Severe Hypoxic-ischemic Encephalopathy Research Articles

Quantitative EEG features during the first day correlate to clinical outcome in perinatal asphyxia.

To assess whether computational electroencephalogram (EEG) measures during the first day of life correlate to clinical outcomes in infants with perinatal asphyxia with or without hypoxic-ischemic encephalopathy (HIE). We analyzed four-channel EEG monitoring data from 91 newborn infants after perinatal asphyxia. Altogether 42 automatically computed amplitude- and synchrony-related EEG features were extracted as 2-hourly average at very early (6 h) and early (24 h) postnatal age; they were correlated to the severity of HIE in all infants, and to four clinical outcomes available in a subcohort of 40 newborns: time to full oral feeding (nasogastric tube NGT), neonatal brain MRI, Hammersmith Infant Neurological Examination (HINE) at three months, and Griffiths Scales at two years. At 6 h, altogether 14 (33%) EEG features correlated significantly to the HIE grade ([r]= 0.39-0.61, p < 0.05), and one feature correlated to NGT ([r]= 0.50). At 24 h, altogether 13 (31%) EEG features correlated significantly to the HIE grade ([r]= 0.39-0.56), six features correlated to NGT ([r]= 0.36-0.49) and HINE ([r]= 0.39-0.61), while no features correlated to MRI or Griffiths Scales. Our results show that the automatically computed measures of early cortical activity may provide outcome biomarkers for clinical and research purposes. The early EEG background and its recovery after perinatal asphyxia reflect initial severity of encephalopathy and its clinical recovery, respectively. Computational EEG features from the early hours of life show robust correlations to HIE grades and to early clinical outcomes. Computational EEG features may have potential to be used as cortical activity biomarkers in early hours after perinatal asphyxia.

Early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy: a multicentre double-blind pilot randomised controlled trial

ObjectiveTo examine the feasibility of early and extended erythropoietin monotherapy after hypoxic ischaemic encephalopathy (HIE).DesignDouble-blind pilot randomised controlled trial.SettingEight neonatal units in South Asia.PatientsNeonates (≥36 weeks) with moderate or severe...

Survival, but not the severity of hypoxic–ischemic encephalopathy, is associated with higher mean arterial blood pressure after cardiac arrest: a retrospective cohort study

BackgroundThis study investigates the association between the mean arterial blood pressure (MAP), vasopressor requirement, and severity of hypoxic–ischemic encephalopathy (HIE) after cardiac arrest (CA).MethodsBetween 2008 and 2017, we retrospectively analyzed the MAP 200 h after CA and quantified the vasopressor requirements using the cumulative vasopressor index (CVI). Through a postmortem brain autopsy in non-survivors, the severity of the HIE was histopathologically dichotomized into no/mild and severe HIE. In survivors, we dichotomized the severity of HIE into no/mild cerebral performance category (CPC) 1 and severe HIE (CPC 4). We investigated the regain of consciousness, causes of death, and 5-day survival as hemodynamic confounders.ResultsAmong the 350 non-survivors, 117 had histopathologically severe HIE while 233 had no/mild HIE, without differences observed in the MAP (73.1 vs. 72.0 mmHg, pgroup = 0.639). Compared to the non-survivors, 211 patients with CPC 1 and 57 patients with CPC 4 had higher MAP values that showed significant, but clinically non-relevant, MAP differences (81.2 vs. 82.3 mmHg, pgroup &amp;lt; 0.001). The no/mild HIE non-survivors (n = 54), who regained consciousness before death, had higher MAP values compared to those with no/mild HIE (n = 179), who remained persistently comatose (74.7 vs. 69.3 mmHg, pgroup &amp;lt; 0.001). The no/mild HIE non-survivors, who regained consciousness, required fewer vasopressors (CVI 2.1 vs. 3.6, pgroup &amp;lt; 0.001). Independent of the severity of HIE, the survivors were weaned faster from vasopressors (CVI 1.0).ConclusionsAlthough a higher MAP was associated with survival in CA patients treated with a vasopressor-supported MAP target above 65 mmHg, the severity of HIE was not. Awakening from coma was associated with less vasopressor requirements. Our results provide no evidence for a MAP target above the current guideline recommendations that can decrease the severity of HIE.

