Neonatal seizures are a common medical emergency, necessitating prompt treatment. The most common etiologies include hypoxic-ischemic encephalopathy, ischemic stroke, and intracranial hemorrhage, with numerous other uncommon etiologies. Accurate diagnosis requires conventional video-electroencephalogram (cvEEG) to distinguish seizures from nonepileptic movements and to detect electrographic-only (subclinical) seizures. Treatment prioritizes rapid medication administration, with phenobarbital as first-line treatment and the only Federal Drug Administration (FDA)-approved medication for neonatal seizures. Prognosis depends on seizure etiology and severity. Advances in artificial intelligence show promise for improved seizure detection and prognostication. Further research and randomized controlled trials of novel medications are needed.

This study investigated the roles and mechanisms of PINK1 activity in neonatal hypoxia-induced seizures with shRNA intervention targeting translocase outer mitochondrial membrane 7 (TOM7), the positive regulator of PINK1 autophosphorylation, or overlapping with the m-AAA protease 1 homolog (OMA1), the negative regulator of PINK1 autophosphorylation. Studies have suggested that in hypoxia-induced neonatal seizures, the phosphorylation level of PINK1 is significantly increased and the mitophagic pathway is activated, accompanied by neuronal damage and learning-memory deficits. Inhibiting PINK1 phosphorylation by reducing TOM7 expression alleviated mitophagy, mitochondrial oxidative stress, neuronal damage and seizures. In contrast, the inhibition of OMA1 expression resulted in a further increase in PINK1 phosphorylation and aggravated hypoxia-induced seizures and neuronal injury. This study implicated PINK1 activity in neonatal hypoxia and suggest that attenuated PINK1 autophosphorylation may have neuroprotective and anti-seizure effects in neonatal hypoxia.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of perinatal brain injury. Creatine is a dietary supplement that can increase intracellular phosphocreatine to improve the provision of intracellular adenosine triphosphate (ATP) to meet the increase in metabolic demand of oxygen deprivation. Here, we assessed prophylactic fetal creatine supplementation in reducing acute asphyxia-induced seizures, disordered electroencephalography (EEG) activity and cerebral inflammation and cell death histopathology.

Fetal sheep (118 ± 1 days' gestational age [dGA]; 0.8 gestation) were implanted with electrodes to continuously record EEG and nuchal electromyogram activity. At 121 dGA, fetuses were randomly assigned to sham control (i.v. saline infusion without umbilical cord occlusion [UCO]; SalCon), continuous i.v. creatine infusion (6 mg/kg/h; CrUCO) or isovolumetric saline (SalUCO) followed by UCO at 128 ± 2 dGA that lasted until the mean arterial blood pressure reached 19 mmHg. Brain tissue was collected for histopathology after 72 hours of recovery.

Creatine supplementation had no effects on basal systemic or neurological physiology. UCO duration did not differ between CrUCO and SalUCO. After reperfusion, CrUCO fetuses had improved EEG power and frequency recovery and reduced electrographic seizure incidence (SalUCO, 86% vs CrUCO, 29%) and burden. At 72 hours after UCO, cell death in the cerebral cortex and astrogliosis in the periventricular white matter were reduced in CrUCO fetuses compared with SalUCO.

Creatine supplementation reduced post-asphyxial seizures and improved EEG recovery. Improvements in functional recovery with creatine were associated with regional reductions in cell death and astrogliosis. Prophylactic creatine treatment has the potential to mitigate functional indices of HIE in the late gestation fetal brain. ANN NEUROL 2025;97:673-687.

This study aimed to investigate the associations among seizures, clinical characteristics, and brain injury on Magnetic Resonance Imaging (MRI) in infants with Hypoxic Ischemic Encephalopathy (HIE), and to determine whether these findings can predict unfavorable neurodevelopmental outcomes.

Clinical and electrographic seizures were assessed by amplitude-integrated electroencephalogram, and the extent of brain injury was evaluated by using MRI. At 12‒24 months of age, developmental impairment or death was assessed. Between 2012 and 2020, 143 newborns were admitted for HIE, and 8 infants were excluded from the study.

Eighty-five infants were diagnosed with greater than moderate HIE and 65 infants underwent therapeutic hypothermia. In addition, 38 infants experienced clinical seizures (clinical seizure group, CSG), 49 infants had electrographic seizures (Electrographic Seizure Group, ESG), and 48 infants had no seizures (no seizure group, NSG). The proportion of infants with neurodevelopmental impairment or death was significantly higher in the CSG than in the NSG (57.7 % and 26.1 %, p = 0.026). A risk factor analysis indicated that cord blood pH (adjusted Odds Ratio [aOR = 0.01]; 95 % Confidence Interval [95 % CI 0.001‒0.38]; p = 0.015) and MRI findings (aOR = 4.37; 95 % CI 1.25‒15.30; p = 0.012) were independently associated with abnormal neurodevelopment, after adjustment.

Clinical seizures in infants with HIE were independently associated with abnormal neurodevelopment. However, cord blood pH and abnormal brain MRI findings were consistently linked to long-term neurodevelopmental outcomes.

Early diagnosis of impaired myocardial function and timely therapeutic hypothermia is vital among patients with Neonatal Encephalopathy (NE). Traditional markers of myocardial function (Left Ventricular Ejection Fraction (LV EF) & LV Fractional Shortening (LV FS) can be variably reduced. Speckle tracking echocardiography (STE) is a more sensitive marker for impairment but remains inadequately studied in this patient population.

A retrospective study of neonates who underwent therapeutic hypothermia (TH) for NE from 2009 to2020 were matched 1:1 with normal neonates with normal echocardiograms performed for indications other than NE. Matching was based on gestational age, birth weight, days of age, and sex. Left ventricular 4 Chamber (4Ch) strain, right ventricular 4 Chamber (RV 4Ch), and RV free wall strain (RV FWS) were measured offline using vendor independent strain software (TomTec, GMBH, Munich, Germany).

Ninety pairs of NE patients and controls were studied. Compared to controls, RV 4Ch strain (-17.3 % vs. -19.6 %), RV FWS (-18.8 % vs. -21.9 %), and RV fractional area change (FAC) (35 % vs. 37 %) were lower in NE cases (all p < 0.001), while differences in LV 4Ch strain, LV EF, and LV FS did not reach statistical significance. Moderate/severe NE (72 %) was associated with lower LV 4Ch strain compared to mild NE (-22.2 %/-19.3 % vs. -25.4 %, p = 0.004). RV 4Ch strain (-14.9 % vs. -18.8 %, p = 0.020) and RV FAC (27 % vs. 36 %, p = 0.006) were lower in severe NE compared to mild NE. Lower LV 4Ch was associated with need for chest compressions (-18.5 % vs. -23.3 %), epinephrine at delivery (-19.3 % vs. -23.4 %), and decreased survival to discharge (-15.9 % vs. -22.7 %).

