Predictors of Long-Term Neurodevelopmental Outcome of Hypoxic-Ischemic Encephalopathy Treated with Therapeutic Hypothermia

2020 ◽  
Vol 40 (03) ◽  
pp. 322-334
Author(s):  
Ipsita Goswami ◽  
Mireille Guillot ◽  
Emily W. Y. Tam
Keyword(s):  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Prognostic Markers ◽  
Neurodevelopmental Outcome ◽  
Hypoxic Ischemic Encephalopathy ◽  
Secondary Brain Injury ◽  
Prognostic Utility ◽  
Initial Injury ◽  
Ischemic Encephalopathy

AbstractHypoxic-ischemic encephalopathy (HIE) is a manifestation of perinatal asphyxial insult that continues to evolve over days to weeks following the initial injury. Therapeutic hypothermia has demonstrated that a proportion of this secondary brain injury may indeed be preventable. However, therapeutic hypothermia has also altered the prognostic utility of many bedside tools that are commonly used as predictors of long-term neurodevelopmental outcome in HIE. Clinicians are often confronted with uncertainty when assessing the prognosis of infants with HIE. Improved understanding of the implications and limitations of individual investigations may inform clinical decisions and allow for timely intervention. This review summarizes the predictive value of currently available prognostic markers in HIE infants in the therapeutic hypothermia era, including clinical, biochemical, neurophysiological, physiological, and neuroimaging predictors.

scholarly journals Mammillary body atrophy and other MRI correlates of school-age outcome following neonatal hypoxic-ischemic encephalopathy

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kim V. Annink ◽  
Linda S. de Vries ◽  
Floris Groenendaal ◽  
Rian M. J. C. Eijsermans ◽  
Manouk Mocking ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Memory Function ◽  
Neurodevelopmental Outcome ◽  
Standard Of Care ◽  
Hypoxic Ischemic Encephalopathy ◽  
School Age ◽  
Brain Volumes ◽  
Mammillary Bodies ◽  
Memory Problems ◽  
Ischemic Encephalopathy

AbstractThe mammillary bodies (MB) and hippocampi are important for memory function and are often affected following neonatal hypoxic ischemic encephalopathy (HIE). The aim of this study was to assess neurodevelopmental outcome in 10-year-old children with HIE with and without therapeutic hypothermia. Additional aims were to assess the associations between MB atrophy, brain volumes (including the hippocampi), white matter microstructure and neurodevelopmental outcome at school-age. Ten-year-old children with HIE were included, who were treated with therapeutic hypothermia (n = 22) or would have qualified but were born before this became standard of care (n = 28). Children completed a neuropsychological and motor assessment and MRI. Mammillary bodies were scored as normal or atrophic at 10 years. Brain volumes were segmented on childhood MRI and DTI scans were analysed using tract-based spatial statistics. Children with HIE suffered from neurocognitive and memory problems at school-age, irrespective of hypothermia. Hippocampal volumes and MB atrophy were associated with total and performance IQ, processing speed and episodic memory in both groups. Normal MB and larger hippocampi were positively associated with global fractional anisotropy. In conclusion, injury to the MB and hippocampi was associated with neurocognition and memory at school-age in HIE and might be an early biomarker for neurocognitive and memory problems.

scholarly journals Wavelet Autoregulation Monitoring Identifies Blood Pressures Associated With Brain Injury in Neonatal Hypoxic-Ischemic Encephalopathy

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiuyun Liu ◽  
Aylin Tekes ◽  
Jamie Perin ◽  
May W. Chen ◽  
Bruno P. Soares ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Near Infrared ◽  
Brain Regions ◽  
Hypoxic Ischemic Encephalopathy ◽  
Volume Index ◽  
Arterial Blood ◽  
Blood Pressures ◽  
Ischemic Encephalopathy

