Long-term neuropsychological and behavioral outcome of mild and moderate hypoxic ischemic encephalopathy

Halpin, Stephen; McCusker, Christopher G.; Fogarty, Leanna; White, Jennie; Cavalière, Emilie; Boylan, Geraldine B.; Murray, Deirdre M.

doi:10.1016/j.earlhumdev.2022.105541

Cited by 15 publications

(8 citation statements)

References 35 publications

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“…Children who have suffered neonatal HIE can present decreased sensorimotor function, memory, cognitive and learning difficulties, and diminished motor capability, including locomotor and reduced fine motor skills compared with healthy peers [20][21][22][23]. Although the reduction of brain lesions and neuroinflammation are good indicators of recovery, inducing long-term functional improvement is especially important for the clinical translation of the therapies used.…”

Section: Discussionmentioning

confidence: 99%

“…After HIE, affected neonates can present long-term motor and cognitive deficits that deeply affect their health-related quality of life [20][21][22][23]. To determine if the positive impact of UCBC on brain lesion extension and glial activation led to improved functional outcomes, sensorimotor, motor, and cognitive skills were assessed at different neurodevelopmental stages.…”

Section: Impact Of Hypothermia and Umbilical Cord Blood Cells In The ...mentioning

confidence: 99%

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Hypothermia Does Not Boost the Neuroprotection Promoted by Umbilical Cord Blood Cells in a Neonatal Hypoxia-Ischemia Rat Model

Serrenho

Cardoso²,

Grãos

et al. 2022

IJMS

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Neonatal hypoxic-ischemic encephalopathy (HIE) is one of the leading causes of death and long-term disability in the perinatal period. Currently, therapeutic hypothermia is the standard of care for this condition with modest efficacy and strict enrollment criteria. Therapy with umbilical cord blood cells (UCBC) has come forward as a strong candidate for the treatment of neonatal HIE, but no preclinical studies have yet compared the action of UCBC combined with hypothermia (HT) with the action of each therapy by itself. Thus, to evaluate the potential of each therapeutic approach, a hypoxic-ischemic brain lesion was induced in postnatal day ten rat pups; two hours later, HT was applied for 4 h; and 24, 48, and 72 h post-injury, UCBC were administered intravenously. The neonatal hypoxic-ischemic injury led to a brain lesion involving about 48% of the left hemisphere that was not improved by HT (36%) or UCBC alone (28%), but only with the combined therapies (25%; p = 0.0294). Moreover, a decrease in glial reactivity and improved functional outcomes were observed in both groups treated with UCBC. Overall, these results support UCBC as a successful therapeutic approach for HIE, even when treatment with therapeutic hypothermia is not possible.

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Section: Discussionmentioning

confidence: 99%

Section: Impact Of Hypothermia and Umbilical Cord Blood Cells In The ...mentioning

confidence: 99%

Hypothermia Does Not Boost the Neuroprotection Promoted by Umbilical Cord Blood Cells in a Neonatal Hypoxia-Ischemia Rat Model

Serrenho

Cardoso²,

Grãos

et al. 2022

IJMS

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“…Survivors of hypoxic-ischemic encephalopathy (HIE) have shown reduced neuropsychological functioning, behavioral adjustment, and school outcomes during adolescence among other neonatal morbidities, mortalities, and outcomes ( 1 ).…”

Section: Introductionmentioning

confidence: 99%

Clinical practice guidelines for neonatal hypoxic-ischemic encephalopathy: A systematic review using the appraisal of guidelines for research and evaluation (AGREE) II instrument

et al. 2023

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Background and ObjectiveTo systematically review, critically appraise the quality of recent clinical practice guidelines (CPGs) for neonatal hypoxic ischemic encephalopathy (HIE), and map their recommendations.Data SourcesCPG databases (GIN, ECRI, NICE, SIGN, DynaMed), Bibliographic databases (PubMed, Embase, CINAHL), and related specialized professional societies (e.g., AAP, CPS, BAPM, RCPCH, and SNS).Study SelectionOriginal de-novo developed evidence-based CPGs for HIE, group authorship, Arabic or English languages, and international or national scope. The systematic review was drafted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement and Johnston et al methodological guide.Data ExtractionQuality assessment of the included HIE CPGs by the Appraisal of Guidelines for REsearch & Evaluation II (AGREE II) Instrument and report their characteristics, AGREE II ratings, and recommendationsData SynthesisOur search retrieved 2,489 citations, of which two recent HIE CPGs were eligible and appraised: Canadian Paediatric Society (CPS) and Queensland Maternity and Neonatal Services (QMN). The overall assessment of the QMN CPG was superior (83%). Domain 1 (Scope & Purpose) scored (47%, 63%), Domain 2 (Stakeholder Involvement) (72%, 39%), Domain 3 (Rigour of Development) (48%, 43%), Domain 4 (Clarity & Presentation) (100%, 96%), Domain 5 (Applicability) (59%, 9%), and Domain 6 (Editorial Independence) (67%, 17%) for the QMN and CPS CPGs respectively. All appraisers recommended the QMN CPG for use in practice.ConclusionThe methodological quality of the QMN CPG was superior with the relevant recommendations for its use in neonatal practice.Limitationslimited to Arabic and English languages.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=258291, identifier: CRD42021258291.

