Hypoxic-ischemic Encephalopathy Patients Research Articles

Correlation Study on the Prognostic Value of miR-21 and S-100B Protein Levels in Neonatal Hypoxic-Ischemic Encephalopathy Undergoing Hypothermia Therapy

: Objective To evaluate the variations in serum levels of microRNA-21 (miR-21) and S-100B protein in neonates with hypoxic-ischemic encephalopathy (HIE) after receiving hypothermia therapy and explore the correlation of these biomarkers with the neurodevelopmental prognosis of the infants. Methods This retrospective analysis included 90 neonatal HIE patients diagnosed and treated between January 2019 and December 2022. Real-time quantitative PCR and enzyme-linked immunosorbent assay (ELISA) methods were used to measure miR-21 and S-100B protein levels. Neurodevelopmental assessments were conducted at one year, and follow-up was performed using the Bayley Scales of Infant and Toddler Development third edition. Statistical analysis was carried out using SPSS software, with t-tests for continuous variables, chi-square tests for categorical data, Pearson correlation coefficient for correlation analysis, and multivariate regression analysis to adjust for confounding factors. Results After hypothermia therapy, the observation group showed a significant decrease in miR-21 and S-100B protein levels (P < 0.001), and neurodevelopmental scores were significantly higher than the control group (P < 0.05). Correlation analysis indicated a negative correlation between miR-21 and neurodevelopmental scores (r=-0.62, P < 0.001), as well as a negative correlation between S-100B protein levels (r=-0.76, P < 0.001). Multivariate regression analysis demonstrated that miR-21 levels and S-100B protein levels maintained independent negative correlations with neurodevelopmental scores (P < 0.001). Conclusion Hypothermia therapy significantly reduces serum levels of miR-21 and S-100B protein in neonatal HIE patients and may be associated with better prognosis. miR-21 and S-100B serve as prognostic biomarkers, aiding in predicting and improving the treatment outcomes and long-term prognosis of neonatal HIE.

The association between plasma IgG N-glycosylation and neonatal hypoxic-ischemic encephalopathy: a case-control study.

Hypoxic-ischemic encephalopathy (HIE) is one of severe neonatal brain injuries, resulting from inflammation and the immune response after perinatal hypoxia and ischemia. IgG N-glycosylation plays a crucial role in various inflammatory diseases through mediating the balance between anti-inflammatory and pro-inflammatory responses. This study aimed to explore the effect of IgG N-glycosylation on the development of HIE. This case-control study included 53 HIE patients and 57 control neonates. An ultrahigh-performance liquid chromatography (UPLC) method was used to determine the features of the plasma IgG N-glycans, by which 24 initial glycan peaks (GPs) were quantified. Multivariate logistic regression was used to examine the association between initial glycans and HIE, by which the significant parameters were used to develop a diagnostic model. Though receiver operating characteristic (ROC) curves, area under the curve (AUC) and 95% confidence interval (CI) were calculated to assess the performance of the diagnostic model. There were significant differences in 11 initial glycans between the patient and control groups. The levels of fucosylated and galactosylated glycans were significantly lower in HIE patients than in control individuals, while sialylated glycans were higher in HIE patients (p < 0.05). A prediction model was developed using three initial IgG N-glycans and fetal distress, low birth weight, and globulin. The ROC analysis showed that this model was able to discriminate between HIE patients and healthy individuals [AUC = 0.798, 95% CI: (0.716-0.880)]. IgG N-glycosylation may play a role in the pathogenesis of HIE. Plasma IgG N-glycans are potential noninvasive biomarkers for screening individuals at high risk of HIE.

Unconjugated bilirubin is correlated with the severeness and neurodevelopmental outcomes in neonatal hypoxic-ischemic encephalopathy

Unconjugated bilirubin (UB) levels during the first week after birth are related to outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). Clinical Sarnat staging of HIE, brain magnetic resonance imaging (MRI), hearing outcomes, and neurodevelopmental outcomes ≥ 1 year were used to correlate UB in 82 HIE patients. The initial UB level was significantly correlated with lactic acid levels. The peak UB was higher (p < 0.001) in stage I (10.13 ± 4.03 mg/dL, n = 34) than in stages II and III (6.11 ± 2.88 mg/dL, n = 48). Among the 48 patients receiving hypothermia treatment, a higher peak UB was significantly (p < 0.001) correlated with unremarkable brain MRI scans and unremarkable neurodevelopmental outcomes at age ≥ 1 year. The peak UB were higher (P = 0.015) in patients free of seizures until 1 year of age (6.63 ± 2.91 mg/dL) than in patients with seizures (4.17 ± 1.77 mg/dL). Regarding hearing outcomes, there were no significant differences between patients with and without hearing loss. The UB level in the first week after birth is an important biomarker for clinical staging, MRI findings, seizures after discharge before 1 year of age, and neurodevelopmental outcomes at ≥ 1 year of age.