Association between decreased cord blood inter-alpha inhibitor levels and neonatal encephalopathy at birth

BackgroundInter-alpha inhibitor proteins (IAIPs) are structurally related proteins found in the systemic circulation with immunomodulatory anti-inflammatory properties. Reduced levels are found in inflammatory related conditions including sepsis and necrotizing enterocolitis, and in neonatal rodents after exposure to hypoxia ischemia. In the current study, cord blood IAIP levels were measured in neonates with and without exposure to hypoxic-ischemic encephalopathy (HIE). MethodsThis is a prospective cohort study including infants born ≥36 weeks over a one-year period. Term pregnancies were divided into two groups: a “reference control” (uncomplicated term deliveries), and “moderate to severe HIE” (qualifying for therapeutic hypothermia). IAIPs were quantified using a sensitive ELISA on the cord blood samples. ResultsThe study included 57 newborns: Reference control group (n = 13) and moderate/severe HIE group (n = 44). Measurement of IAIP cord blood concentrations in moderate to severe HIE group [278.2 (138.0, 366.0) μg/ml] revealed significantly lower IAIP concentrations compared with the control group [418.6 (384.5, 445.0) μg/ml] (p = 0.002). ConclusionsThese findings suggest a potential role for IAIPs as indicators of neonates at risk for HIE. IAIP levels could have diagnostic implications in the management of HIE. Future research is required to explore the relationship between HIE and IAIPs as biomarkers for disease severity. Category of studyTranslational.

Main features and disease outcome of congenital myotonic dystrophy - experience from a single tertiary center

Congenital myotonic dystrophy type 1 (CDM1) is a rare neuromuscular disease. The aim of our study was to evaluate clinical variability of CDM1 and factors that may influence survival in CDM1. Research included 24 pediatric patients with CDM1. Most of our patients had some form of hypoxic ischemic encephalopathy (HIE) (74%), from mild to severe. Prolonged and complicated deliveries (75%), high percentage of children resuscitated at birth (57%) and respiratory insufficiency (46%) with consequent hypoxia were the main reasons that could explain high percentage of HIE. Therapeutic hypothermia was applied in three children with poor outcome. Median survival of all CDM1 was 14.2 ±1.5 years. Six patients had a fatal outcome (25%). Their mean age of death was 3.0±2.8 years. Poor prognostic factors for the survival of our CDM1 patients were: preterm delivery, resuscitation at birth, severe HIE, hypothermia treatment and permanent mechanical ventilation. Respiratory insufficiency was the main life-threatening factor. Our data clearly indicates the need to develop natural history studies in CDM1 in order to enhance the standards of care and to develop clinical trials investigating causative therapies in pediatric patients with CDM1.

Association between Early Basal Ganglia and Thalami Perfusion Assessed by Color Doppler Ultrasonography and Brain Injury in Infants with Hypoxic-Ischemic Encephalopathy: A Prospective Cohort Study

ObjectiveTo evaluate associations between neurologic outcomes and early measurements of basal ganglia (BG) and thalamic (Th) perfusion using color Doppler ultrasonography (CDUS) in infants with hypoxic-ischemic encephalopathy (HIE). Study designProspective study of infants with mild (n=18), moderate (n=17), and severe HIE (n=14) and controls (n=17). Infants with moderate-severe HIE received therapeutic hypothermia (TH). CDUS was performed at 24-36h and brain magnetic resonance imaging (MRI) at a median of 10 days. Development was followed through 2.5 to 5 years. The primary outcome was the association between BG and Th perfusion and brain MRI injury. Secondary analyses focused on associations between perfusion measurements and admission neurologic examinations, MRI scores in infants treated with TH, and motor and sensory disability, or death. An exploratory analysis assessed the accuracy of BG and Th perfusion to predict brain MRI injury in infants treated with TH. ResultsIncreased BG and Th perfusion on CDUS was observed in infants with severe MRI scores and those with significant motor and neurosensory disability or death through 2.5 to 5 years (p<0.05). Infants with severe HIE showed increased BG and Th perfusion (p< .005) compared with infants with moderate HIE. No differences were identified between the between the control and mild HIE groups. Th perfusion ≥ 0.237 cm/sec (AUC of 0.824) correctly classified 80% of infants with severe MRI scores. ConclusionEarly dynamic CDUS of the BG and Th is a potential biomarker of severe brain injury in infants with HIE and may be a useful adjunct to currently used assessments.

