Hypoxic-ischemic Encephalopathy Outcome Research Articles

Clinical and prognostic significance of neurosonography of lateral ventricles for infants treated with therapeutic hypothermia during the early neonatal period

Background. Currently, therapeutic hypothermia (TH) is the only approved method for treating hypoxic-ischemic encephalopathy (HIE) that helps improve outcomes. However, it also has significant drawbacks, including the necessity for expensive equipment and treatment technologies, poorly understood pathophysiological mechanisms, and, most importantly, not always well-understood long-term results. Numerous scientific studies report the potential benefits of TH, but the actual risk/benefit ratio is still unknown. The results of long-term follow-up of children who underwent TH and did not have serious neuromotor or intellectual disorders are variable. It is believed that the correlation between neonatal neuroimaging and the degree of nervous system impairment remains poorly defined. Chronic brain injuries diagnosed after the neonatal period, such as parenchymal volume loss, appear to be more prognostically significant, which may be reflected by moderate enlargement of the ventricular system of the brain. The method for determining the size of the ventricular system using ultrasound can be accessible for infants of the first year of life who had HIE but do not have direct indications for magne­tic resonance imaging. Therefore, this study aimed to explore the characteristics of the cerebral ventricular system in infants of the first year of life who suffered severe asphyxia at birth, depen­ding on the method of post-resuscitation care (with or without TH). Materials and ­methods. The study examined the results of neurosonographic examinations of 309 infants during their first year of life. Inclusion criteria were gestational age at birth ≥ 36 weeks and birth weight ≥ 2000 g, manifestations of HIE in the early neonatal period without adverse short-term outcomes (at the time of discharge from the neonatal hospital, the children showed no signs of destructive hypoxic-ischemic lesions of the central nervous system (CNS), seizures, or pathological muscle tone, and had full oral feeding). Exclusion criteria were diagnosed congenital CNS abnormalities, neuroinfections, psychomotor development delay of more than 3 months during the first years of life, progressive obstructive ventriculomegaly or ventriculomegaly associated with non-atrophic subarachnomegaly. The children were divided into three groups: hypothermia group — 19 infants who underwent TH after birth; normothermia group — 14 children who conditio­nally had indications for TH but did not undergo it; comparison group — 276 children in their first year of life who did not require TH (Apgar score > 5 at 10 minutes of life, manifestations of mild or moderate HIE (according to the Sarnat scale) during the first days of life). Neurosonographic examinations were conducted at the age of 2–7 months (mean of 2.12 ± 0.07 months). The sizes of the lateral ventricles were assessed in comparison with the results from the control group of infants of the same age (34 healthy children with no recorded factors of complicated perinatal period, no signs of neurological dysfunction during the neonatal period, and the seven-month observation). Enlargement of the lateral ventricles was recorded when the size of the anterior horn or body of the ventricle in the parasagittal projection exceeded the 95th percentile of the corresponding measurements from the control group. Results. Enlargement of the lateral ventricles during the neurosonographic examination was detected in 36.8 % of children in the hypothermia group, 14.3 % in the normothermia group, and 8.0 % of children in the comparison group. Significant differences were registered only when comparing the results of the hypothermia group with the comparison group (p < 0.05, Fisher’s exact test). Significant correlations (p < 0.05) were found between the size of the lateral ventricles and clinical signs such as sleep disturbances, decreased muscle tone in the arms, increased tendon reflexes, delayed motor development, increased muscle tone in a pyramidal pattern, and diffuse muscle hypotonia. Conclusions. Thus, infants who had severe asphyxia at birth and underwent TH significantly more often had enlargement of the cerebral ventri­cular system (versus the comparison group). Therefore, although therapeutic hypothermia improves outcomes for the development of the nervous system in children who have moderate and severe hypoxic-ischemic encephalopathy, brain morphology (particularly the state of the ventricular system) may still be altered in infants during the first year of life. And the presence of significant correlations between the size of the lateral ventricles and clinical signs of neurological dysfunction argues for further clinical monitoring of children after therapeutic hypothermia throughout the first years of life and in the absence of short-term adverse outcomes of HIE or significant delays in psychomotor development during the first year of life.