Characteristics of neonatal hypoxic-ischemic encephalopathy at high altitude and early results of therapeutic hypothermia

BackgroundAltitude hypoxia and limited socioeconomic conditions may result in distinctive features of neonatal hypoxic-ischemic encephalopathy (HIE). Therapeutic hypothermia (TH) has not been used at altitude. We examined characteristics of HIE and early outcomes of TH in 3 centers at two high altitudes, 2 at 2,261 m and 1 at 3,650 m.MethodsThe incidence of HIE at NICUs was noted. TH was conducted when personnel and devices were available in 2019~2020. Standard inclusion criteria were used, with the addition of admission age >6 hours and mild HIE. Demographic and clinical data included gestational age, gender, weight, Apgar score, ethnics, age on admission, age at TH and clinical degree of HIE. EEG was monitored for 96 hours during hypothermia and rewarming. MRI was performed before discharge.ResultsThere was significant difference in ethnics, HIE degree, age at TH across 3 centers. The overall NICU incidence of HIE was 4.0%. Among 566 HIE patients, 114 (20.1%) received TH. 63 (55.3%) patients had moderate/severe HIE. Age at TH >6 hours occurred in 34 (29.8%) patients. EEG discharges showed seizures in 7~11% of patients, whereas spikes/sharp waves in 94~100%, delta brushes in 50~100%. After TH, MRI showed moderate to severe brain injury in 77% of patients, and correlated with center, demographic and clinical variables (Ps≤0.0003). Mortality was 5% during hospitalization and 11% after discharge until 1 year.ConclusionsAt altitude, the incidence of HIE was high and brain injury was severe. TH was limited and often late >6 hours. EEG showed distinct patterns attributable to altitude hypoxia. TH was relatively safe.Trial registrationThe study was registered on February 23, 2019 in Chinese Clinical Trial Register (ChiCTR1900021481).

Exploring the genetic landscape of neurotransmitter alterations in hypoxic-ischemic encephalopathy: A personalized medicine perspective

\textbf{Background:} Hypoxic-ischemic encephalopathy (HIE) is a neurological condition due to perinatal asphyxia, affecting brain areas with high metabolic rates and active myelination processes. The HIE has various origins and can be challenging to diagnose and treat. This study aimed to determine the origin of the clinical phenotype of patients who met the criteria for perinatal asphyxia at birth from personalized medicine. \textbf{Methods:} We evaluated 28 patients classified according to the SARNAT scale (i.e., clinical staging of HIE) and neurological anomalies by MRI scans. We used a next-generation sequencing panel for genes related to neurotransmitters and analyzed the statistical association between sequelae and other clinical variables using Fisher’s exact test. We also evaluated odds ratios (OR) with 95\% confidence intervals by binary logistic regression analysis adjusted for SARNAT, seizure, MRI scans, and genetic findings. \textbf{Results:} We identified 11 patients with neurotransmitter-related genetic alterations, such as glycine encephalopathy. Three had pathogenic variants (ALDH7A1, AMT, and SLC1A4), and eight had uncertain significance (TH, DBH, MYH2, CGH1, SLC6A5, ABAT, ALDH5A1, GLRB). One patient had 8p11.2 deletion, 14q11.2 deletion, and 10q11.22 duplication. Statistical analyses indicated that the presence or absence of mutations had a statistically significant association with sequelae (p-value = 0.054). Patients with a pathogenetic or uncertain mutation are associated with an increased risk of neurological sequelae (OR: 6.43; 95\% CI: 1.2 – 51.5; p-value = 0.044) regardless of clinical conditions such as the presence of seizures, severity of encephalopathy, alterations in the RMI or hypothermia therapy. \textbf{Conclusions:} Our findings suggest that neurotransmitter alterations are a critical factor significantly increasing the risk of HIE-related sequelae. Identifying these genetic alterations could lead to earlier and more precise diagnosis and treatment of HIE patients.