Early Postnatal Administration of Erythropoietin and Its Association with Neurodevelopmental Outcomes and Incidence of Intraventricular Hemorrhage and Hypoxic-Ischemic Encephalopathy: A Four-Week Observational Study

This study aimed to investigate the impact of early erythropoietin (EPO) administration on the neurodevelopment of newborns, specifically focusing on its effects on hypoxic-ischemic encephalopathy (HIE) and intraventricular hemorrhage (IVH). The primary objective was to determine whether early EPO administration could impact the short-term neurodevelopmental outcomes and provide safety in neonates at risk for neurodevelopmental disorders. Conducted at the “Louis Turcanu” Children’s Emergency Clinical Hospital in Timisoara, Romania, this observational study included 121 neonates receiving EPO and 130 No EPO controls. EPO was administered within the first 48 h of life, with doses of 1000 U/kg that escalated to 2000 U/kg if necessary. Besides observing the occurrence of IVH and HIE, this study measured clinical and biochemical markers, including LDH, blood glucose, urea, creatinine, CPK, CRP, PCT, and erythropoietin levels alongside hematology and coagulation profiles. There were no significant differences in baseline characteristics between the groups. The EPO group showed significant reductions in LDH levels from days 1–3 to 7–10 (695.0 U/L to 442.0 U/L) and the APTT value (54.0 s) compared with the No EPO group (38.0 s). Notably, early EPO administration was associated with a significant decrease in HIE severity (beta coefficient: −0.38, p = 0.001). Additionally, lower gestational ages and hemoglobin levels correlated with increased severity of HIE. By week four, there was a significant reduction in moderate and severe HIE cases in the EPO group compared with controls (p = 0.001). Early administration of EPO in neonates significantly reduced the severity of IVH and HIE, suggesting its potential as a neuroprotective agent in neonatal care.

Coma Prevalence in Critical Care Units in Chile: Results of a Cross-Sectional Survey on World Coma Day.

The purpose of this study was to assess the prevalence of coma among patients in critical care units in Chile. We also aimed to provide insight into the demographic characteristics, etiologies, and complications associated with coma. A single day cross-sectional study was conducted through a national survey of public and private hospitals with critical and intensive cardiac care units across Chile. Data were collected using an online questionnaire that contained questions regarding critically ill patients' information, demographic characteristics, etiology and duration of coma, medical complications, and support requirements. A total of 84% of all health facilities answered, accounting for a total of 2,708 patients. The overall coma prevalence was 2.9%. The median age of the comatose patients was 61 years (interquartile range 50-72) and 66.2% were male. The median coma duration was five days (interquartile range 2-9). Cerebral hemorrhage was the most common etiology, followed by severe hypoxic-ischemic encephalopathy, acute ischemic stroke, and traumatic brain injury. A total of 48.1% of coma patients experienced acute and ongoing treatment complications, with pneumonia being the most common complication, and 97.4% required support during comatose management. This study provides an overview of the prevalence of coma in Chilean critical and cardiac care units. Coma is a common condition. Comatose patients frequently experience medical complications during their hospitalization.