RV and LV strain mechanics are impaired in NE patients. Lower RV Strain and LV 4Ch strain were associated with need for increased medical support and decreased survival to discharge.

Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs).

Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews.

Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities.

The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care.

Effective post-resuscitation care is crucial for improving outcomes in neonates post-asphyxia. This review aimed to provide a comprehensive overview of post-asphyxial aftercare strategies and forms part of a supplement describing an extensive synthesis of effective newborn interventions in low- and middle-income countries (LMICs).

Evidence was generated by performing de novo reviews, updates to reviews via systematic searches, and reanalyses of studies conducted in LMICs from existing reviews.

Sixty-one trials recruiting 5,046 term infants post-asphyxia were included across all intervention domains. Limited studies were available from LMICs related to fluid restriction, antiseizure medications, and early interventions to improve developmental outcomes. Our reanalysis of whole-body cooling trials in LMICs found effects on neonatal mortality and mortality or neurological disability in infancy differed significantly based on the care center and type of cooling device used. Pharmacological therapies for neuroprotection evaluated in 27 trials in middle-income countries had varied effects in neonates with encephalopathy. Majority of the trials (60%) focused on magnesium sulfate therapy and showed significant improvements in short-term mortality and morbidities.

The sample sizes of included trials were relatively small, and the certainty of evidence ranged from very low to moderate. Evidence on long-term survival and neurodevelopmental outcomes was limited. Further research on promising neuroprotective therapies and factors affecting their implementation in low-resource contexts is required. To reduce the high burden related to asphyxia in LMICs, this review underscores the need for a paradigm shift toward prevention, and strategies that emphasize improving antenatal and obstetric care.

Neonatal encephalopathy represents a broad neurological syndrome which encompasses newborn foals presenting a variety of non-infectious neurologic signs and/or abnormal behaviors in the immediate postpartum period. It is recognized as the most predominant neurological disorder in neonatal foals. Prognostic factors can guide clinicians in medical decision-making, aiding in the establishment of survival probabilities. The aim of this work was to scrutinize the prognostic value of clinical and laboratorial findings upon admission and posterior comorbidities developed during hospitalization, assessing their influence on the outcome of foals with NE. For this purpose, the medical records of 61 neonatal foals with a primary diagnosis of NE were retrospectively analyzed. The overall survival rate was 57.4%. Most foals presented recumbency at admission, which was associated with higher mortality rates (p = 0.002). Hypothermic foals at admission were 4.85 times more likely to succumb (p = 0.015). The presence of hypoglycemia at admission was associated with higher mortality rates (p = 0.002). Foals with hypercreatinemia at admission had 6.67 times greater odds of dying. The development of seizures contributed to 4.14 greater odds of dying. Foals that developed comorbidities during hospitalization had 40.1 times greater odds of dying, with pneumonia and sepsis being the most relevant comorbidities. In foals with NE, rectal temperature, hematocrit, blood glucose, and creatinine concentrations are simple, quick-to-measure parameters that may have prognostic value during admission.

We aimed to evaluate epidemiology, seizure type, EEG, and etiology of neonatal seizures (NS) in a tertiary neonatal intensive care unit.

Data on infants with a neurophysiological confirmation of NS were collected between 2009 and 2022. Seizure types and epileptic syndromes were classified by the ILAE classification and EEG by the Italian Neonatal Seizure Collaborative Network (INNESCO) score.

Out of 91,253 neonates, 145 presented with NS; 69.7 % were born at term and 30.3 % were preterm infants. The incidence of NS in neonates born at our center was 1.2 per 1,000 live newborns (96/80697 neonates) while in the entire neonatal population admitted to our center it was 1.6 per 1,000 live births, increasing with lower preterm age. Compared to previous studies, we found a lower proportion of hypoxic-ischemic encephalopathy (HIE) (23.4 %) and a higher rate of genetic contribution (26.2 %). The infection rate was higher in preterm (31.8 %) than in full term (9.9 %) infants. Electrographic seizures were associated with acute provoked seizures (35.9 %), preterm age (52.3 %), and HIE (52.9 %). Vascular etiology was associated with focal clonic seizures (56.8 %). Non-structural neonatal genetic epilepsy was associated with sequential seizures (68.2 %), particularly KCNQ2 and SCN2A epilepsy. Background EEG was abnormal in all HIE, infections (85.7 %) and metabolic NS (83.3 %). In genetic epilepsy, background EEG depended on the epileptic syndrome: normal in 80 % of self-limited neonatal epilepsy and abnormal in 77.8 % of developmental and epileptic encephalopathy. Electroclinical seizures were associated with focal onset, while electrographic seizures correlated with a multifocal onset.

A low incidence of HIE and a high incidence of genetic etiology were observed in our cohort of NS. Seizure type and EEG features are fundamental to address etiology.

Early life seizures (ELS) are commonly associated with autism spectrum disorder (ASD); however, the exact role of ELS in the pathology is unknown. Prior studies have demonstrated social deficits, a core feature of ASD, following ELS; consequently, alterations in sensory modalities may contribute to the overall social deficits. Considering the speculated contribution of sensory deficit to social communication, we examined the developmental consequences of early postnatal kainic acid (KA)-induced seizures on olfactory preference and neural markers in the olfactory bulb in both male and female Sprague Dawley rats.

KA-induced seizures or saline was administered. Rats were then exposed to a series of biologically relevant scents including male scent, female scent, nest scent, and phenylethylamine during the juvenile period and again during adulthood. Alterations in sensory modalities were expected to be expressed via abnormal preference for certain scents and/or production of abnormal ultrasonic vocalizations in response to scents. The olfactory bulbs were also assessed for the biologically relevant markers glial fibrillary acidic protein (GFAP) and calcium/calmodulin-dependent protein kinase II (CAMKII).

