Amplitude-Integrated EEG in Infants at Risk of Hypoxic-Ischemic Encephalopathy: A Feasibility Study in Road and Air Transport in Western Australia.

Infants at risk of HIE require early identification and initiation of therapeutic hypothermia (TH). Earlier treatment with TH is associated with better outcomes. aEEG is frequently used when making the decision whether to commence TH. As this is often limited to tertiary centers, TH may be delayed if the infant requires transport to a center that provides it. We aimed to provide a method for the application of amplitude-integrated electroencephalogram (aEEG) and to determine the feasibility of acquiring clinically meaningful information during transport. All infants ≥35 weeks, at risk of HIE at referral, were eligible for inclusion. Scalp electrodes were placed in the C3-C4; P3-P4 position on the infant's scalp and connected to the aEEG amplifier. The aEEG amplifier was, in turn, connected to a clinical tablet computer with EEG software to collect and analyze aEEG information. Recordings were reviewed by the chief principal investigator and two independent reviewers (blinded) for background trace and artifact. Predefined criteria for data quality were set to movement artifacts and software impedance notifications. Surveys were completed by healthcare staff and parents for acceptability and ease of use.

Emergent Management of Hypoxic-Ischemic Brain Injury.

OBJECTIVE: This article outlines interventions used to improve outcomes for patients with hypoxic-ischemic brain injury after cardiac arrest. LATEST DEVELOPMENTS: Emergent management of patients after cardiac arrest requires prevention and treatment of primary and secondary brain injury. Primary brain injury is minimized by excellent initial resuscitative efforts. Secondary brain injury prevention requires the detection and correction of many pathophysiologic processes that may develop in the hours to days after the initial arrest. Key physiologic parameters important to secondary brain injury prevention include optimization of mean arterial pressure, cerebral perfusion, oxygenation and ventilation, intracranial pressure, temperature, and cortical hyperexcitability. This article outlines recent data regarding the treatment and prevention of secondary brain injury. Different patients likely benefit from different treatment strategies, so an individualized approach to treatment and prevention of secondary brain injury is advisable. Clinicians must use multimodal sources of data to prognosticate outcomes after cardiac arrest while recognizing that all prognostic tools have shortcomings. ESSENTIAL POINTS: Neurologists should be involved in the postarrest care of patients with hypoxic-ischemic brain injury to improve their outcomes. Postarrest care requires nuanced and patient-centered approaches to the prevention and treatment of primary and secondary brain injury and neuroprognostication.

Evaluation of Myocardial Injury Using Serum Cardiac Troponin-I in Asphyxiated Neonates at Enugu State University Teaching Hospital, Enugu, South-East Nigeria.

BACKGROUND: The burden of perinatal asphyxia remains high in our environment and when asphyxia is severe, vital organs are affected, with resultant multiorgan hypoxic-iscahemic injury to the heart, the brain, adrenals and other organs. STUDY AIM: To evaluate for myocardial injury in asphyxiated term neonates with hypoxic ischaemic encephalopathy using serum cardiac troponin-I (cTnI). METHODS: The study was a hospital-based descriptive cross-sectional study involving sixty term asphyxiated neonates and sixty gestational age-and sex-matched controls. The subjects were term neonates with five-minute Apgar score ≤ 6 and HIE while the controls were healthy term neonates with five-minute Apgar score > 6. Five-minute Apgar score was utilized to classify asphyxia into mild, moderate and severe asphyxia. The degree of encephalopathy was determined by modified Sarnat and Sarnat criteria. The serum cTnI was measured in subjects and controls at 12-24 hours of life using Enzyme-linked immunosorbent assay technique. The serum bilirubin levels were also measured in participants to exclude hyperbilirubinemia. RESULTS: The median serum cTnI levels was significantly higher in the subjects (0.56ng/mL; 0.25-0.94ng/mL) than in the controls (0.50ng/mL; 0.00-0.67ng/mL), respectively; p=0.001. Similarly, the median serum cTnI level in HIE stage II (0.56ng/mL; 0.38-0.72ng/mL) or III (0.56ng/ml; 0.50-0.94ng/mL) was also significantly higher than the median value in HIE stage I (0.38ng/mL;0.25-0.72ng/mL) or in controls (0.50ng/mL; 0.00-0.67ng/mL); p<0.001. There was significant positive correlation between serum cTnI levels and severity of HIE in asphyxiated neonates (rs = 0.505, p < 0.001). CONCLUSION: serum cTnI levels were elevated in severely asphyxiated neonates with HIE. The concentration of serum cTnI demonstrated significant positive correlation with HIE severity. Hence, the presence of HIE in asphyxiated neonates should prompt an evaluation for myocardial injury using serum cTnI. Any derangement noted should warrant instituting cardiovascular support in order to improve outcome and reduce asphyxia-related mortality.

