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Background and ObjectivesClinicians often communicate complex, uncertain, and distressing information about neurologic prognosis to parents of critically ill infants. Although communication tools have been developed in other disciplines and settings, none address the unique needs of the neonatal and pediatric neurology context. We aimed to develop a parent-informed framework to guide clinicians in communicating information about neurologic prognosis.MethodsParents of infants with neurologic conditions in the intensive care unit were enrolled in a longitudinal study of shared decision-making from 2018 to 2020. Parents completed semistructured interviews following recorded family meetings with the health care team, at hospital discharge, and 6 months after discharge. All interviews targeted information about parent preferences for prognostic disclosure. We analyzed the data using a conventional content analysis approach. Two study team members independently coded all interview transcripts, and discrepancies were resolved in consensus. We used NVIVO 12 qualitative software to index and organize codes.ResultsFifty-two parents of 37 infants completed 123 interviews. Parents were predominantly mothers (n = 37/52, 71%) with a median age of 31 (range 19–46) years. Half were Black (n = 26/52, 50%), and a minority reported Hispanic ethnicity (n = 2/52, 4%). Inductive analysis resulted in the emergence of 5 phases of prognostic communication (Approach, Learn, Inform, Give support, and Next steps: ALIGN): (1) Approach: parents appreciated receiving consistent information about their child's neurologic outcome from clinicians who knew their child well. (2) Learn: parents valued when clinicians asked them how they preferred receiving information and what they already knew about their child's outcome prior to information delivery. (3) Inform: parents valued honest, thorough, and balanced information that disclosed prognostic uncertainty and acknowledged room for hope. (4) Give support: parents valued empathic communication and appreciated clinicians who offered real-time emotional support. (5) Next steps: parents appreciated clinicians who connected them to resources, including peer support.DiscussionThe ALIGN framework offers a novel, parent-informed strategy to effectively communicate neurologic prognosis. Although ALIGN represents key elements of a conversation about prognosis, each clinician can adapt this framework to their own approach. Future work will assess the effectiveness of this framework on communication quality and prognostic understanding.

Congenital cerebral arteriovenous fistulas (AVFs), including vein of Galen malformations, presenting in infancy carry variable mortality and morbidity. This study aimed to describe the outcome of neonates with cerebral AVFs who present with refractory cardiac failure.Retrospective chart review of neonates with refractory cardiac failure due to cerebral AVFs presenting before 28 days of age in a single-center neuro-intensive care nursery over a 12-year period (2008-2020) was conducted.Seventeen neonates were included. Twelve had a vein of Galen malformation, four a non-galenic pial AVF, and one a dural AVF. Seven neonates (41%) died without receiving an embolization procedure. The remaining ten were critically ill. Seven (70%) were mechanically ventilated and on nitric oxide, 5 (50%) were on pressors, and 6 (60%) had renal and/or hepatic dysfunction. Seven (70%) had pre-existing brain injury on imaging. The first embolization procedure occurred at a median age of 4 days (range: 0-8 d). Complications included intracranial hemorrhage in 8 of 10 (80%) and seizures in 5 of 8 (62%). Five (50%) neonates who underwent embolization died. Among the 5 neonates who survived, all have motor impairment. Four (80%) developed hydrocephalus requiring a ventriculoperitoneal shunt, and 2 (40%) developed epilepsy and are nonverbal.In this cohort of critically ill neonates with cerebral AVF, all seven who did not receive embolization and half of ten who were treated died. The five survivors all have neurodevelopmental impairment. This information may be helpful to parents and providers who make decisions regarding life-sustaining treatments for neonates with cerebral AVFs and refractory cardiac failure.

ObjectiveTo compare key seizure and outcome characteristics between neonates with and without cardiopulmonary disease.Study designThe Neonatal Seizure Registry is a multicenter, prospectively acquired cohort of neonates with clinical or electroencephalographic (EEG)-confirmed seizures. Cardiopulmonary disease was defined as congenital heart disease, congenital diaphragmatic hernia, and exposure to extracorporeal membrane oxygenation. We assessed continuous EEG monitoring strategy, seizure characteristics, seizure management, and outcomes for neonates with and without cardiopulmonary disease.ResultsWe evaluated 83 neonates with cardiopulmonary disease and 271 neonates without cardiopulmonary disease. Neonates with cardiopulmonary disease were more likely to have EEG-only seizures (40% vs 21%, P&nbsp

Background In newborns with hypoxic-ischemic encephalopathy (HIE), the correlation between neonatal neuroimaging and the degree of neurodevelopmental impairment (NDI) is unclear. Methods Infants with HIE enrolled in a randomized controlled trial underwent neonatal MRI/MR spectroscopy (MRS) using a harmonized protocol at 4–6 days of age. The severity of brain injury was measured with a validated scoring system. Using proportional odds regression, we calculated adjusted odds ratios (aOR) for the associations between MRI/MRS measures of injury and primary ordinal outcome (i.e., normal, mild NDI, moderate NDI, severe NDI, or death) at age 2 years. Results Of 451 infants with MRI/MRS at a median age of 5 days (IQR 4.5–5.8), outcomes were normal (51%); mild (12%), moderate (14%), severe NDI (13%); or death (9%). MRI injury score (aOR 1.06, 95% CI 1.05, 1.07), severe brain injury (aOR 39.6, 95% CI 16.4, 95.6), and MRS lactate/n-acetylaspartate (NAA) ratio (aOR 1.6, 95% CI 1.4,1.8) were associated with worse primary outcomes. Infants with mild/moderate MRI brain injury had similar BSID-III cognitive, language, and motor scores as infants with no injury. Conclusion In the absence of severe injury, brain MRI/MRS does not accurately discriminate the degree of NDI. Given diagnostic uncertainty, families need to be counseled regarding a range of possible neurodevelopmental outcomes. Impact Half of all infants with hypoxic-ischemic encephalopathy (HIE) enrolled in a large clinical trial either died or had neurodevelopmental impairment at age 2 years despite receiving therapeutic hypothermia. Severe brain injury and a global pattern of brain injury on MRI were both strongly associated with death or neurodevelopmental impairment. Infants with mild or moderate brain injury had similar mean BSID-III cognitive, language, and motor scores as infants with no brain injury on MRI. Given the prognostic uncertainty of brain MRI among infants with less severe degrees of brain injury, families should be counseled regarding a range of possible neurodevelopmental outcomes.

