Corrigendum: Building an open source classifier for the neonatal EEG background: a systematic feature-based approach from expert scoring to clinical visualization.

[This corrects the article DOI: 10.3389/fnhum.2021.675154.].

Neonatal Hypoxic-Ischemic Encephalopathy Spectrum: Severity-Stratified Analysis of Neuroimaging Modalities and Association with Neurodevelopmental Outcomes.

OBJECTIVE: To compare hypoxic-ischemic injury on early cranial ultrasonography (cUS) and post-rewarming brain magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy (HIE) and to correlate that neuroimaging with neurodevelopmental outcomes. STUDY DESIGN: This was a retrospective cohort study of infants with mild, moderate, and severe HIE treated with therapeutic hypothermia and evaluated with early cUS and postrewarming MRI. Validated scoring systems were used to compare the severity of brain injury on cUS and MRI. Neurodevelopmental outcomes were assessed at 18 months of age. RESULTS: Among the 149 included infants, abnormal white matter (WM) and deep gray matter (DGM) hyperechogenicity on cUS in the first 48 hours after birth were more common in the severe HIE group than the mild HIE group (81% vs 39% and 50% vs 0%, respectively; P < .001). In infants with a normal cUS, 95% had normal or mildly abnormal brain MRIs. In infants with severely abnormal cUS, none had normal and 83% had severely abnormal brain MRIs. Total abnormality scores on cUS were higher in neonates with near-total brain injury on MRI than in neonates with normal MRI or WM-predominant injury pattern (adjusted P < .001 for both). In the multivariable model, a severely abnormal MRI was the only independent risk factor for adverse outcomes (OR: 19.9, 95% CI: 4.0-98.1; P < .001). CONCLUSION: The present study shows the complementary utility of cUS in the first 48 hours after birth as a predictive tool for the presence of hypoxic-ischemic injury on brain MRI.

Severity and duration of dysglycemia and brain injury among patients with neonatal encephalopathy.

Background: Evidence is needed to inform thresholds for glycemic management in neonatal encephalopathy (NE). We investigated how severity and duration of dysglycemia relate to brain injury after NE. Methods: A prospective cohort of 108 neonates ≥36 weeks gestational age with NE were enrolled between August 2014 and November 2019 at the Hospital for Sick Children, in Toronto, Canada. Participants underwent continuous glucose monitoring for 72 h, MRI at day 4 of life, and follow-up at 18 months. Receiver operating characteristic curves were used to assess the predictive value of glucose measures (minimum and maximum glucose, sequential 1 mmol/L glucose thresholds) during the first 72 h of life (HOL) for each brain injury pattern (basal ganglia, watershed, focal infarct, posterior-predominant). Linear and logistic regression analyses were used to assess the relationship between abnormal glycemia and 18-month outcomes (Bayley-III composite scores, Child Behavior Checklist [CBCL] T-scores, neuromotor score, cerebral palsy [CP], death), adjusting for brain injury severity. Findings: Of 108 neonates enrolled, 102 (94%) had an MRI. Maximum glucose during the first 48 HOL best predicted basal ganglia (AUC = 0.811) and watershed (AUC = 0.858) injury. Minimum glucose was not predictive of brain injury (AUC <0.509). Ninety-one (89%) infants underwent follow-up assessments at 19.0 ± 1.7 months. A glucose threshold of >10.1 mmol/L during the first 48 HOL was associated with 5.8-point higher CBCL Internalizing Composite T-score (P = 0.029), 0.3-point worse neuromotor score (P = 0.035), 8.6-fold higher odds for CP diagnosis (P = 0.014). While the glucose threshold of >10.1 mmol/L during the first 48 HOL was associated with higher odds of the composite outcome of severe disability or death (OR 3.0, 95% CI 1.0-8.4, P = 0.042), it was not associated with the composite outcome of moderate-to-severe disability or death (OR 0.9, 95% CI 0.4-2.2, P = 0.801). All associations with outcome lost significance after adjusting for brain injury severity. Interpretation: Maximum glucose concentration in the first 48 HOL is predictive of brain injury after NE. Further trials are needed to assess if protocols to control maximum glucose concentrations improve outcomes after NE. Funding: Canadian Institutes for Health Research, National Institutes of Health, and SickKids Foundation.