Neonatal Seizures.

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

Quality assessment of clinical practice guidelines on hypoxic-ischaemic encephalopathy in newborns using the AGREE II tool: a systematic review.

INTRODUCTION: Hypoxic-ischaemic encephalopathy is a clinical syndrome of neurological dysfunction that occurs immediately after birth following an episode of perinatal asphyxia. We conducted a scoping review to assess the methodological quality of clinical practice guidelines that address this condition. METHODOLOGY: We conducted the evaluation using the AGREE II tool. High methodological quality was defined as a score greater than 70% in every domain. RESULTS: The analysis included three clinical practice guidelines; the highest scores were in the scope and purpose domain (84.26%; SD, 14.25%) and the clarity of presentation domain (84.26%; SD, 17.86%), while the lowest score corresponded to the applicability domain (62.50%; SD, 36.62%). Two guidelines were classified as high quality and one guideline as low-quality. CONCLUSIONS: Two of the assessed guidelines were classified as being of high quality; however, the analysis identified shortcomings in the applicability domain, in addition to methodological variation between guidelines developed in middle- or low-income countries versus high-income countries. Efforts are needed to make high-quality guidelines available to approach the management of hypoxic-ischaemic encephalopathy in newborns.

Clinical outcome prediction with an automated EEG trend, Brain State of the Newborn, after perinatal asphyxia.

OBJECTIVE: To evaluate the utility of a fully automated deep learning -based quantitative measure of EEG background, Brain State of the Newborn (BSN), for early prediction of clinical outcome at four years of age. METHODS: The EEG monitoring data from eighty consecutive newborns was analyzed using the automatically computed BSN trend. BSN levels during the first days of life (a of total 5427 hours) were compared to four clinical outcome categories: favorable, cerebral palsy (CP), CP with epilepsy, and death. The time dependent changes in BSN-based prediction for different outcomes were assessed by positive/negative predictive value (PPV/NPV) and by estimating the area under the receiver operating characteristic curve (AUC). RESULTS: The BSN values were closely aligned with four visually determined EEG categories (p < 0·001), as well as with respect to clinical milestones of EEG recovery in perinatal Hypoxic Ischemic Encephalopathy (HIE; p < 0·003). Favorable outcome was related to a rapid recovery of the BSN trend, while worse outcomes related to a slow BSN recovery. Outcome predictions with BSN were accurate from 6 to 48 hours of age: For the favorable outcome, the AUC ranged from 95 to 99% (peak at 12 hours), and for the poor outcome the AUC ranged from 96 to 99% (peak at 12 hours). The optimal BSN levels for each PPV/NPV estimate changed substantially during the first 48 hours, ranging from 20 to 80. CONCLUSIONS: We show that the BSN provides an automated, objective, and continuous measure of brain activity in newborns. SIGNIFICANCE: The BSN trend discloses the dynamic nature that exists in both cerebral recovery and outcome prediction, supports individualized patient care, rapid stratification and early prognosis.

General movement assessment efficacy for assessment of nervous system integrity in children after hypoxic-ischemic encephalopathy in middle income countries.