Dysfunctional cerebrovascular autoregulation may contribute to neurologic injury in neonatal hypoxic-ischemic encephalopathy (HIE). Identifying the optimal mean arterial blood pressure (MAPopt) that best supports autoregulation could help identify hemodynamic goals that support neurologic recovery. In neonates who received therapeutic hypothermia for HIE, we hypothesized that the wavelet hemoglobin volume index (wHVx) would identify MAPopt and that blood pressures closer to MAPopt would be associated with less brain injury on MRI. We also tested a correlation-derived hemoglobin volume index (HVx) and single- and multi-window data processing methodology. Autoregulation was monitored in consecutive 3-h periods using near infrared spectroscopy in an observational study. The neonates had a mean MAP of 54 mmHg (standard deviation: 9) during hypothermia. Greater blood pressure above the MAPopt from single-window wHVx was associated with less injury in the paracentral gyri (p = 0.044; n = 63), basal ganglia (p = 0.015), thalamus (p = 0.013), and brainstem (p = 0.041) after adjustments for sex, vasopressor use, seizures, arterial carbon dioxide level, and a perinatal insult score. Blood pressure exceeding MAPopt from the multi-window, correlation HVx was associated with less injury in the brainstem (p = 0.021) but not in other brain regions. We conclude that applying wavelet methodology to short autoregulation monitoring periods may improve the identification of MAPopt values that are associated with brain injury. Having blood pressure above MAPopt with an upper MAP of ~50–60 mmHg may reduce the risk of brain injury during therapeutic hypothermia. Though a cause-and-effect relationship cannot be inferred, the data support the need for randomized studies of autoregulation and brain injury in neonates with HIE.

scholarly journals Neurodevelopmental outcome of babies with hypoxic ischemic encephalopathy

2017 ◽  
Vol 5 (7) ◽  
pp. 3197
Author(s):  
Sirajuddin Nazeer ◽  
Senthilkumar K. ◽  
Thangavel A. ◽  
Uma Maheswari M.
Keyword(s):  
Neurological Outcome ◽  
Neurodevelopmental Outcome ◽  
Hypoxic Ischemic Encephalopathy ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Mri Brain ◽  
Early Markers ◽  
Cdc Grading ◽  
Ischemic Encephalopathy

Background: The aim of the study was to find out the neurodevelopmental outcome of babies with hypoxic ischemic encephalopathy at 6 months of age and to predict early markers of abnormal neurological outcome in those babies.Methods: 50 babies admitted with hypoxic ischemic encephalopathy were enrolled in this prospective study and followed up at 3 and 6 months of age at Mahatma Gandhi Memorial Government Hospital, Trichy. The neurological outcome of the babies was assessed by CDC grading of motor milestones, Trivandrum development screening chart, Amiel Tison angles head circumference and weight measured. USG cranium was done for all the babies and MRI brain was done in babies with abnormal neuro sonogram and abnormal outcome. Vision and hearing were tested clinically.Results: The incidence of abnormal neurological outcome was 14%. The early markers predicting abnormal neurological sequele are identified.Conclusions: Early identification of abnormal neuro behaviour helps in starting early intervention to improve the long term outcome.

scholarly journals Is Erythropoietin Combining with Therapeutic Hypothermia an Efficient and Safe Therapy in Neonatal Hypoxic Ischemic Encephalopathy: A Prospective and Randomized Clinical Trial

2020 ◽  
Author(s):  
Liang-yan Zou ◽  
Bing-xue Huang ◽  
Peng Zhang ◽  
Guo-qiang Cheng ◽  
Chun-mei Lu ◽  
...  
Keyword(s):  
Brain Injury ◽  
Adverse Events ◽  
Therapeutic Hypothermia ◽  
Brain Mri ◽  
Adverse Outcomes ◽  
Hypoxic Ischemic Encephalopathy ◽  
Control Group ◽  
Term Infants ◽  
Basal Nuclei ◽  
Ischemic Encephalopathy

