Neonatal EEG graded for severity of background abnormalities in hypoxic-ischaemic encephalopathy.
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ABSTRACT:
SUBMITTER: O'Toole JM
PROVIDER: S-EPMC10006081 | biostudies-literature | 2023 Mar
REPOSITORIES: biostudies-literature
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Neonatal EEG graded for severity of background abnormalities in hypoxic-ischaemic encephalopathy.
O'Toole John M JM Mathieson Sean R SR Raurale Sumit A SA Magarelli Fabio F Marnane William P WP Lightbody Gordon G Boylan Geraldine B GB
Scientific data 20230310 1
This report describes a set of neonatal electroencephalogram (EEG) recordings graded according to the severity of abnormalities in the background pattern. The dataset consists of 169 hours of multichannel EEG from 53 neonates recorded in a neonatal intensive care unit. All neonates received a diagnosis of hypoxic-ischaemic encephalopathy (HIE), the most common cause of brain injury in full term infants. For each neonate, multiple 1-hour epochs of good quality EEG were selected and then graded fo ...[more]
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Project description:BackgroundInfants with mild HIE are at risk of significant disability at follow-up. In the pre-therapeutic hypothermia (TH) era, electroencephalography (EEG) within 6 hours of birth was most predictive of outcome. This study aims to identify and describe features of early EEG and heart rate variability (HRV) (<6 hours of age) in infants with mild HIE compared to healthy term infants.MethodsInfants >36 weeks with mild HIE, not undergoing TH, with EEG before 6 hours of age were identified from 4 prospective cohort studies conducted in the Cork University Maternity Services, Ireland (2003-2019). Control infants were taken from a contemporaneous study examining brain activity in healthy term infants. EEGs were qualitatively analysed by two neonatal neurophysiologists and quantitatively assessed using multiple features of amplitude, spectral shape and inter-hemispheric connectivity. Quantitative features of HRV were assessed in both the groups.ResultsFifty-eight infants with mild HIE and sixteen healthy term infants were included. Seventy-two percent of infants with mild HIE had at least one abnormal EEG feature on qualitative analysis and quantitative EEG analysis revealed significant differences in spectral features between the two groups. HRV analysis did not differentiate between the groups.ConclusionsQualitative and quantitative analysis of the EEG before 6 hours of age identified abnormal EEG features in mild HIE, which could aid in the objective identification of cases for future TH trials in mild HIE.ImpactInfants with mild HIE currently do not meet selection criteria for TH yet may be at risk of significant disability at follow-up. In the pre-TH era, EEG within 6 hours of birth was most predictive of outcome; however, TH has delayed this predictive value. 72% of infants with mild HIE had at least one abnormal EEG feature in the first 6 hours on qualitative assessment. Quantitative EEG analysis revealed significant differences in spectral features between infants with mild HIE and healthy term infants. Quantitative EEG features may aid in the objective identification of cases for future TH trials in mild HIE.
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Project description:ObjectiveAssess the capacity of brain state of the newborn (BSN) to predict neurodevelopment outcomes in neonatal encephalopathy.MethodsTrends of BSN, a deep learning-based measure translating EEG background to a continuous trend, were studied from a three-channel montage long-term EEG monitoring from a prospective cohort of 92 infants with neonatal encephalopathy and neurodevelopmental outcomes assessed by Bayley Scales of Infant Development, 3rd edition (Bayley-III) at 18 months. Outcome prediction used categories "Severe impairment" (Bayley-III composite score ≤70 or death) or "Any impairment" (score ≤85 or death).Results"Severe impairment" was predicted best for motor outcomes (24 h area under the curve (AUC) = 0.97), followed by cognitive (36 h AUC = 0.90), overall (24 h AUC = 0.84), and language (24 h AUC = 0.82). "Any impairment" was best predicted for motor outcomes (12 h AUC = 0.95), followed by cognitive (24 h AUC = 0.85), overall (12 h AUC = 0.75), and language (12 and 24 h AUC = 0.68). Optimal BSN cutoffs for outcome predictions evolved with the postnatal age. Low BSN scores reached a 100% positive prediction of poor outcomes at 24 h of age.InterpretationBSN is an excellent predictor of adverse neurodevelopmental outcomes in survivors of neonatal encephalopathy after therapeutic hypothermia, even at 24 h of life. The trend provides a fully automated, objective, quantified, and reliable interpretation of EEG background. The high temporal resolution supports continuous bedside brain assessment and early prognostication during the initial dynamic recovery phase.