BACKGROUND: Many infants who survive hypoxic-ischemic encephalopathy (HIE) face long-term complications like epilepsy, cerebral palsy, and developmental delays. Detecting and forecasting developmental issues in high-risk infants is critical. AIM: This study aims to assess the effectiveness of standardized General Movements Assessment (GMA) and Hammersmith Infant Neurological Examinations (HINE) in identifying nervous system damage and predicting neurological outcomes in infants with HIE. DESIGN: Prospective. SUBJECTS AND MEASURES: We examined full-term newborns with perinatal asphyxia, classifying them as Grade 2 HIE according to Sarnat and Sarnat. The study included 31 infants, with 14 (45.2 %) receiving therapeutic hypothermia (Group 1) and 17 (54.8 %) not (Group 2). We evaluated general movements during writhing and fidgety phases and conducted neurological assessments using the HINE. RESULTS: All infants exhibited cramped-synchronized - like movements, leading to cerebral palsy (CP) diagnosis. Three children in Group 1 and four in Group 2 lacked fidgety movements. During active movements, HINE and GMA showed high sensitivity and specificity, reaching 96 % and 100 % for all children. The ROC curve's area under the curve (AUC) was 0.978. CONCLUSION: Our study affirms HINE and GMA as effective tools for predicting CP in HIE-affected children. GMA exhibits higher sensitivity and specificity during fidgety movements. However, study limitations include a small sample size and data from a single medical institution, necessitating further research.

Hypoxic-ischaemic encephalopathy code: A systematic review for resource-limited settings.

It is estimated that 96% of infants with hypoxic-ischaemic encephalopathy (HIE) are born in resource-limited settings with no capacity to provide the standard of care that has been established for nearly 15 years in high-resource countries, which includes therapeutic hypothermia (TH), continuous electroencephalographic monitoring and magnetic resonance imaging (MRI) in addition to close vital signs and haemodynamic monitoring. This situation does not seem to be changing; however, even with these limitations, currently available knowledge can help improve the care of HIE patients in resource-limited settings. The purpose of this systematic review was to provide, under the term "HIE Code", evidence-based recommendations for feasible care practices to optimise the care of infants with HIE and potentially help reduce the risks associated with comorbidity and improve neurodevelopmental outcomes. The content of the HIE code was grouped under 9 headings: (1) prevention of HIE, (2) resuscitation, (3) first 6h post birth, (4) identification and grading of encephalopathy, (5) seizure management, (6) other therapeutic interventions, (7) multiple organ dysfunction, (8) diagnostic tests and (9) family care.

Clinical exome sequencing uncovers genetic disorders in neonates with suspected hypoxic-ischemic encephalopathy: A retrospective analysis.

Hypoxic-ischemic encephalopathy (HIE) occurs in up to 7 out of 1000 births and accounts for almost a quarter of neonatal deaths worldwide. Despite the name, many newborns with HIE have little evidence of perinatal hypoxia. We hypothesized that some infants with HIE have genetic disorders that resemble encephalopathy. We reviewed genetic results for newborns with HIE undergoing exome or genome sequencing at a clinical laboratory (2014-2022). Neonates were included if they had a diagnosis of HIE and were delivered ≥35 weeks. Neonates were excluded for cardiopulmonary pathology resulting in hypoxemia or if neuroimaging suggested postnatal hypoxic-ischemic injury. Of 24 patients meeting inclusion criteria, six (25%) were diagnosed with a genetic condition. Four neonates had variants at loci linked to conditions with phenotypic features resembling HIE, including KIF1A, GBE1, ACTA1, and a 15q13.3 deletion. Two additional neonates had variants in genes not previously associated with encephalopathy, including DUOX2 and PTPN11. Of the six neonates with a molecular diagnosis, two had isolated HIE without apparent comorbidities to suggest a genetic disorder. Genetic diagnoses were identified among neonates with and without sentinel labor events, abnormal umbilical cord gasses, and low Apgar scores. These results suggest that genetic evaluation is clinically relevant for patients with perinatal HIE.

Acute kidney injury in neonates with hypoxic ischemic encephalopathy based on serum creatinine decline compared to KDIGO criteria.

