Cardiopulmonary Impact of Hypoxic Ischemic Encephalopathy in Newborn Infants. The Emerging Role of Early Hemodynamic Assessment in Determining Adverse Neurological Outcomes.
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ABSTRACT:
SUBMITTER: Altit G
PROVIDER: S-EPMC6857497 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Burst suppression (BS) is an electroencephalographic state associated with a profound inactivation of the brain. BS and pathological discontinuous electroencephalography (EEG) are often observed in term-age infants with neurological injury and can be indicative of a poor outcome and lifelong disability. Little is known about the neurophysiological mechanisms of BS or how the condition relates to the functional state of the neonatal brain. We used simultaneous EEG and diffuse optical tomography (DOT) to investigate whether bursts of EEG activity in infants with hypoxic ischemic encephalopathy are associated with an observable cerebral hemodynamic response. We were able to identify significant changes in concentration of both oxy and deoxyhemoglobin that are temporally correlated with EEG bursts and present a relatively consistent morphology across six infants. Furthermore, DOT reveals patient-specific spatial distributions of this hemodynamic response that may be indicative of a complex pattern of cortical activation underlying discontinuous EEG activity that is not readily apparent in scalp EEG.
| S-EPMC4945004 | biostudies-literature
Project description:Hypoxic ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. Our study sought to examine whether patterns of newborn screening analytes differed between infants with and without neonatal HIE in order to identify opportunities for potential use of these analytes for diagnosis in routine clinical practice. We linked a population-based newborn screening registry with health databases to identify cases of HIE among term infants (?37 weeks' gestation) in Ontario from 2010-2015. Correlations between HIE and screening analytes were examined using multivariable logistic regression models containing clinical factors and individual screening analytes (acyl-carnitines, amino acids, fetal-to-adult hemoglobin ratio, endocrine markers, and enzymes). Among 731,841 term infants, 3,010 were diagnosed with HIE during the neonatal period. Multivariable models indicated that clinical variables alone or in combination with hemoglobin values were not associated with HIE diagnosis. Although the model was improved after adding acyl-carnitines and amino acids, the ability of the model to identify infants with HIE was moderate. Our findings indicate that analytes associated with catabolic stress were altered in infants with HIE; however, future research is required to determine whether amino acid and acyl-carnitine profiles could hold clinical utility in the early diagnosis or clinical management of HIE. In particular, further research should examine whether cord blood analyses can be used to identify HIE within a clinically useful timeframe or to guide treatment and predict long-term health outcomes.
| S-EPMC6823438 | biostudies-literature
Project description:Abstract This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the efficacy and safety of stem cell‐based interventions for the treatment of hypoxic‐ischaemic encephalopathy (HIE) in newborn infants.
| S-EPMC6516966 | biostudies-literature
Project description:BackgroundHypoxic-ischaemic encephalopathy (HIE) is a leading cause of mortality and long-term neurological sequelae, affecting thousands of children worldwide. Current therapies to treat HIE are limited to cooling. Stem cell-based therapies offer a potential therapeutic approach to repair or regenerate injured brain tissue. These preclinical findings have now culminated in ongoing human neonatal trials.ObjectivesTo determine the efficacy and safety of stem cell-based interventions for the treatment of hypoxic-ischaemic encephalopathy (HIE) in newborn infants.Search methodsWe used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL; 2020, Issue 5), MEDLINE via PubMed (1966 to 8 June 2020), Embase (1980 to 8 June 2020), and CINAHL (1982 to 8 June 2020). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials.Selection criteriaRandomised controlled trials, quasi-randomised controlled trials and cluster trials comparing 1) stem cell-based interventions (any type) compared to control (placebo or no treatment); 2) use of mesenchymal stem/stromal cells (MSCs) of type (e.g. number of doses or passages) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus MSCs of other type or source; 3) use of stem cell-based interventions other than MSCs of type (e.g. mononuclear cells, oligodendrocyte progenitor cells, neural stem cells, hematopoietic stem cells, and inducible pluripotent stem cells) or source (e.g. autologous versus allogeneic, or bone marrow versus cord) versus stem cell-based interventions other than MSCs of other type or source; or 4) MSCs versus stem cell-based interventions other than MSCs.Data collection and analysisFor each of the included trials, two authors independently planned to extract data (e.g. number of participants, birth weight, gestational age, type and source of MSCs or other stem cell-based interventions) and assess the risk of bias (e.g. adequacy of randomisation, blinding, completeness of follow-up). The primary outcomes considered in this review are all-cause neonatal mortality, major neurodevelopmental disability, death or major neurodevelopmental disability assessed at 18 to 24 months of age. We planned to use the GRADE approach to assess the quality of evidence.Main resultsOur search strategy yielded 616 references. Two review authors independently assessed all references for inclusion. We did not find any completed studies for inclusion. Fifteen RCTs are currently registered and ongoing. We describe the three studies we excluded.Authors' conclusionsThere is currently no evidence from randomised trials that assesses the benefit or harms of stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants.