PURPOSE: Parents of neonates with seizures are at risk of mental health symptoms due to the impact of illness on family life, prognostic uncertainty, and the emotional toll of hospitalization. A family-centered approach is the preferred model to mitigate these challenges. We aimed to identify strategies to promote family-centered care through an analysis of parent-offered advice to clinicians caring for neonates with seizures. BASIC PROCEDURES: This prospective, observational, and multi-center (Neonatal Seizure Registry) study enrolled parents of neonates with acute symptomatic seizures. Parents completed surveys about family well-being at 12 months, 18 months, and 24 months corrected gestational age. Parents were asked open-ended questions eliciting their advice to clinicians caring for neonates with seizures. Responses were analyzed using a conventional content analysis approach. MAIN FINDINGS: Among the 310 parents who completed surveys, 118 (38%) shared advice for clinicians. These parents were predominantly mothers (n=103, 87%). Three overarching themes were identified. (1) Communicate information effectively: Parents appreciate when clinicians offer transparent and balanced information in an accessible way. (2) Understand and validate parent experience: Parents value clinicians who display empathy, compassion, and a commitment to parent-partnered clinical care. (3) Provide support and resources: Parents benefit from emotional support, education, connection with peers, and help navigating the healthcare system. PRINCIPAL CONCLUSIONS: Parents caring for neonates with seizures appreciate a family-centered approach in healthcare encounters, including skilled communication, understanding and validation of the parent experience, and provision of support and resources. Future interventions should focus on building structures to reinforce these priorities.

Background We previously reported that increasing severity of watershed (WS) injury in neonatal magnetic resonance imaging (MRI) is associated with worse language outcomes in early childhood. In the present study, we investigated the relationship between neonatal injury patterns and cognitive profile in adolescents with neonatal encephalopathy. Methods Term neonates with encephalopathy were prospectively enrolled and imaged using brain MRI from 1999 to 2008. Neonatal brain injury was scored according to the degree of injury in WS and basal ganglia/thalamus (BG/T) areas. The children underwent a neurocognitive assessment and follow-up brain MRI at the age of 10–16 years. The relationship between neonatal brain injury patterns and adolescent cognitive outcomes was assessed. Results In a cohort of 16 children, neonatal MRI showed WS injury in 7, BG/T injury in 2, and normal imaging in 7. Children with WS injury had lower estimated overall cognitive ability than those with normal imaging. Increasing WS injury score was associated with decreasing estimated overall cognitive ability, Perceptual Reasoning Index, and digit span score. Conclusions Children with the WS injury are at an increased risk of having problems in long-term intellectual ability. These cognitive outcomes may underlie early language difficulties seen in children with neonatal WS injury. Impact Adolescents with a history of neonatal encephalopathy and watershed pattern of injury on neonatal brain magnetic resonance imaging (MRI) had lower overall cognitive ability, perceptual reasoning skills, and auditory working memory than those with normal neonatal imaging. Children with post-neonatal epilepsy and cerebral palsy had the worst cognitive outcomes. Watershed pattern of injury confers high long-term differences in intellectual ability.

Little is known about parent and family well-being after acute neonatal seizures. In thus study, we aimed to characterize parent mental health and family coping over the first two years after their child’s neonatal seizures. Parents of 303 children with acute neonatal seizures from nine pediatric hospitals completed surveys at discharge and 12-, 18- and 24-months corrected age. Outcomes included parental anxiety, depression, quality of life, impact on the family, post-traumatic stress and post-traumatic growth. We used linear mixed effect regression models and multivariate analysis to examine relationships among predictors and outcomes. At the two-year timepoint, parents reported clinically significant anxiety (31.5%), depression (11.7%) and post-traumatic stress (23.7%). Parents reported moderately high quality of life and positive personal change over time despite ongoing challenges to family coping. Families of children with longer neonatal hospitalization, functional impairment, post-neonatal epilepsy, receiving developmental support services and families of color reported poorer parental mental health and family coping. Parents of color were more likely to report symptoms of post-traumatic stress and positive personal change. Clinicians caring for children with neonatal seizures should be aware of lasting risks to parent mental health and family coping. Universal screening would enable timely referral for support services to mitigate further risk to family well-being and child development.

ObjectiveTo determine whether screening continuous EEG monitoring (cEEG) is associated with greater odds of treatment success for neonatal seizures.MethodsWe included term neonates with acute symptomatic seizures enrolled in the Neonatal Seizure Registry (NSR), a prospective, multicenter cohort of neonates with seizures. We compared 2 cEEG approaches: (1) screening cEEG, initiated for indications of encephalopathy or paralysis without suspected clinical seizures; and (2) confirmatory cEEG, initiated for the indication of clinical events suspicious for seizures, either alone or in addition to other indications. The primary outcome was successful response to initial seizure treatment, defined as seizures resolved without recurrence within 30 minutes after initial loading dose of antiseizure medicine. Multivariable logistic regression analyses assessed the association between cEEG approach and successful seizure treatment.ResultsAmong 514 neonates included, 161 (31%) had screening cEEG and 353 (69%) had confirmatory cEEG. Neonates with screening cEEG had a higher proportion of successful initial seizure treatment than neonates with confirmatory cEEG (39% vs 18%; p < 0.0001). After adjusting for covariates, there remained a greater odds ratio (OR) for successful initial seizure treatment in the screening vs confirmatory cEEG groups (adjusted OR 2.44, 95% confidence interval 1.45–4.11, p = 0.0008).ConclusionsThese findings provide evidence from a large, contemporary cohort of neonates that a screening cEEG approach may improve odds of successful treatment of acute seizures.Classification of EvidenceThis study provides Class III evidence that for neonates a screening cEEG approach, compared to a confirmatory EEG approach, increases the probability of successful treatment of acute seizures.

Background Cerebral palsy (CP) is the most common motor disability of childhood. Its early identification is an important priority for parents and is critical for access to early intervention resources, which may optimize function. Methods A prospective cohort of term neonates at high risk for CP was assessed by neonatal magnetic resonance imaging (MRI) to determine myelination of the posterior limb of the internal capsule, General Movements Assessment to assess typical fidgety movements at age three months, and followed to at least age two years to determine diagnosis of CP based on neurological examination. Results Seven of 58 children developed CP (12%), two with moderate/severe CP. Sensitivity and specificity for abnormal myelination of the posterior limb of the internal capsule were (PLIC) was 29% and 94%, and for absent fidgety movements, 29% and 98%, respectively. Negative predictive value of both absent myelination of the PLIC and absent fidgety movements was 90% (79% to 96%) for any CP and 98% (90% to 100%) for moderate/severe CP cerebral palsy. None of the children with both normal PLIC and normal fidgety movements had moderate/severe CP. Conclusion Normal neonatal MRI and General Movements Assessment at age three months are reassuring that a high-risk term-born child is at low risk for moderate/severe CP. These results are important for counseling parents and individualizing therapy resources in the community.