Our findings resulted in no significant differences in olfactory preference following ELS for juveniles or adults compared to controls. Similarly, there were no differences in GFAP expression or the ratio of phosphorylated CAMKII to CAMKII in either olfactory bulb. Interestingly, despite a lack of treatment differences, different scents were shown to elicit different responses in juvenile rats, yet these differences subsided in adulthood.

Overall, the results of this study suggest that olfaction does not contribute to socialization deficit following ELS within the KA model.

Hypoxic-ischemic encephalopathy is the most common cause of neonatal seizures. Continuous electroencephalographic monitoring is recommended given high rates of subclinical seizures. Prompt diagnosis and treatment of seizures may improve neurodevelopmental outcomes. International League Against Epilepsy guidelines indicate that (1) phenobarbital remains the first-line treatment of neonatal seizures and (2) early discontinuation of antiseizure medications following resolution of acute provoked seizures, and prior to discharge home, is recommended. Long-term follow-up of these infants is necessary to screen for postneonatal epilepsy and support neurodevelopment.

GABA modulators such as phenobarbital (PB) and sodium channel blockers such as phenytoin (PHT) have long been the mainstay of pharmacotherapy for the epilepsies. In the context of neonatal seizures, both PB and PHT display incomplete clinical efficacy. Moreover, in animal models, neonatal exposure to these medications result in neurodegeneration raising concerns about safety. Cenobamate, a more recently approved medication, displays unique pharmacology as it is both a positive allosteric modulator of GABA-A receptors, and a voltage-gated sodium channel blocker. While cenobamate is approved for adult use, its efficacy and safety profile against neonatal seizures is poorly understood. To address this gap, we assessed the efficacy and safety of cenobamate in immature rodents. Postnatal day (P)7 rat pups were pretreated with cenobamate and challenged with the chemoconvulsant pentylenetetrazole (PTZ) to screen for anti-seizure effects. In a separate experiment, P7 rats were treated with cenobamate, and brains were processed to assess induction of cell death. Cenobamate displays dose-dependent anti-seizure efficacy in neonatal rats. Unlike PHB and PHT, it does not induce neurotoxicity in P7 rats. Thus, cenobamate may be effective at treating neonatal seizures while avoiding unwanted neurotoxic side effects such as cell death.

Neonatal neurocritical intensive care is dedicated to safeguarding the newborn brain by prioritising clinical practices that promote early identification, diagnosis and treatment of brain injuries. The most common newborn neurological emergency is neonatal seizures, which may also be the initial clinical indication of neurological disease. A high seizure burden in the newborn period independently contributes to increased mortality and morbidity. The majority of seizures in newborns are subclinical (without clinical presentation), and hence identification may be difficult. Neuromonitoring techniques most frequently used to monitor brain wave activity include conventional electroencephalography (cEEG) or amplitude-integrated EEG (aEEG). cEEG with video is the gold standard for diagnosing and treating seizures. Many neonatal units do not have access to cEEG, and frequently those that do, have little access to real-time interpretation of monitoring. IMPACT: EEG monitoring is of no benefit to an infant without expert interpretation. Whilst EEG is a reliable cot-side tool and of diagnostic and prognostic use, both conventional EEG and amplitude-integrated EEG have strengths and limitations, including sensitivity to seizure activity and ease of interpretation. Automated seizure detection requires a sensitive and specific algorithm that can interpret EEG in real-time and identify seizures, including their intensity and duration.

Neonatal seizures are common among patients with acute brain injury or critical illness and can be difficult to diagnose and treat. The most common etiology of neonatal seizures is hypoxic-ischemic encephalopathy, with other common causes including ischemic stroke and intracranial hemorrhage. Neonatal clinicians can use a standardized approach to patients with suspected or confirmed neonatal seizures that entails laboratory testing, neuromonitoring, and brain imaging. The primary goals of management of neonatal seizures are to identify the underlying cause, correct it if possible, and prevent further brain injury. This article reviews recent evidence-based guidelines for the treatment of neonatal seizures and discusses the long-term outcomes of patients with neonatal seizures.

Electroencephalography (EEG), a widely used noninvasive neurophysiological diagnostic tool, has experienced substantial advancements from 2004 to 2022, particularly in neonatal applications. Utilizing a bibliometric methodology, this study delineates the knowledge structure and identifies emergent trends within neonatal EEG research.

An exhaustive literature search was conducted on the Web of Science Core Collection (WoSCC) database to identify publications related to neonatal EEG from 2004 to 2022. Analytical tools such as VOSviewer, CiteSpace, and the R package "bibliometrix" were employed to facilitate this investigation.

The search yielded 2501 articles originating from 79 countries, with the United States and England being the predominant contributors. A yearly upward trend in publications concerning neonatal EEG was observed. Notable research institutions leading this field include the University of Helsinki, University College London, and University College Cork. Clinical Neurophysiology is identified as the foremost journal in this realm, with Pediatrics as the most frequently co-cited journal. The collective body of work from 9977 authors highlights Sampsa Vanhatalo as the most prolific contributor, while Mark Steven Scher is recognized as the most frequently co-cited author. Key terms such as "seizures," "epilepsy," "hypoxic-ischemic encephalopathy," "amplitude-integrated EEG," and "brain injury" represent the focal research themes.

This bibliometric analysis offers the first comprehensive review, encapsulating research trends and progress in neonatal EEG. It reveals current research frontiers and crucial directions, providing an essential resource for researchers engaged in neonatal neuroscience.

To investigate the association between the presence and severity of seizures in asphyxiated newborns and their neurodevelopmental outcome at ages two and five years.

Retrospective data analysis from a prospectively collected multicenter cohort of 186 term-born asphyxiated newborns undergoing therapeutic hypothermia (TH) in 11 centers in the Netherlands and Belgium. Seizures were diagnosed by amplitude-integrated electroencephalography (EEG) and raw EEG signal reading up to 48 hours after rewarming. Neurodevelopmental outcome was assessed by standardized testing at age two and five years. Primary outcome was death or long-term neurodevelopmental impairment (NDI) including cerebral palsy. Associations were calculated using univariate and multivariate logistic regression analyses adjusting for Thompson score and a validated brain magnetic resonance imaging (MRI) score.

Seventy infants (38%) had seizures during TH or rewarming, and 44 (63%) of these needed two or more antiseizure medications (ASMs). Overall mortality was 21%. Follow-up data from 147 survivors were available for 137 infants (93%) at two and for 94 of 116 infants (81%) at five years. NDI was present in 26% at two and five years. Univariate analyses showed a significant association between seizures and death or NDI, but this was no longer significant after adjusting for Thompson and MRI score in the multivariate analysis; this was also true for severe seizures (need for two or more ASMs) or seizures starting during rewarming.