Association between continuous glucose profile during therapeutic hypothermia and unfavorable outcome in neonates with hypoxic-ischemic encephalopathy209 23-32

BackgroundThe detection and management of blood glucose abnormalities in high-risk neonates are crucial for clinical care. The objective of the study was to investigate the continuous glucose profile of hypoxic-ischemic encephalopathy (HIE) patients in the whole-process of therapeutic hypothermia (TH) and its association with clinical and neurological outcomes. MethodIn this single-center retrospective study, HIE patients who received both TH and continuous glucose monitoring (CGM) were recruited from March 2016 to September 2021. ResultsOf 47 neonates recruited, 24 had unfavorable outcome. Dysglycemia was most prevalent in the first 24 h of TH, among which hyperglycemia occurred more frequently. CGM showed that the duration, episodes and area under curve (AUC) of hypoglycemia were statistically different in neonates with different outcomes. The occurrence, longer duration, greater AUC of hypoglycemia and an early high coefficient of variation (CV%, CV = SD/mean) were associated with unfavorable outcomes (aOR 26.55 [2.02–348.5], aOR 2.11 [1.08–4.14], aOR 1.80 [1.11–2.91] and aOR respectively), while hyperglycemia was not. ConclusionDuring the whole process of TH, hypoglycemia and early unstable glycemic variability were strongly associated with unfavorable outcomes. CGM can instantly detect dysglycemia and facilitate precise glucose management in HIE neonates.

Troponin I, CK-MB, and inotropic score in hypoxic-ischemic encephalopathy and associated infant mortality

PurposeCardiovascular dysfunction is common in hypoxic-ischemic encephalopathy (HIE), which is one of the leading causes of multi-organ failure in neonates. We aimed to assess troponin I and creatine kinase myocardial band (CK-MB) levels, inotropic score (IS) in HIE patients, and their associations with HIE staging and mortality.MethodThe medical records of all HIE infants admitted to our unit between 2016 and 2018 were retrospectively analyzed. Demographic characteristics of the infants, seizures, anticonvulsive therapies, maximum inotrope doses, and the derived IS (dopamine dose [µg/kg/min] + dobutamine dose [µg/kg/min] + 100 × epinephrine dose [µg/kg/min]) and CK-MB and troponin-I levels obtained in the first six hours of life were compared according to HIE staging. Comparisons between survivors and non-survivors were made.ResultsThe study included data from 195 patients. Twenty-five patients were classified as stage 3, 116 as stage 2, and 54 as stage 1 HIE. Median Troponin-I, CK-MB level, and IS significantly differed by HIE staging (p < 0.01). The deceased infants had significantly higher median troponin I level [0.36 (0.02-3) vs. 0.16 (0.01–1.1) ng/ml; p = 0.006], median IS [20 (5-120) vs. 5 (5–10); p < 0.001], however, CK-MB values were comparable with survivors [129 (51–300) vs. 60.7 (31–300) ng/ml; p = 0.57]. The area under the curve was 0.93 for IS and 0.81 for Troponin I to predict mortality.ConclusionTroponin I, CK-MB, and IS could be successfully used as disease severity markers in HIE furthermore, troponin I and IS, are good predictors of mortality. These results need to be confirmed with larger prospective multi-center studies.

Acute Kidney Injury in Neonatal Hypoxic-Ischemic Encephalopathy Patients Treated with Therapeutic Hypothermia: Incidence and Risk Factors.

Studies in infants with hypoxic-ischemic encephalopathy (HIE) due to perinatal asphyxia have generally focused on neurological outcomes. Although acute kidney injury (AKI) rate decreased in advent of therapeutic hypothermia (TH), it is still a common and important entity. In this retrospective study, we aimed to investigate the risk factors for AKI in HIE patients treated with hypothermia. Infants treated with TH due to HIE were reviewed retrospectively and infants who developed AKI and not were compared. Ninety-six patients were enrolled in the study. AKI developed in 27 (28%) patients and 4 (14.8%) of them were stage III AKI. In the AKI group, gestational age of the patients was significantly higher (p = 0.035), the 1st minute Apgar score was significantly lower (p = 0.042), and convulsions (p = 0.002), amplitude-integrated electroencephalography disorders (p = 0.025), sepsis (p = 0.017), need for inotropic therapy (p = 0.001), need of invasive mechanical ventilation (p = 0.03), and systolic dysfunction in echocardiography (p = 0.022) were significantly higher. In logistic regression tests, Apgar score at the 1st minute was found to be independent risk factor for developing AKI. AKI has the potential to worsen the neurological damage and correlates with morbidities of perinatal asphyxia. It is important to determine the incidence and risk factors for developing AKI in this delicate group of patients to prevent further renal damage.

Maternal and Fetal Risk Factors for Neonatal Hypoxic-Ischemic Encephalopathy: A Retrospective Study.

