Utilization of Therapeutic Hypothermia and Neurological Injury in Neonates with Mild Hypoxic-Ischemic Encephalopathy: A Report from Children's Hospital Neonatal Consortium

2020 ◽  
Author(s):  
Rakesh Rao ◽  
Ulrike Mietzsch ◽  
Robert DiGeronimo ◽  
Shannon E. Hamrick ◽  
Maria L. V. Dizon ◽  
...  
Keyword(s):  
Brain Injury ◽  
White Matter ◽  
Therapeutic Hypothermia ◽  
Fetal Distress ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neurological Injury ◽  
Mri Scans ◽  
History Of ◽  
Magnetic Resonance Imaging Mri ◽  
Ischemic Encephalopathy

Objective This study was aimed to describe utilization of therapeutic hypothermia (TH) in neonates presenting with mild hypoxic-ischemic encephalopathy (HIE) and associated neurological injury on magnetic resonance imaging (MRI) scans in these infants. Study Design Neonates ≥ 36 weeks' gestation with mild HIE and available MRI scans were identified. Mild HIE status was assigned to hyper alert infants with an exaggerated response to arousal and mild HIE as the highest grade of encephalopathy recorded. MRI scans were dichotomized as “injury” versus “no injury.” Results A total of 94.5% (257/272) neonates with mild HIE, referred for evaluation, received TH. MRI injury occurred in 38.2% (104/272) neonates and affected predominantly the white matter (49.0%, n = 51). Injury to the deep nuclear gray matter was identified in (10.1%) 20 infants, and to the cortex in 13.4% (n = 14 infants). In regression analyses (odds ratio [OR]; 95% confidence interval [CI]), history of fetal distress (OR = 0.52; 95% CI: 0.28–0.99) and delivery by caesarian section (OR = 0.54; 95% CI: 0.31–0.92) were associated with lower odds, whereas medical comorbidities during and after cooling were associated with higher odds of brain injury (OR = 2.31; 95% CI: 1.37–3.89). Conclusion Majority of neonates with mild HIE referred for evaluation are being treated with TH. Odds of neurological injury are over two-fold higher in those with comorbidities during and after cooling. Brain injury predominantly involved the white matter. Key Points

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 Correlation Between White Matter Injury Identified by Neonatal Diffusion Tensor Imaging and Neurodevelopmental Outcomes Following Term Neonatal Asphyxia and Therapeutic Hypothermia: An Exploratory Pilot Study

2019 ◽  
Vol 34 (10) ◽  
pp. 556-566 ◽  
Author(s):  
Gwendolyn J. Gerner ◽  
Eric I. Newman ◽  
V. Joanna Burton ◽  
Brenton Roman ◽  
Elizabeth A. Cristofalo ◽  
...  
Keyword(s):  
Diffusion Tensor Imaging ◽  
White Matter ◽  
Pilot Study ◽  
Therapeutic Hypothermia ◽  
Diffusion Tensor ◽  
White Matter Injury ◽  
Hypoxic Ischemic Encephalopathy ◽  
Group Differences ◽  
Neurodevelopmental Outcomes ◽  
Ischemic Encephalopathy

Aim: Hypoxic-ischemic encephalopathy is associated with damage to deep gray matter; however, white matter involvement has become recognized. This study explored differences between patients and clinical controls on diffusion tensor imaging, and relationships between diffusion tensor imaging and neurodevelopmental outcomes. Method: Diffusion tensor imaging was obtained for 31 neonates after hypoxic-ischemic encephalopathy treated with therapeutic hypothermia and 10 clinical controls. A subgroup of patients with hypoxic-ischemic encephalopathy (n = 14) had neurodevelopmental outcomes correlated with diffusion tensor imaging scalars. Results: Group differences in diffusion tensor imaging scalars were observed in the putamen, anterior and posterior centrum semiovale, and the splenium of the corpus callosum. Differences in these regions of interest were correlated with neurodevelopmental outcomes between ages 20 and 32 months. Conclusion: Therapeutic hypothermia may not be a complete intervention for hypoxic-ischemic encephalopathy, as neonatal white matter changes may continue to be evident, but further research is warranted. Patterns of white matter change on neonatal diffusion tensor imaging correlated with neurodevelopmental outcomes in this exploratory pilot study.

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.

Cardiac Dysfunction in Neonatal HIE Is Associated with Increased Mortality and Brain Injury by MRI

2021 ◽  
Author(s):  
Gabriel Altit ◽  
Sonia L. Bonifacio ◽  
Carolina V. Guimaraes ◽  
Shazia Bhombal ◽  
Ganesh Sivakumar ◽  
...  
Keyword(s):  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Cardiac Dysfunction ◽  
Systolic Function ◽  
Brain Magnetic Resonance Imaging ◽  
Lv Function ◽  
Severe Brain Injury ◽  
Key Points ◽  
Magnetic Resonance Imaging Mri ◽  
Ischemic Encephalopathy