Abstract BackgroundTo evaluate the efficacy and safety of erythropoietin (Epo) combined with therapeutic hypothermia (TH) in neonatal hypoxic-ischemic encephalopathy (HIE).MethodsA total of 78 term infants with HIE were assigned randomly to receive Epo (n = 40) or placebo (n = 38). All infants received TH. Blood samples before TH, after TH and after Epo/placebo were collected for measuring TH associated adverse events, Epo associated factors and potential neural biomarkers. Basal ganglia/ watershed (BG/W) scoring system was used to assess brain injury in MRI. Neurodevelopmental evaluations were performed at 18 months by using BayleyScales of Infant Development II (Bayley II).ResultsEpo-treated group tend to have lower serum creatine kinase (CK) concentration (114 vs 202, P = .04) and higher serum K+, Mg2+ concentration (5.0 vs 4.5, P = .03; 1.0 vs 0.9, P = .02) than control group after intervention. Brain MRI was performed in 65 (83%) neonatal. Totally brain injury score was in even distribution between two groups (median, 0 vs 0, P = .61), but injury region in cortex plus basal nuclei comparing with in basal nuclei solely was less common in the Epo than in the control group (21% vs 31%, P = .046). Only forty patients (40/78, 51%) succeeded in achieving 18-month follow up data. The totally adverse outcomes were trend to decline in the Epo group (35% vs 60%, P = .21). No adverse events were ascribed to Epo treatment.ConclusionsThe combination of Epo and TH is proved to be feasible, safe and potential effective.Trial registration: ChiCTR-TRC-14004532, date of registration: April 18th, 2014.

scholarly journals Correlation of Thompson Score in Predicting Early Outcome of Newborn with Birth Asphyxia

2020 ◽  
Vol 18 (3) ◽  
pp. 406-410
Author(s):  
Sabina Shrestha ◽  
Sangita Puree Dhungana ◽  
Sujit Shrestha ◽  
Gentle Sunder Shrestha
Keyword(s):  
Neurodevelopmental Outcome ◽  
Birth Asphyxia ◽  
Neonatal Morbidity ◽  
Clinical Score ◽  
Hypoxic Ischemic Encephalopathy ◽  
Early Outcome ◽  
Medical College ◽  
A Prospective Study ◽  
Ischemic Encephalopathy

Background: Birth asphyxia is one of the important causes of neonatal morbidity and mortality, accounting up to 30% of neonatal death in Nepal. It is also an important cause of long term neurological disability and impairment. Thompson encephalopathy score is a clinical score which can be used to assess the newborn with hypoxic ischemic encephalopathy for the prognosis and their neurodevelopmental outcome. The aim of the study was to assess the role of Thompson score in predicting the early outcome of neonates with birth asphyxia. Methods: A prospective study was conducted from May 2019 to April 2020 in Nepal Medical College. All the term babies during the period with Apgar score of less than seven at five minutes were considered to have birth asphyxia and included in the study. Neurological examination was done on first, second and third day using HIE score proposed by Thompson and severity of hypoxic ischemic encephalopathy was classified accordingly. Outcome was measured as normal, morbidity with encephalopathy, seizure, organ dysfunction and death. Results: Out of 391 newborn admitted to neonatal unit, 84 (21.4%) had birth asphyxia. Mild Thompson score on day 1,2,3 were 49(58.3%), 49 (58.3%), 51(60.7%); moderate Thompson score on day 1,2,3 were 21 (25%), 21 (25%), 18(21.4%) and severe Thompson score on day 1, 2, 3 were 14 (16.7%), 14 (16.7%), 15(17.9%) respectively. Out of 14 babies who had severe Thompson score on day 1, 11(91.7%) expired and 3 (16.7%) developed encephalopathy. Conclusions: There was strong correlation of severity of Thompson score with the outcome. Keywords: Birth asphyxia; hypoxic ischemic encephalopathy; thompson score

Current Practice of Therapeutic Hypothermia for Mild Hypoxic Ischemic Encephalopathy

2019 ◽  
Vol 34 (7) ◽  
pp. 402-409 ◽  
Author(s):  
Chia L. Saw ◽  
Abhijeet Rakshasbhuvankar ◽  
Shripada Rao ◽  
M Bulsara ◽  
Sanjay Patole
Keyword(s):  
Adverse Effects ◽  
Therapeutic Hypothermia ◽  
Meta Analysis ◽  
Significant Proportion ◽  
Small Sample ◽  
Hypoxic Ischemic Encephalopathy ◽  
Cochrane Library ◽  
Short And Long Term ◽  
Ischemic Encephalopathy

