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 | 2019 Nov
REPOSITORIES: biostudies-literature
Publications
Cardiopulmonary Impact of Hypoxic Ischemic Encephalopathy in Newborn Infants. The Emerging Role of Early Hemodynamic Assessment in Determining Adverse Neurological Outcomes.
Altit Gabriel G Levy Philip T PT
American journal of respiratory and critical care medicine 20191101 10
Similar Datasets
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.
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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: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:Despite advances in obstetric care, hypoxic ischemic encephalopathy (HIE) remains a significant disease burden. We determined the national trends of HIE prevalence, therapeutic hypothermia (TH) use, mortality, and outcomes from 2012 to 2019. This study included term infants diagnosed with HIE between 2012 and 2019 from the National Health Insurance Service database. The prevalence of HIE was 2.4 per 1000 births without significant change during the period. TH was performed in approximately 6.7% of infants with HIE, and the annual variation ranged from 2.4 to 12.5%. The mortality among all term infants with HIE was 4.6%. The mortality rate among infants with HIE and TH significantly declined from 40 to 16.9% during the eight years. Infants with TH had higher mortality, increased use of inhaled nitric oxide, and more invasive ventilator use, indicating greater disease severity in the TH group. Infants with TH also showed significantly poorer outcomes, including delayed development, cerebral palsy, sensorineural hearing loss, and seizure, compared to infants without TH (p < 0.0001). With the increasing application of TH, mortality and developmental outcomes among infants with HIE have been improving in the past eight years in Korea. Further efforts to improve outcomes should be needed.
| S-EPMC10754824 | 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:BackgroundAdults 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).MethodsWe 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/-.ResultsA 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.ConclusionDisability 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:Perinatal hypoxia-ischemia represents a significant risk to CNS development, leading to high mortality rates, diverse damages, and persistent neurological deficits. Despite advances in neonatal medicine in recent decades, the incidence of HIE remains substantial. Motor deficits can manifest early, while cognitive impairments may be diagnosed later, emphasizing the need for extended follow-up. This review aims to explore potential candidates for therapeutic interventions for hypoxic-ischemic encephalopathy (HIE), with a focus on cognitive deficits. We searched randomized clinical trials (RCT) that tested drug treatments for HIE and evaluated cognitive outcomes. The results included studies on erythropoietin, melatonin, magnesium sulfate, topiramate, and a combination of vitamin C and ibuprofen. Although there are several indications of the efficacy of these drugs among animal models, considering neuroprotective properties, the RCTs failed to provide complete effectiveness in the context of cognitive impairments derived from HIE. More robust RCTs are still needed to advance our knowledge and to establish standardized treatments for HIE.
| S-EPMC10925695 | biostudies-literature
Project description:ObjectiveTo assess feasibility and safety of providing autologous umbilical cord blood (UCB) cells to neonates with hypoxic-ischemic encephalopathy (HIE).Study designWe 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.ResultsTwenty-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.ConclusionsCollection, 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
Project description:Moderate to severe hypoxic-ischemic injury in newborn infants, manifested as encephalopathy immediately or within hours after birth, is associated with a high risk of either death or a lifetime with disability. In recent multicenter clinical trials, hypothermia initiated within the first 6 postnatal hours has emerged as a therapy that reduces the risk of death or impairment among infants with hypoxic-ischemic encephalopathy. Prior to hypothermia, no therapies directly targeting neonatal encephalopathy secondary to hypoxic-ischemic injury had convincing evidence of efficacy. Hypothermia therapy is now becoming increasingly available at tertiary centers. Despite the deserved enthusiasm for hypothermia, obstetric and neonatology caregivers, as well as society at large, must be reminded that in the clinical trials more than 40% of cooled infants died or survived with impairment. Although hypothermia is an evidence-based therapy, additional discoveries are needed to further improve outcome after HIE. In this article, we briefly present the epidemiology of neonatal encephalopathy due to hypoxic-ischemic injury, describe the rationale for the use of hypothermia therapy for hypoxic-ischemic encephalopathy, and present results of the clinical trials that have demonstrated the efficacy of hypothermia. We also present findings noted during and after these trials that will guide care and direct research for this devastating problem.
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