Mesenchymal Stromal Cell therapy for Hypoxic Ischemic Encephalopathy: Future directions for combination therapy with hypothermia and/or melatonin

Hypoxic ischemic encephalopathy (HIE) remains a leading cause of neonatal mortality and lifelong disability across the world. While therapeutic hypothermia (HT) is beneficial, it is only partially protective and adjuvant treatments that further improve outcomes are urgently needed. In high-income countries where HT is standard care, novel treatments are tested in conjunction with HT. Mesenchymal stromal cells (MSC) represent a paradigm shift in brain protection, uniquely adapting to the host cellular microenvironment. MSC have low immunogenicity and potent paracrine effects stimulating the host tissue repair and regeneration and reducing inflammation and apoptosis. Preclinical studies in perinatal brain injury suggest that MSC are beneficial after hypoxia-ischemia (HI) and most preclinical studies of MSC with HT show protection. Preclinical and early phase clinical trials have shown that allogenic administration of MSC to neonates with perinatal stroke and HIE is safe and feasible but further safety and efficacy studies of HT with MSC in these populations are needed. Combination therapies that target all stages of the evolution of injury after HI (eg HT, melatonin and MSC) show promise for improving outcomes in HIE.

Protecting effects of 4-octyl itaconate on neonatal hypoxic-ischemic encephalopathy via Nrf2 pathway in astrocytes

BackgroundNeonatal hypoxic-ischemic encephalopathy (HIE) is one of the most common neurological problems occurring in the perinatal period. However, there still is not a promising approach to reduce long-term neurodevelopmental outcomes of HIE. Recently, itaconate has been found to exhibit anti-oxidative and anti-inflammatory effects. However, the therapeutic efficacy of itaconate in HIE remains inconclusive. Therefore, this study attempts to explore the pathophysiological mechanisms of oxidative stress and inflammatory responses in HIE as well as the potential therapeutic role of a derivative of itaconate, 4-octyl itaconate (4OI).MethodsWe used 7-day-old mice to induce hypoxic-ischemic (HI) model by right common carotid artery ligation followed by 1 h of hypoxia. Behavioral experiments including the Y-maze and novel object recognition test were performed on HI mice at P60 to evaluate long-term neurodevelopmental outcomes. We employed an approach combining non-targeted metabolomics with transcriptomics to screen alterations in metabolic profiles and gene expression in the hippocampal tissue of the mice at 8 h after hypoxia. Immunofluorescence staining and RT-PCR were used to evaluate the pathological changes in brain tissue cells and the expression of mRNA and proteins. 4OI was intraperitoneally injected into HI model mice to assess its anti-inflammatory and antioxidant effects. BV2 and C8D1A cells were cultured in vitro to study the effect of 4OI on the expression and nuclear translocation of Nrf2. We also used Nrf2-siRNA to further validate 4OI-induced Nrf2 pathway in astrocytes.ResultsWe found that in the acute phase of HI, there was an accumulation of pyruvate and lactate in the hippocampal tissue, accompanied by oxidative stress and pro-inflammatory, as well as increased expression of antioxidative stress and anti-inflammatory genes. Treatment of 4OI could inhibit activation and proliferation of microglial cells and astrocytes, reduce neuronal death and relieve cognitive dysfunction in HI mice. Furthermore, 4OI enhanced nuclear factor erythroid-2-related factor (Nfe2l2; Nrf2) expression and nuclear translocation in astrocytes, reduced pro-inflammatory cytokine production, and increased antioxidant enzyme expression.ConclusionOur study demonstrates that 4OI has a potential therapeutic effect on neuronal damage and cognitive deficits in HIE, potentially through the modulation of inflammation and oxidative stress pathways by Nrf2 in astrocytes.