Neonatal hypoxic-ischemic encephalopathy (HIE) leads to different degree of neurological sequelae. The incidence of HIE is relatively high, and the risk factors associated with HIE are still controversial. It is necessary to identify the risk factors associated with HIE. A total of 258 neonates (110 HIE patients and 148 controls) were enrolled in this study. The characteristics of pregnant women and fetuses during pregnancy and delivery were compared between HIE patients and controls, and the risk factors of HIE were analyzed. The proportions of premature infants, low-birth-weight infants and the levels of 1-minute Apgar score, 5-minute Apgar score in HIE group were significantly lower than those in control group, while the proportion of amniotic fluid contamination in the HIE group was significantly higher than those of the controls. When HIE was taken as the end point of 1-minute Apgar score, and 5-minute Apgar score, the cut-off value of 1-minute Apgar score was 3, and 5-minute Apgar score was 7 by receiver operating characteristic (ROC) curve analysis. The results of multivariate logistic regression analysis showed that low birth weight (<2.5 kg) (OR 1.780, 95% CI: 0.124-25.463, P=0.016), amniotic fluid contamination (OR 3.223, 95% CI: 1.049-9.901, P=0.041), low 1-minute Apgar score (≤3) (OR 92.425, 95% CI: 15.522-550.343, P<0.001), and low 5-minute Apgar score (≤7) (OR 12.641, 95% CI: 2.894-55.227, P=0.001) may increase risk of HIE. In addition, amniotic fluid contamination, low 1-minute Apgar score (≤3), and low 5-minute Apgar score (≤7) may increase risk of HIE among newborns born to women without previous childbearing history, but not in newborns born to women with previous childbearing history. Low birth weight (<2.5 kg), amniotic fluid contamination, low 1-minute Apgar score (≤3), and 5-minute Apgar score (≤7) may increase risk of HIE.

Graphic Intelligent Diagnosis of Hypoxic-Ischemic Encephalopathy Using MRI-Based Deep Learning Model

Introduction: Heterogeneous MRI manifestations restrict the efficiency and consistency of neuroradiologists in diagnosing hypoxic-ischemic encephalopathy (HIE) due to complex injury patterns. This study aimed to develop and validate an intelligent HIE identification model (termed as DLCRN, deep learning clinical-radiomics nomogram) based on conventional structural MRI and clinical characteristics. Methods: In this retrospective case-control study, full-term neonates with HIE and healthy controls were collected in two different medical centers from January 2015 to December 2020. Multivariable logistic regression analysis was implemented to establish the DLCRN model based on conventional MRI sequences and clinical characteristics. Discrimination, calibration, and clinical applicability were used to evaluate the model in the training and validation cohorts. Grad-class activation map algorithm was implemented to visualize the DLCRN. Results: 186 HIE patients and 219 healthy controls were assigned to the training, internal validation, and independent validation cohorts. Birthweight was incorporated with deep radiomics signatures to create the final DLCRN model. The DLCRN model achieved better discriminatory power than simple radiomics models, with an area under the curve (AUC) of 0.868, 0.813, and 0.798 in the training, internal validation, and independent validation cohorts, respectively. The DLCRN model was well calibrated and has clinical potential. Visualization of the DLCRN highlighted the lesion areas that conformed to radiological identification. Conclusion: Visualized DLCRN may be a useful tool in the objective and quantitative identification of HIE. Scientific application of the optimized DLCRN model may save time for screening early mild HIE, improve the consistency of HIE diagnosis, and guide timely clinical management.

MiR-19b-3p Inhibits Hypoxia-Ischemia Encephalopathy by Inhibiting SOX6 Expression via Activating Wnt/β-catenin Pathway.