The influence of nutrition on white matter development in preterm infants: a scoping review.

White matter (WM) injury is the most common type of brain injury in preterm infants and is associated with impaired neurodevelopmental outcome (NDO). Currently, there are no treatments for WM injury, but optimal nutrition during early preterm life may support WM development. The main aim of this scoping review was to assess the influence of early postnatal nutrition on WM development in preterm infants. Searches were performed in PubMed, EMBASE, and COCHRANE on September 2022. Inclusion criteria were assessment of preterm infants, nutritional intake before 1 month corrected age, and WM outcome. Methods were congruent with the PRISMA-ScR checklist. Thirty-two articles were included. Negative associations were found between longer parenteral feeding duration and WM development, although likely confounded by illness. Positive associations between macronutrient, energy, and human milk intake and WM development were common, especially when fed enterally. Results on fatty acid and glutamine supplementation remained inconclusive. Significant associations were most often detected at the microstructural level using diffusion magnetic resonance imaging. Optimizing postnatal nutrition can positively influence WM development and subsequent NDO in preterm infants, but more controlled intervention studies using quantitative neuroimaging are needed. IMPACT: White matter brain injury is common in preterm infants and associated with impaired neurodevelopmental outcome. Optimizing postnatal nutrition can positively influence white matter development and subsequent neurodevelopmental outcome in preterm infants. More studies are needed, using quantitative neuroimaging techniques and interventional designs controlling for confounders, to define optimal nutritional intakes in preterm infants.

Fishing for Trouble: A Novel Surgical Technique for Penetrating Fishhook Injuries of the Eyelid.

Fishhook injuries commonly occur and may present as ophthalmic surgical emergencies. Choosing the appropriate removal technique is critical and depends on the involved extra- and intra-ocular structures and hook characteristics. We describe the case of a challenging fishhook removal where a novel surgical technique was developed. An eight-year-old boy presented with a full-thickness fishhook injury to the eyelid. During removal surgery, the thickness and density of the fishhook prevented surgical tools from transecting the shank. A novel approach was deemed necessary for safe removal, termed the clamp and retract technique. To our knowledge, this is its first documented use in the literature.

Semi-Automated Analysis of Foveal Maturity in Premature and Full-Term Infants Using Handheld Swept-Source Optical Coherence Tomography.

Purpose: To develop a semi-automated method of measuring foveal maturity using investigational handheld swept source-optical coherence tomography (SS-OCT). Methods: In this prospective, observational study, full-term newborns and preterm infants undergoing routine retinopathy of prematurity screening were imaged. Semi-automated analysis measured foveal angle and chorioretinal thicknesses at the central fovea and average two-sided parafovea by three-grader consensus, correlating with OCT features and demographics. Results: One hundred ninety-four imaging sessions from 70 infants were included (47.8% girls, 37.6 ± 3.4 weeks postmenstrual age, 26 preterm infants with birth weight 1057 ± 325.0, gestational age 29.0 ± 3.0 weeks). Foveal angle (96.1 ± 22.0 degrees) steepened with increasing birth weight (P = 0.003), decreasing inner retinal layer thickness, and increasing gestational age, postmenstrual age, and foveal and parafoveal choroidal thickness (all P < 0.001). Inner retinal fovea/parafovea ratio (0.4 ± 0.2) correlated with increasing inner foveal layers, decreasing postmenstrual age, gestational age, and birth weight (all P < 0.001). Outer retinal F/P ratio (0.7 ± 0.2) correlated with ellipsoid zone presence (P < 0.001), increased gestational age (P = 0.002), and birth weight (P = 0.003). Foveal (447.8 ± 120.6 microns) and parafoveal (420.9 ± 109.2) choroidal thicknesses correlated with foveal ellipsoid zone presence (P = 0.007 and P = 0.01, respectively), postmenstrual age, birth weight, gestational age, and decreasing inner retinal layers (all P < 0.001). Conclusions: Foveal development is dynamic and partially observed through semi-automated analysis of handheld SS-OCT imaging. Translational Relevance: Semi-automated analysis of SS-OCT images can identify measures of foveal maturity.

Seizure Burden and Neurologic Outcomes After Neonatal Encephalopathy.