Sudden unexpected postnatal collapse and BUB1B mutation: first forensic case report

Sudden unexpected postnatal collapse (SUPC) is a sudden collapse of the clinical conditions of a full-term or near-term newborn, within the first 7 days of life, that requires resuscitation with positive ventilation and who either dies, has hypoxic-ischemic encephalopathy, or requires intensive care. The incidence of SUPC is very low, and most often presents a negative prognosis. The BUB1B gene is a mitotic checkpoint of serine/threonine kinase B that encodes a protein crucial for maintaining the correct number of chromosomes during cell division. Mutations in the BUB1B gene are linked to mosaic variegated aneuploidy syndrome 1 (MVA1), a rare autosomal recessive disorder characterized by diffuse mosaic aneuploidies involving several chromosomes and tissues. This paper discusses a case of a newborn who had a spontaneous delivery. After 2 h and 10 min, the infant showed generalized hypotonia and cyanosis, and his doctors performed orotracheal intubation, cardiac massage, pharmacological hemodynamic therapy, mechanical ventilation, antibiotic therapy, and hypothermic treatment. The newborn was discharged after 5 months with the diagnosis of hypoxic-ischemic encephalopathy. Suspecting an SUPC, a complete genetic analysis was performed demonstrating a compound heterozygous mutations in the BUB1B gene. The newborn died at 6 months of life, 1 month after discharge. A complete autopsy was performed, determining that the cause of death was due to sepsis starting from a brocopneumonic process, with outcomes of hypoxic-ischemic encephalopathy (HIE). In this scenario, it is not possible to demonstrate the causal effect of this mutation, considering that it could play a causal or concausal role in the onset of SUPC. Further research based on multicenter studies, as well as on animal models, could be very useful to clarify the pathological effect of this mutation.

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.

Advances in Therapies to Treat Neonatal Hypoxic-Ischemic Encephalopathy.

Neonatal hypoxic-ischemic encephalopathy (HIE) is a condition that results in brain damage in newborns due to insufficient blood and oxygen supply during or after birth. HIE is a major cause of neurological disability and mortality in newborns, with over one million neonatal deaths occurring annually worldwide. The severity of brain injury and the outcome of HIE depend on several factors, including the cause of oxygen deprivation, brain maturity, regional blood flow, and maternal health conditions. HIE is classified into mild, moderate, and severe categories based on the extent of brain damage and resulting neurological issues. The pathophysiology of HIE involves different phases, including the primary phase, latent phase, secondary phase, and tertiary phase. The primary and secondary phases are characterized by episodes of energy and cell metabolism failures, increased cytotoxicity and apoptosis, and activated microglia and inflammation in the brain. A tertiary phase occurs if the brain injury persists, characterized by reduced neural plasticity and neuronal loss. Understanding the cellular and molecular aspects of the different phases of HIE is crucial for developing new interventions and therapeutics. This review aims to discuss the pathophysiology of HIE, therapeutic hypothermia (TH), the only approved therapy for HIE, ongoing developments of adjuvants for TH, and potential future drugs for HIE.

Placental Histologic Abnormalities and 2-Year Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy

Objective: We aimed to examine the association between placental abnormalities and neurodevelopmental outcomes in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) that underwent therapeutic hypothermia. We hypothesized that subjects with acute placental abnormalities would have reduced risk of death or neurodevelopmental impairment (NDI) at 2 years of age after undergoing therapeutic hypothermia compared to subjects without acute placental changes. Study Design: Among 500 subjects born at ≥36 weeks gestation with moderate or severe HIE enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, a placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute only, chronic only, or both acute and chronic histologic abnormalities. We calculated adjusted relative risks (aRRs) for associations between placental pathologic abnormalities and death or NDI at age 2 years, adjusting for HIE severity, treatment assignment, and site. Result: 321/500 subjects (64%) had available placental pathology reports. Placental abnormalities were characterized as acute only (20%), chronic only (21%), both acute and chronic (43%), and none (15%). The risk of death or NDI was not statistically different between subjects with and without an acute placental abnormality (46 vs. 53%, aRR 1.1, 95% confidence interval (CI): 0.9, 1.4). Subjects with two or more chronic lesions were more likely to have an adverse outcome than subjects with no chronic abnormalities, though this did not reach statistical significance (55 vs. 45%, aRR 1.24, 95% CI: 0.99, 1.56). Conclusion: Placental pathologic findings were not independently associated with risk of death or NDI in subjects with HIE. The relationship between multiple chronic placental lesions and HIE outcomes deserves further study.