The presence or severity of seizures in newborns undergoing TH for hypoxic-ischemic encephalopathy was not independently associated with death or NDI up to age five years after adjusting for several confounders.

Neonatal seizures caused by hypoxic-ischemic encephalopathy (HIE) have significant morbidity and mortality. There is variability in clinical practice regarding treatment duration with antiseizure medication (ASM) after resolution of provoked neonatal seizures. We examined epilepsy incidence and developmental outcomes in post-HIE neonates discharged or not on ASM.

We conducted a retrospective chart review of all HIE-admitted neonates to the University of Iowa Hospitals & Clinics neonatal intensive care unit between January 2008 and February 2021 who presented with encephalopathy, underwent therapeutic hypothermia, and developed seizures. Neonates were divided into two groups depending on whether ASM was continued or discontinued on discharge. We evaluated the incidence of epilepsy and developmental outcomes on follow-up in these two cohorts up to 12 months.

Sixty-nine neonates met the study criteria. ASM was continued on discharge in 41 neonates (59%) and discontinued before discharge in 28 (41%). At the 12-month follow-up, nine neonates (13%) had a diagnosis of epilepsy, out of which seven neonates had ASM continued on discharge (odds ratio [OR]: 2.84; 95% confidence interval [CI]: 0.48, 29.9)]. There was no statistical difference between the development of postneonatal epilepsy between the two groups (P value 0.29). There was no significant difference in developmental outcome between the two groups after adjusting for covariates like magnetic resonance imaging (MRI) brain abnormality and number of seizure days (OR: 0.68; 95% CI: 0.21, 2.22; P = 0.52).

We found no significant risk of seizure recurrence by age 12 months in infants who had discontinued ASM before discharge compared with those who had continued ASM. There was no difference in developmental outcomes at the 12-month follow-up between groups after adjusting for brain MRI abnormality and the number of seizure days during admission. Our results support early discontinuation of ASM after resolution of acute provoked seizures in neonates with HIE.

Many anti-seizure medications (ASMs) trigger neuronal cell death when administered during a confined period of early life in rodents. Prototypical ASMs used to treat early-life seizures such as phenobarbital induce this effect, whereas levetiracetam does not. However, most prior studies have examined the effect of ASMs in naïve animals, and the degree to which underlying brain injury interacts with these drugs to modify cell death is poorly studied. Moreover, the degree to which drug-induced neuronal cell death differs as a function of sex is unknown.

We treated postnatal day 7 Sprague Dawley rat pups with vehicle, phenobarbital (75 mg/kg) or levetiracetam (200 mg/kg). Separate groups of pups were pre-exposed to either normoxia or graded global hypoxia. Separate groups of males and females were used. Twenty-four hours after drug treatment, brains were collected and processed for markers of cell death.

Consistent with prior studies, phenobarbital, but not levetiracetam, increased cell death in cortical regions, basal ganglia, hippocampus, septum, and lateral thalamus. Hypoxia did not modify basal levels of cell death. Females - collapsed across treatment and hypoxia status, displayed a small but significant increase in cell death as compared to males in the cingulate cortex, somatosensory cortex, and the CA1 and CA3 hippocampus; these effects were not modulated by hypoxia or drug treatment.

We found that a history of graded global hypoxia does not alter the neurotoxic profile of phenobarbital. Levetiracetam, which does not induce cell death in normal developing animals, maintained a benign profile on the background of neonatal hypoxia. We found a sex-based difference, as female animals showed elevated levels of cell death across all treatment conditions. Together, these data address several long-standing gaps in our understanding of the neurotoxic profile of antiseizure medications during early postnatal development.

To assess the impact of clinical neonatal seizures on outcome characteristics of preterm and term newborns with neonatal encephalopathy (NE).

We designed a prospective comparative study with 53 babies (preterm neonates: 26 and term neonates: 27) with NE: group 1 (preterm neonates with seizures, n = 13), group 2 (preterm neonates without seizures, n = 13), group 3 (term neonates with seizures, n = 13) and group 4 (term neonates without seizures, n = 14). The functional outcome characteristics of the survivors were assessed by the Ankara Developmental Screening Inventory (ADSI) and the Guide for Monitoring Child Development (GMCD) at 12 months of age.

Clinically defined acute symptomatic seizures were diagnosed with prompt conventional EEG / amplitude-integrated EEG in preterm (92.3%) and term neonates (81.4%) with etiology-specific diagnoses of NE. There were no differences between the study groups regarding seizure semiology and EEG characteristics. A primary adverse outcome was defined in 22 (41.5%) of the cohort. However, only 15.3% of infants had an unfavorable functional outcome with ADSI at 12 months. Among the survivors, there was no significant difference between the study groups regarding ADSI scores. The GMDC test revealed normal development in 50% of survivors with seizures in the preterm group and 83% in the term group.

There was no significant difference between the characteristics of functional outcomes at 12 months in preterm and term neonates with NE for clinical seizures.

To assess among a cohort of neonates with hypoxic-ischemic encephalopathy (HIE) the association of pretreatment maximal hourly seizure burden and total seizure duration with successful response to initial antiseizure medication (ASM).

This was a retrospective review of data collected from infants enrolled in the HEAL Trial (NCT02811263) between January 25, 2017, and October 9, 2019. We evaluated a cohort of neonates born at ≥36 weeks of gestation with moderate-to-severe HIE who underwent continuous electroencephalogram monitoring and had acute symptomatic seizures. Poisson regression analyzed associations between (1) pretreatment maximal hourly seizure burden, (2) pretreatment total seizure duration, (3) time from first seizure to initial ASM, and (4) successful response to initial ASM.

Among 39 neonates meeting inclusion criteria, greater pretreatment maximal hourly seizure burden was associated with lower chance of successful response to initial ASM (adjusted relative risk for each 5-minute increase in seizure burden 0.83, 95% CI 0.69-0.99). There was no association between pretreatment total seizure duration and chance of successful response. Shorter time-to-treatment was paradoxically associated with lower chance of successful response to treatment, although this difference was small in magnitude (relative risk 1.007, 95% CI 1.003-1.010).

Maximal seizure burden may be more important than other, more commonly used measures in predicting response to acute seizure treatments.