Background The contribution of pathogenic gene variants with development of epilepsy after acute symptomatic neonatal seizures is not known. Methods Case–control study of 20 trios in children with a history of acute symptomatic neonatal seizures: 10 with and 10 without post-neonatal epilepsy. We performed whole-exome sequencing (WES) and identified pathogenic de novo, transmitted, and non-transmitted variants from established and candidate epilepsy association genes and correlated prevalence of these variants with epilepsy outcomes. We performed a sensitivity analysis with genes associated with coronary artery disease (CAD). We analyzed variants throughout the exome to evaluate for differential enrichment of functional properties using exploratory KEGG searches. Results Querying 200 established and candidate epilepsy genes, pathogenic variants were identified in 5 children with post-neonatal epilepsy yet in only 1 child without subsequent epilepsy. There was no difference in the number of trios with non-transmitted pathogenic variants in epilepsy or CAD genes. An exploratory KEGG analysis demonstrated a relative enrichment in cell death pathways in children without subsequent epilepsy. Conclusions In this pilot study, children with epilepsy after acute symptomatic neonatal seizures had a higher prevalence of coding variants with a targeted epilepsy gene sequencing analysis compared to those patients without subsequent epilepsy. Impact We performed whole-exome sequencing (WES) in 20 trios, including 10 children with epilepsy and 10 without epilepsy, both after acute symptomatic neonatal seizures. Children with post-neonatal epilepsy had a higher burden of pathogenic variants in epilepsy-associated genes compared to those without post-neonatal epilepsy. Future studies evaluating this association may lead to a better understanding of the risk of epilepsy after acute symptomatic neonatal seizures and elucidate molecular pathways that are dysregulated after brain injury and implicated in epileptogenesis.

Neonatal hypoxic-ischemic encephalopathy is an important cause of death as well as long-term disability in survivors. Erythropoietin has been hypothesized to have neuroprotective effects in infants with hypoxic-ischemic encephalopathy, but its effects on neurodevelopmental outcomes when given in conjunction with therapeutic hypothermia are unknown.In a multicenter, double-blind, randomized, placebo-controlled trial, we assigned 501 infants born at 36 weeks or more of gestation with moderate or severe hypoxic-ischemic encephalopathy to receive erythropoietin or placebo, in conjunction with standard therapeutic hypothermia. Erythropoietin (1000 U per kilogram of body weight) or saline placebo was administered intravenously within 26 hours after birth, as well as at 2, 3, 4, and 7 days of age. The primary outcome was death or neurodevelopmental impairment at 22 to 36 months of age. Neurodevelopmental impairment was defined as cerebral palsy, a Gross Motor Function Classification System level of at least 1 (on a scale of 0 [normal] to 5 [most impaired]), or a cognitive score of less than 90 (which corresponds to 0.67 SD below the mean, with higher scores indicating better performance) on the Bayley Scales of Infant and Toddler Development, third edition.Of 500 infants in the modified intention-to-treat analysis, 257 received erythropoietin and 243 received placebo. The incidence of death or neurodevelopmental impairment was 52.5% in the erythropoietin group and 49.5% in the placebo group (relative risk, 1.03; 95% confidence interval [CI], 0.86 to 1.24; P = 0.74). The mean number of serious adverse events per child was higher in the erythropoietin group than in the placebo group (0.86 vs. 0.67; relative risk, 1.26; 95% CI, 1.01 to 1.57).The administration of erythropoietin to newborns undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy did not result in a lower risk of death or neurodevelopmental impairment than placebo and was associated with a higher rate of serious adverse events. (Funded by the National Institute of Neurological Disorders and Stroke; ClinicalTrials.gov number, NCT02811263.).

We characterize the content and role of prognostic discussion for infants with neurologic conditions.In this descriptive qualitative study, we prospectively enrolled infants (age 1 year) in the intensive care unit with a neurologic condition anticipated to have ≥1 family conference about prognosis or goals of care. We audiorecorded family conferences as they occurred. We used a rapid-cycle qualitative approach to identify and refine themes.Forty infants and 61 parents were enrolled; 68 family conferences occurred for 24 infants. The majority of infant cases (n = 23/24, 96%) and conferences (n = 64/68, 94%) included discussion of neurologic prognosis. Common infant diagnoses included prematurity (n = 12, 52%), genetic conditions (n = 9, 35%), and brain malformations (n = 7, 30%). We identified 2 themes relating to the characterization of the infant's prognosis: (1) predictions of impairment and (2) rationale for prognostic predictions. We identified 3 themes characterizing the role of prognostic discussion: (1) aligning parent and clinician understanding of infant outcome, (2) influencing decision-making, and (3) preparing for life at home. We identified 2 themes characterizing discussion of prognostic uncertainty: (1) multilayered types of uncertainty and (2) holding space for hope alongside uncertainty.In this cohort of infants with neurologic conditions and their parents, we identified salient themes characterizing the content and role of discussion about neurologic outcome. Our findings highlight that prognostic discussion focuses on anticipated impairments, informs decision-making, and helps families prepare for home life. Future work should characterize whether these findings align with parent preferences for prognostic disclosure. ANN NEUROL 2022;92:699-709.

Background Neonatal seizures are associated with death and neurological morbidity; however, little is known about how neonates with seizures die. Methods This was a prospective, observational cohort study of neonates with seizures treated at seven sites of the Neonatal Seizure Registry. We characterized the mode of death, evaluated the association between infant characteristics and mode of death, and evaluated predictors of death or transfer to hospice. Results We enrolled 611 consecutive neonates with seizures, and 90 neonates (15%) died before hospital discharge at a median age of 11 days (range: 1 to 163 days); 32 (36%) died in the first postnatal week. An additional 19 neonates (3%) were transferred to hospice. The most common mode of in-hospital death was death after extubation amidst concerns for poor neurological prognosis, in the absence of life-threatening physiologic instability (n = 43, 48%). Only one infant died while actively receiving cardiopulmonary resuscitation. In an adjusted analysis, premature birth (odds ratio: 3.06, 95% confidence interval 1.59 to 5.90) and high seizure burden (odds ratio: 4.33, 95% confidence interval 1.88 to 9.95) were associated with increased odds of death or transfer to hospice. Conclusion In a cohort of neonates with seizures, death occurred predominantly after decisions to withdraw or withhold life-sustaining intervention(s). Future work should characterize how these decisions occur and develop optimized approaches to support families and clinicians caring for newborns with seizures.