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Project description:BackgroundHypoxic ischaemic encephalopathy (HIE) in newborns can cause significant long-term neurological disability. The insult is a complex injury characterised by energy failure and disruption of cellular homeostasis, leading to mitochondrial damage. The importance of individual metabolic pathways, and their interaction in the disease process is not fully understood. The aim of this study was to describe and quantify the metabolomic profile of umbilical cord blood samples in a carefully defined population of full-term infants with HIE.Methods and findingsThe injury severity was defined using both the modified Sarnat score and continuous multichannel electroencephalogram. Using these classification systems, our population was divided into those with confirmed HIE (n = 31), asphyxiated infants without encephalopathy (n = 40) and matched controls (n = 71). All had umbilical cord blood drawn and biobanked at -80 °C within 3 hours of delivery. A combined direct injection and LC-MS/MS assay (AbsolutIDQ p180 kit, Biocrates Life Sciences AG, Innsbruck, Austria) was used for the metabolomic analyses of the samples. Targeted metabolomic analysis showed a significant alteration between study groups in 29 metabolites from 3 distinct classes (Amino Acids, Acylcarnitines, and Glycerophospholipids). 9 of these metabolites were only significantly altered between neonates with Hypoxic ischaemic encephalopathy and matched controls, while 14 were significantly altered in both study groups. Multivariate Discriminant Analysis models developed showed clear multifactorial metabolite associations with both asphyxia and HIE. A logistic regression model using 5 metabolites clearly delineates severity of asphyxia and classifies HIE infants with AUC = 0.92. These data describe wide-spread disruption to not only energy pathways, but also nitrogen and lipid metabolism in both asphyxia and HIE.ConclusionThis study shows that a multi-platform targeted approach to metabolomic analyses using accurately phenotyped and meticulously biobanked samples provides insight into the pathogenesis of perinatal asphyxia. It highlights the potential for metabolomic technology to develop a diagnostic test for HIE.
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Project description:BackgroundNeonatal hypoxic ischaemic encephalopathy due to perinatal asphyxia, can result in severe neurodevelopmental disability or mortality. Hypothermia is at present the only proven neuroprotective intervention. During hypothermia, the neonate may need a variety of drugs with their specific pharmacokinetic profile. The aim of this paper is to determine the effect that hypothermia for neonates suffering from hypoxic ischaemic encephalopathy has on the pharmacokinetics and to what extent dosing regimens need adjustments.MethodA systematic search was performed on PubMed, Embase and Cochrane Library of literature (2000-2020) using a combination of the following search terms: therapeutic hypothermia, neonate, hypoxic ischemic encephalopathy and pharmacokinetics. Titles and abstracts were screened, and inclusion/exclusion criteria were applied. Finally, relevant full texts were read, and secondary inclusion was applied on the identified articles.ResultsA total of 380 articles were retrieved, and 34 articles included after application of inclusion/exclusion criteria and duplicate removal, two additional papers were included as suggested by the reviewers. Twelve out of 36 studies on 15 compounds demonstrated a significant decrease in clearance, be it that the extent differs between routes of elimination and compounds, most pronounced for renal elimination (phenobarbital no difference, midazolam metabolite -21%, lidocaine -24%; morphine -21% to -47%, gentamicin -25% to -35%, amikacin -40%) during hypothermia. The data as retrieved in literature were subsequent compared with the dosing regimen as stated in the Dutch paediatric formulary.ConclusionDepending on the drug-specific disposition characteristics, therapeutic hypothermia in neonates with hypoxic ischaemic encephalopathy affects pharmacokinetics.