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“…Using different clinical categories (e.g., heart rate and neurological examination), HIE can be grouped in three degrees of severity: mild, moderate, and severe. Poor long-term outcomes are more generally described in moderate–severe HIE, but still vary from no (or only mild) effects to more severe and permanent disability [ 5 ]. In addition, neonates with mild HIE have been increasingly linked to adverse outcomes in the last years [ 6 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of Hypoxia-Ischemia on Neurogenesis and Structural and Functional Outcomes in a Mild–Moderate Neonatal Hypoxia-Ischemia Brain Injury Model

Ehlting

Zweyer

Maes

et al. 2022

Life

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Hypoxic-ischemic encephalopathy (HIE) is a common type of brain injury caused by a lack of oxygen and blood flow to the brain during the perinatal period. The incidence of HIE is approximately 2–3 cases per 1000 live births in high-income settings; while in low- and middle-income countries, the incidence is 3–10-fold higher. Therapeutic hypothermia (TH) is the current standard treatment for neonates affected by moderate–severe HIE. However, more than 50% of all infants with suspected HIE have mild encephalopathy, and these infants are not treated with TH because of their lower risk of adverse outcomes. Despite this, several analyses of pooled data provide increasing evidence that infants who initially have mild encephalopathy may present signs of more significant brain injury later in life. The purpose of this study was to expand our knowledge about the effect of mild–moderate hypoxia-ischemia (HI) at the cellular, structural, and functional levels. An established rat model of mild–moderate HI was used, where postnatal day (P) 7 rats were exposed to unilateral permanent occlusion of the left carotid artery and 90 min of 8% hypoxia, followed by TH or normothermia (NT) treatment. The extent of injury was assessed using histology (P14 and P42) and MRI (P11 and P32), as well as with short-term and long-term behavioral tests. Neurogenesis was assessed by BrdU staining. We showed that mild–moderate HI leads to a progressive loss of brain tissue, pathological changes in MRI scans, as well as an impairment of long-term motor function. At P14, the median area loss assessed by histology for HI animals was 20% (p < 0.05), corresponding to mild–moderate brain injury, increasing to 55% (p < 0.05) at P42. The data assessed by MRI corroborated our results. HI led to a decrease in neurogenesis, especially in the hippocampus and the lateral ventricle at early time points, with a delayed partial recovery. TH was not neuroprotective at early time points following mild–moderate HI, but prevented the increase in brain damage over time. Additionally, rats treated with TH showed better long-term motor function. Altogether, our results bring more light to the understanding of pathophysiology following mild-moderate HI. We showed that, in the context of mild-moderate HI, TH failed to be significantly neuroprotective. However, animals treated with TH showed a significant improvement in motor, but not cognitive long-term function. These results are in line with what is observed in some cases where neonates with mild HIE are at risk of neurodevelopmental deficits in infancy or childhood. Whether TH should be used as a preventive treatment to reduce adverse outcomes in mild-HIE remains of active interest, and more research has to be carried out in order to address this question.

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Long-term neuropsychological and behavioral outcome of mild and moderate hypoxic ischemic encephalopathy

Cited by 15 publications

References 35 publications

Hypothermia Does Not Boost the Neuroprotection Promoted by Umbilical Cord Blood Cells in a Neonatal Hypoxia-Ischemia Rat Model

Hypothermia Does Not Boost the Neuroprotection Promoted by Umbilical Cord Blood Cells in a Neonatal Hypoxia-Ischemia Rat Model

Clinical practice guidelines for neonatal hypoxic-ischemic encephalopathy: A systematic review using the appraisal of guidelines for research and evaluation (AGREE) II instrument

Impact of Hypoxia-Ischemia on Neurogenesis and Structural and Functional Outcomes in a Mild–Moderate Neonatal Hypoxia-Ischemia Brain Injury Model

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