| S-EPMC7438027 | biostudies-literature
Project description:ObjectiveTo determine the association of persistent pulmonary hypertension of the newborn (PPHN) with death or disability among infants with moderate or severe hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia.MethodsWe compared infants with and without PPHN enrolled in the hypothermia arm from three randomized controlled trials (RCTs): Induced Hypothermia trial, "usual care" arm of Optimizing Cooling trial, and Late Hypothermia trial. Primary outcome was death or disability at 18-22 months adjusted for severity of HIE, center, and RCT.ResultsAmong 280 infants, 67 (24%) were diagnosed with PPHN. Among infants with and without PPHN, death or disability was 47% vs. 29% (adjusted OR: 1.65, 0.86-3.14) and death was 26% vs. 12% (adjusted OR: 2.04, 0.92-4.53), respectively.ConclusionsPPHN in infants with moderate or severe HIE was not associated with a statistically significant increase in primary outcome. These results should be interpreted with caution given the limited sample size.
| S-EPMC7954876 | biostudies-literature
Project description:Hypoxic ischemic encephalopathy is a serious condition affecting infants which can result in death and disability. This is a summary of pathogenesis of HIE, animal studies of cooling for hypoxic and ischemic models, human hypothermia trials, and the American Academy of Pediatrics publication on hypothermia for HIE. Hypothermia for neonatal HIE is continuing to evolve as a therapy. Studies, gaps in knowledge and opportunities for research are presented herein.
| S-EPMC2813680 | biostudies-other
Project description:BACKGROUND:Adults with the apolipoprotein E (APOE) gene alleles e4 and e2 are at high risk of poor neurological outcome after brain injury. The e4 allele has been associated with cerebral palsy (CP), and the e2 allele has been associated with worse neurological outcome with congenital heart disease. This study was done to test the hypothesis that the APOE genotype is associated with outcome among neonates who survive after hypoxic-ischemic encephalopathy (HIE). METHODS:We conducted a cohort study of infants who survived HIE and had 18-22 mo standardized neurodevelopmental evaluations to assess associations between disability and the APOE genotypes e3/e3, e4/-, and e2/-. RESULTS:A total of 139 survivors were genotyped. Of these, 86 (62%) were of the e3/e3, 41 (29%) were of the e4/-, and 14 (10%) were of the e2/- genotypes. One hundred and twenty-nine infants had genotype and follow-up data; 26% had moderate or severe disabilities. Disability prevalence was 30 and 19% among those with and without the e3/e3 genotype, 25 and 26% among those with and without the e2 allele, and 18 and 29% among those with and without the e4 allele, respectively. None of the differences were statistically significant. CP prevalence was also similar among genotype groups. CONCLUSION:Disability was not associated with the APOE genotype in this cohort of HIE survivors.