BACKGROUND: Neonates with hypoxic ischemic encephalopathy receiving therapeutic hypothermia (HIE + TH) are at risk for acute kidney injury (AKI). The standardized Kidney Disease Improving Global Outcomes (KDIGO) criteria identifies AKI based on a rise in serum creatinine (SCr) or reduced urine output. This definition is challenging to apply in neonates given the physiologic decline in SCr during the first week of life. Gupta et al. proposed alternative neonatal criteria centered on rate of SCr decline. This study aimed to compare the rate of AKI based on KDIGO and Gupta in neonates with HIE and to examine associations with mortality and morbidity. METHODS: A retrospective review was performed of neonates with moderate to severe HIE + TH from 2008 to 2020 at a single center. AKI was assessed in the first 7 days after birth by KDIGO and Gupta criteria. Mortality, brain MRI severity of injury, length of stay, and duration of respiratory support were compared between AKI groups. RESULTS: Among 225 neonates, 64 (28%) met KDIGO, 69 (31%) neonates met Gupta but not KDIGO, and 92 (41%) did not meet either definition. Both KDIGO-AKI and GuptaOnly-AKI groups had an increased risk of the composite mortality and/or moderate/severe brain MRI injury along with longer length of stay and prolonged duration of respiratory support compared to those without AKI. CONCLUSIONS: AKI in neonates with HIE + TH was common and varied by definition. The Gupta definition based on rate of SCr decline identified additional neonates not captured by KDIGO criteria who are at increased risk for adverse outcomes. Incorporating the rate of SCr decline into the neonatal AKI definition may increase identification of clinically relevant kidney injury in neonates with HIE + TH.

Identifying Newborns with Hypoxic-Ischemic Encephalopathy in Hospital Discharge Data: A Validation Study.

Hospital discharge databases (HDDs) are increasingly used for research on health of newborns. Linkage between a French population-based cohort of newborns with hypoxic-ischemic encephalopathy (HIE) and national HDD showed that the HIE ICD-10 code was not accurately reported. Our results suggest that HDD should not be used for research on neonatal HIE without prior validation of HIE ICD-10 codes.

Epilepsy Incidence and Developmental Outcomes After Early Discontinuation of Antiseizure Medication in Neonatal Hypoxic-Ischemic Encephalopathy.

BACKGROUND: Neonatal seizures caused by hypoxic-ischemic encephalopathy (HIE) have significant morbidity and mortality. There is variability in clinical practice regarding treatment duration with antiseizure medication (ASM) after resolution of provoked neonatal seizures. We examined epilepsy incidence and developmental outcomes in post-HIE neonates discharged or not on ASM. METHODS: We conducted a retrospective chart review of all HIE-admitted neonates to the University of Iowa Hospitals & Clinics neonatal intensive care unit between January 2008 and February 2021 who presented with encephalopathy, underwent therapeutic hypothermia, and developed seizures. Neonates were divided into two groups depending on whether ASM was continued or discontinued on discharge. We evaluated the incidence of epilepsy and developmental outcomes on follow-up in these two cohorts up to 12 months. RESULTS: Sixty-nine neonates met the study criteria. ASM was continued on discharge in 41 neonates (59%) and discontinued before discharge in 28 (41%). At the 12-month follow-up, nine neonates (13%) had a diagnosis of epilepsy, out of which seven neonates had ASM continued on discharge (odds ratio [OR]: 2.84; 95% confidence interval [CI]: 0.48, 29.9)]. There was no statistical difference between the development of postneonatal epilepsy between the two groups (P value 0.29). There was no significant difference in developmental outcome between the two groups after adjusting for covariates like magnetic resonance imaging (MRI) brain abnormality and number of seizure days (OR: 0.68; 95% CI: 0.21, 2.22; P = 0.52). CONCLUSION: We found no significant risk of seizure recurrence by age 12 months in infants who had discontinued ASM before discharge compared with those who had continued ASM. There was no difference in developmental outcomes at the 12-month follow-up between groups after adjusting for brain MRI abnormality and the number of seizure days during admission. Our results support early discontinuation of ASM after resolution of acute provoked seizures in neonates with HIE.