Cardiac Troponin I as an Early Prognostic Indicator in Asphyxiated Neonates

Background: Myocardial damage, estimated to occur in 28%–73% of asphyxiated neonates, 1 is a major cause of mortality in perinatal asphyxia, and survivors can show significant myocardial morbidity as well. 2 Study Setting and Design: This study is a hospital-based prospective cohort study, done at the pediatrics department of a tertiary care hospital in northern India, from December 2020 to June 2022. Materials and Methods: 40 asphyxiated neonates with an APGAR score of &lt;7 at 1 minute of life, as per the WHO–Neonatal Perinatal Database, were included in the study. They were graded as hypoxic ischemic encephalopathy (HIE) I (mild), II (moderate), and III (severe) based on Sarnat and Sarnat staging. The blood samples at 0 and 6 hours of life were taken for studying successive changes in the values of high-sensitivity cardiac troponin I (hs-cTnI) and creatinine phospho-kinase-myocardium-bound (CPK-MB). These were compared with various parameters such as electrocardiograph (ECG) findings, 2D-ECHO abnormalities, HIE severity, and outcome. Results: Among the two biomarkers that were assessed, hs-cTnI had the highest diagnostic value for detecting myocardial injury and was corelated with the severity of HIE and higher chances of death. Conclusion: The troponin I levels, in contrast to CPK-MB levels, were significantly associated with the outcome of the patient, implying that asphyxiated babies with elevated troponin I levels have a poorer prognosis and a higher mortality rate.

Incidence of encephalopathy and comorbidity in infants with perinatal asphyxia: a comparative prospective cohort study.

Programs that aim to improve the detection hypoxic-ischemic encephalopathy (HIE) should establish which neonates suffering from perinatal asphyxia need to be monitored within the first 6 h of life. An observational prospective cohort study of infants with gestational age ≥35 weeks, and above 1,800g, were included according to their arterial cord pH value (ApH): ≤7.00 vs. 7.01-7.10. Data was collected including obstetrical history, as well as neonatal comorbidities, including the presence of HIE, that happened within 6 h of life. A standardized neurological exam was performed at discharge. There were 9,537 births; 176 infants with ApH 7.01-7.10 and 117 infants with ApH ≤7.00. All 9 cases with moderate-to-severe HIE occurred among infants with ApH ≤7.00. The incidence of global and moderate-severe HIE was 3/1,000 and 1/1,000 births, respectively. Outcome at discharge (abnormal exam or death) showed an OR 12.03 (95% CI 1.53, 94.96) in infants with ApH ≤7.00 compared to ApH 7.01-7.10 cohort. Ventilation support was 5.1 times (95% CI 2.87, 9.03) more likely to be needed by those with cord ApH ≤7.00 compared to those with ApH 7.01-7.10, as well as hypoglycemia (37% vs. 25%; p = 0.026). In 55%, hypoglycemia occurred despite oral and/or intravenous glucose administration had been already initiated. Cord pH 7.00 might be a safe pH cut-off point when developing protocols to monitor infants born with acidemia in order to identify infants with moderate or severe HIE early on. There is non-negligible comorbidity in the ApH ≤7.00 cohort, but also in the 7.01-7.10 cohort.

Malondialdehyde as a Prognosticating Marker for Staging of HIE - A Prospective Cohort Study

Introduction: Prediction of outcomes of asphyxiated neonates is imperative. Timely intervention and effective resuscitation are beneficial for intact neurodevelopmental outcomes. In this study, we assessed the level of oxidative stress at birth in cord blood and correlated it with the Hypoxic Ischemic Encephalopathy (HIE) staging and outcomes.&#x0D; Methodology: This Prospective Cohort Study was conducted between January 2020 and June 2022. All neonates requiring resuscitation at birth were enrolled in a study group. The control group included neonates who did not require resuscitation. Cord blood was collected at birth, centrifuged, serum separated, and stored at -200C. Malondialdehyde (MDA) was read at 535nm on spectrometry.&#x0D; Results: 102 neonates were enrolled, among which 29 neonates were asphyxiated and 73 non-asphyxiated. The cord blood mean MDA level was significantly high in Severe HIE, with a p-value of &lt;0.001. The serum MDA level in cord blood had a significant difference in asphyxiated neonates (8.59±1.99) and normal neonates (3.18±1.04) (P&lt;0.001). There is a significant difference in MDA levels in cord blood; the mean MDA level was significantly higher in HIE III (10.93±2.50), compared to HIE II (9.98±2.34) and HIE I(7.72±1.09) with a p-value of &lt;0.001. Deceased neonates had higher MDA levels than those neonates who survived.&#x0D; Conclusion: Neonates with high oxidative stress at birth require advanced resuscitation. MDA levels above 7.64 mm/L have 100% sensitivity and 81.4% specificity with respect to mortality in asphyxiated neonates. Hence, cord blood MDA can be a prognostic marker of oxidative stress to predict the outcomes in asphyxiated neonates.