BACKGROUND AND OBJECTIVES: 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. METHODS: 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. RESULTS: 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). DISCUSSION: 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.

Pearls & Oy-sters: Genetic Epilepsy: An Important Cause of Neonatal Seizures in Infants With Complex Congenital Heart Disease.

Genetic epilepsies, such as KCNQ2 gene variants, though uncommon, are potential causes of neonatal seizures in infants with complex congenital heart disease (CHD). KCNQ2-related seizures commonly present as tonic posturing with autonomic changes and a distinctive amplitude-integrated EEG (aEEG) pattern with increase in amplitude immediately followed by background suppression. Seizures are typically refractory to commonly used antiepileptics in this age group and respond best to sodium channel blockers such as carbamazepine and fosphenytoin. We report the cases of two neonates with complex CHD who presented with seizures secondary to KCNQ2 gene variation and how early recognition of clinical and EEG features led to early treatment and improved seizure burden. When investigating the etiology of neonatal seizures in the perioperative complex cardiac infant, genetic etiologies, such as KCNQ2 variants should be considered, particularly in the absence of clinical exam and neuroimaging features consistent with brain injury. These two cases highlight the importance of a precision medicine approach utilizing clinical examination and seizure semiology, bedside aEEG monitoring, genetic testing, and targeted treatments to improve patient care and outcomes.

Ocular syphilis resurgence in an urban underserved community in the United States.

AIM: To evaluate the clinical characteristics, demographics, and visual outcomes of patients with ocular syphilis at an urban hospital to increase awareness and assist in earlier diagnosis and treatment of the resurgent disease. METHODS: A retrospective chart review was performed on patients with ICD-9 and ICD-10 diagnosis codes correlating with syphilis or syphilis-related ocular diseases between 2010 and 2019. Variables evaluated included age, gender, race, vision, ocular findings, human immunodeficiency virus (HIV) status and men who have sex with men status, recreational drug and alcohol use. RESULTS: Ocular syphilis was diagnosed in 40 patients (53 eyes) of a total of 229 patients who tested positive for syphilis via serum and/or cerebrospinal fluid treponemal testing from 2010-2019. Among patients with ocular syphilis, most patients were males, aged 45 or above and Black, and had no diagnosed HIV infection. Approximately 50% patients had 20/40 vision or better. Nearly 50% had non-granulomatous anterior uveitis as their initial presentation, and 49% of patients had involvement of the posterior segment. Neovascular glaucoma (5.7%), papillitis (7.5%), vasculitis (5.7%), and retinal detachment (5.7%) were rarer presentations of the disease and were associated with a poorer visual prognosis. CONCLUSION: Given the increased prevalence and protean manifestations of syphilis, early diagnosis and treatment are paramount. More studies on ocular syphilis are warranted to understand this resurging disease.

Optic Perineuritis Associated With Cryptococcal Meningitis Presenting With a "Hot Orbit" in a Patient With Chronic Lymphocytic Leukemia.

ABSTRACT: A 75-year-old man presented with 3 days of progressive left retro-orbital pain, eyelid swelling, tearing, and pain with extraocular movement. His medical history was significant for type II diabetes mellitus and chronic lymphocytic leukemia, stable on no therapy since diagnosis 8 years prior. The initial examination was significant for diffuse restriction of left ocular motility, marked lid edema, and mild dyschromatopsia. Computed tomography demonstrated asymmetric left periorbital soft tissue swelling and intraconal fat stranding with an irregular left optic nerve sheath complex and clear paranasal sinuses. He was hospitalized for orbital cellulitis and treated empirically with broad-spectrum intravenous antibiotics, but his visual acuity declined over the ensuing 2 days. Subsequent MRI demonstrated left-greater-than-right circumferential optic nerve sheath enhancement, and leptomeningeal enhancement. An orbital biopsy demonstrated monoclonal B-cell lymphocyte aggregation, whereas a lumbar puncture was positive for Cryptococcus antigen with subsequent demonstration of abundant Cryptococcus by Papanicolaou stain. The final diagnosis was optic perineuritis secondary to cryptococcal meningitis presenting with orbital inflammation. Although his clinical course was complicated by immune reconstitution inflammatory syndrome, symptoms and signs of optic neuropathy ultimately resolved after 1 month of intensive antifungal therapy.