ObjectiveNeonates with seizures have a high risk of mortality and neurological morbidity. We aimed to describe the experience of parents caring for neonates with seizures.DesignThis prospective, observational and multicentre (Neonatal Seizure Registry) study enrolled parents of neonates with acute symptomatic seizures. At the time of hospital discharge, parents answered six open-ended response questions that targeted their experience. Responses were analysed using a conventional content analysis approach.Results144 parents completed the open-ended questions (732 total comments). Four themes were identified. Sources of strength: families valued medical team consensus, opportunities to contribute to their child’s care and bonding with their infant. Uncertainty: parents reported three primary types of uncertainty, all of which caused distress: (1) the daily uncertainty of the intensive care experience; (2) concerns about their child’s uncertain future and (3) lack of consensus between members of the medical team. Adapting family life: parents described the many ways in which they anticipated their infant’s condition would lead to adaptations in their family life, including adjusting their family’s lifestyle, parenting approach and routine. Many parents described financial and work challenges due to caring for a child with medical needs. Emotional and physical toll: parents reported experiencing anxiety, fear, stress, helplessness and loss of sleep.ConclusionsParents of neonates with seizures face challenges as they adapt to and find meaning in their role as a parent of a child with medical needs. Future interventions should target facilitating parent involvement in clinical and developmental care, improving team consensus and reducing the burden associated with prognostic uncertainty.

Limited data exist regarding seizure burden, electroencephalogram (EEG) background, and associated outcomes in neonates with acute intracranial infections.This secondary analysis was from a prospective, multicenter study of neonates enrolled in the Neonatal Seizure Registry with seizures due to intracranial infection. Sites used continuous EEG monitoring per American Clinical Neurophysiology Society guidelines. High seizure burden was defined a priori as seven or more EEG-confirmed seizures. EEG background was categorized using standardized terminology. Primary outcome was neurodevelopment at 24-months corrected age using Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS). Secondary outcomes were postneonatal epilepsy and motor disability.Twenty-seven of 303 neonates (8.9%) had seizures due to intracranial infection, including 16 (59.3%) bacterial, 5 (18.5%) viral, and 6 (22.2%) unknown. Twenty-three neonates (85%) had at least one subclinical seizure. Among 23 children with 24-month follow-up, the WIDEA-FS score was, on average, 23 points lower in children with high compared with low seizure burden (95% confidence interval, [-48.4, 2.1]; P = 0.07). After adjusting for gestational age, infection etiology, and presence of an additional potential acute seizure etiology, the effect size remained unchanged (β = -23.8, P = 0.09). EEG background was not significantly associated with WIDEA-FS score. All children with postneonatal epilepsy (n = 4) and motor disability (n = 5) had high seizure burden, although associations were not significant.High seizure burden may be associated with worse neurodevelopment in neonates with intracranial infection and seizures. EEG monitoring can provide useful management and prognostic information in this population.

Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures - about half of neonates treated with therapeutic hypothermia for NE have EEG-confirmed seizures. These seizures are best identified with continuous EEG monitoring, as clinical diagnosis leads to under-diagnosis of subclinical seizures and over-treatment of events that are not seizures. High seizure burden, especially status epilepticus, is thought to augment brain injury. Treatment, therefore, is aimed at minimizing seizure burden. Phenobarbital remains the mainstay of treatment, as it is more effective than levetiracetam and easier to administer than fosphenytoin. Emerging evidence suggests that, for many neonates, it is safe to discontinue the phenobarbital after acute seizures resolve and prior to hospital discharge.

Children with a history of acute provoked neonatal seizures are at high risk for disability, often requiring developmental services. The coronavirus disease 2019 (COVID-19) pandemic has led to widespread changes in how health care is delivered. Our objective was to determine the magnitude of service interruption of among children born between October 2014 and December 2017 and enrolled in the Neonatal Seizure Registry (NSR), a nine-center collaborative of pediatric centers in the United States.This is a prospective cohort study of children with acute provoked seizures with onset ≤44 weeks' gestation and evaluated at age three to six years. Parents of children enrolled in the NSR completed a survey about their child's access to developmental services between June 2020 and April 2021.Among 144 children enrolled, 72 children (50%) were receiving developmental services at the time of assessment. Children receiving services were more likely to be male, born preterm, and have seizure etiology of infection or ischemic stroke. Of these children, 64 (89%) experienced a disruption in developmental services due to the pandemic, with the majority of families (n = 47, 73%) reporting that in-person services were no longer available.Half of children with acute provoked neonatal seizures were receiving developmental services at ages three to six years. The COVID-19 pandemic has led to widespread changes in delivery of developmental services. Disruptions in services have the potential to impact long-term outcomes for children who rely on specialized care programs to optimize mobility and learning.

Background Neonatal neurocritical care (NNCC) is a rapidly advancing field with limited fellowship training available in locally developed, non-accredited programs. A standardized survey aimed to understand the training backgrounds of individuals practicing NNCC, the structure of existing clinical NNCC services/training programs, and suggested clinical competencies for new graduates. Methods We developed an anonymous survey electronically sent to members of societies related to NNCC. Using the survey results as a guide, we discuss a competence by design (CBD) curriculum as a complementary approach to traditional time-based training. Results There were 82 responses to the survey from 30 countries; 95% of respondents were physicians. Thirty-one (42%) institutions reported having an NNCC service, 24 (29%) individuals reported formal NNCC training, 81% reported "significant variability" across NNCC training programs, and 88% were both in favor of standardizing training programs and pursuing formal accreditation for NNCC in the next 5 years. Conclusions The survey results demonstrate international interest in standardizing NNCC training and development of an accreditation or certification process. We propose consideration of a CBD-type curriculum as a training approach to focus on the development of specific NNCC competencies, rather than assuming the acquisition of these competencies based on time as a surrogate. Impact Continued growth and development in the field of NNCC has led to increasing need for training programs suited to meet the diverse needs of trainees from varied backgrounds. We present the results of an international survey that assessed the structure of existing training programs and the priority areas in which graduates must demonstrate competence, highlighting the combination of CBD and time-based training as one approach to address these recommendations. The survey results support interest in translating published training competencies, existing expertise, and infrastructure across centers into a standardized curriculum for NNCC including certification opportunities.