Correlation analysis between the amniotic fluid contamination and clinical grading of neonatal hypoxic–ischemic encephalopathy and biomarkers of brain damage

BackgroundAmniotic fluid contamination (AFC) is a risk factor for neonatal hypoxic ischemic encephalopathy (HIE); however, the correlation between AFC level and the incidence and clinical grading of HIE, in addition to relevant biomarkers of brain damage, have not been assessed.MethodsThis single-center observational study included 75 neonates with moderate-to-severe HIE. The neonates with HIE were divided into four subgroups according to the AFC level: normal amniotic fluid with HIE group (NAF-HIE), I°AFC with HIE group (I°AFC-HIE), II°AFC with HIE group (II°AFC-HIE), and III°AFC with HIE group (III°AFC-HIE). The control groups consisted of 35 healthy neonates. The clinical grading of neonatal HIE was performed according to the criteria of Sarnat and Sarnat. Serum tau protein and S100B were detected by enzyme-linked immunosorbent assay kits. Correlations of serum tau protein and S100B were evaluated using the Pearson correlation analysis.Results(1) The incidence of neonatal HIE in the NAF-HIE group was 20 cases (26. 7%), I°AFC-HIE was 13 cases (17.3%), II°AFC-HIE was 10 cases (13.3%), and III°AFC-HIE was 32 cases (42. 7%). The incidence of moderate-to-severe HIE in the I°–III°AFC-HIE groups was 73.3% (55/75). (2) In 44 cases with severe HIE, 26 cases (59.1%) occurred in the III°AFC-HIE group, which had a significantly higher incidence of severe HIE than moderate HIE (p < 0.05). In NAF-HIE and I°AFC-HIE groups, the incidence of moderate HIE was 45.2% and 29.0%, respectively, which was higher than that of severe HIE (X2 = 9.2425, p < 0.05; X2 = 5.0472, p < 0.05, respectively). (3) Serum tau protein and S100B levels in the HIE groups were significantly higher than in the control group (all p < 0.05), and were significantly higher in the III°AFC-HIE group than in the NAF-HIE and I°AFC-HIE groups (all p < 0.05). (4) Serum tau protein and S100B levels in the severe HIE group were significantly higher in the moderate HIE group (all p < 0.05). (5) Serum tau protein and S100B levels were significantly positively correlated (r = 0.7703, p < 0.0001).ConclusionAmong children with severe HIE, the incidence of III°AFC was higher, and the levels of serum tau protein and S100B were increased. AFC level might be associated with HIE grading.