To compare seizure burden between newborn infants treated with therapeutic hypothermia (TH) and those that were not and to compare the need for antiseizure medications (ASM) in a cohort of infants who were diagnosed with neonatal hypoxic-ischemic encephalopathy (HIE).

This was a retrospective cohort study on infants born after 35 weeks' gestation, diagnosed with moderate to severe HIE, monitored with amplitude-integrated electroencephalography (aEEG) and eligible for TH. Infants born before the implementation of TH in 2008 were compared with infants born thereafter who received TH. Seizure burden was assessed from aEEG as total time in minutes of seizures activity per hour of recording. Other clinical and demographic data were retrieved from a prospective local database of infants with HIE.

Overall, 149 of 207 infants were included in the study: 112 exposed to TH and 37 not exposed. Cooled infants had a lower seizure burden overall (0.4 vs 2.3 min/h, P < 0.001) and were also less likely to be treated with ASM (74% vs 100%, P < 0.001). In multivariable regression models, not exposed to TH, having a depressed aEEG background, and having higher Apgar scores were associated with higher seizure burden (incidence rate ratio: 4.78 for noncooled infants, P < 0.001); also, not exposed to TH was associated with a higher likelihood of multidrug ASM (odds ratio: 4.83, P < 0.001).

TH in infants with moderate to severe HIE is associated with significant reduction of seizure burden and ASM therapy.

To examine acute seizure activity and neuronal damage in a neonatal mouse model of inflammation-sensitized hypoxic-ischemic (IS-HI) brain injury utilizing continuous electroencephalography (cEEG) and neurohistology.

Neonatal mice were exposed to either IS-HI with Escherichia coli lipopolysaccharide (LPS) or HI alone on postnatal (p) day 10 using unilateral carotid artery ligation followed by global hypoxia (n = 10 [5 female, 5 male] for IS-HI, n = 12 [5 female, 7 male] for HI alone). Video cEEG was recorded for the duration of the experiment and analyzed for acute seizure activity and behavior. Brain tissue was stained and scored based on the degree of neuronal injury in the hippocampus, cortex, and thalamus.

There was no significant difference in acute seizure activity among mice exposed to IS-HI compared to HI with regards to seizure duration (mean = 63 ± 6 seconds for HI vs mean 62 ± 5 seconds for IS-HI, p = 0.57) nor EEG background activity. Mice exposed to IS-HI had significantly more severe neural tissue damage at p30 as measured by neuropathologic scores (mean = 8 ± 1 vs 23 ± 3, p < 0.0001).

In a neonatal mouse model of IS-HI, there was no significant difference in acute seizure activity among mice exposed to IS-HI compared to HI. Mice exposed to IS-HI did show more severe neuropathologic damage at a later age, which may indicate the presence of chronic inflammatory mechanisms of brain injury distinct from acute seizure activity.

Artificial intelligence (AI) offers tremendous potential to transform neonatology through improved diagnostics, personalized treatments, and earlier prevention of complications. However, there are many challenges to address before AI is ready for clinical practice. This review defines key AI concepts and discusses ethical considerations and implicit biases associated with AI. Next we will review literature examples of AI already being explored in neonatology research and we will suggest future potentials for AI work. Examples discussed in this article include predicting outcomes such as sepsis, optimizing oxygen therapy, and image analysis to detect brain injury and retinopathy of prematurity. Realizing AI's potential necessitates collaboration between diverse stakeholders across the entire process of incorporating AI tools in the NICU to address testability, usability, bias, and transparency. With multi-center and multi-disciplinary collaboration, AI holds tremendous potential to transform the future of neonatology.

Neonatal seizures are relatively common, but their diagnosis and management remain challenging. We reviewed the scientific literature on neonatal seizures from July 1973 to November 2023. Several parameters were considered, including pathophysiology, diagnostic criteria, electroencephalographic findings and treatment. Recent classification system of seizures and epilepsies in the newborn, as well as treatment recommendations of neonatal seizures, have been proposed. Nonetheless, the approach to neonatal seizures varies among clinicians and centres, including detection, investigation, treatment and follow-up of patients. There are still many issues on the diagnosis and treatment of neonatal seizures, including the meaning or relevance of some electroencephalographic findings, the precise estimation of the seizure burden, the limited efficacy and side effects risk of antiseizure medications, and the best measures to establish the outcome.

Seizures are common in preterm newborns and are associated with poor neurodevelopmental outcomes. Current anticonvulsants have poor efficacy, and many have been associated with upregulation of apoptosis in the developing brain. Apigenin, a natural bioactive flavonoid, is a potent inhibitor of hyaluronidase and reduces seizures in adult animal models. However, its impact on perinatal seizures is unclear. In the present study, we examined the effect of apigenin and S3, a synthetic, selective hyaluronidase inhibitor, on seizures after cerebral ischemia in preterm fetal sheep at 0.7 gestation (98-99 days, term ~147 days). Fetuses received sham ischemia (n = 9) or ischemia induced by bilateral carotid occlusion for 25 min. Immediately after ischemia, fetuses received either a continuous infusion of vehicle (0.036% dimethyl sulfoxide, n = 8) or apigenin (50 µM, n = 6). In a pilot study, we also tested infusion of S3 (2 µM, n = 3). Fetuses were monitored continuously for 72 h after ischemia. Infusion of apigenin or S3 were both associated with reduced numbers of animals with seizures, total seizure time, and mean seizure burden. S3 was also associated with a reduction in the total number of seizures over the 72 h recovery period. In animals that developed seizures, apigenin was associated with earlier cessation of seizures. However, apigenin or S3 treatment did not alter recovery of electroencephalographic power or spectral edge frequency. These data support that targeting brain hyaluronidase activity with apigenin or S3 may be an effective strategy to reduce perinatal seizures following ischemia. Further studies are required to determine their effects on neurohistological outcomes.