Etiology and outcomes of childhood glaucoma at a tertiary referral center.

PURPOSE: To describe the etiology, clinical features, and outcomes for a large contemporary cohort of children presenting with glaucoma at a tertiary referral center. METHODS: The medical records of patients presenting to Boston Children's Hospital from January 2014 to July 2019 with a diagnosis of childhood glaucoma were retrospectively reviewed. Data regarding etiology, treatment, and visual and anatomic outcomes were collected; visual acuity outcomes were analyzed by laterality and diagnosis categories, using the Childhood Glaucoma Research Network (CGRN) classifications. RESULTS: A total of 373 eyes of 246 patients (51% males) diagnosed with glaucoma before 18 years of age were identified. Mean follow-up was 7.04 ± 5.61 years; 137 cases were bilateral. The mean age at diagnosis was 4.55 ± 5.20 years. The most common diagnoses were glaucoma following cataract surgery (GFCS, 36.5%) and primary congenital glaucoma (PCG, 29.0%). Overall, 164 eyes (44.0%) underwent at least one glaucoma surgery. Intraocular pressure (IOP) was ≤21 mm Hg with or without glaucoma medications in 300 eyes (80.4%) at the last follow-up visit. Poor final best-corrected visual acuity (≤20/200) was found in 110 eyes; patients with poor final visual acuity tended to have poor visual acuity at presentation. The most common reason for poor vision was amblyopia. Uncontrolled IOP was an uncommon cause for vision loss. CONCLUSIONS: Childhood glaucoma can be challenging to manage, but poor vision usually results from amblyopia or presence of other ocular abnormalities or syndromes rather than glaucomatous optic neuropathy.

ARHGEF-10 gene mutation presenting as orbital inflammatory syndrome.

Rho guanine nucleotide exchange factor 10 (ARHGEF-10) is a RHO GTPase that has a role for neural morphogenesis, however its effect on the eyes remains unknown. Here, we report a 44-year-old man who presented with eyelid swelling along with a history of bilateral hand contractures, high-arched feet and muscle wasting, who was found to have an ARHGEF-10 mutation. Neuroimaging was significant for numerous nerve-based cystic abnormalities in the bilateral orbits and throughout the neuraxis, and an orbital biopsy revealed S-100 and SOX-10 positive lesion consistent with pseudocysts. While the role of ARHGEF-10 remains unclear, further research is warranted to further describe its clinical manifestations.

Early neonatal heart rate variability patterns in different subtypes of perinatal hypoxic-ischemic brain injury.

BACKGROUND: This study aims to compare the longitudinal changes in heart rate variability (HRV) during therapeutic hypothermia in neonates with different subtypes of hypoxic-ischemic brain injury. METHODS: HRV was computed from 1 hour time-epochs q6 hours for the first 48 hours. Primary outcome was brain-injury pattern on MRI at 4(3-5) days. We fitted linear mixed-effect regression models with HRV metric, brain injury subtype and postnatal age. RESULTS: Among 89 term neonates, 40 neonates had abnormal brain MRI (focal infarct 15 (38%), basal-ganglia predominant 8 (20%), watershed-predominant 5 (13%), and mixed pattern 12 (30%)). There was no significant difference in the HRV metrics between neonates with normal MRI, focal infarcts and basal ganglia pattern. At any given postnatal age, the degree of HRV suppression (HRV measure in the brain-injury subtype group/HRV measure in Normal MRI group) was significant in neonates with watershed pattern (SDNN(0.63, p = 0.08), RMSSD(0.74, p = 0.04)) and mixed pattern injury (SDNN (0.64, p < 0.001), RMSSD (0.75, p = 0.02)). HRV suppression was most profound at the postnatal age of 24-30 h in all brain injury subtypes. CONCLUSION: Neonates with underlying watershed injury with or without basal-ganglia injury demonstrates significant HRV suppression during first 48 hour of hypothermia therapy. IMPACT: Our study suggests that suppression of heart rate variability in neonates during therapeutic hypothermia varies according to the pattern of underlying hypoxic-ischemic brain injury. Neonates with watershed predominant pattern and mixed pattern of brain injury have the most severe suppression of heart rate variability measures. Heart rate variability monitoring may provide early insights into the pattern of hypoxic-ischemic brain injury in neonates undergoing therapeutic hypothermia earlier than routine clinical MRI.