Genetic and Congenital Anomalies in Infants With Hypoxic-Ischemic Encephalopathy

BackgroundInfants with hypoxic ischemic encephalopathy (HIE) may have underlying conditions predisposing them to hypoxic-ischemic injury during labor and delivery. It is unclear how genetic and congenital anomalies impact outcomes of HIE. MethodsInfants with HIE enrolled in a phase III trial underwent genetic testing when clinically indicated. Infants with known genetic or congenital anomalies were excluded. The primary outcome, i.e., death or neurodevelopmental impairment (NDI), was determined at age two years by a standardized neurological examination, Bayley Scales of Infant Development, Third Edition (BSID-III), and the Gross Motor Function Classification Scales. Secondary outcomes included cerebral palsy and BSID-III motor, cognitive, and language scores at age two years. ResultsOf 500 infants with HIE, 24 (5%, 95% confidence interval 3% to 7%) were diagnosed with a genetic (n = 15) or congenital (n = 14) anomaly. Infants with and without genetic or congenital anomalies had similar rates of severe encephalopathy and findings on brain magnetic resonance imaging. However, infants with genetic or congenital anomalies were more likely to have death or NDI (75% vs 50%, P = 0.02). Among survivors, those with a genetic or congenital anomaly were more likely to be diagnosed with cerebral palsy (32% vs 13%, P = 0.02), and had lower BSID-III scores in all three domains than HIE survivors without such anomalies. ConclusionsAmong infants with HIE, 5% were diagnosed with a genetic or congenital anomaly. Despite similar clinical markers of HIE severity, infants with HIE and a genetic or congenital anomaly had worse neurodevelopmental outcomes than infants with HIE alone.

Racial and Ethnic Inequities in Therapeutic Hypothermia and Neonatal Hypoxic–Ischemic Encephalopathy: A Retrospective Cohort Study

ObjectiveTo investigate racial inequities in the use of therapeutic hypothermia (TH) and outcomes in infants with hypoxic ischemic encephalopathy (HIE). Study designWe queried an administrative birth cohort of mother-baby pairs in California from 2010 through 2019 using ICD codes to evaluate the association between race and ethnicity and the application of TH in infants with HIE. We identified 4,779 infants with HIE. Log-linear regression was used to calculate risk ratios (RR) for TH, adjusting for hospital transfer, rural location, gestational age between 35 and 37 weeks, and HIE severity. Risk of adverse infant outcome was calculated by race and ethnicity and stratified by TH. ResultsFrom our identified cohort, 1338 (28.0%) neonates underwent TH. White infants were used as the reference sample and 410 (28.4%) received TH. Black infants were significantly less likely to receive TH with 74 (20.0%) with an adjusted risk ratio (aRR) of 0.7 (95% confidence interval 0.5 to 0.9). Black infants with any HIE who did not receive TH were more likely to have a hospital readmission (aRR 1.36, 95% CI 1.10 to 1.68) and a tracheostomy (aRR 3.07, 95% CI 1.19 to 7.97). Black infants with moderate/severe HIE who did not receive TH were more likely to have cerebral palsy (aRR 2.72, 95% CI 1.07 to 6.91). ConclusionsIn this study cohort, Black infants with HIE were significantly less likely to receive TH. Black infants also had significantly increased risk of some adverse outcomes of HIE. Possible reasons for this inequity include systemic barriers to care and systemic bias.

Deep learning-enabled detection of hypoxic-ischemic encephalopathy after cardiac arrest in CT scans: a comparative study of 2D and 3D approaches.

To establish a deep learning model for the detection of hypoxic-ischemic encephalopathy (HIE) features on CT scans and to compare various networks to determine the best input data format. 168 head CT scans of patients after cardiac arrest were retrospectively identified and classified into two categories: 88 (52.4%) with radiological evidence of severe HIE and 80 (47.6%) without signs of HIE. These images were randomly divided into a training and a test set, and five deep learning models based on based on Densely Connected Convolutional Networks (DenseNet121) were trained and validated using different image input formats (2D and 3D images). All optimized stacked 2D and 3D networks could detect signs of HIE. The networks based on the data as 2D image data stacks provided the best results (S100: AUC: 94%, ACC: 79%, S50: AUC: 93%, ACC: 79%). We provide visual explainability data for the decision making of our AI model using Gradient-weighted Class Activation Mapping. Our proof-of-concept deep learning model can accurately identify signs of HIE on CT images. Comparing different 2D- and 3D-based approaches, most promising results were achieved by 2D image stack models. After further clinical validation, a deep learning model of HIE detection based on CT images could be implemented in clinical routine and thus aid clinicians in characterizing imaging data and predicting outcome.