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Project description:ObjectiveWe aimed to examine the association between placental abnormalities and neurodevelopmental outcomes in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) that underwent therapeutic hypothermia. We hypothesized that subjects with acute placental abnormalities would have reduced risk of death or neurodevelopmental impairment (NDI) at 2 years of age after undergoing therapeutic hypothermia compared to subjects without acute placental changes.Study designAmong 500 subjects born at ≥36 weeks gestation with moderate or severe HIE enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, a placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute only, chronic only, or both acute and chronic histologic abnormalities. We calculated adjusted relative risks (aRRs) for associations between placental pathologic abnormalities and death or NDI at age 2 years, adjusting for HIE severity, treatment assignment, and site.Result321/500 subjects (64%) had available placental pathology reports. Placental abnormalities were characterized as acute only (20%), chronic only (21%), both acute and chronic (43%), and none (15%). The risk of death or NDI was not statistically different between subjects with and without an acute placental abnormality (46 vs. 53%, aRR 1.1, 95% confidence interval (CI): 0.9, 1.4). Subjects with two or more chronic lesions were more likely to have an adverse outcome than subjects with no chronic abnormalities, though this did not reach statistical significance (55 vs. 45%, aRR 1.24, 95% CI: 0.99, 1.56).ConclusionPlacental pathologic findings were not independently associated with risk of death or NDI in subjects with HIE. The relationship between multiple chronic placental lesions and HIE outcomes deserves further study.
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Project description:AimTo determine the prognostic value of conventional electroencephalography (EEG) monitoring in neonatal hypoxic-ischemic encephalopathy (HIE).MethodIn this multicentre retrospective study, 95 full-term neonates (mean of 39.3wks gestational age [SD 1.4], 36 [38%] females, 59 [62%] males) with HIE (2013-2016) undergoing therapeutic hypothermia were divided between favourable or adverse outcomes. Background EEG activity (French classification scale: 0-1-2-3-4-5) and epileptic seizure burden (epileptic seizure scale: 0-1-2) were graded for seven 6-hour periods. Conventional EEG monitoring was investigated by principal component analysis (PCA), with clustering methods to extract prognostic biomarkers of development at 2 years and infant death.ResultsEighty-one per cent of infants with an adverse outcome had a French classification scale equal to or greater than 3 after H48 (100% at H6-12). The H6-12 epileptic seizure scale was equal to or greater than 1 for 39%, increased to 52% at H30-36 and then remained equal to or greater than 1 for 39% after H48. Forty-five per cent of infants with a favourable outcome had a H6-12 French classification scale equal to or greater than 3, which dropped to 5% after H48; 13% had a H6-12 epileptic seizure scale equal to or greater than 1 but no seizures after H48. Clustering methods based on PCA showed the high efficiency (96%) of conventional EEG monitoring for outcome prediction and allowed the definition of three prognostic EEG biomarkers: H6-78 French classification scale mean, H6-78 French classification scale slope, and H30-78 epileptic seizure scale mean.InterpretationEarly lability and recovery of physiological features is prognostic of a favourable outcome. Seizure onset from the second day should also be considered to accurately predict neurodevelopment in HIE and support the importance of conventional EEG monitoring in HIE in infants cooled with therapeutic hypothermia.What this paper addsComprehensive analysis showed the high prognostic efficiency (96%) of conventional electroencephalography (EEG) monitoring. Prognostic EEG biomarkers consist of the grade of background EEG activity, its evolution, and the mean seizure burden. Persistent seizures (H48) without an improvement in background EEG activity were consistently associated with an adverse outcome.
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