Hypoxic-ischemic encephalopathy (HIE) is a detrimental factor in infant death and chronic disease. The specific pathogenesis is not entirely clear. Therefore, exploring the pathogenesis of HIE is critical. The expression of miR-19b-3p and SOX6 in umbilical blood of HIE patients was detected by qRT-PCR assay. HT22 cells were triggered with oxygen-glucose deprivation/reoxygenation (OGD/R) to construct the HIE cell model. Cell Counting Kit-8 (CCK-8) assay was used to estimate viability. SOD and MDA levels were detected by enzyme linked immunosorbent assay. Flow cytometry was implemented to ascertain neurocyte apoptosis. Cellular β-catenin immunofluorescence staining was used to detect the expression and distribution of β-catenin protein. Wnt signaling pathway activation was detected by TOPFlash/FOPFlash luciferase reporter assay. The targeting correlation of SOX6 and miR-19b-3p was corroborated by dual-luciferase reporter gene assay and RNA pull-down assay. MiR-19b-3p expression was once down-regulated, whilst SOX6 expression was up-regulated in HIE patients. MiR-19b-3p overexpression promoted cell proliferation, repressed cell apoptosis, oxidative stress response, and Wnt/β-catenin pathway activation in OGD/R-triggered HT22 cells. MiR-19b-3p negatively regulated SOX6 expression. SOX6 knockdown improved OGD/R-triggered HT22 cells injury via Wnt/β-catenin pathway activation. MiR-19b-3p overexpression suppressed OGD/R-triggered HT22 cell injury via inhibiting SOX6 expression via activating Wnt/β-catenin pathway.

Diagnostic role of optic nerve sheath diameter and brain blood flow in neonates with hypoxic-ischemic encephalopathy.

The primary aim was to study the optic nerve sheath diameter (ONSD) measurements and cerebral blood flows in neonates with hypoxic-ischemic encephalopathy (HIE) who were at risk of cerebral edema and to compare the measurements with healthy neonates. Neonates diagnosed as Stage II and III HIE patients were enrolled in the study group. ONSD measurements and blood flow Doppler studies in the first 24-48h of life during hypothermia and following hypothermia treatment. Magnetic resonance imaging (MRI) and transfontanelle ultrasonography were performed within the first 4-7days of life in all HIE patients. Saved US and MRI images were assessed by a blind pediatric radiologist later on. Data from a total of 63 infants (42 in the HIE group and 21 in the control group) were analyzed. Both the right and left ONSD measurements were comparable between HIE and control groups. However, both resistive index (RI) and pulsatility index (PI) of the middle cerebral artery were found to be significantly lower in HIE (0.69 ± 0.09 and 1.14 (0.98-1.30)) group when compared with controls (0.75 ± 0.04 and 1.41 (1.25-1.52)) (p < 0.01). Ultrasonographic ONSD measurements were significant and strongly correlated with MRI ONSD measurements for both sides (r = 0.91 and r = 0.93, p < 0.01). Doppler studies during normothermia were comparable with the control group and significantly increased following therapeutic hypothermia. Ultrasonographic ONSD measurements can be reliably performed in term neonates with high compatibility to MRI. No significant effect on ONSD measurements was found related to asphyxia and therapeutic hypothermia despite the significant alteration observed in Doppler studies.

Whole-volume ADC histogram of the brain as an image biomarker in evaluating disease severity of neonatal hypoxic-ischemic encephalopathy.

PurposeTo examine the diagnostic significance of the apparent diffusion coefficient (ADC) histogram in quantifying neonatal hypoxic ischemic encephalopathy (HIE).MethodsAn analysis was conducted on the MRI data of 90 HIE patients, 49 in the moderate-to-severe group, and the other in the mild group. The 3D Slicer software was adopted to delineate the whole brain region as the region of interest, and 22 ADC histogram parameters were obtained. The interobserver consistency of the two radiologists was assessed by the interclass correlation coefficient (ICC). The difference in parameters (ICC > 0.80) between the two groups was compared by performing the independent sample t-test or the Mann–Whitney U test. In addition, an investigation was conducted on the correlation between parameters and the neonatal behavioral neurological assessment (NBNA) score. The ROC curve was adopted to assess the efficacy of the respective significant parameters. Furthermore, the binary logistic regression was employed to screen out the independent risk factors for determining the severity of HIE.ResultsThe ADCmean, ADCmin, ADCmax,10th−70th, 90th percentile of ADC values of the moderate-to-severe group were smaller than those of the mild group, while the group's variance, skewness, kurtosis, heterogeneity, and mode-value were higher than those of the mild group (P < 0.05). All the mentioned parameters, the ADCmean, ADCmin, and 10th−70th and 90th percentile of ADC displayed positive correlations with the NBNA score, mode-value and ADCmax displayed no correlations with the NBNA score, the rest showed negative correlations with the NBNA score (P < 0.05). The area under the curve (AUC) of variance was the largest (AUC = 0.977; cut-off 972.5, sensitivity 95.1%; specificity 87.8%). According to the logistic regression analysis, skewness, kurtosis, variance, and heterogeneity were independent risk factors for determining the severity of HIE (OR > 1, P < 0.05).ConclusionsThe ADC histogram contributes to the HIE diagnosis and is capable of indicating the diffusion information of the brain objectively and quantitatively. It refers to a vital method for assessing the severity of HIE.