Whole-Blood Gene Expression Profile After Hypoxic-Ischemic Encephalopathy

Induced hypothermia, the standard treatment for hypoxic-ischemic encephalopathy (HIE) in high-income countries (HICs), is less effective in the low-income populations in South Asia, who have the highest disease burden. To investigate the differences in blood genome expression profiles of neonates with HIE from an HIC vs neonates with HIE from South Asia. This case-control study analyzed data from (1) a prospective observational study involving neonates with moderate or severe HIE who underwent whole-body hypothermia between January 2017 and June 2019 and age-matched term healthy controls in Italy and (2) a randomized clinical trial involving neonates with moderate or severe HIE in India, Sri Lanka, and Bangladesh recruited between August 2015 and February 2019. Data were analyzed between October 2020 and August 2023. Whole-blood RNA that underwent next-generation sequencing. The primary outcomes were whole-blood genome expression profile at birth associated with adverse outcome (death or disability at 18 months) after HIE in the HIC and South Asia cohorts and changes in whole-genome expression profile during the first 72 hours after birth in neonates with HIE and healthy controls from the HIC cohort. Blood samples for RNA extraction were collected before whole-body hypothermia at 4 time points (6, 24, 48, and 72 hours after birth) for the HIC cohort. Only 1 blood sample was drawn within 6 hours after birth for the South Asia cohort. The HIC cohort was composed of 35 neonates (21 females [60.0%]) with a median (IQR) birth weight of 3.3 (3.0-3.6) kg and gestational age of 40.0 (39.0-40.6) weeks. The South Asia cohort consisted of 99 neonates (57 males [57.6%]) with a median (IQR) birth weight of 2.9 (2.7-3.3) kg and gestational age of 39.0 (38.0-40.0) weeks. Healthy controls included 14 neonates (9 females [64.3%]) with a median (IQR) birth weight of 3.4 (3.2-3.7) kg and gestational age of 39.2 (38.9-40.4) weeks. A total of 1793 significant genes in the HIC cohort and 99 significant genes in the South Asia cohort were associated with adverse outcome (false discovery rate <0.05). Only 11 of these genes were in common, and all had opposite direction in fold change. The most significant pathways associated with adverse outcome were downregulation of eukaryotic translation initiation factor 2 signaling in the HIC cohort (z score = -4.56; P < .001) and aldosterone signaling in epithelial cells in the South Asia cohort (z score = null; P < .001). The genome expression profile of neonates with HIE (n = 35) at birth, 24 hours, 48 hours, and 72 hours remained significantly different from that of age-matched healthy controls in the HIC cohort (n = 14). This case-control study found that disease mechanisms underlying HIE were primarily associated with acute hypoxia in the HIC cohort and nonacute hypoxia in the South Asia cohort. This finding might explain the lack of hypothermic neuroprotection.

Therapeutic hypothermia after perinatal asphyxia in Vietnam: medium-term outcomes at 18 months – a prospective cohort study

AimTo determine neurodevelopmental outcome at 18 months after therapeutic hypothermia for hypoxic-ischaemic encephalopathy (HIE) infants in Vietnam, a low-middle-income country.MethodProspective cohort study investigating outcomes at 18 months in severely asphyxiated...

Esophageal Versus Rectal Temperature Monitoring During Whole-Body Therapeutic Hypothermia for Hypoxic–Ischemic Encephalopathy: Association with Short- and Long-Term Outcomes

To compare the short- and long-term outcomes of infants with hypoxic-ischemic encephalopathy (HIE) treated with whole-body therapeutic hypothermia (TH), monitored by esophageal vs rectal temperature. We conducted a secondary analysis of the multicenter High-Dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) trial. All infants had moderate or severe HIE and were treated with whole-body TH. The primary outcome was death or neurodevelopmental impairment (NDI) at 22-36months of age. Secondary outcomes included seizures, evidence of brain injury on magnetic resonance imaging, and complications of hypothermia. Logistic regression was used with adjustment for disease severity and site as clustering variable because cooling modality differed by site. Of the 500 infants who underwent TH, 294 (59%) and 206 (41%) had esophageal and rectal temperature monitoring, respectively. There were no differences in death or NDI, seizures, or evidence of injury on magnetic resonance imaging between the 2 groups. Infants treated with TH and rectal temperature monitoring had lower odds of overcooling (OR 0.52, 95% CI 0.34-0.80) and lower odds of hypotension (OR 0.57, 95% CI 0.39-0.84) compared with those with esophageal temperature monitoring. Although infants undergoing TH with esophageal monitoring were more likely to experience overcooling and hypotension, the rate of death or NDI was similar whether esophageal monitoring or rectal temperature monitoring was used. Further studies are needed to investigate whether esophageal temperature monitoring during TH is associated with an increased risk of overcooling and hypotension.