Desarrollo motor, cognitivo y conductual tras encefalopatía hipóxico-isquémica neonatal / Motor, cognitive and behavioural outcomes after neonatal hypoxic-ischaemic encephalopathy

Introducción: El neurodesarrollo actual de pacientes con encefalopatía hipóxico-isquémica (EHI) neonatal en España se desconoce. Recientes estudios europeos destacan el desplazamiento de la patología grave hacia trastornos motores leves y problemas emocionales. El objetivo de este estudio fue analizar el estado neuroevolutivo integral a los 3años de una cohorte de neonatos con EHI. Pacientes y métodos: Estudio observacional multicéntrico de neonatos ≥35 semanas de edad gestacional con EHI moderada-grave nacidos entre 2011 y 2013 en 12 hospitales de una extensa región española (91.217m2) y ampliado hasta 2017 en el hospital coordinador. Se evaluaron los estudios de neuroimagen neonatal y del neurodesarrollo a los 3años mediante Bayley-III, Peabody Picture Vocabulary Test y Child Behaviour Checklist. Se incluyeron 79 controles sin asfixia perinatal. Resultados: Se reclutaron 63 pacientes, de los cuales 5/63 (7,9%) se excluyeron por presentar otra patología, y 14/58 (24%) fallecieron. De los 44 supervivientes, 42/44 (95,5%) fueron evaluados. De ellos, 10/42 (24%) presentaron evolución adversa (alteraciones visuales o auditivas, epilepsia, parálisis cerebral [PC] o retraso del desarrollo). Adicionalmente se detectaron otras alteraciones: trastorno motor mínimo (TMM) en 6/42 (14%) y más problemas de introversión (10,5% vs 1,3%), ansiedad (34,2% vs 11,7%) y depresión (28,9% vs 7,8%) que los controles (p<0,05). La gravedad de las lesiones en neuroimagen fue significativamente mayor en pacientes con trastorno motor (PC o TMM) (p=0,004) y muerte o evolución adversa (p=0,027). Conclusiones: Además de las secuelas clásicas, el seguimiento de los pacientes con EHI neonatal debería incluir el diagnóstico y el manejo de trastornos motores mínimos y problemas emocionales.(AU)

Introduction: The current neurodevelopmental status of patients with neonatal hypoxic-ischaemic encephalopathy (HIE) in Spain is unknown. Recent European studies highlight a shift of severe pathology towards mild motor disorders and emotional problems. The aim of this study was to analyse neurodevelopmental outcomes in a cohort of neonates with HIE at age 3years. Patients and method: Multicentre observational study of neonates born at 35 or more weeks of gestation with moderate to severe HIE in 2011-2013 in 12 hospitals in a large Spanish region (91,217m2), with the recruitment extended through 2017 in the coordinating hospital. We analysed the findings of neonatal neuroimaging and neurodevelopmental test scores at 3years (Bayley-III, Peabody Picture Vocabulary Test and Child Behavior Checklist). The sample included 79 controls with no history of perinatal asphyxia. Results: Sixty-three patients were recruited, of whom 5 (7.9%) were excluded due to other pathology and 14 (24%) died. Of the 44 survivors, 42 (95.5%) were evaluated. Of these 42, 10 (24%) had adverse outcomes (visual or hearing impairment, epilepsy, cerebral palsy or developmental delay). Other detected problems were minor neurological signs in 6 of the 42 (14%) and a higher incidence of emotional problems compared to controls: introversion (10.5% vs. 1.3%), anxiety (34.2% vs. 11.7%) and depression (28.9% vs. 7.8%) (P<.05). The severity of the lesions on neuroimaging was significantly higher in patients with motor impairment (P=.004) or who died or had an adverse outcome (P=.027). Conclusion: In addition to classical sequelae, the follow-up of patients with neonatal HIE should include the diagnosis and treatment of minor motor disorders and social and emotional problems.(AU)

Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia.

OBJECTIVES: Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. METHODS: We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. RESULTS: S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 µg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. CONCLUSIONS: The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE.

Detailed statistical analysis plan for ALBINO: effect of Allopurinol in addition to hypothermia for hypoxic-ischemic Brain Injury on Neurocognitive Outcome - a blinded randomized placebo-controlled parallel group multicenter trial for superiority (phase III).