OBJECTIVES Prolonged neonatal seizures are associated with poor neurodevelopmental outcomes. The aim of this quality improvement project was to decrease the time to medical treatment of seizures by 45% within 15 months for neonates admitted to the intensive care nursery (ICN) in an academic children’s hospital. METHODS A multidisciplinary team developed key drivers for timely treatment of seizures. Targeted interventions included optimizing a seizure rescue process with a mechanism that brings a pharmacist to the bedside for expedited medication delivery, in addition to interactive educational sessions. The outcome measure was time from the decision to treat seizures to medication administration. The process measure was use of the seizure rescue process with a balancing measure of unnecessary activations of this process. Data were collected from monthly chart review and displayed on statistical process control charts for analysis. The intervention period was from January 2019 to March 2020. RESULTS Between January 2016 and March 2020, there were 203 seizure treatment events (160 preintervention and 43 postintervention) in the ICN. Time to treatment of neonatal seizures decreased by 48%, from a baseline of 27 minutes (January 2016 to December 2018) to 14 minutes by March 2020, which reflected significant and sustained improvement. This was associated with improvement in the process metric during the same time periods. Unnecessary seizure rescue process activations were stable postintervention. CONCLUSIONS Implementation of an innovative seizure rescue process, in conjunction with staff and provider education, expedited antiseizure therapy in the ICN without requiring code resources.

Author(s): Cornet, Marie-Coralie; Morabito, Valeria; Lederer, Damien; Glass, Hannah C; Ferrao Santos, Susana; Numis, Adam L; Ferriero, Donna M; Sands, Tristan T; Cilio, Maria Roberta | Abstract: ObjectiveAlthough most seizures in neonates are due to acute brain injury, some represent the first sign of neonatal onset genetic epilepsies. Delay in recognition and lack of expert assessment of neonates with epilepsy may result in worse developmental outcomes. As in older children and adults, seizure semiology in neonates is an essential determinant in diagnosis. We aimed to establish whether seizure type at presentation in neonates can suggest a genetic etiology.MethodsWe retrospectively analyzed the clinical and electroencephalographic (EEG) characteristics of seizures in neonates admitted in two Level IV neonatal intensive care units, diagnosed with genetic epilepsy, for whom a video-EEG recording at presentation was available for review, and compared them on a 1:2 ratio with neonates with seizures due to stroke or hypoxic-ischemic encephalopathy.ResultsTwenty neonates with genetic epilepsy were identified and compared to 40 neonates with acute provoked seizures. Genetic epilepsies were associated with pathogenic variants in KCNQ2 (nn=n12), KCNQ3 (nn=n2), SCN2A (nn=n2), KCNT1 (nn=n1), PRRT2 (nn=n1), and BRAT1 (nn=n2). All neonates with genetic epilepsy had seizures with clinical correlates that were either tonic (18/20) or myoclonic (2/20). In contrast, 17 of 40 (42%) neonates with acute provoked seizures had electrographic only seizures, and the majority of the remainder had clonic seizures. Time to first seizure was longer in neonates with genetic epilepsies (median = 60nh of life) compared to neonates with acute provoked seizures (median = 15nh of life, pnln.001). Sodium channel-blocking antiseizure medications were effective in 13 of 14 (92%) neonates with tonic seizures who were trialed at onset or during the course of the epilepsy.SignificanceSeizure semiology is an easily accessible sign of genetic epilepsies in neonates. Early identification of the seizure type can prompt appropriate workup and treatment. Tonic seizures are associated with channelopathies and are often controlled by sodium channel-blocking antiseizure medications.

Although seizures in neonates are common and often due to acute brain injury, 10-15% are unprovoked from congenital brain malformations. A better understanding of the risk of neonatal-onset epilepsy by the type of brain malformation is essential for counseling and monitoring. In this retrospective cohort study, we evaluated 132 neonates with congenital brain malformations and their risk of neonatal-onset epilepsy. Malformations were classified into one of five categories based on imaging patterns on prenatal or postnatal imaging. Infants were monitored with continuous video EEG (cEEG) for encephalopathy and paroxysmal events in addition to abnormal neuroimaging. Seventy-four of 132 (56%) neonates underwent EEG monitoring, and 18 of 132 (14%) were diagnosed with neonatal-onset epilepsy. The highest prevalence of epilepsy was in neonates with disorders of neuronal migration/organization (9/34, 26%; 95% confidence interval [CI] = 13-44%), followed by disorders of early prosencephalic development (6/38, 16%; 95% CI = 6-31%), complex total brain malformations (2/16, 13%; 95% CI = 2-38%), and disorders of midbrain/hindbrain malformations (1/30, 3%; 95% CI = 0-17%). Of neonates with epilepsy, 5 of 18 (28%) had only electrographic seizures, 13 of 18 (72%) required treatment with two or more antiseizure medicines (ASMs), and 7 of 18 (39%) died within the neonatal period. Our results demonstrate that disorders of neuronal migration/organization represent the highest-risk group for early-onset epilepsy. Seizures are frequently electrographic only, require treatment with multiple ASMs, and portend a high mortality rate. These results support American Clinical Neurophysiology Society recommendations for EEG monitoring during the neonatal period for infants with congenital brain malformations.

Objective Seizures are a common neonatal neurologic emergency. Many centers have developed pathways to optimize management. We evaluated neonatal seizure management pathways at level IV neonatal intensive care units (NICUs) in the United States to highlight areas of consensus and describe aspects of variability. Methods We conducted a descriptive analysis of 11 neonatal seizure management pathways from level IV NICUs that specialize in neonatal neurocritical care including guidelines for electroencephalography (EEG) monitoring, antiseizure medication (ASM) choice, timing, and dose. Results Study center NICUs had a median of 70 beds (interquartile range: 52-96). All sites had 24/7 conventional EEG initiation, monitoring, and review capability. Management pathways uniformly included prompt EEG confirmation of seizures. Most pathways included a provision for intravenous benzodiazepine administration if either EEG or loading of ASM was delayed. Phenobarbital 20 mg/kg IV was the first-line ASM in all pathways. Pathways included either fosphenytoin or levetiracetam as the second-line ASM with variable dosing. Third-line ASMs were most commonly fosphenytoin or levetiracetam, with alternatives including topiramate or lacosamide. All pathways provided escalation to continuous midazolam infusion with variable dosing for seizures refractory to initial medication trials. Three pathways also included lidocaine infusion. Nine pathways discussed ASM discontinuation after resolution of acute symptomatic seizures with variable timing. Conclusions Despite a paucity of data from controlled trials regarding optimal neonatal seizure management, there are areas of broad agreement among institutional pathways. Areas of substantial heterogeneity that require further research include optimal second-line ASM, dosage, and timing of ASM discontinuation.