| S-EPMC4095992 | biostudies-literature
Project description:PurposeTo detect retinal features and abnormalities on optical coherence tomography (OCT) without pupil dilation and relate these to brain injury in infants with a clinical diagnosis of hypoxic ischemic encephalopathy (HIE).MethodsUnder an institutional review board-approved protocol, we imaged eight infants without pharmacologic mydriasis, using handheld, non-contact spectral-domain (Leica Microsystems, IL) or investigational swept-source OCT at the bedside in an intensive care nursery, after birth (depending on primary clinical care team permission based on health status) and weekly until discharge. The newborn infant with HIE is neurologically unstable; therefore, pharmacologic mydriasis and stimulation with visible light for retinal examination are usually avoided. We analyzed images for retinal pathologies, central foveal thickness, and retinal nerve fiber layer (RNFL) thickness at the papillomacular bundle and compared them to historical controls and published normative data, HIE clinical assessment, and abnormalities on brain magnetic resonance imaging (MRI).ResultsOn OCT, three of eight infants had bilateral multiple small macular and perimacular cystoid spaces; two of these three infants also had pronounced retinal ganglion cell layer thinning and severe brain injury on MRI and the third had bilateral paracentral acute middle maculopathy and mild brain injury on MRI. Other findings in HIE infant eyes included abnormally thin fovea and thin RNFL and markers of retinal immaturity such as the absence of sub-foveal photoreceptor development and sub-foveal fluid.ConclusionsBedside handheld OCT imaging within the first 2 weeks of life revealed retinal injury in infants with HIE-related brain injury. Future studies may determine the relationship between acute/subacute retinal abnormalities and brain injury severity and neurodevelopmental outcomes in HIE.
| S-EPMC7442701 | biostudies-literature
Project description:Background: Studies have suggested that neurological outcome may differ in newborns with encephalopathy with and without perinatal infection. We aimed to systematically review this association. Methods: We conducted this systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Studies were obtained from four databases including Pubmed, Embase, Web of Science, and The Cochrane Database. Newborns with encephalopathy with and without markers of perinatal infection were compared with regard to neurodevelopmental assessments, neurological disorders, and early biomarkers of brain damage. Risk of bias and quality of evidence were assessed by the Newcastle-Ottawa scale and Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: We screened 4,284 studies of which eight cohort studies and one case-control study met inclusion criteria. A narrative synthesis was composed due to heterogeneity between studies. Six studies were classified as having low risk of bias, while three studies were classified as having high risk of bias. Across all outcomes, the quality of evidence was very low. The neurological outcome was similar in newborns with encephalopathy with and without markers of perinatal infection. Conclusions: Further studies of higher quality are needed to clarify whether perinatal infection may affect neurological outcome following newborn encephalopathy. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020185717.
| S-EPMC8721111 | biostudies-literature
Project description:To assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE).We enrolled infants in the intensive care nursery who were cooled for HIE and had available UCB in an open-label study of non-cyropreserved autologous volume- and red blood cell-reduced UCB cells (up to 4 doses adjusted for volume and red blood cell content, 1-5 × 10(7) cells/dose). We recorded UCB collection and cell infusion characteristics, and pre- and post-infusion vital signs. As exploratory analyses, we compared cell recipients' hospital outcomes (mortality, oral feeds at discharge) and 1-year survival with Bayley Scales of Infant and Toddler Development, 3rd edition scores ?85 in 3 domains (cognitive, language, and motor development) with cooled infants who did not have available cells.Twenty-three infants were cooled and received cells. Median collection and infusion volumes were 36 and 4.3 mL. Vital signs including oxygen saturation were similar before and after infusions in the first 48 postnatal hours. Cell recipients and concurrent cooled infants had similar hospital outcomes. Thirteen of 18 (74%) cell recipients and 19 of 46 (41%) concurrent cooled infants with known 1-year outcomes survived with scores >85.Collection, preparation, and infusion of fresh autologous UCB cells for use in infants with HIE is feasible. A randomized double-blind study is needed.
| S-EPMC3992180 | biostudies-literature