. Of 212 randomized neonates, the mean (SD) gestational age was 39.2 (1.7) weeks and 122 (58%) were male; 152 (72%) had moderate to severe hypoxic-ischemic encephalopathy (HIE) and 147 (84%) had electrographic seizures. A total of 86 neonates were included in the ESG group and 86 were included in the CSG group. Ten of 86 (9%) neonates in the ESG and 4 of 86 (4%) in the CSG died before the 2-year assessment. The odds of the primary outcome were not significantly different in the ESG group compared with the CSG group (ESG, 38 of 86 [44%] vs CSG, 27 of 86 [31%]; odds ratio [OR], 1.83; 95% CI, 0.96 to 3.49; P = .14). There was also no significant difference in those with HIE (OR, 1.77; 95% CI, 0.84 to 3.73; P = .26). There was evidence that cognitive outcomes were worse in the ESG (mean [SD] scores, ESG: 97.4 [17.7] vs CSG: 103.8 [17.3]; mean difference, -6.5 [95% CI, -1.2 to -11.8]; P = .01). There was little evidence of a difference in secondary outcomes, including time to suck feeds, seizure burden, or brain injury score. Treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures. http://anzctr.org.au Identifier: ACTRN12611000327987.

Background: Seizures represents the most distinctive signal of the neurological disease in the newborn period. Neonatal seizures are associated with unfavourable short and long term neurodevelopmental outcome. Objective: Our study was aimed at finding incidence, etiological factors, and clinical profile seizures in late preterm and term infants.Subject and Method:A retrospective study was conducted in an intramural tertiary care hospital, IOG, Chennai, India. Detailed antenatal, intrapartum history and baseline characteristics of both mother and infants, clinical details of seizures, investigations and neuroimaging details of 113 late preterm and term neonates with seizures data was collected from January 2018 to December 2018. Results:The incidence of seizures in late preterm and term neonates was 0.76% in our study. Hypoxic ischemic encephalopathy(HIE) was the commonest etiology(50.4%) followed by sepsis(24.8%). Majority of HIE neonates presented within 12 hrs of life (89%). Hypoglycemia(21.2%) was the commonest primary metabolic abnormality followed by hypocalcemia(9.7%). Clonic type was the most commonest type (82.3%) of seizure followed by subtle (73.5%) seizure. Conclusion:Hypoxic ischemic encephalopathy was the commonest etiology along with clonic seizures most commonest types. Hypoglycemia was the most commonest biochemical abnormality.

Background: The prevalence of neonatal seizure in term neonates is 3 per 1000 births, but in preterm newborns is 50 per 1000 births. Babies who have seizures are at high risk of death or neurological disabilities. Seizure is often the first sign of neonatal dysfunction and may be effective in long-term prognosis. EEG is the only available method for the diagnosis of seizures in neonates. Therefore, authors compared EEG changes in the first EEG infant seizure with 3 months of age in newborns who referred to the Aristotelian hospital in Bouali Hospital.Methods: The present study is a cross-sectional descriptive analytical method. In this study, neonates referred to Ardabil Booali Hospital, EEG, were screened for seizure and EEG was monitored 3 months later and the results were evaluated. Finally, all the data were entered into the SPSS-24 statistical analysis program and authors analyzed the data according to the type of variables by statistical tests.Results: In this study, 50 neonates with seizure were enrolled in this study, 70% of which had an average age of 14.92 days. 80% of infants were born at the time of term. The average birth weight was 3.208 kg. 6.2% of infants had abnormal CT scan findings, with an IVH infant and one baby showing brain edema. In this study, only 14% of neonates with abnormal brain strain were observed in the neonatal period and near the seizure. However, after 3 months, 40% of infants experienced abnormal brain stroke findings. Among the changes in EEG with age (p=0.173), gestational age (p=0.616), gender (p=0.176), seizure (p=0.145), neonatal hypoglycemia (p=0.594), hypocalcaemia (p=0.607) no statistic was found.Conclusions: The results of this study showed that a small percentage of neonates had abnormal EEG in the neonate, but after 3 months of seizure, the larger percentage of them found abnormal EEG.