Elevated S100B urine levels predict seizures in infants complicated by perinatal asphyxia and undergoing therapeutic hypothermia.

Seizures (SZ) are one of the main complications occurring in infants undergoing therapeutic hypothermia (TH) due to perinatal asphyxia (PA) and hypoxic ischemic encephalopathy (HIE). Phenobarbital (PB) is the first-line therapeutic strategy, although data on its potential side-effects need elucidation. We investigated whether: i) PB administration in PA-HIE TH-treated infants affects S100B urine levels, and ii) S100B could be a reliable early predictor of SZ. We performed a prospective case-control study in 88 PA-HIE TH infants, complicated (n=44) or not (n=44) by SZ requiring PB treatment. S100B urine levels were measured at 11 predetermined monitoring time-points from first void up to 96-h from birth. Standard-of-care monitoring parameters were also recorded. S100B significantly increased in the first 24-h independently from HIE severity in the cases who later developed SZ and requested PB treatment. ROC curve analysis showed that S100B, as SZ predictor, at a cut-off of 2.78 μg/L achieved a sensitivity/specificity of 63 and 84 %, positive/negative predictive values of 83 and 64 %. The present results offer additional support to the usefulness of S100B as a trustable diagnostic tool in the clinical daily monitoring of therapeutic and pharmacological procedures in infants complicated by PA-HIE.

Frequency of Hypoglycemia in Neonates with Hypoxic-Ischemic Encephalopathy in the Neonatal Intensive Care Unit of Sir Ganga Ram Hospital, Lahore

Background: Hypoxic-ischemic encephalopathy (HIE) often necessitates admission to neonatal intensive care units (NICUs) for specialized care.– Among the various complications associated with HIE, hypoglycemia is a notable concern due to its potential to exacerbate neurological injury and compromise neurodevelopmental outcomes. However, the frequency of hypoglycemia in neonates with HIE, particularly in resource-limited settings like Pakistan, remains poorly characterized. Objectives: Aim of this study is to determine the frequency of hypoglycemia in neonates with HIE admitted to the NICU of Sir Ganga Ram Hospital, Lahore, Pakistan. By systematically reviewing medical records, this study is aimed to describe the prevalence of hypoglycemia in this population.Methods: Medical records of neonates diagnosed with HIE and admitted to the NICU were reviewed from July 2023 to October 2023. Data on demographic characteristics, perinatal history, clinical presentation, laboratory investigations including blood glucose levels, and neurodevelopmental outcomes were extracted. The frequency of hypoglycemia was determined as the proportion of neonates with documented hypoglycemia among all neonates diagnosed with HIE during the study period. Results: Among the cohort of neonates diagnosed with HIE (n = 120), 20.8% were found to experience hypoglycemic episodes during their hospital stay. Subgroup analyses revealed associations between hypoglycemia and variables such as gestational age, birth weight, and severity of HIE. Descriptive statistics were used to summarize the demographic characteristics of this population, providing context for understanding the prevalence and implications of hypoglycemia in neonates with HIE. Conclusion: This study highlights the prevalence of hypoglycemia as a common metabolic disturbance in neonates with HIE, underscoring the need for vigilant monitoring and prompt intervention in this vulnerable population. Standardized protocols for managing hypoglycemia in neonates with HIE are imperative to optimize clinical outcomes.