OBJECTIVE We aimed to evaluate early-life epilepsy incidence, seizure types, severity, risk factors, and treatments among survivors of acute neonatal seizures. METHODS Neonates with acute symptomatic seizures born 7/2015-3/2018 were prospectively enrolled at nine Neonatal Seizure Registry sites. One-hour EEG was recorded at age three months. Post-neonatal epilepsy and functional development (Warner Initial Developmental Evaluation of Adaptive and Functional Skills - WIDEA-FS) were assessed. Cox regression was used to assess epilepsy-free survival. RESULTS Among 282 infants, 37 (13%) had post-neonatal epilepsy by 24-months [median age of onset 7-months (IQR 3-14)]. Among those with post-neonatal epilepsy, 13/37 (35%) had infantile spasms and 12/37 (32%) had drug-resistant epilepsy. Most children with post-neonatal epilepsy had abnormal neurodevelopment at 24-months (WIDEA-FS >2SD below normal population mean for 81% of children with epilepsy vs 27% without epilepsy, RR 7.9, 95% CI 3.6-17.3). Infants with severely abnormal neonatal EEG background patterns were more likely to develop epilepsy than those with mild/moderate abnormalities (HR 3.7, 95% CI 1.9-5.9). Neonatal EEG with ≥3 days of seizures also predicted hazard of epilepsy (HR 2.9, 95% CI 1.4-5.9). In an adjusted model, days of neonatal EEG-confirmed seizures (HR 1.4 per day, 95% CI 1.2-1.6) and abnormal discharge examination (HR 3.9, 95% CI 1.9-7.8) were independently associated with time to epilepsy onset. Abnormal (vs. normal) three-month EEG was not associated with epilepsy. SIGNIFICANCE In this multicenter study, only 13% of infants with acute symptomatic neonatal seizures developed post-neonatal epilepsy by age 24-months. However, there was a high risk of severe neurodevelopmental impairment and drug-resistant seizures among children with post-neonatal epilepsy. Days of EEG-confirmed neonatal seizures was a potentially modifiable epilepsy risk factor. An EEG at three months was not clinically useful for predicting epilepsy. These practice changing findings have implications for family counseling, clinical follow-up planning, and future research to prevent post-neonatal epilepsy.

Author(s): Bach, Ashley M; Fang, Annie Y; Bonifacio, Sonia; Rogers, Elizabeth E; Scheffler, Aaron; Partridge, J Colin; Xu, Duan; Barkovich, A James; Ferriero, Donna M; Glass, Hannah C; Gano, Dawn | Abstract: ObjectiveTo evaluate the association of therapeutic hypothermia with magnetic resonance imaging (MRI) findings and 30-month neurodevelopment in term neonatal encephalopathy.Study designCross-sectional analysis of 30-month neurodevelopment (IQR 19.0-31.4) in a prospective cohort of mild-to-severe neonatal encephalopathy imaged on day 4 (1993-2017 with institutional implementation of therapeutic hypothermia in 2007). MRI injury was classified as normal, watershed, or basal ganglia/thalamus. Abnormal motor outcome was defined as Bayley-II psychomotor developmental index l70, Bayley-III motor score l85 or functional motor deficit. Abnormal cognitive outcome was defined as Bayley-II mental developmental index l70 or Bayley-III cognitive score l85. Abnormal composite outcome was defined as abnormal motor and/or cognitive outcome, or death. The association of therapeutic hypothermia with MRI and outcomes was evaluated with multivariable logistic regression adjusted for propensity to receive therapeutic hypothermia.ResultsFollow-up was available in 317 (78%) surviving children, of whom 155 (49%) received therapeutic hypothermia. Adjusting for propensity, therapeutic hypothermia was independently associated with decreased odds of abnormal motor (OR 0.15, 95% CI 0.06-0.40, Pnln.001) and cognitive (OR 0.11, 95% CI 0.04-0.33, Pnln.001) outcomes. This association remained statistically significant after adjustment for injury pattern. The predictive accuracy of MRI pattern for abnormal composite outcome was unchanged between therapeutic hypothermia-treated (area under the receiver operating curve 0.76; 95% CI 0.61-0.91) and untreated (area under the receiver operating curve 0.74; 95% CI 0.67-0.81) infants. The negative predictive value of normal MRI was high in therapeutic hypothermia-treated and untreated infants (motor 96% vs 90%; cognitive 99% vs 95%).ConclusionsTherapeutic hypothermia is associated with lower rates of brain injury and adverse 30-month outcomes after neonatal encephalopathy. The predictive accuracy of MRI in the first week of life is unchanged by therapeutic hypothermia. Normal MRI remains reassuring for normal 30-month outcome after therapeutic hypothermia.

Neonatal encephalopathy is a clinical syndrome of neurologic dysfunction that encompasses a broad spectrum of symptoms and severity, from mild irritability and feeding difficulties to coma and seizures. It is vital for providers to understand that the term “neonatal encephalopathy” is simply a description of the neonate’s neurologic status that is agnostic to the underlying etiology. Unfortunately, hypoxic-ischemic encephalopathy (HIE) has become common vernacular to describe any neonate with encephalopathy, but this can be misleading. The term should not be used unless there is evidence of perinatal asphyxia as the primary cause of encephalopathy. HIE is a common cause of neonatal encephalopathy; the differential diagnosis also includes conditions with infectious, vascular, epileptic, genetic/congenital, metabolic, and toxic causes. Because neonatal encephalopathy is estimated to affect 2 to 6 per 1,000 term births, of which HIE accounts for approximately 1.5 per 1,000 term births, (1)(2)(3)(4)(5)(6) neonatologists and child neurologists should familiarize themselves with the evaluation, diagnosis, and treatment of the diverse causes of neonatal encephalopathy. This review begins by discussing HIE, but also helps practitioners extend the differential to consider the broad array of other causes of neonatal encephalopathy, emphasizing the epidemiology, neurologic presentations, diagnostics, imaging findings, and therapeutic strategies for each potential category.

AimTo determine the concurrent validity of the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA-FS), a criterion-specified questionnaire that assesses a child's adaptive skills in everyday contexts, and the Bayley Infant and Toddler Scales of Development, Third Edition (Bayley-III).MethodIn a prospective cohort study, 431 WIDEA-FS and Bayley-III assessments were completed among 341 children, aged 10 to 36months corrected age (158 females, 183 males; median [interquartile range] gestational age at birth 32wks [29-38]), monitored in a high-risk neonatal intensive care unit follow-up clinic.ResultsWIDEA-FS scores were significantly associated with Bayley-III scores in all domains. Lower scores on the WIDEA-FS were significantly associated with an increased risk of adverse developmental performance on all Bayley-III scales. The association was strongest for motor and language Bayley-III scores when tested at