Brain Metabolic Connectivity Patterns in Patients with Prolonged Disorder of Consciousness after Hypoxic-Ischemic Injury: A Preliminary Study.

Understanding the patterns of brain glucose metabolism and connectivity in hypoxic-ischemic encephalopathy (HIE) patients with prolonged disorders of consciousness (DOC) may be of positive significance to the accurate assessment of consciousness and the optimization of neuromodulation strategy. We retrospectively analyzed the brain glucose metabolism pattern and its correlation with clinical Coma Recovery Scale-Revised (CRS-R) score in six HIE patients with prolonged DOC who had undergone 18F-deoxyglucose brain positron emission tomography scanning (FDG-PET). We also compared the differences in global metabolic connectivity patterns and the characteristics of several brain networks between HIE patients and healthy controls (HC). The metabolism of multiple brain regions decreased significantly in HIE patients, and the degree of local metabolic preservation was correlated with CRS-R score. The internal metabolic connectivity of occipital lobe and limbic system in HIE patients decreased, and their metabolic connectivity with frontal lobe, parietal lobe and temporal lobe also decreased. The metabolic connectivity patterns of default mode network, dorsal attention network, salience network, executive control network and subcortex network of HIE also changed compared with HC. The present study suggested that pattern of cerebral glucose metabolism and network connectivity of HIE patients with prolonged DOC were significantly different from those of healthy people.

A STUDY ON CLINICO-EPIDEMIOLOGICAL PROFILE AND CORRELATION BETWEEN CRANIAL ULTRASONOGRAPHY FINDINGS AND SEVERITY OF HYPOXIC ISCHAEMIC ENCEPHALOPATHY IN TERM NEONATES WITH PERINATAL ASPHYXIA ADMITTED AT SNCU IN A RURAL MEDICAL COLLEGE AND HOSPITAL IN WEST BENGAL, INDIA

Introduction: Perinatal asphyxia (PNA) is dened as failure to initiate and sustain breathing after birth. PNA leading to Hypoxic ischemic encephalopathy (HIE) is a dreaded neurological condition of the newborn. HIE is one of the important causes of neonatal morbidityBackground: and mortality in the rst week of life. Neuroimaging plays an essential role in the assessment of brain injury in HIE patients. 1.To studyObjectives: the clinico-epidemiological prole of term neonates with PNA 2.To study the serial cranial USG ndings in asphyxiated term neonates in rst week of life. 3. To assess the correlation between concurrent use of serial cranial ultrasonography ndings in term neonates with PNA and with regards to the severity of HIE. This hospital based cross-sectional study was conducted at SNCU of Bankura Smmilani MedicalMaterials And Methods: College and Hospital, Bankura. 100 cases of term neonates with HIE admitted at SNCU from 1st December 2021 to 31st January 2022 were taken as study population. All the relevant history was taken based on clinico-epidemiological parameters and detailed clinical- examination was done. Serial cranial USG was perfomed in rst week of life. In our study among 100 neonates, 62 (62%) cases belonged to HIE-I, 29 (29%) casesResult: with HIE-II, and 9(9%) cases with HIE-III. 42(42%) cases showed normal Cranial USG nding, 24(24%) cases showed cerebral oedema, 14 (14%) cases showed Gr-I IVH, 10(10%) cases showed Gr-II IVH, 6(6%) cases showed Gr-III IVH and 4(4%) cases showed Gr-IV IVH. Among HIE-I neonates, 42(67.7%) cases had normal cranial USG ndings and 20(32.2%) cases showed cerebral oedema. In HIE-II neonates, 4(13.7%) cases showed cerebral oedema, 14(48.2%) cases showed Gr-I IVH, 10(34.4%) cases showed Gr-II IVH and 1(3.44%) case showed Gr-III IVH. In neonates with HIE-III, 5 (55.5%) cases showed Gr-III IVH and 4 (44.4%) cases showed Gr-IV IVH. Correlation of cranial USG shows worsening trend with increasing severity of HIE as per Sarnat and Sarnat staging. Chi-square test revealed strong positive correlation. (p= 0.0001, rs=0.9) Conclusion: This study concluded that the serial cranial USG ndings in PNA neonates when done in rst week of life, revealed a strong positive correlation with the severity of HIE. Cranial USG is cost effective, easily available and is ideal for the initial assessment of neonates with HIE.