Objective Describe the association between cardiac dysfunction and death or moderate-to-severe abnormalities on brain magnetic resonance imaging (MRI) in neonates undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE). Study Design Retrospective study in neonates with moderate or severe HIE undergoing therapeutic hypothermia between 2008 and 2017. Primary outcome was death or moderate-to-severe brain injury using the Barkovich score. Conventional and speckle-tracking echocardiography measures were extracted from available echocardiograms to quantify right (RV) and left (LV) ventricular functions. Results A total of 166 newborns underwent therapeutic hypothermia of which 53 (36.5%) had echocardiography performed. Ten (19%) died prior to hospital discharge, and 11 (26%) had moderate-to-severe brain injury. There was no difference in chronologic age at echocardiography between the normal and adverse outcome groups (22 [±19] vs. 28 [±21] hours, p = 0.35). Cardiac findings in newborns with abnormal outcome included lower systolic and diastolic blood pressure (BP) at echocardiography (p = 0.004) and decreased tricuspid annular plane systolic excursion (a marker of RV systolic function; p = 0.01), while the ratio of systolic pulmonary artery (PA) pressure to systolic BP indicated isosystemic pressures (>2/3 systemic) in both groups. A multilogistic regression analysis, adjusting for weight and seizure status, indicated an association between abnormal outcome and LV function by longitudinal strain, as well as by ejection fraction. Conclusion Newborns who died or had moderate–to-severe brain injury had a higher incidence of cardiac dysfunction but similar PA pressures when compared with those who survived with mild or no MRI abnormalities. Key Points

Epilepsy Outcome in Cooled Hypoxic–Ischemic Encephalopathic Newborns

2018 ◽  
Vol 07 (01) ◽  
pp. 008-013
Author(s):  
Barbara Podestà ◽  
Eleonora Briatore ◽  
Andrea Boghi ◽  
Giulia Pomero ◽  
Luigi Gozzoli ◽  
...  
Keyword(s):  
Status Epilepticus ◽  
Therapeutic Hypothermia ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neurologically Impaired ◽  
Continuous Eeg ◽  
Continuous Eeg Monitoring ◽  
Spontaneous Improvement ◽  
Eeg Recordings ◽  
Magnetic Resonance Imaging Mri ◽  
Ischemic Encephalopathy

AbstractEpilepsy is a frequent consequence of neonatal hypoxic–ischemic encephalopathy. It is not yet known if the introduction of therapeutic hypothermia modifies the rate and the characteristics of epilepsy. We report on 59 infants who suffered from hypoxic–ischemic encephalopathy and underwent therapeutic hypothermia. Birth, physiological and biochemical data, frequent electroencephalography (EEG) recordings or continuous EEG monitoring, and magnetic resonance imaging (MRI) were documented in the neonatal period. Prechtl's General Movements evaluation was performed and the Griffiths Scales of Mental Development were applied at 3 and 24 months of age, respectively. Children were followed up for at least 3 years (mean 5 ± 1.6 years). Six children (10%) developed epilepsy. All of them had a severe hypoxic–ischemic encephalopathy and were neurologically impaired at 2 years of age. Furthermore, all of them had a severe pattern of MRI injury and poor neonatal EEG backgrounds. Four of them suffered from neonatal status epilepticus. Four out of six showed a similar epileptic pattern: their epilepsy started early; it was drug resistant; it required an aggressive polytherapy; and it showed a spontaneous improvement after 2 years. The rate of epilepsy in our cooled infants was similar to those reported in other studies on noncooled ones. Only severe hypoxic–ischemic encephalopathy predisposed the cooled infants toward epilepsy. Neonatal status epilepticus and persisting poor EEG backgrounds were predictive of the development of epilepsy in our sample.

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 Association of brain injury and neonatal cytokine response during therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy

2015 ◽  
Vol 79 (5) ◽  
pp. 742-747 ◽  
Author(s):  
Janet E. Orrock ◽  
Karuna Panchapakesan ◽  
Gilbert Vezina ◽  
Taeun Chang ◽  
Kari Harris ◽  
...  
Keyword(s):  
Brain Injury ◽  
Therapeutic Hypothermia ◽  
Cytokine Response ◽  
Hypoxic Ischemic Encephalopathy ◽  
Ischemic Encephalopathy

scholarly journals Neurodevelopmental Outcomes in Neonates with Mild Hypoxic Ischemic Encephalopathy Treated with Therapeutic Hypothermia

2019 ◽  
Vol 36 (13) ◽  
pp. 1337-1343 ◽  
Author(s):  
Rakesh Rao ◽  
Shamik Trivedi ◽  
Amy Distler ◽  
Steve Liao ◽  
Zachary Vesoulis ◽  
...  
Keyword(s):  
Therapeutic Hypothermia ◽  
Infant Development ◽  
Developmental Outcomes ◽  
Hypoxic Ischemic Encephalopathy ◽  
Neurological Injury ◽  
Control Group ◽  
Neurodevelopmental Outcomes ◽  
Severe Injuries ◽  
The Mean ◽  
Ischemic Encephalopathy

Objective To review developmental outcomes of neonates with mild hypoxic-ischemic encephalopathy (HIE) treated with therapeutic hypothermia (TH). Study Design Neonates ≥35 weeks' gestation with mild HIE/TH (TH group, n = 30) were matched with healthy term-born infants (control group, n = 30) and reviewed for the presence and severity of magnetic resonance imaging (MRI)-detected neurological injury. Neurodevelopmental outcomes were assessed using the Bayley Scales of Infant Development (BSID). Results MRI injury was present in 13/30 (43.3%) neonates (11 mild, 1 moderate, and 1 severe injuries) in the TH group. The mean (standard deviation [SD]) corrected age at BSID III was 29.3 (3.9) months in the controls compared with 14.7 (3.9) months in the TH group (p < 0.01). The mean (SD) cognitive, language, and motor composite scores in neonates in the TH group (n = 16, 53.3%) and control groups (n = 30, 100%) were 99.4 (17.1) versus 93.0 (12.3), (p = 0.15), 89.5 (15.5) versus 100.2 (18.4), (p = 0.054), and 93.1 (15.4) versus 100.8 (16.3) (p = 0.13), respectively. Conclusion Developmental outcomes of neonates with mild HIE/TH were similar to healthy, term-born neonates.

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