Conflicting findings on the effectiveness of hydrogen therapy for ameliorating vascular leakage in a 5-day post hypoxic-ischemic survival piglet model

Neonatal hypoxic-ischemic encephalopathy (HIE) is a major cause of morbidity and mortality in newborns in both high- and low-income countries. The important determinants of its pathophysiology are neural cells and vascular components. In neonatal HIE, increased vascular permeability due to damage to the blood–brain barrier is associated with seizures and poor outcomes in both translational and clinical studies. In our previous studies, hydrogen gas (H2) improved the neurological outcome of HIE and ameliorated the cell death. In this study, we used albumin immunohistochemistry to assess if H2 inhalation effectively reduced the cerebral vascular leakage. Of 33 piglets subjected to a hypoxic-ischemic insult, 26 piglets were ultimately analyzed. After the insult, the piglets were grouped into normothermia (NT), H2 ventilation (H2), therapeutic hypothermia (TH), and H2 combined with TH (H2-TH) groups. The ratio of albumin stained to unstained areas was analyzed and found to be lower in the H2 group than in the other groups, although the difference was not statistically significant. In this study, H2 therapy did not significantly improve albumin leakage despite the histological images suggesting signs of improvement. Further investigations are warranted to study the efficacy of H2 gas for vascular leakage in neonatal HIE.

3D doppler ultrasound imaging of cerebral blood flow for assessment of neonatal hypoxic-ischemic brain injury in mice.

Cerebral blood flow (CBF) acutely reduces in neonatal hypoxic-ischemic encephalopathy (HIE). Clinic studies have reported that severe CBF impairment can predict HIE outcomes in neonates. Herein, the present study uses a non-invasive 3D ultrasound imaging approach to evaluate the changes of CBF after HI insult, and explores the correlation between CBF alterations and HI-induced brain infarct in mouse pups. The neonatal HI brain injury was induced in postnatal day 7 mouse pups using the Rice-Vannucci model. Non-invasive 3D ultrasound imaging was conducted to image CBF changes with multiple frequencies on mouse pups before common carotid artery (CCA) ligation, immediately after ligation, and 0 or 24 hours after HI. Vascularity ratio of the ipsilateral hemisphere was acutely reduced after unilateral ligation of the CCA alone or in combination with hypoxia, and partially restored at 24 hours after HI. Moreover, regression analysis showed that the vascularity ratio of ipsilateral hemisphere was moderately correlated with brain infarct size 24 hours after HI, indicating that CBF reduction contributes to of HI brain injury. To further verify the association between CBF and HI-induced brain injury, a neuropeptide C-type natriuretic peptide (CNP) or PBS was intranasally administrated to the brain of mouse pups one hour after HI insult. Brain infarction, CBF imaging and long-term neurobehavioral tests were conducted. The result showed that intranasal administration of CNP preserved ipsilateral CBF, reduced the infarct size, and improved neurological function after HI brain injury. Our findings suggest that CBF alteration is an indicator for neonatal HI brain injury, and 3D ultrasound imaging is a useful non-invasive approach for assessment of HI brain injury in mouse model.

The factors affecting neurodevelopmental outcomes in HIE.