For quick detection of neonatal early-onset bacterial infection (EOBI) pro-inflammatory cytokines like Interleukin-6 (IL-6) and Interleukin-8 (IL-8) in combiantion with C-reactive Protein (CRP) have been used. Automated determination of immature myeloid information (IMI) seems to be an additional useful tool in the diagnosis of NBI. To compare the diagnostic value of IMI, I/T-Ratio, plasma IL-6 and IL-8 levels and CRP in term and preterm neonates at time of clinical suspicion of EOBI. 31 preterm and 123 term neonates with clinical and serological signs of EOBI were analysed. 91 preterm and 159 term neonates with risk factors but without proven EOBI served as non-infected controls. Neonates with EOBI showed significantly elevated IMI levels at time of first clinical suspicion of EOBI (Preterm: 1 028/µL (38-8 759) vs. 289/µL (6-3 126); Term: 1 268/µL (48-14 035) vs. 856/µL (19-5 735); p<0.05 respectively). I/T-Ratio, IL-6, IL-8 and CRP values were significantly higher in preterm and term neonates with EOBI (p<0.05). Sensitivity of IMI at a cut-off level of 650/µL was 84.2% [95%-CI: 74.0-91.6%] in preterm and 65.4% [95%-CI: 56.8-73.3%] in term infants. Specificity was 66.7% [95%-CI: 47.1-82.7%] and 53.9% [95%-CI: 43.8-63.7%], respectively. Combination of different infection parameters improved sensitivity up to 93.5% and specificity up to 98.9%. The diagnostic value of IMI in diagnosing EOBI in preterm and term neonates is not comparable to IL-6, IL-8 and CRP. Combination of IMI-Channel with IL-6, IL-8 or CRP improves their sensitivity, specificity and predictive value.

Term and preterm neonates have very few circulating Tfh-like cells (cTfh), and no circulating Tfr-like cells. Neonatal cTfh are CXCR5lo PD-1lo CD45RAhi , suggestive of a naive, possibly recently activated phenotype. CXCL13 is high at birth, but decreases rapidly in the first weeks of life. Overall, signs of GC activity in human neonates are weak, even in those born prematurely or after sepsis.

The net impact of clinical seizures on outcome characteristics in infants with neonatal encephalopathies at 12 months of age

Seizures in Preterm Neonates: A Multicenter Observational Cohort Study

Neonatal seizures in term infants are rare but have important potential implications for brain development. Risk factors for neonatal seizures in term infants have been less well defined than those among preterm infants. To evaluate the relationship between maternal risk factors and neonatal seizures in the first 72 hours of life in term infants, a case-control study using the Colorado Birth Certificate Registry was conducted. Term neonates in all hospitals in Colorado with and without seizures in the first 72 hours were studied. After adjusting for vaginal delivery in the setting of herpes infection and post-term delivery, preexisting diabetes in the mother (odds ratio 4.30, 95% confidence interval 1.64-11.27, P < .01) and fetal distress (odds ratio 5.88, 95% confidence interval 4.60-7.13, P < .0001) were independent risk factors for neonatal seizures in term infants. These findings are confirmatory of previous reports that maternal preexisting diabetes and fetal distress increase the risk of neonatal seizure in term infants. Although we cannot establish the pathophysiology of neonatal seizures from this analysis, hypoxic-ischemic brain injury and hypoglycemia in infants of diabetic mothers are known causes of neonatal seizures that can be represented in this analysis by fetal distress and maternal preexisting diabetes, respectively. Maternal diabetic vasculopathy can also be a contributing factor.

Introduction: Neonatal renal function is a critical determinant of early health outcomes, especially in preterm neonates whose nephrogenesis may be incomplete at birth. Acute kidney injury (AKI) contributes significantly to neonatal morbidity and mortality worldwide, yet remains underdiagnosed, particularly in resource-limited settings like Bangladesh. Aim of the Study: The study aimed to conduct a comparative analysis of renal function status in term versus preterm neonates to evaluate implications for clinical care. Methods: This hospital-based comparative cross-sectional study was conducted at Dhaka Shishu Hospital, Bangladesh over a period of six months, from May to November 2024. Fifty neonates (25 term ≥37 weeks and 25 preterm &lt;37 weeks) were enrolled consecutively. Serum creatinine, urea, sodium, potassium, calcium, and phosphorus were measured at 24 hours and 7 days of life. AKI was defined according to modified neonatal KDIGO criteria. Statistical analysis included t-tests, chi-square tests, and logistic regression; p&lt;0.05 was considered significant. Results: Among the 50 neonates studied, preterm neonates had significantly lower birth weights (1.78±0.35 kg) than term neonates (2.77±0.41 kg; p&lt;0.001). Cesarean section was the predominant mode of delivery overall (80.0%), more common in preterms (88.0%) than terms (72.0%; p=0.028) Cesarean delivery was the predominant mode overall (80.0%), being more common in preterm (88.0%) than term neonates (72.0%; p=0.028). Male neonates predominated in both groups, though not statistically significant. Preterm neonates had higher serum creatinine at 24 hours (0.82±0.31 vs. 0.68±0.24 mg/dL; p=0.041) and 7 days (0.71±0.28 vs. 0.52±0.19 mg/dL; p=0.003). Blood urea at 7 days was also elevated in preterms (31.2±14.7 vs. 22.8±9.4 mg/dL; p=0.014). Reduced urine output was more common in preterms at 24 hours (40.0% vs. 12.0%; p=0.008) and 7 days (24.0% vs. 4.0%; p=0.023). AKI prevalence was significantly higher in preterms (48.0%) than in term neonates (16.0%; p=0.013). Preterm birth was an independent predictor of AKI (adjusted OR=4.12; p=0.038). Conclusion: Preterm neonates demonstrated significantly higher rates of AKI and impaired renal function compared to term neonates, underscoring the need for routine renal function monitoring and early intervention in this high-risk population.