Clinical Feasibility of Structural and Functional MRI in Free-Breathing Neonates and Infants.

BACKGROUND: Evaluation of structural lung abnormalities with magnetic resonance imaging (MRI) has previously been shown to be predictive of clinical neonatal outcomes in preterm birth. MRI during free-breathing with phase-resolved functional lung (PREFUL) may allow for complimentary functional information without exogenous contrast. PURPOSE: To investigate the feasibility of structural and functional pulmonary MRI in a cohort of neonates and infants with no cardiorespiratory disease. Macrovascular pulmonary blood flows were also evaluated. STUDY TYPE: Prospective. POPULATION: Ten term infants with no clinically defined cardiorespiratory disease were imaged. Infants recruited from the general population and neonatal intensive care unit (NICU) were studied. FIELD STRENGTH/SEQUENCE: T1 -weighted VIBE, T2 -weighted BLADE uncorrected for motion. Ultrashort echo time (UTE) and 3D-flow data were acquired during free-breathing with self-navigation and retrospective reconstruction. Single slice 2D-gradient echo (GRE) images were acquired during free-breathing for PREFUL analysis. Imaging was performed at 3 T. ASSESSMENT: T1 , T2 , and UTE images were scored according to the modified Ochiai scheme by three pediatric body radiologists. Ventilation/perfusion-weighted maps were extracted from free-breathing GRE images using PREFUL analysis. Ventilation and perfusion defect percent (VDP, QDP) were calculated from the segmented ventilation and perfusion-weighted maps. Time-averaged cardiac blood velocities from three-dimensional-flow were evaluated in major pulmonary arteries and veins. STATISTICAL TEST: Intraclass correlation coefficient (ICC). RESULTS: The ICC of replicate structural scores was 0.81 (95% CI: 0.45-0.95) across three observers. Elevated Ochiai scores, VDP, and QDP were observed in two NICU participants. Excluding these participants, mean ± standard deviation structural scores were 1.2 ± 0.8, while VDP and QDP were 1.0% ± 1.1% and 0.4% ± 0.5%, respectively. Main pulmonary arterial blood flows normalized to body surface area were 3.15 ± 0.78 L/min/m2 . DATA CONCLUSION: Structural and functional pulmonary imaging is feasible using standard clinical MRI hardware (commercial whole-body 3 T scanner, table spine array, and flexible thoracic array) in free-breathing infants. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 1.

Early transient dysautonomia predicts the risk of infantile epileptic spasm syndrome onset: A prospective cohort study.

Background: Infantile epileptic spasm syndrome (IESS) is an age-dependent epileptic encephalopathy with a significant risk of developmental regression. This study investigates the association between heart rate variability (HRV) in infants at risk of IESS and the clinical onset of IESS. Methods: Sixty neonates at risk of IESS were prospectively followed from birth to 12 months with simultaneous electroencephalogram (EEG) and electrocardiogram recordings for 60 min at every 2-month interval. HRV metrics were calculated from 5 min time-epoch during sleep including frequency domain measures, Poincare analysis including cardiac vagal index (CVI) and cardiac sympathetic index (CSI), and detrended fluctuation analysis (DFA α1, DFA α2). To assess the effect of each HRV metric at the 2-month baseline on the time until the first occurrence of either hypsarrhythmia on EEG and/or clinical spasm, univariate cox-proportional hazard models were fitted for each HRV metric. Results: Infantile epileptic spasm syndrome was diagnosed in 20/60 (33%) of the cohort in a 12-month follow-up and 3 (5%) were lost to follow-up. The median age of developing hypsarrhythmia was 25 (7-53) weeks and clinical spasms at 24 (8-40) weeks. Three (5%) patients had clinical spasms without hypsarrhythmia, and 5 (8%) patients had hypsarrhythmia before clinical spasms at the initial presentation. The infants with high CSI (hazard ratio 2.5, 95% CI 1.2-5.2, P = 0.01) and high DFA α1 (hazard ratio 16, 95% CI 1.1-240, P = 0.04) at 2 months were more likely to develop hypsarrhythmia by the first year of age. There was a trend toward decreasing CSI and DFA α1 and increasing CVI in the first 8 months of age. Conclusion: Our data suggest that relative sympathetic predominance at an early age of 2 months may be a potential predictor for developing IESS. Hence, early HRV patterns may provide valuable prognostic information in children at risk of IESS allowing early detection and optimization of cognitive outcomes. Whether early intervention to restore sympathovagal balance per se would provide clinical benefit must be addressed by future studies.