BACKGROUND: Despite therapeutic hypothermia (TH) and neonatal intensive care, 45-50% of children affected by moderate-to-severe neonatal hypoxic-ischemic encephalopathy (HIE) die or suffer from long-term neurodevelopmental impairment. Additional neuroprotective therapies are sought, besides TH, to further improve the outcome of affected infants. Allopurinol - a xanthine oxidase inhibitor - reduced the production of oxygen radicals and subsequent brain damage in pre-clinical and preliminary human studies of cerebral ischemia and reperfusion, if administered before or early after the insult. This ALBINO trial aims to evaluate the efficacy and safety of allopurinol administered immediately after birth to (near-)term infants with early signs of HIE. METHODS/DESIGN: The ALBINO trial is an investigator-initiated, randomized, placebo-controlled, double-blinded, multi-national parallel group comparison for superiority investigating the effect of allopurinol in (near-)term infants with neonatal HIE. Primary endpoint is long-term outcome determined as survival with neurodevelopmental impairment versus death versus non-impaired survival at 2 years. RESULTS: The primary analysis with three mutually exclusive responses (healthy, death, composite outcome for impairment) will be on the intention-to-treat (ITT) population by a generalized logits model according to Bishop, Fienberg, Holland (Bishop YF, Discrete Multivariate Analysis: Therory and Practice, 1975) and ."will be stratified for the two treatment groups. DISCUSSION: The statistical analysis for the ALBINO study was defined in detail in the study protocol and implemented in this statistical analysis plan published prior to any data analysis. This is in accordance with the Declaration of Helsinki and the International Conference on Harmonization Good Clinical Practice guidelines. TRIAL REGISTRATION: ClinicalTrials.gov NCT03162653. Registered on 22 May 2017.

Evaluating Injury Severity in Neonatal Encephalopathy Using Automated Quantitative Electroencephalography Analysis: A Pilot Study.

Quantitative analysis of electroencephalography (qEEG) is a potential source of biomarkers for neonatal encephalopathy (NE). However, prior studies using qEEG in NE were limited in their generalizability due to individualized techniques for calculating qEEG features or labor-intensive pre-selection of EEG data. We piloted a fully automated method using commercially available software to calculate the suppression ratio (SR), absolute delta power, and relative delta, theta, alpha, and beta power from EEG of neonates undergoing 72 h of therapeutic hypothermia (TH) for NE between April 20, 2018, and November 4, 2019. We investigated the association of qEEG with degree of encephalopathy (modified Sarnat score), severity of neuroimaging abnormalities following TH (National Institutes of Child Health and Development Neonatal Research Network [NICHD-NRN] score), and presence of seizures. Thirty out of 38 patients met inclusion criteria. A more severe modified Sarnat score was associated with higher SR during all phases of TH, lower absolute delta power during all phases except rewarming, and lower relative delta power during the last 24 h of TH. In 21 patients with neuroimaging data, a worse NICHD-NRN score was associated with higher SR, lower absolute delta power, and higher relative beta power during all phases. QEEG features were not significantly associated with the presence of seizures after correction for multiple comparisons. Our results are consistent with those of prior studies using qEEG in NE and support automated qEEG analysis as an accessible, generalizable method for generating biomarkers of NE and response to TH. Additionally, we found evidence of an immature relative frequency composition in neonates with more severe brain injury, suggesting that automated qEEG analysis may have a use in the assessment of brain maturity.

Hypoxic Ischemic Encephalopathy with Cervical Spinal Cord Injury: A Diagnostic Dilemma.

Perinatal spinal cord injury is a relatively uncommon, but a frequently misdiagnosed disorder. Improvements in obstetric care have certainly led to a decrease in the incidence of birth related spinal cord trauma but unfortunately the incidence of hypoxic-ischemic encephalopathy is still very high. The exact incidence of spinal cord trauma is difficult to determine because the spinal cord is not routinely examined in far and few neonatal autopsies done in India. Here, authors present a neonate who received treatment for birth asphyxia and then had extubation failure which made the clock tick towards cervical cord injury. This baby had a hemorrhagic contusion of cervical spinal cord.

A comparative proteomic analysis for non-invasive early prediction of hypoxic-ischemic injury in asphyxiated neonates.

