Predictors of Outcomes in Hypoxic-Ischemic Encephalopathy following Hypothermia: A Meta-Analysis

Abstract

<b><i>Introduction:</i></b> Prediction of neurodevelopmental outcome in infants with hypoxic-ischemic encephalopathy remains an important challenge. Various studies have shown that the predictive ability of different modalities changed after the introduction of therapeutic hypothermia. This paper reviews the diagnostic test accuracy of the different modalities that are being used to predict neurodevelopmental outcomes following therapeutic hypothermia. <b><i>Methods:</i></b> A systematic literature search was performed using Embase and PubMed. Two reviewers independently included eligible studies and extracted data. The quality of the studies was assessed using the Quality in Prognosis Studies Tool. Meta-analyses were performed where possible. <b><i>Results:</i></b> Forty-seven articles and 3 conference abstracts were included, reporting on 3,072<i></i>infants of whom 39% died or had an adverse neurodevelopmental outcome. A meta-analysis could be performed using 37 articles on (amplitude-integrated) electroencephalography (EEG), conventional magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI), and proton magnetic resonance spectroscopy (<sup>1</sup>H-MRS). Amplitude-integrated EEG (aEEG) at 24 and 72 h showed similar high diagnostic OR, while aEEG at 6 h and EEG performed less, both due to a low specificity. For MRI, most studies reported scoring systems in which early (<8 days) MRI performed better than late (≥8 days) MRI. Injury to the posterior limb of the internal capsule on MRI or to the thalami on DWI were strong individual predictors, as was an increased lactate/N-acetylaspartate peak on <sup>1</sup>H-MRS. <b><i>Conclusions:</i></b> In the era of therapeutic hypothermia, the different modalities remain good predictors of neurodevelopmental outcome. However, timing should be taken into account. aEEG may initially be false positive and gets more reliable after 24 h. In contrast, MRI should be used during the first week, as its predictive value decreases afterwards.

Connexin Hemichannel Mimetic Peptide Attenuates Cortical Interneuron Loss and Perineuronal Net Disruption Following Cerebral Ischemia in Near-Term Fetal Sheep

“…Damage to the parasagittal cortex in term infants after HI is highly associated with poor neurodevelopmental outcomes including cognitive and learning deficits and epilepsy [28][29][30][31]. In the present study, cerebral ischemia in near-term fetal sheep was associated with a pattern of parasagittal cortical damage after 7 days of recovery, which included a marked reduction in the survival of cortical GAD + , parvalbumin + , calretinin + , and calbindin + interneuron populations.…”

Early Diagnostics and Early Intervention in Neurodevelopmental Disorders—Age-Dependent Challenges and Opportunities

“…These tools are certainly useful but generally, they are used on specific indication. For instance, continuous and amplitude-integrated EEG and somatosensory evoked potentials are applied in infants with hypoxic-ischemic encephalopathy (HIE) [ 41 , 42 ] and sensory assessments are used in preterm infants with behavioral issues [ 43 , 44 ]. Therefore, these instruments fall beyond the scope of this review.…”

Which factors predict outcomes of neonates with hypoxic-ischemic encephalopathy following therapeutic hypothermia?

“…4) A brain magnetic resonance imaging (MRI) scan is conducted to determine the extent and degree of brain injury in infants with HIE. 3,4) Many additional tests, such as diffusion-weighted imaging (DWI), diffusion-tensor imaging, and proton magnetic resonance spectroscopy ( 1 H-MRS), have recently been used. [3][4][5] Ouwehand et al 4) performed a meta-analysis of the predictors of outcomes in HIE following hypothermia using 37 articles on aEEG, MRI, DWI, and 1 H-MRS.…”

“…3,4) Many additional tests, such as diffusion-weighted imaging (DWI), diffusion-tensor imaging, and proton magnetic resonance spectroscopy ( 1 H-MRS), have recently been used. [3][4][5] Ouwehand et al 4) performed a meta-analysis of the predictors of outcomes in HIE following hypothermia using 37 articles on aEEG, MRI, DWI, and 1 H-MRS. This study showed that abnormal aEEG findings at 36 h (diagnostic odds ratio [DOR], 62.7; 95% CI, 19.5-202.0; P < 0.001), injury to the posterior limb of the internal capsule on MRI (DOR, 39.5; 95% CI, 16.9-92.3; P < 0.001) or the thalami on DWI (DOR, 50.2; 95% CI, 19.1-131.7; P < 0.001), and an increased lactate/N-acetylaspartate peak on 1 H-MRS within 7 days (DOR, 64.8; 95% CI, 28.8-145.9; P < 0.001) are strong predictors of adverse neurodevelopmental outcomes.…”

“…5) Some studies have suggested that additional tests, such as near-infrared spectroscopy and somatosensory-evoked potentials, could also be used as predictive factors. 2,4) Bhasin et al suggested that elevated cardiac enzymes, such as serum CK-T (P < 0.001), CK-MB (P < 0.001), and troponin T (P = 0.002); abnormal electrocardiography findings (P < 0.001); and a decreased left ventricular ejection fraction and right ventricular ejection fraction on echocardiography (P < 0.001), were associated with mortality and severity in infants with HIE. 6) In addition,…”