The effects of hypothermia on neonatal encephalopathy may vary topographically and cytopathologically in the neocortex with manifestations potentially influenced by seizures that alter the severity, distribution, and type of neuropathology. We developed a neonatal piglet survival model of hypoxic-ischemic (HI) encephalopathy and hypothermia (HT) with continuous electroencephalography (cEEG) for seizures. Neonatal male piglets received HI-normothermia (NT), HI-HT, sham-NT, or sham-HT treatments. Randomized unmedicated sham and HI piglets underwent cEEG during recovery. Survival was 2-7 days. Normal and pathological neurons were counted in different neocortical areas, identified by cytoarchitecture and connectomics, using hematoxylin and eosin staining and immunohistochemistry for RNA-binding FOX-1 homolog 3 (Rbfox3/NeuN). Seizure burden was determined. HI-NT piglets had a reduced normal/total neuron ratio and increased ischemic-necrotic/total neuron ratio relative to sham-NT and sham-HT piglets with differing severities in the anterior and posterior motor, somatosensory, and frontal cortices. Neocortical neuropathology was attenuated by HT. HT protection was prominent in layer III of the inferior parietal cortex. Rbfox3 immunoreactivity distinguished cortical neurons as: Rbfox3-positive/normal, Rbfox3-positive/ischemic-necrotic, and Rbfox3-depleted. HI piglets had an increased Rbfox3-depleted/total neuron ratio in layers II and III compared to sham-NT piglets. Neuronal Rbfox3 depletion was partly rescued by HT. Seizure burdens in HI-NT and HI-HT piglets were similar. We conclude that the neonatal HI piglet neocortex has: (1) suprasylvian vulnerability to HI and seizures; (2) a limited neuronal cytopathological repertoire in functionally different regions that engages protective mechanisms with HT; (3) higher seizure burden, insensitive to HT, that is correlated with more panlaminar ischemic-necrotic neurons in the somatosensory cortex; and (4) pathological RNA splicing protein nuclear depletion that is sensitive to HT. This work demonstrates that HT protection of the neocortex in neonatal HI is topographic and laminar, seizure unmitigating, and restores neuronal depletion of RNA splicing factor.

Seizures are a complication for pediatric patients requiring extracorporeal membrane oxygenation (ECMO). There are no standardized guidelines regarding continuous electroencephalography (EEG) monitoring to detect seizures in these patients, and the impact of protocolized monitoring has not been evaluated. Here we examined the effects of continuous EEG protocol implementation in our pediatric ECMO population.

Retrospective chart reviews were conducted on 57 patients who underwent extracorporeal membrane oxygenation and concurrent continuous EEG out of 165 patients supported on extracorporeal membrane oxygenation. Timing of continuous EEG initiation and seizures detected by continuous EEG was determined for 5 years prior to and 15 months after protocol implementation.

Protocol implementation was associated with increased ECMO-supported patients who were concurrently monitored by continuous EEG. Time from ECMO cannulation to continuous EEG initiation was shorter (median 7 hours after versus 16.2 hours before; P < .001). Patients who had ongoing seizures at the start of continuous EEG recording decreased from 64% preprotocol to 0% postprotocol (P < .001), and there was an associated earlier time to break in status epilepticus postprotocol. Seizures were detected past 48 hours after cannulation in 50% of patients in the postprotocol group.

Protocol implementation resulted in earlier continuous EEG initiation and more EEGs initiated before seizure onset with evidence of altered seizure dynamics. Although current recommendations suggest that continuous EEG duration of 24-48 hours results in seizure detection for >90% of critically ill adults, longer monitoring may be needed to reliably detect seizures in children supported with ECMO, particularly if monitoring is initiated earlier in the post-cannulation period.

Organ dysfunction (ODF) in late-onset bloodstream infection (LBSI) is associated with increased risk of adverse outcomes. However, no established definition of ODF exists among preterm neonates. Our objective was to describe an outcome-based ODF definition for preterm infants, and assess factors associated with mortality.

This is a six-year retrospective study of neonates <35 weeks gestational age, >72 h of age, with non-CONS bacterial/fungal LBSI. Discriminatory ability of each parameter for mortality was evaluated: base deficit ≤-8 mmol/L (BD8), renal dysfunction (urine output <1 cc/kg/h or creatinine ≥100 μmol/L), hypoxic respiratory failure (HRF, ventilated, FiO2 = 1.0), or vasopressor/inotrope use (V/I). Multivariable logistic regression analysis was performed to derive a mortality score.

One hundred and forty-eight infants had LBSI. BD8 had the highest individual predictive ability for mortality (AUROC = 0.78). The combination BD8 + HRF + V/I was used to define ODF (AUROC = 0.84). Fifty-seven (39%) infants developed ODF, among which 28 (49%) died. Mortality increased inversely relative to GA at LBSI-onset (aOR 0.81 [0.67, 0.98]) and directly relative to ODF occurrence (12.15 [4.48, 33.92]). Compared to no-ODF, ODF infants had lower GA and age at illness, and higher frequency of Gram-negative pathogen.

Among preterm neonates with LBSI, significant metabolic acidosis, HRF, and vasopressor/inotrope use may identify infants high risk for mortality. These criteria could help identify patients for future studies of adjunctive therapies.

Sepsis-related organ dysfunction is associated with increased risk of adverse outcomes. Among preterm neonates, significant metabolic acidosis, use of vasopressors/inotropes, and hypoxic respiratory failure may identify high-risk infants. This can be used to target research and quality improvement efforts toward the most vulnerable infants.

Febrile seizure (FS) is the most common convulsive disorder in children. This study analyzed the national proportion of congenital heart disease (CHD) and hospital resource utilization among children admitted for FSs in the U.S.

This is a retrospective cross-sectional analysis of pediatric patients up to six years with a primary diagnosis of FS in 2016 and 2019 using the Kids Inpatient Database (KID). The demographic, hospital, and clinical characteristics of children with and without CHD were compared using the chi-square test for categorical variables and linear regressions for continuous variables. Multivariate logistic analysis was conducted to evaluate the impact of CHD on the mean length of hospital stay.

An estimated 10,039 children were admitted with the primary diagnosis of FS. Out of these, 117 (1.2%) had a discharge diagnosis of CHD. The mean age for children with and without CHD was 1.4 years (SD 1.60) and 1.5 years (SD 1.501), respectively. Children with CHD who required hospitalization for FS had longer mean lengths of hospital stay (2.1 days vs. 1.6 days), with an adjusted odd ratio of 0.43 (95% CI: 0.07-0.99; p-value: 0.017). Similarly, the hospital charges for children with CHD were higher than those without CHD ($30,960.28 vs. $21,005.11).

Children with CHD who required inpatient admission for FSs in the U.S. were associated with increased length of hospital stay and higher resource utilization when compared with those without CHD. This highlights the need for preventive measures among this vulnerable population.