AIM: Hypoxic Ischemic Encephalopathy (HIE) is one of the principal causes of neonatal mortality and long-term morbidity worldwide. The neonatal signs of mild cerebral injury are subtle, making an early precise diagnosis difficult. Delayed detection, poor prognosis, and lack of specific biomarkers for the disease are increasing mortality rates. In this study, we intended to identify specific biomarkers using comparative proteomic analysis to predict the severity of perinatal asphyxia so that its outcome can also be prevented. EXPERIMENTAL DESIGN: A case-control study was conducted on 38 neonates, and urine samples were collected within 24 and 72 h of life. A tandem mass spectrometry-based quantitative proteomics approach, followed by validation via sandwich ELISA, was performed. RESULTS: The LC-MS/MS-based proteomics analysis resulted in the identification of 1201 proteins in urine, with 229, 244, and 426 being differentially expressed in HIE-1, HIE-2, and HIE-3, respectively. Axon guidance, Diseases of programmed cell death, and Detoxification of reactive oxygen species pathways were significantly enriched in mild HIE versus severe HIE. Among the differentially expressed proteins in various stages of HIE, we chose to validate four proteins - APP, AGT, FABP1, and FN1 - via sandwich ELISA. Individual and cumulative ROC curves were plotted. AGT and FABP1 together showed high sensitivity, specificity, and accuracy as potential biomarkers for early diagnosis of HIE. CONCLUSION: Establishing putative urinary biomarkers will facilitate clinicians to more accurately screen neonates for brain injury and monitor the disease progression. Prompt treatment of neonates may reduce mortality and neurodevelopmental impairment.

The Association of Therapeutic Hypothermia With Seizure Burden in Neonates With Hypoxic-Ischemic Encephalopathy.

OBJECTIVES: To compare seizure burden between newborn infants treated with therapeutic hypothermia (TH) and those that were not and to compare the need for antiseizure medications (ASM) in a cohort of infants who were diagnosed with neonatal hypoxic-ischemic encephalopathy (HIE). METHODS: This was a retrospective cohort study on infants born after 35 weeks' gestation, diagnosed with moderate to severe HIE, monitored with amplitude-integrated electroencephalography (aEEG) and eligible for TH. Infants born before the implementation of TH in 2008 were compared with infants born thereafter who received TH. Seizure burden was assessed from aEEG as total time in minutes of seizures activity per hour of recording. Other clinical and demographic data were retrieved from a prospective local database of infants with HIE. RESULTS: Overall, 149 of 207 infants were included in the study: 112 exposed to TH and 37 not exposed. Cooled infants had a lower seizure burden overall (0.4 vs 2.3 min/h, P < 0.001) and were also less likely to be treated with ASM (74% vs 100%, P < 0.001). In multivariable regression models, not exposed to TH, having a depressed aEEG background, and having higher Apgar scores were associated with higher seizure burden (incidence rate ratio: 4.78 for noncooled infants, P < 0.001); also, not exposed to TH was associated with a higher likelihood of multidrug ASM (odds ratio: 4.83, P < 0.001). CONCLUSIONS: TH in infants with moderate to severe HIE is associated with significant reduction of seizure burden and ASM therapy.

The influence of late prematurity on the encephalopathy exam of infants with neonatal encephalopathy.

BACKGROUND: Late preterm (LPT) infants are increasingly treated for hypoxic-ischemic encephalopathy (HIE). However, neurodevelopmental differences of LPT infants may independently influence the neurologic exam and confound care. METHODS: Perinatal and outcome characteristics were extracted along with the worst autonomic and state/neuromuscular/reflex Sarnat components in a cross-section of infants with moderate/severe HIE. Infants were classified as late preterm (LPT, 34-36 weeks) or term (>36 weeks). RESULTS: 250 infants were identified, 55 were late preterm. LPT infants had lower mean gestational age and birthweight and greater length of stay (LOS). LPT infants had higher median scores for the Moro and respiratory autonomic components, but no difference in total score. CONCLUSIONS: LPT infants had increased LOS, worse Moro reflex, and respiratory status, but no clinically or statistically significant differences in total Sarnat scores. Although it is important to note the impact of immaturity on the exam, it is unlikely to independently alter management.