Context: Therapeutic hypothermia is the recommended treatment for neonates with moderate or severe hypoxic ischemic encephalopathy (HIE). There is an increasing trend to use therapeutic hypothermia even in infants with mild hypoxic ischemic encephalopathy, even though there is little evidence to support/refute this. Objective: To estimate the incidences of mild hypoxic ischemic encephalopathy among infants who received therapeutic hypothermia, and its short- and long-term outcomes. Data Sources and Study Selection: PubMed, Embase, CINAHL, and Cochrane library were searched to identify observational studies reporting on therapeutic hypothermia in term and near-term infants with mild hypoxic ischemic encephalopathy. The JBI (Joanna Briggs Institute) tools were used to assess the risk of bias in the included studies. Random effects meta-analysis was conducted to find out the percentage of cooled infants who had only mild hypoxic ischemic encephalopathy. Results: A total of 3590 citations were screened, of which 13 were included. Of the 2783 infants who received therapeutic hypothermia, 573 had mild hypoxic ischemic encephalopathy. Meta-analysis found that 22% of the infants who underwent therapeutic hypothermia had only mild hypoxic ischemic encephalopathy (95% confidence interval: 16%-27%; I2 statistic = 90.5%). Five studies provided information on adverse effects of therapeutic hypothermia in mild hypoxic ischemic encephalopathy. The reported adverse effects were extreme hypothermia, bradycardia, hypoglycemia, sepsis, skin necrosis, pulmonary hypertension, and systemic hypotension. Limitation: The limitations included relatively small sample size and the lack of data for short- and long-term neurodevelopmental outcome. Conclusions: A significant proportion of infants who received therapeutic hypothermia had mild hypoxic ischemic encephalopathy. Randomized trials are urgently needed to evaluate the efficacy and safety of therapeutic hypothermia in infants with mild hypoxic ischemic encephalopathy.

scholarly journals Novel Neuroprotective Agents to Treat Neonatal Hypoxic-Ischemic Encephalopathy: Inter-Alpha Inhibitor Proteins

2020 ◽  
Vol 21 (23) ◽  
pp. 9193
Author(s):  
Liam M. Koehn ◽  
Xiaodi Chen ◽  
Aric F. Logsdon ◽  
Yow-Pin Lim ◽  
Barbara S. Stonestreet
Keyword(s):  
Brain Injury ◽  
Premature Infants ◽  
Time Window ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Neonatal Rat ◽  
Hypoxic Ischemic Encephalopathy ◽  
Limited Effectiveness ◽  
Ischemic Encephalopathy

Perinatal hypoxia-ischemia (HI) is a major cause of brain injury and mortality in neonates. Hypoxic-ischemic encephalopathy (HIE) predisposes infants to long-term cognitive deficits that influence their quality of life and place a large burden on society. The only approved treatment to protect the brain after HI is therapeutic hypothermia, which has limited effectiveness, a narrow therapeutic time window, and is not considered safe for treatment of premature infants. Alternative or adjunctive therapies are needed to improve outcomes of full-term and premature infants after exposure to HI. Inter-alpha inhibitor proteins (IAIPs) are immunomodulatory molecules that are proposed to limit the progression of neonatal inflammatory conditions, such as sepsis. Inflammation exacerbates neonatal HIE and suggests that IAIPs could attenuate HI-related brain injury and improve cognitive outcomes associated with HIE. Recent studies have shown that intraperitoneal treatment with IAIPs can decrease neuronal and non-neuronal cell death, attenuate glial responses and leukocyte invasion, and provide long-term behavioral benefits in neonatal rat models of HI-related brain injury. The present review summarizes these findings and outlines the remaining experimental analyses necessary to determine the clinical applicability of this promising neuroprotective treatment for neonatal HI-related brain injury.

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