Hypoxic ischemic encephalopathy (HIE) has different neurological outcomes. We wanted to see if there was any developmental delay in neonates with hypoxia ischemic encephalopathy who were given therapeutic hypothermia. Retrospective cohort study. The Denver developmental screening test II (DDST-II) was performed to newborns who had been applied to therapeutic hypothermia. There were 69 male and 36 female newborns. The mean 1-min and 5-min Apgar scores were 4.72 ± 2.51 and 7.03 ± 2.017, respectively. The mean pH and mean base excess were 6.92 ± 0.1 and -18.05 ± 5.72, respectively. The most common risk factors were meconium staining (17.1%). There were 67 patients with Stage I, 20 with Stage II, and 18 with Stage III. Diffusion restriction was seen in 13 patients. 28 patients had seizures. In aEEG, 12 patients had burst suppression. Three (2.9%) infants died during hospitalization. 19 patients missed follow-up appointments. Thirteen patients had abnormal development according to DDST-II. Seven patients had gross motor function delays and were diagnosed with cerebral palsy. Three had language skill delays, but two of them had speech disorders after two years of age. Two had delayed milestones. Two had delays in fine motor skills but did not have any sequels after two years of age. A significant difference was found between seizures and the severity of Sarnat stage, intubation in the delivery room with developmental delay. Apgar scores were significantly lower in patients with CP. We should closely follow-up neonates who had low Apgar scores, seizures, a high Sarnat stage, were intubated in the delivery room.

Therapeutic hypothermia demonstrates sex-dependent improvements in motor function in a rat model of neonatal hypoxic ischemic encephalopathy

Neonatal hypoxic ischemic encephalopathy (HIE) is a neurological disease caused by restricted oxygen and blood flow to the brain at or around the time of birth. Long term cognitive and motor sequelae are common and demonstrate sexual dimorphism in animal studies. Therapeutic hypothermia (TH) is the standard of care for HIE, but provides incomplete neuroprotection. Using the Vannucci model of neonatal HIE, term-equivalent 11-day old rat pups were subjected to mild-moderate hypoxic-ischemic injury (HII), and a subset of animals were treated with TH. Sex-dependent neuroprotection was measured with gross and fine motor control assays, and functional deficits detected with these assays were correlated to injury in specific brain structures. At the equivalent of human adolescence and adulthood (P51–89), accelerod and beam walking tests were used to assess gross motor function, and string-pulling and food handling tests were used to assess fine motor function. At necropsy (P94–97), brain lesions were primarily focused to the posterior cerebrum and characterized by variable reduction in cortical, thalamic and hippocampal regions and glial scarring. Gross motor impairment was detected in male rats with untreated and TH-treated HIE in the accelerod test, but beam walk test data was confounded by the lower body mass of untreated male rats. HIE animals of both sexes demonstrated deficit in the forelimb contralateral to ischemic surgery, observed as unilaterally impaired food handling behaviors, and in string pulling as decreased string contacts and increased in bracing behavior. However, kinematic analyses revealed sex-specific decreases in peak speeds in string reaching and pulling movements. In both sexes, treatment with TH improved body mass, some measures of contralateral forelimb impairment, and the severity of brain lesions to levels not different to Sham surgery rats. Unique differences in behavior following TH were observed in female rats, who took longer to consume food items but traversed beams and approached strings faster than untreated and Sham females. Future use of these motor assays may unravel the subtle, sex-specific differences in HIE outcomes and in developing a customized therapeutic approach to neonatal brain injury.

Blanket temperature during therapeutic hypothermia and outcomes in hypoxic ischemic encephalopathy.

Determine whether blanket temperatures during therapeutic hypothermia (TH) are associated with 18-22 month outcomes for infants with hypoxic ischemic encephalopathy (HIE). Retrospective cohort study of 181 infants with HIE who received TH in two randomized trials within the Neonatal Research Network. We defined summative blanket temperature constructs and evaluated for association with a primary composite outcome of death or moderate/ severe disability at 18-22 months. Each 0.5 °C above 33.5 °C in the mean of the highest quartile blanket temperature was associated with a 52% increase in the adjusted odds of death/ disability (aOR 1.52, 95% CI 1.09-2.11). Having >8 consecutive blanket temperatures above 33.5 °C rendered an aOR of death/disability of 5.04 in the first 24 h (95% CI 1.54-16.6) and 6.92 in the first 48 h (95% CI 2.20-21.8) of TH. Higher blanket temperature during TH may be an early, clinically useful biomarker of HIE outcome.