Spectrum of magnetic resonance imaging (MRI) patterns in hospitalised hypoxic ischemic encephalopathy babies in a tertiary care hospital of Odisha

Background: Hypoxic ischemic encephalopathy (HIE) refers to the CNS dysfunction associated with Perinatal Asphyxia (PA) which is an important causes of permanent damage to CNS tissue. MRI imaging methods attributes to better understanding of pathological events and disease progression that may provide decision regarding intervention. MRI has a higher sensitivity and is extremely valuable in assessing the extent of hypoxic-ischemic brain damage during the early postnatal period and later infancy. It is also more specific which clearly differentiates fluid filled cavities, oedema, gliosis and hemorrhage. On this background this study was undertaken to evaluate the MRI changes of all grades of HIE patients. They were also followed up at different time intervals for upto 1 year to correlate the MRI changes and neurodevelopmental outcome. Objectives: To find out different MRI findings in hypoxic ischemic encephalopathy babies. Assesment of severity of HIE from MR imaging and correlate these findings with clinical &amp; neurodevelopmental outcome. Methods: All hemodynamically stable HIE babies irrespective of their severity were subjected to MRI between day 7 and day 21 of life and their findings were interpreted.

Dihydroartemisinin attenuates hypoxic-ischemic brain damage in neonatal rats by inhibiting oxidative stress

Neonatal hypoxic-ischemic encephalopathy (HIE) induced by perinatal asphyxia is a major cause of neurological disability among infants. Dihydroartemisinin (DHA), derived from artemisinin, well known as an anti-malarial medicine, was proved to be able to inhibit oxidative stress and inflammation. However, whether those functions of DHA play roles in hypoxic-ischemic brain damage (HIBD), an animal model of HIE in patient which also been observed to have oxidative stress and inflammation, is unknown. In this study, we demonstrated that the DHA treatment on newborn rats significantly relieved the neuron loss and motor and cognitive impairment caused by HIBD. One of the underlying mechanisms is that DHA enhanced the anti-oxidant capacity of HIBD rats by up-regulating the total antioxidant capacity (T-AOC), gluathione reductase (GR) and catalase (CAT) while down regulating the pro-oxidative substances including hydrogen peroxide (H2O2), total nitric oxide synthase (T-NOS) and inducible nitric oxide synthase (iNOS). Thus, our study illustrated that DHA could alleviate the damage of brains and improve the cognitive and motor function of HIBD rats by inhibiting oxidative stress, provided an opportunity to interrogate potential therapeutics for affected HIE patients.

Efficacy and Prognosis of Hyperbaric Oxygen as Adjuvant Therapy for Neonatal Hypoxic-Ischemic Encephalopathy: A Meta-Analysis Study.

BackgroundPreclinical and clinical evidence suggests that hyperbaric oxygen therapy (HBOT) may benefit newborns. The effectiveness of HBOT for neonatal hypoxic-ischemic encephalopathy (HIE) remains controversial. We conducted a meta-analysis to evaluate the efficacy and prognosis of HBOT in neonates with HIE.MethodsA systematic search of eight databases was performed for available articles published between January 1, 2015, and September 30, 2020, to identify randomized controlled clinical trials (RCTs) on HBOT for neonatal HIE. Methodological quality assessment was performed by applying the simple procedure detailed by the Cochrane collaboration. Afterward, quality assessment and data analysis were performed using Revman 5.3 software. STATA 15 software was used to detect publication bias as well as for sensitivity analysis.ResultsA total of 46 clinical RCTs were selected for the study and included 4,199 patients with neonatal HIE. The results indicated that HBOT significantly improved the total efficiency (TEF) of treatment for neonatal HIE patients [odds ratio (OR) = 4.61, 95% confidence interval (CI) (3.70, 5.75), P < 0.00001] and reduced the risk of sequelae (OR = 0.23, 95% CI (0.16, 0.33), P < 0.00001) and the neonatal behavioral neurological assessment (NBNA) scores [mean difference (MD) = 4.51, 95%CI (3.83,5.19, P < 0.00001)].ConclusionIn light of the effectiveness of HBOT neonatal HIE, this meta-analysis suggested that HBOT can be a potential therapy for the treatment of neonatal HIE. Due to the heterogeneity of studies protocol and patient selection being only from China, more research is needed before this therapy can be widely implemented in the clinic.Protocol RegistrationPROSPERO (ID: CRD42020210639). Available online at: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020210639.

Efficacy of Magnesium Sulfate in Addition to Melatonin Therapy in Neonates With Hypoxic-Ischemic Encephalopathy.