We previously reported that increasing severity of watershed (WS) injury in neonatal magnetic resonance imaging (MRI) is associated with worse language outcomes in early childhood. In the present study, we investigated the relationship between neonatal injury patterns and cognitive profile in adolescents with neonatal encephalopathy.Term neonates with encephalopathy were prospectively enrolled and imaged using brain MRI from 1999 to 2008. Neonatal brain injury was scored according to the degree of injury in WS and basal ganglia/thalamus (BG/T) areas. The children underwent a neurocognitive assessment and follow-up brain MRI at the age of 10-16 years. The relationship between neonatal brain injury patterns and adolescent cognitive outcomes was assessed.In a cohort of 16 children, neonatal MRI showed WS injury in 7, BG/T injury in 2, and normal imaging in 7. Children with WS injury had lower estimated overall cognitive ability than those with normal imaging. Increasing WS injury score was associated with decreasing estimated overall cognitive ability, Perceptual Reasoning Index, and digit span score.Children with the WS injury are at an increased risk of having problems in long-term intellectual ability. These cognitive outcomes may underlie early language difficulties seen in children with neonatal WS injury.Adolescents with a history of neonatal encephalopathy and watershed pattern of injury on neonatal brain magnetic resonance imaging (MRI) had lower overall cognitive ability, perceptual reasoning skills, and auditory working memory than those with normal neonatal imaging. Children with post-neonatal epilepsy and cerebral palsy had the worst cognitive outcomes. Watershed pattern of injury confers high long-term differences in intellectual ability.

Objective Infantile spasms (IS) is a severe epilepsy in early childhood. Early treatment of IS provides the best chance of seizure remission and favorable developmental outcome. We aimed to develop a prediction rule to accurately predict which neonates with acute symptomatic seizures will develop IS. Methods We used data from the Neonatal Seizure Registry, a prospective, multicenter cohort of infants with acute symptomatic neonatal seizures born from July 2015 to March 2018. Neonates with acute symptomatic seizures who received clinical electroencephalography (EEG) and magnetic resonance imaging (MRI) and were younger than 2 years of age at the time of enrollment were included. We evaluated the association of neonatal EEG, MRI, and clinical factors with subsequent IS using bivariate analysis and best subsets logistic regression. We selected a final model through a consensus process that balanced statistical significance with clinical relevance. Results IS developed in 12 of 204 infants (6%). Multiple potential predictors were associated with IS, including Apgar scores, EEG features, seizure characteristics, MRI abnormalities, and clinical status at hospital discharge. The final model included three risk factors: (a) severely abnormal EEG or ≥3 days with seizures recorded on EEG, (b) deep gray or brainstem injury on MRI, and (c) abnormal tone on discharge exam. The stratified risk of IS was the following: no factors 0% (0/82, 95% confidence interval [CI] 0%-4%), one or two factors 4% (4/108, 95% CI 1%-9%), and all three factors 57% (8/14, 95% CI 29%-83%). Significance IS risk after acute symptomatic neonatal seizures can be stratified using commonly available clinical data. No child without risk factors, vs >50% of those with all three factors, developed IS. This risk prediction rule may be valuable for clinical counseling as well as for selecting participants for clinical trials to prevent post-neonatal epilepsy. This tailored approach may lead to earlier diagnosis and treatment and improve outcomes for a devastating early life epilepsy.

Background The year 2020 marked a fundamental shift in the pediatric neurology field. An impressive positive trajectory of advances in patient care and research faced sudden global disruptions by the coronavirus disease 2019 pandemic and by an international movement protesting racial, socioeconomic, and health disparities. The disruptions revealed obstacles and fragility within the pediatric neurology research mission. However, renewed commitment offers unique opportunities for the pediatric neurology research community to enhance and prioritize research directions for the coming decades. Methods The Research Committee of the Child Neurology Society evaluated the challenges and opportunities facing the pediatric neurology research field, including reviewing published literature, synthesizing publically available data, and conducting a survey of pediatric neurologists. Results We identified three priority domains for the research mission: funding levels, active guidance, and reducing disparities. Funding levels: to increase funding to match the burden of pediatric neurological disease; to tailor funding mechanisms and strategies to support clinical trial efforts unique to pediatric neurology; and to support investigators across their career trajectory. Active guidance: to optimize infrastructure and strategies, to leverage novel therapeutics, enhance data collection, and improve inclusion of children in clinical trials. Reducing disparities: to reduce health disparities in children with neurological disease, to develop proactive measures to enhance workforce diversity and inclusion, and increase avenues to balance work-life obligations for investigators. Conclusions In this uniquely challenging epoch, the pediatric neurology research community has a timely and important mission to re-engage the public and government, advancing the health of children with neurological conditions.

OBJECTIVES: To characterize decisional satisfaction, regret, and conflict among parents of critically ill infants with neurologic conditions. STUDY DESIGN: In this prospective cohort study, we enrolled parents of infants with neurologic conditions in the intensive care unit (ICU). Hospital discharge surveys included the validated Family Satisfaction with the ICU (FS-ICU) decision-making subscale, Decision Regret Scale (DRS), and Decisional Conflict Scale (DCS). We defined high satisfaction with decision-making as FS-ICU score ≥ 75, high decisional regret/conflict as DRS/DCS score > 25, and within-couple disagreement as a difference between scores of at least 25 points. RESULTS: We enrolled 61 parents of 40 infants (n = 40 mothers, n = 21 fathers); 35mothers and 15 fathers completed surveys. Most mothers reported high satisfaction with decision-making (n = 27/35, 77%) and low decision regret (n = 28/35, 80%); 40% reported high decisional conflict (n = 14/35). Mothers and fathers reported higher decisional conflict in the domains of uncertainty and values clarity as compared with the domain of effective decision-making (Bonferroni-corrected p-values < 0.05). There were no differences in decision outcomes between paired mothers and fathers. However, within any given couple, there were numerous instances of disagreement (n = 7/15 for decision regret and n = 5/15 for decisional conflict). CONCLUSIONS: Many parents experience decisional conflict even if they ultimately have high satisfaction and low regret, underscoring the need for decision aids targeting uncertainty and values clarity. Couples frequently experience different levels of decisional regret and conflict.

Acute symptomatic seizures are a common sign of neurological dysfunction and brain injury in neonates and occur in approximately one to three per 1000 live births. Seizures in neonates are usually a sign of underlying brain injury and, as such, are commonly associated with adverse outcomes. Neurological morbidities in survivors often co-occur; epilepsy, cerebral palsy, and intellectual disability often occur together in the most severely affected children. Risk factors for adverse outcome include prematurity, low Apgar scores, low pH on the first day of life, seizure onset24 or72 h after birth, abnormal neonatal neurological examination, abnormal neonatal electroencephalographic background, status epilepticus, and presence and pattern of brain injury (particularly deep gray or brainstem injury). Despite this list of potential indicators, accurate prediction of outcome in a given child remains challenging. There is great need for long-term, multicenter studies to examine risk factors for, and pathogenesis of, adverse outcomes following acute symptomatic seizures in neonates.