Patient and Clinician Satisfaction With Shared Medical Appointments for Glaucoma.

Shared Medical Appointments (SMAs) are patient-centered care tools designed to administer patient counseling and education, typically delivered individually, in a group setting. SMAs are effective in facilitating peer-learning, resulting in improvement in knowledge and health behavior. This study aimed to implement what we know of as the first ophthalmology SMA done in the United States. We evaluated the implementation feasibility, patient and provider experience, changes in patient knowledge, and provider stress. Five glaucoma patients who expressed issues with adherence during their clinic visit at Boston Medical Center (BMC) who were interested in the SMA were recruited. Patients and staff had a positive experience with the SMA. There was a marked increase in patient glaucoma knowledge and a decrease in average staff member stress level score during the SMA. From all standpoints, including billing and management, we conclude that SMA implementation is feasible in ophthalmology departments in academic settings.

Hyperglycemia associated with acute brain injury in neonatal encephalopathy.

OBJECTIVE: To identify how alterations in glucose levels are associated with regional brain injury in neonatal encephalopathy. METHODS: This was a prospective cohort study of 102 newborns with neonatal encephalopathy, with continuous glucose monitoring for 72 h. 97 (95%) completed 72 h of therapeutic hypothermia. Brain imaging around day 5 of life included diffusion tensor imaging and MR spectroscopy. Regions of interest were placed for both DTI and MR spectroscopy, and tractography of the optic radiation and corticospinal tract were evaluated. Linear regression models related each MR metric with minimum and maximum glucose values during each day of life, adjusting for 5-minute Apgar scores and umbilical artery pH. RESULTS: Higher maximum glucose levels on the first day of life were associated with widespread changes in mean diffusivity in the anterior and posterior white matter, splenium of the corpus callosum, lentiform nucleus, pulvinar nucleus of the thalamus, posterior limb of the internal capsule, and optic radiations, thus including regions traditionally associated with hypoxia-ischemia or hypoglycemia. No associations were found between lower minimum glucose levels and DTI changes in any regions tested, or between glucose levels and MR spectroscopy. CONCLUSIONS: In this cohort of neonatal encephalopathy with therapeutic hypothermia, higher maximal glucose on the first day of life was associated with widespread microstructural changes, but lower minimum glucose levels were not associated with changes in any of the regions tested. Long-term follow-up will determine if imaging findings translate to long-term outcomes.

Training in neonatal neurocritical care: a proposal for a hybrid model of competence by design and time-based methods.

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.

Building an Open Source Classifier for the Neonatal EEG Background: A Systematic Feature-Based Approach From Expert Scoring to Clinical Visualization.

Neonatal brain monitoring in the neonatal intensive care units (NICU) requires a continuous review of the spontaneous cortical activity, i.e., the electroencephalograph (EEG) background activity. This needs development of bedside methods for an automated assessment of the EEG background activity. In this paper, we present development of the key components of a neonatal EEG background classifier, starting from the visual background scoring to classifier design, and finally to possible bedside visualization of the classifier results. A dataset with 13,200 5-minute EEG epochs (8-16 channels) from 27 infants with birth asphyxia was used for classifier training after scoring by two independent experts. We tested three classifier designs based on 98 computational features, and their performance was assessed with respect to scoring system, pre- and post-processing of labels and outputs, choice of channels, and visualization in monitor displays. The optimal solution achieved an overall classification accuracy of 97% with a range across subjects of 81-100%. We identified a set of 23 features that make the classifier highly robust to the choice of channels and missing data due to artefact rejection. Our results showed that an automated bedside classifier of EEG background is achievable, and we publish the full classifier algorithm to allow further clinical replication and validation studies.