The purpose of the study was to describe the evolution of outcomes among full-term infants with moderate hypoxic-ischemic encephalopathy (HIE); from their early swallowing and feeding abilities during hospitalization, to their later developmental outcomes at 6 and 12 months. Four participants with moderate HIE were recruited. Early feeding and swallowing were assessed using the Neonatal Feeding Assessment Scale and video fluoroscopic swallow studies. Developmental assessments were conducted at 6 and 12 months using the Rossetti Infant-Toddler Language Scale and Vineland-3 Scale. All participants displayed atypical outcomes throughout the study, including oropharyngeal dysphagia initially during hospitalization. All participants were discharged on oral feeds but some breastfeeding difficulties persisted. Variable but pervasive developmental delays were found among all participants at 6 and 12 months. This study emphasizes the need for consistent early intervention from the neonatal period onward, for all infants with moderate HIE. Future studies should use larger cohorts, longer follow-up, and correlational designs.

To assess variability in continuation of antiseizure medication (ASM) at discharge and to evaluate if continuation of ASM at discharge is associated with death or disability among infants with hypoxic-ischaemic encephalopathy (HIE) and seizures.

Retrospective study of infants enrolled in three National Institute of Child Health and Human Development Neonatal Research Network Trials of therapeutic hypothermia.

22 US centres.

Infants with HIE who survived to discharge and had clinical or electrographic seizures treated with ASM.

ASM continued or discontinued at discharge.

Death or moderate-to-severe disability at 18-22 months, using trial definitions. Multivariable logistic regression evaluated the association between continuation of ASM at discharge and the primary outcome, adjusting for severity of HIE, hypothermia trial treatment arm, use of electroencephalogram, discharge on gavage feeds, Apgar Score at 5 min, birth year and centre.

Of 302 infants included, 61% were continued on ASMs at discharge (range 13%-100% among 22 centres). Electroencephalogram use occurred in 92% of the cohort. Infants with severe HIE comprised 24% and 22% of those discharged with and without ASM, respectively. The risk of death or moderate-to-severe disability was greater for infants continued on ASM at discharge, compared with those infants discharged without ASM (44% vs 28%, adjusted OR 2.14; 95% CI 1.13 to 4.05).

In infants with HIE and seizures, continuation of ASM at discharge varies substantially among centres and may be associated with a higher risk of death or disability at 18-22 months of age.

Seizures are common during neonatal encephalopathy (NE), but the contribution of seizure burden (SB) to outcomes remains controversial. This study aims to examine the relationship between electrographic SB and neurologic outcomes after NE.

This prospective cohort study recruited newborns ≥36 weeks postmenstrual age around 6 hours of life between August 2014 and November 2019 from a neonatal intensive care unit (NICU). Participants underwent continuous electroencephalography for at least 48 hours, brain MRI within 3-5 days of life, and structured follow-up at 18 months. Electrographic seizures were identified by board-certified neurophysiologists and quantified as total SB and maximum hourly SB. A medication exposure score was calculated based on all antiseizure medications given during NICU admission. Brain MRI injury severity was classified based on basal ganglia and watershed scores. Developmental outcomes were measured using the Bayley Scales of Infant Development, Third Edition. Multivariable regression analyses were performed, adjusting for significant potential confounders.

Of 108 enrolled infants, 98 had continuous EEG (cEEG) and MRI data collected, of which 5 were lost to follow-up, and 6 died before age 18 months. All infants with moderate-severe encephalopathy completed therapeutic hypothermia. cEEG-confirmed neonatal seizures occurred in 21 (24%) newborns, with a total SB mean of 12.5 ± 36.4 minutes and a maximum hourly SB mean of 4 ± 10 min/h. After adjusting for MRI brain injury severity and medication exposure, total SB was significantly associated with lower cognitive (-0.21, 95% CI -0.33 to -0.08, p = 0.002) and language (-0.25, 95% CI -0.39 to -0.11, p = 0.001) scores at 18 months. Total SB of 60 minutes was associated with 15-point decline in language scores and 70 minutes for cognitive scores. However, SB was not significantly associated with epilepsy, neuromotor score, or cerebral palsy (p > 0.1).

Higher SB during NE was independently associated with worse cognitive and language scores at 18 months, even after adjusting for exposure to antiseizure medications and severity of brain injury. These observations support the hypothesis that neonatal seizures occurring during NE independently contribute to long-term outcomes.

Placental dysfunction can lead to perinatal hypoxic events including stillbirth. Unless there is overt severe fetal growth restriction, placental dysfunction is frequently not identified in (near) term pregnancy, particularly because fetal size is not necessarily small. This study aimed to evaluate, among (near) term births, the burden of hypoxia-related adverse perinatal outcomes reflected in an association with birth weight centiles as a proxy for placental function.

A nationwide 5-year cohort of the Dutch national birth registry (PeriNed) including 684,938 singleton pregnancies between 36+0 and 41+6 weeks of gestation. Diabetes, congenital anomalies, chromosomal abnormalities and non-cephalic presentations at delivery were excluded. The main outcome was antenatal mortality rate according to birthweight centiles and gestational age. Secondary outcomes included perinatal hypoxia-related outcomes, including perinatal death and neonatal morbidity, analyzed according to birthweight centiles.

Between 2015 and 2019, 1,074 perinatal deaths (0.16%) occurred in the study population (n = 684,938), of which 727 (0.10%) antenatally. Of all antenatal- and perinatal deaths, 29.4% and 27.9% occurred in birthweights below the 10th centile. The incidence of perinatal hypoxia-related outcomes was highest in fetuses with lowest birthweight centiles (18.0%), falling gradually up to the 50th and 90th centile where the lowest rates of hypoxia-related outcomes (5.4%) were observed.

Perinatal hypoxia-related events have the highest incidence in the lowest birthweight centiles but are identifiable throughout the entire spectrum. In fact, the majority of the adverse outcome burden in absolute numbers occurs in the group with a birthweight above the 10th centile. We hypothesize that in most cases these events are attributable to reduced placental function. Additional diagnostic modalities that indicate placental dysfunction at (near) term gestation throughout all birth weight centiles are eagerly wanted.