Background: Bronchopulmonary dysplasia (BPD) continues to be an important problem in neonates especially premature infants despite improved facilities of care, monitoring and treatment. Pulmonary hypertension (PH) is a major complicating factor and key cause of mortality in this population. Altered vascular and alveolar growth particularly in canalicular and early saccular stages of lung development following mechanical ventilation and oxygen therapy result in arrest of the lung development leading to BPD with PH. Early recognition of PH in infants with these risk factors is important for optimal management. We tested the hypothesis that asymmetric dimethylarginine, would be greater in infants with bronchopulmonary dysplasia associated pulmonary hypertension than in infants with BPD alone. The Aim: The aim of the current study was to measure the Asymmetric dimethylarginine (ADMA) levels, arginine levels & the plasma arginine-to-ADMA ratio in newborn infants with broncho-pulmonary dysplasia, to evaluate echocardiographic parameters among neonates with bronchopulmonary dysplasia, to correlate between plasma ADMA & arginine-to-ADMA ratio and echocardiographic (ECHO) parameters in those patients and to compare full term & preterm neonates with bronchopulmonary dysplasia as regard to plasma ADMA level. Methods: A case-control study was carried out of ninety (90) newborns selected from those admitted to Neonatal Intensive Care Unit at Maternity & Children Hospital and Alzhraa University hospital during the period from October 2015 to March 2018. Neonates were divided into 2 groups: Patient with BPD with PH (cases group): It included 45 neonates with BPD & PH, 35 preterm neonates and 10 full term neonates. Patient with BPD only (Control group): It included 45 neonates with BPD without PH. These 45 neonates were divided as 22 preterm neonates and 23 full term neonates. Laboratory work was done in Alzhraa University hospital. Asymmetric dimethylarginine (ADMA) levels & arginine levels were measured using competitive enzyme linked immune-assay (ELISA). Results: Patients with both BPD and PH had greater plasma levels of ADMA than patients with BPD alone (P value 0.000). ADMA level > 186 ng/dl can predict development of PH in patient with BPD with sensitivity 100% and specify 100%. Preterm neonates with BPD had greater level of ADMA than full term neonates (P value 0.002). There was no statically significance difference between level of ADMA if withdrawn before or after 28 days of age (range of age at time of sampling in our study was 23 - 40 days) (P value 0.878), even ADMA level increased above the cut point early in the disease before we screened some cases by ECHO. There was no statically significance difference between level of arginine in cases and control groups with P value 0.530. The plasma arginine-to-ADMA ratio was lower in cases than in controls suggesting a greater likelihood of inhibition of nitric oxide production in patients with both BPD and PH than in patients with BPD alone (P value 0.000). ADMA level can predict severity of pulmonary hypertension in patient with BPD, as it was positively correlated with the grade of pulmonary hypertension (P value 0.006). ADMA level is higher in neonates with BPD and PH who died than those who survived; it can predict death in neonates with BPD &PH at cut off point > 643 ng/dl. Conclusion: ADMA increased in newborn infants with BPD, who developed PH. ADMA may have diagnostic and prognostic values. ADMA level was higher in preterm neonates than full term neonates and its level was correlated positively with severity of PH. ADMA levels were significant higher in infants with BPD with PH who died later than those who survived. There was no statically significance difference between levels of ADMA, whether it was drawn before or after 28 days of age (range 23 - 40 days). Echocardiographic screening and ADMA measurement could help in prevention of PH, diagnosis and early treatment of newborn infants suffering from BPD.

A Phase II/III, Multicenter, Safety, Efficacy, and Pharmacokinetic Study of Dexmedetomidine in Preterm and Term Neonates