BACKGROUND:Brain injury (BI) is reported in 60% of newborns with critical congenital heart disease as white matter injury (WMI) or stroke. Neurodevelopmental (ND) impairments are reported in these patients. The relationship between neonatal BI and ND outcome has not been established. OBJECTIVES:This study sought to determine the association between peri-operative BI and ND outcomes in infants with single ventricle physiology (SVP) and d-transposition of the great arteries (d-TGA). METHODS:Term newborns with d-TGA and SVP had pre-operative and post-operative brain magnetic resonance imaging and ND outcomes assessed at 12 and 30months with the Bayley Scales of Infant Development-II. BI was categorized by the brain injury severity score and WMI was quantified by volumetric analysis. RESULTS:A total of 104 infants had follow-up at 12months and 70 had follow-up at 30months. At 12months, only clinical variables were associated with ND outcome. At 30months, subjects with moderate-to-severe WMI had significantly lower Psychomotor Development Index (PDI) scores (13 points lower) as compared with those with none or minimal WMI for d-TGA and SVP (p=0.03 and p=0.05, respectively) after adjusting for various factors. Quantitative WMI volume was likewise associated. Stroke was not associated with outcome. The Bland-Altman limits of agreement for PDI scores at 12 and 30months were wide (-40.3 to 31.2) across the range of mean PDI values. CONCLUSIONS:Increasing burden of WMI is associated with worse motor outcomes at 30months for infants with criticalcongenital heart disease, whereas no adverse association was seen between small strokes and outcome. Theseresults support the utility of neonatal brain magnetic resonance imaging in this population to aid in predictinglateroutcomes and the importance of ND follow-up beyond 1 year of age.

OBJECTIVE To characterize intracranial hemorrhage (ICH) as a seizure etiology in infants born at term and preterm. For term infants, to compare seizure severity and treatment response for multi-site vs single-site ICH and hypoxic-ischemic encephalopathy (HIE) with vs. without ICH. STUDY DESIGN We studied 112 newborn infants with seizures attributed to ICH, and 201 infants born at term with seizures attributed to HIE, using a cohort of consecutive infants with clinically diagnosed and/or electrographic seizures prospectively enrolled in the multicenter Neonatal Seizure Registry. We compared seizure severity and treatment response among infants with complicated ICH, defined as multi-site vs. single-site ICH and HIE with vs. without ICH. RESULTS ICH was a more common seizure etiology in infants born preterm vs. term (27% vs. 10%, p

Neonatal encephalopathy is the most common condition in neonates encountered by child neurologists. The etiology is most often global hypoxia-ischemia due to failure of cerebral perfusion to the fetus caused by uterine, placental, or umbilical cord compromise prior to or during delivery. Other etiologies of neonatal encephalopathy include ischemic stroke and intracranial hemorrhage, infection, developmental anomalies, and inborn errors of metabolism.Therapeutic hypothermia is standard of care for the treatment of neonatal encephalopathy presumed to be caused by hypoxia-ischemia. The number needed to treat is approximately 6 to 7 to prevent one child from either death or disability at age 18 to 22 months. EEG monitoring and MRI are important tools in determining the etiology of encephalopathy and prognosis of the infant.Neonatal encephalopathy is a heterogeneous disorder that is characterized by alterations in mental status, hypotonia, seizures, and abnormalities in feeding and respiration. The most common cause of neonatal encephalopathy is hypoxic-ischemic encephalopathy, for which treatment with 72 hours of therapeutic hypothermia is associated with reduced death or disability.

Although hospitals increasingly offer therapeutic hypothermia (TH), there is variable implementation of related services. We assessed current practices and opinions regarding what services should be required of centers providing TH in California.We surveyed neonatal intensive care unit physicians statewide regarding practices and opinions about services related to TH.Of the 50 participating centers (47% response rate), 66% offer TH. Most TH centers reported using: an evidence-based protocol (92%), neurology consultation (92%), amplitude-integrated electroencephalography (aEEG) or EEG (88%), magnetic resonance imagings (MRIs) interpreted by pediatric neuroradiologists (71%) and developmental follow-up (93%). TH centers reported treating a median of 11 patients annually (interquartile range (IQR) 4 to 24). Respondents considered it 'critical' that TH centers offer: aEEG monitoring (70%), MRI (69%), occupational and physical therapy (67%) and developmental follow-up (94%). Over 70% thought TH centers should treat a minimum volume annually (median=10, IQR 5 to 12).Physicians across practice settings in California endorsed minimum standards for TH centers to promote quality of care.

Objective:Although individual neonatal epilepsy syndromes are rare, as a group they represent a sizable subgroup of neonatal seizure etiologies. We evaluated the profile of neonatal epilepsies in a prospective cohort of newborns with seizures.Methods:Consecutive newborns with seizures were enrolled in the Neonatal Seizure Registry (an association of 7 US children's hospitals). Treatment and diagnostic testing were at the clinicians' discretion. Neonates with seizures related to epileptic encephalopathies (without structural brain abnormalities), brain malformations, or benign familial epilepsies were included in this analysis.Results:Among 611 consecutive newborns with seizures, 79 (13%) had epilepsy (35 epileptic encephalopathy, 32 congenital brain malformations, 11 benign familial neonatal epilepsy [BFNE], 1 benign neonatal seizures). Twenty-nine (83%) with epileptic encephalopathy had genetic testing and 24/29 (83%) had a genetic etiology. Pathogenic or likely pathogenic KCNQ2 variants (n = 10) were the most commonly identified etiology of epileptic encephalopathy. Among 23 neonates with brain malformations who had genetic testing, 7 had putative genetic etiologies. Six infants with BFNE had genetic testing; 3 had pathogenic KCNQ2 variants and 1 had a pathogenic KCNQ3 variant. Comorbid illnesses that predisposed to acute symptomatic seizures occurred in 3/35 neonates with epileptic encephalopathy vs 10/32 with brain malformations (p = 0.03). Death or discharge to hospice were more common among newborns with brain malformations (11/32) than those with epileptic encephalopathy (3/35, p = 0.01).Conclusions:Neonatal epilepsy is often due to identifiable genetic causes. Genetic testing is now warranted for newborns with epilepsy in order to guide management and inform discussions of prognosis.

Although the coronavirus disease 2019 pandemic has served as a flashlight, illuminating and unmasking deep socio-economic and health care divides in our country, the terrible events surrounding the horrific murder of Mr. George Floyd in Minneapolis has spawned even greater outrage. As we all know, Mr. Floyd’s death is not an isolated incident, as there have been a tragic string of such deaths in recent years that further reflect deep issues regarding racism and systemic underlying causes of injustice. Unfortunately, the country’s inability to fully address these systemic foundations of injustice persists.