Роль нейронспецифической енолазы в патогенезе гипоксически-ишемической энцефалопатии у новорожденных детей

The literature data on the clinical and diagnostic significance of neuron-specific enolase in the development of hypoxic-ischemic encephalopathy in newborns are presented. The expediency of determining this marker in various variants of the disease course is shown. The study of the content of this neurospecific protein is valuable for diagnosing, monitoring and predicting the course and outcomes of hypoxic-ischemic encephalopathy.

Subacute AMD3100 Treatment Is Not Efficient in Neonatal Hypoxic-Ischemic Rats.

Despite the advances in treating neonatal hypoxic-ischemic encephalopathy (HIE) with induced hypothermia, the rates of severe disability are still high among survivors. Preclinical studies have indicated that cell therapies with hematopoietic stem/progenitor cells could improve neurological outcomes in HIE. In this study, we investigated whether the administration of AMD3100, a CXCR4 antagonist that mobilizes hematopoietic stem/progenitor cells into the circulation, has therapeutic effects in HIE. P10 Wistar rats of both sexes were subjected to right common carotid artery occlusion or sham procedure, and then were exposed to hypoxia for 120 minutes. Two subcutaneous injections of AMD3100 or vehicle were given on the third and fourth day after HIE. We first assessed the interindividual variability in brain atrophy after experimental HIE and vehicle treatment in a small cohort of rats. Based on this exploratory analysis, we designed and conducted an experiment to test the efficacy of AMD3100. Brain atrophy on day 21 after HIE was defined as the primary end point. Secondary efficacy end points were cognitive (T-water maze) and motor function (rotarod) on days 17 and 18 after HIE, respectively. AMD3100 did not decrease the brain atrophy in animals of either sex. Cognitive impairments were not observed in the T-water maze, but male hypoxic-ischemic animals exhibited motor coordination deficits on the rotarod, which were not improved by AMD3100. A separate analysis combining data from animals of both sexes also revealed no evidence of the effectiveness of AMD3100 treatment. These results indicate that the subacute treatment with AMD3100 does not improve structural and functional outcomes in a rat HIE model.

Сравнение динамики биомаркеров нейронспецифической енолазы и протеина S-100 у новорожденных с гипоксически-ишемической энцефалопатией в зависимости от времени начала проведения лечебной гипотермии (0–6 часов и 6–24 часа после родов)

Актуальность. Сегодня остается невыясненным соответствие абсолютных сывороточных концентраций нейронспецифической енолазы (NSE) и протеина S-100 степени тяжести и возможным последствиям гипоксически-ишемической энцефалопатии (ГИЭ), а также динамика этих показателей на протяжении острого периода ГИЭ в зависимости от времени начала проведения лечебной гипотермии. Цель: исследовать динамику сывороточных показателей нейронспецифической енолазы и протеина S-100 у доношенных новорожденных в течение острого периода ГИЭ в зависимости от времени начала проведения лечебной гипотермии. Материалы и методы. Проспективное одноцентровое когортное исследование 205 доношенных младенцев, которые в 2012–2017 гг. находились на лечении в отделении анестезиологии и интенсивной терапии для новорожденных с диагнозом «гипоксически-ишемическая энцефалопатия». Дети были стратифицированы по времени от рождения до поступления в отделение интенсивной терапии (ОАИТН). Были исследованы сывороточные концентрации нейронспецифической енолазы и протеина S-100 в 1, 3 и 5-й день лечения как в целом во всей когорте, так и в группах: 0–6 часов (группа 1, n = 56) и более 6 часов после рождения (группа 2, n = 149). Результаты. Динамика S-100 была существенной в течение 5 дней в обеих группах новорожденных (p < 0,001). Однако не было найдено достоверного различия в тенденции изменения концентрации протеина S-100 в течение первых 5 дней в обеих группах (р = 0,082). Также не было статистически значимой разницы между пациентами, поступившими в первые 6 часов и позже, относительно значения S-100 (р = 0,320) в течение всех пяти дней, за исключением первого дня при поступлении (р = 0,002). Не было найдено статистически значимой разницы уровня NSE в группах как в динамике от 1-го до 5-го дней (р = 0,217), так и относительно раннего (0–6 часов) или позднего (более 6 часов) поступления в ОАИТН (р = 0,845). Нет также достоверного различия концентрации NSE между группами (р = 0,719). Выводы. Отсутствие достоверного различия динамики уровня протеина S-100 и NSE у новорожденных до 6 часов и после от момента рождения свидетельствует о возможности начала проведения лечебной гипотермии более чем через 6 часов после родов, если по организационным причинам ее не успели начать раньше.