Birth asphyxia and the resulting hypoxic-ischemic encephalopathy (HIE) are highly associated with perinatal and neonatal death, neonatal seizures, and an adverse later-life outcome. Currently used drugs, including phenobarbital and midazolam, have limited efficacy to suppress neonatal seizures. There is a medical need to develop new therapies that not only suppress neonatal seizures but also prevent later-life consequences. We have previously shown that the loop diuretic bumetanide does not potentiate the effects of phenobarbital in a rat model of birth asphyxia. Here we compared the effects of bumetanide (0.3 or 10 mg/kg i.p.), midazolam (1 mg/kg i.p.), and a combination of bumetanide and midazolam on neonatal seizures and later-life outcomes in this model. While bumetanide at either dose was ineffective when administered alone, the higher dose of bumetanide markedly potentiated midazolam's effect on neonatal seizures. Median bumetanide brain levels (0.47-0.53 µM) obtained with the higher dose were in the range known to inhibit the Na-K-Cl-cotransporter NKCC1 but it remains to be determined whether brain NKCC1 inhibition was underlying the potentiation of midazolam. When behavioral and cognitive alterations were examined over three months after asphyxia, treatment with the bumetanide/midazolam combination, but not with bumetanide or midazolam alone, prevented impairment of learning and memory. Furthermore, the combination prevented the loss of neurons in the dentate hilus and aberrant mossy fiber sprouting in the CA3a area of the hippocampus. The molecular mechanisms that explain that bumetanide potentiates midazolam but not phenobarbital in the rat model of birth asphyxia remain to be determined.

Intercenter variation exists in the management of hypoxic-ischemic encephalopathy (HIE). It is unclear whether increased resource utilization translates into improved neurodevelopmental outcomes.

To determine if higher resource utilization during the first 4 days of age, quantified by hospital costs, is associated with survival without neurodevelopmental impairment (NDI) among infants with HIE.

Retrospective cohort analysis of neonates with HIE who underwent therapeutic hypothermia (TH) at US children's hospitals participating in the Children's Hospitals Neonatal Database between 2010 and 2016. Data were analyzed from December 2021 to December 2022.

Infants who survived to 4 days of age and had neurodevelopmental outcomes assessed at greater than 11 months of age were divided into 2 groups: (1) death or NDI and (2) survived without NDI. Resource utilization was defined as costs of hospitalization including neonatal neurocritical care (NNCC). Data were linked with Pediatric Health Information Systems to quantify standardized costs by terciles.

The main outcome was death or NDI. Characteristics, outcomes, hospitalization, and NNCC costs were compared.

Among the 381 patients who were included, median (IQR) gestational age was 39 (38-40) weeks; maternal race included 79 (20.7%) Black mothers, 237 (62.2%) White mothers, and 58 (15.2%) mothers with other race; 80 (21%) died, 64 (17%) survived with NDI (combined death or NDI group: 144 patients [38%]), and 237 (62%) survived without NDI. The combined death or NDI group had a higher rate of infants with Apgar score at 10 minutes less than or equal to 5 (65.3% [94 of 144] vs 39.7% [94 of 237]; P < .001) and a lower rate of infants with mild or moderate HIE (36.1% [52 of 144] vs 82.3% [195 of 237]; P < .001) compared with the survived without NDI group. Compared with low-cost centers, there was no association between high- or medium-hospitalization cost centers and death or NDI. High- and medium-EEG cost centers had lower odds of death or NDI compared with low-cost centers (high vs low: OR, 0.30 [95% CI, 0.16-0.57]; medium vs low: OR, 0.29 [95% CI, 0.13-0.62]). High- and medium-laboratory cost centers had higher odds of death or NDI compared with low-cost centers (high vs low: OR, 2.35 [95% CI, 1.19-4.66]; medium vs low: OR, 1.93 [95% CI, 1.07-3.47]). High-antiseizure medication cost centers had higher odds of death or NDI compared with low-cost centers (high vs. low: OR, 3.72 [95% CI, 1.51-9.18]; medium vs low: OR, 1.56 [95% CI, 0.71-3.42]).

Hospitalization costs during the first 4 days of age in neonates with HIE treated with TH were not associated with neurodevelopmental outcomes. Higher EEG costs were associated with lower odds of death or NDI yet higher laboratory and antiseizure medication costs were not. These findings serve as first steps toward identifying aspects of NNCC that are associated with outcomes.

This article aims to critically review the literature on continuous electroencephalography (cEEG) monitoring in the intensive care unit (ICU) from an Australian and New Zealand perspective and provide recommendations for clinicians.

A taskforce of adult and paediatric neurologists, selected by the Epilepsy Society of Australia, reviewed the literature on cEEG for seizure detection in critically ill neonates, children, and adults in the ICU. The literature on routine EEG and cEEG for other indications was not reviewed. Following an evaluation of the evidence and discussion of controversial issues, consensus was reached, and a document that highlighted important clinical, practical, and economic considerations regarding cEEG in Australia and New Zealand was drafted.

This review represents a summary of the literature and consensus opinion regarding the use of cEEG in the ICU for detection of seizures, highlighting gaps in evidence, practical problems with implementation, funding shortfalls, and areas for future research.

While cEEG detects electrographic seizures in a significant proportion of at-risk neonates, children, and adults in the ICU, conferring poorer neurological outcomes and guiding treatment in many settings, the health economic benefits of treating such seizures remain to be proven. Presently, cEEG in Australian and New Zealand ICUs is a largely unfunded clinical resource that is subsequently reserved for the highest-impact patient groups. Wider adoption of cEEG requires further research into impact on functional and health economic outcomes, education and training of the neurology and ICU teams involved, and securement of the necessary resources and funding to support the service.

Neonatal seizures are common, but the impact of neonatal seizures on long-term neurologic outcome remains unclear. We addressed this question by analyzing data from an early-phase controlled trial of bumetanide to treat neonatal seizures.

Neonatal seizure burden was calculated from continuous video-EEG data. Neurologic outcome was determined by standardized developmental tests and post-neonatal seizure recurrence.

Of 111 enrolled neonates, 43 were randomized to treatment or control groups. There were no differences in neurologic outcome between treatment and control groups. A subgroup analysis was performed for 84 neonates with acute perinatal brain injury (57 HIE, 18 stroke, 9 ICH), most of whom (70%) had neonatal seizures. There was a significant negative correlation between seizure burden and developmental scores (p<0.01). Associations between seizure burden and developmental scores were stronger in HIE and stroke groups compared with ICH (p<0.05).

Bumetanide showed no long-term beneficial or adverse effects, as expected based on treatment duration versus duration of neonatal seizures. For neonates with perinatal brain injury, higher neonatal seizure burden correlated significantly with worse developmental outcome, particularly for ischemic versus hemorrhagic brain injury. These data highlight the need for further investigation of the long-term effects of both neonatal seizure severity and etiology.