Background: One of the most important causes of neonatal deaths in developing nations is birth asphyxia. Though the probability of a complete recovery is very low, hypoxic-ischemic encephalopathy (HIE) associated with asphyxia can be managed with multiple treatment options. The study evaluated the efficacy of the addition of magnesium sulfate (MgSO4) to melatonin therapy in neonates with HIE.Methodology: A prospective, observational study was conducted in the department of neonatal intensive care, Pakistan Institute of Medical Sciences Hospital, Islamabad, Pakistan from October 2020 to March 2021. All neonates with an Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score of less than five at five minutes, umbilical blood pH of less than 7.0, and moderate neonatal encephalopathy as detected on the modified Sarnat score which is a clinical tool used for the assessment of the severity of HIE were included in the study. Neonates with congenital abnormalities, intrauterine growth retardation, neonatal sepsis, and infants born to mothers with diabetes mellitus type 2 were excluded from the study. The infants were randomly assigned to either of the groups, i.e., i) group 1 included neonates who were administered at least three doses of magnesium sulfate (MgSO4) infusion in addition to melatonin, or ii) group 2 included neonates who were administered melatonin only. Blood samples of all neonates were evaluated and compared between the two groups.Results: A total of 90 neonates with HIE were included in the study. There was a predominance of female neonates. The mean ages of babies in group 1 and group 2 were 37.2 ± 0.43 and 37.3 ± 0.59 weeks, respectively. The mean weight on the term was 2.88 ± 0.11 and 2.89 ± 0.10, respectively. The Apgar score at 5 mins in group 1 was 1.73 ± 0.81 while in group 2, 1.82 ± 0.94. It was found that there was a more significant improvement in pH after 3 days and after one week of treatment in group 1 as compared to group 2. The mean pH in babies after three days of intervention was 7.23 ± 0.03 in group 1 which was significantly better than group 2 (p<0.0001). After seven days, the mean normalized to 7.39 ± 0.04 in group 1 (p < 0.0001). It was found that in patients in group 1, the mortality was lower than in group 2 (p < 0.0001).Conclusion: HIE patients who were administered melatonin in combination with magnesium sulfate yielded better patient outcomes. Thus, it was concluded that the use of magnesium sulfate as dual therapy with melatonin improved patient outcomes for HIE. However, it is recommended that similar studies are conducted with a wider range of parameters, such as duration of hospital stay and assessment of the neurological outcomes of the patients.

LncRNA HOTAIR mediates OGD/R-induced cell injury and angiogenesis in a EZH2-dependent manner.

Long non-coding RNAs (lncRNA) serve an important role in neonatal hypoxic-ischemic encephalopathy (HIE) have been reported to regulate the activity of HIE-associated proteins. The present study aimed to elucidate the role of Hox transcript antisense intergenic RNA (HOTAIR) in oxygen-glucose deprivation/reperfusion (OGD/R)-induced injury in human brain microvascular endothelial cells (hBMVECs). The levels of HOTAIR were evaluated in the serum of neonatal patients with HIE, and the effects of HOTAIR were evaluated using in vitro assays, such as reverse transcription-quantitative PCR to detect lncRNA and mRNA levels and western blot analysis to determine protein levels. Moreover, RNA immunoprecipitation assays were used to evaluate the association between HOTAIR and enhancer of zeste homolog 2 (EZH2), Cell Counting Kit-8 was used to detect cell viability, an endothelial monolayer cell permeability assay was used to analyze cell viability, TUNEL staining was used to detect the levels of apoptosis, a Transwell assay was used to evaluate cell invasion and a tube formation assay was used to analyze tube formation ability. In addition, the effects of HOTAIR and EZH2 on cell apoptosis and the invasive and tube formation abilities of hBMVECs were investigated using TUNEL, Transwell and tube formation assays, respectively. The results showed that the expression levels of HOTAIR were markedly increased both in neonatal HIE patients and in the OGD/R injury in vitro model. HOTAIR knockdown reduced hBMVEC viability, enhanced cell permeability and apoptosis, in addition to decreasing the expression levels of tight junction-related proteins, such as zonula occludens-1, occluden, Claudin5 and vascular endothelial-cadherin. However, EZH2 overexpression reversed the effects of HOTAIR silencing on hBMVECs. Additionally, HOTAIR knockdown enhanced the migratory and tube formation abilities of OGD/R-induced hBMVECs, which were also reversed by EZH2 overexpression. Overall, the present study revealed an association between the HOTAIR/EZH2 axis and brain microvascular endothelial cell injury and angiogenesis, which provides a novel insight into the molecular mechanism underlying stroke or the development of new pharmacotherapies.