Hypoxic Ischemic Encephalopathy in Neonates with Birth Asphyxia - A Hospital Based Study

Introduction: Each year approximately 4 million babies are born asphyxiated, which results in 1 million deaths and an equal number of serious neurological sequelae. One of the commonest organs involved in birth asphyxia is brain which may lead to a syndrome of clinical manifestation called Hypoxic Ischemic Encephalopathy (HIE).
 Aims: To find out possible maternal and neonatal risk factors for Hypoxic Ischemic Encephalopathy, to analyze clinical presentations and outcome of HIE in asphyxiated newborns.
 Methods: Hospital based observational study was carried out among fifty newborns with Apgar score less than 7 at 1 minute of life admitted in Nepalgunj Medical College Teaching Hospital, Kohalpur, Banke.
 Results: The incidence of birth asphyxia and birth asphyxia with HIE were 37.2 per 1000 live births and 14 per 1000 live births with male: female ratio of 1.27:1. Most of the neonates 22(44%) were in HIE stage II. Meconium stained amniotic fluid 18 (36%) was the most common intrapartum risk factor followed by maternal use of intrapartum medications 14 (28%), Premature Rupture of Membrane (PROM) 8 (16%), prolonged labor 5 (10%) and obstructed labor 6 (12%). Four (8%) asphyxiated neonates with HIE had cord prolapse and 7 (14%) had cord around the neck. The most common resuscitation done was bag and mask ventilation (56%) (P<0.05). Majority of the studied neonates were of normal birth weight (76%) and head circumference (84%) (P<0.05) with clinical presentations of respiratory distress (88%), seizures (44%), apnea (22%), bradycardia (8%), tachycardia (6%) and bulged anterior fontanel (6%). The overall mortality of neonates with HIE was 20% of which most were of HIE stage III.
 Conclusion: Certain measures could be taken to prevent birth asphyxia: early detection and intervention of high risk pregnancy, prompt and effective resuscitation of asphyxiates newborns.

Amplitude Integrated Electroencephalography and Continuous Electroencephalography Monitoring Is Crucial in High-Risk Infants and Their Findings Correlate With Neurodevelopmental Outcomes.

Background: To evaluate seizure diagnosis in sick infants in the neonatal intensive care unit (NICU) based on electroencephalography (EEG) monitoring combined with amplitude integrated electroencephalography (aEEG).Methods: We retrospectively reviewed EEG and aEEG findings and determined their correlations with neurodevelopmental outcomes at the age of >1 year in 65 patients with diagnosed seizures, encephalopathy, or both.Results: Seizure identification rate was 43.1%. The rate in nonstructural groups (hypocalcemic, hypoglycemic, and genetic seizures) was 71.4%, which was higher (p < 0.05) than the rate of 35.3% of structural brain lesion group [hypoxic–ischemic encephalopathy (HIE) and congenital brain structural malformation]. The aEEG background correlating with neurodevelopmental outcomes had 70.0% positive prediction value (PPV), 65.5%% negative prediction value (NPV), 67.7% specificity, and 67.9% sensitivity (p < 0.005). The aEEG background strongly (PPV, 93.8%; p < 0.005) correlated with the outcomes in HIE. For genetic seizures, the detected rate was high. The ictal recordings for the nonstructural seizures revealed downflected on the aEEG background initially, which differed from the structural lesion.Conclusions: EEG monitoring combined with aEEG can detect seizures, facilitating early treatment. EEG changes during seizures could exhibit delta-theta waves with or without clinical seizures in patients with brain lesions. In non-structural etiologies (hypocalcemic and KCNQ2 seizures), aEEG initially exhibited lower background during seizures that could aid in differentiating these EEG changes from those of other etiologies. The aEEG background was correlated with neurodevelopmental outcome and exhibited high PPV but not NPV in neonatal HIE.

Clinical, biological and electroencephalographic monitoring of newborns with neurological risk in the Neonatal Intensive Care Unit.

Newborns admitted to the Neonatal Intensive Care Unit (NICU) require increased attention regarding neurological assessment and monitoring, due to immaturity or certain conditions that occur during the perinatal and neonatal period. Hypoxic-ischemic encephalopathy (HIE) following perinatal asphyxia is one of the most studied clinical conditions due to the risk of medium- and long-term neurobehavioral outcome. We studied 43 newborns with HIE, for all 3 degrees of impairment, performed amplitude-integrated electroencephalography (aEEG) in the first hours of life and collected common laboratory tests, following serum glycemia at admission and creatinine, creatine kinase (CK) and lactate dehydrogenase (LDH) at admission and in the 3rd day of life. Newborns with mild HIE presented normal aEEG pattern and slightly elevated CK. A total of 80.9% of the newborns with moderate HIE had seizure patterns in aEEG, while among those with severe HIE, 71.4% had seizure patterns in aEEG and 28.5% burst suppression. CK and LDH were mean elevated in those with moderate HIE, and the newborns with severe HIE had also high creatinine values at admission and in the 3rd day of life. Statistically significant differences between the 3 degrees of HIE were noted in terms of creatinine (P=0.009) and CK (P=0.008) at admission and LDH in the 3rd day of life (P=0.036). Hypoglycemia was common in our study group. In conclusion, common blood tests in association with aEEG monitoring and rigorous neurological assessment can predict short-term outcome of HIE and multiorgan dysfunction and can help clinicians predict even long-term outcomes in severe HIE.

CLINICAL PROFILE AND SHORT TERM OUTCOME OF HYPOXIC ISCHEMIC ENCEPHALOPATHY AMONG BIRTH ASPHXIATED BABIES IN A TERTIARY CARE HOSPITAL

Objective: To determine the clinical profile, selected antepartum and intrapartum risk factor for adverse shortterm outcomes of hypoxic ischemic encephalopathy in babies with birth asphyxia.&#x0D; Study Design: Cross sectional study.&#x0D; Place and Duration of Study: Neonatal Intensive Care Unit of Pak Emirates Military Hospital, Rawalpindi, fromJan to Dec 2018.&#x0D; Methodology: This study including all birth asphyxiated babies born who fulfilled the inclusion criteria.Following data was collected prospectively regarding gender, gestational age, birth weight and mode of delivery, maternal age, antenatal follow up, history of premature rupture of membranes and meconium stained liquor. Babies were categorized into different stages of hypoxic ischemic encephalopathy according to Sarnat and Sarnat staging. Selected antepartum and intrapartum risk factors leading to hypoxic insult at birth were studied and short-term outcome was recorded in the form of need of mechanical ventilation, mortality and discharge from the hospital.Results: The frequency of birth asphyxia turned out to be 122/5986 (2.03%) at our center. Thirty four (27.87%)required mechanical ventilation, mortality was recorded at 20/122 (16.39%). While 61 (50%) babies suffered from stage I hypoxic ischemic encephalopathy, 13/20 (65%) of newborn who expired were suffering from grade III hypoxic ischemic encephalopathy.&#x0D; Conclusion: The severity of hypoxic ischemic encephalopathy affects the outcome of newborns having birthasphyxia with hypoxic ischemic encephalopathy grade III associated with maximum mortality. Early identifycation of pregnancies at risk for asphyxia, with appropriate intervention in selected cases is the key to prevent birth asphyxia and its ensuing neonatal complications.