Development Of Hypoxic-ischemic Encephalopathy Research Articles

Umbilical arterial blood lactate as predictor of early neonatal outcome and evaluation of intrapartum asphyxia

BackgroundPerinatal asphyxia is a leading cause of under-5 mortality and exerts great pressure on the health system. Adequate foetal monitoring in labour is paramount in the early detection of foetal distress to prevent perinatal asphyxia. Several methods of foetal monitoring are in use with varying efficacy. This study investigated the efficacy of umbilical arterial (UA) lactate assay in predicting adverse perinatal outcomes. MethodologyThis was a prospective longitudinal study involving 160 pregnant women in the active phase of labour at term who met the inclusion criteria. They were recruited using a consecutive sampling technique and underwent a cardiotocography. Then they were classified into normal and abnormal cardiotocographic groups. At delivery, the UA blood of all of the babies was collected and assayed for serum lactate, and the levels were correlated with the perinatal outcome. The perinatal outcomes were measured by Apgar scores, admission into the neonatal unit, and hypoxic ischaemic encephalopathy. Analysis was done to determine the sensitivity and specificity of UA lactate in predicting birth asphyxia, hypoxic ischaemic encephalopathy, and neonatal unit admission. ResultsThe mean age ± standard deviation (SD) between the two cardiotocography (CTG) groups, normal years (30.55 ± 5.59) and abnormal years (29.86 ± 5.51), were similar. A critical UA lactate concentration >9.1 mmol/L predicted Apgar scores <7 at 5 min with a sensitivity and specificity of 76.47% (CI: 50.1–93.2) and 91.55% (CI: 85.7–95.6%), respectively. Also, the need for neonatal unit admission was predicted at a cut-off point >9.1 mmol/L with a sensitivity of 61.90% (CI: 38.4–81.9) and specificity of 91.30% (CI: 85.3–95.4). Umbilical artery lactate levels >11.2 mmol/L predicted the development of hypoxic ischaemic encephalopathy in neonates with a sensitivity of 100% (CI: 39.8–100.0) and specificity of 88.39% (CI: 82.3–93.0). ConclusionUmbilical artery lactate correlates with adverse pregnancy outcomes and is an excellent tool for predicting adverse neonatal outcome.

Risk factors for neonatal hypoxic ischemic encephalopathy and therapeutic hypothermia: a matched case-control study

BackgroundPeripartum asphyxia is one of the main causes of neonatal morbidity and mortality. In moderate and severe cases of asphyxia, a condition called hypoxic-ischemic encephalopathy (HIE) and associated permanent neurological morbidities may follow. Due to the multifactorial etiology of asphyxia, it may be difficult prevent, but in term neonates, therapeutic cooling can be used to prevent or reduce permanent brain damage. The aim of this study was to assess the significance of different antenatal and delivery related risk factors for moderate and severe HIE and the need for therapeutic hypothermia.MethodsWe conducted a retrospective matched case-control study in Helsinki University area hospitals during 2013–2017. Newborn singletons with moderate or severe HIE and the need for therapeutic hypothermia were included. They were identified from the hospital database using ICD-codes P91.00, P91.01 and P91.02. For every newborn with the need for therapeutic hypothermia the consecutive term singleton newborn matched by gender, fetal presentation, delivery hospital, and the mode of delivery was selected as a control. Odds ratios (OR) between obstetric and delivery risk factors and the development of HIE were calculated.ResultsEighty-eight cases with matched controls met the inclusion criteria during the study period. Maternal and infant characteristics among cases and controls were similar, but smoking was more common among cases (aOR 1.46, CI 1.14–1.64, p = 0.003). The incidence of preeclampsia, diabetes and intrauterine growth restriction in groups was equal. Induction of labour (aOR 3.08, CI 1.18–8.05, p = 0.02) and obstetric emergencies (aOR 3.51, CI 1.28–9.60, p = 0.015) were more common in the case group. No difference was detected in the duration of the second stage of labour or the delivery analgesia.ConclusionsSmoking, induction of labour and any obstetric emergency, especially shoulder dystocia, increase the risk for HIE and need for therapeutic hypothermia. The decisions upon induction of labour need to be carefully weighed, since maternal smoking and obstetric emergencies can hardly be controlled by the clinician.

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.

The Role of Cystathionine-β-Synthase, H2S, and miRNA-377 in Hypoxic-Ischemic Encephalopathy: Insights from Human and Animal Studies.

We aimed to investigate the mechanism underlying the roles of miRNA-377, Cystathionine-β-synthase (CBS), and hydrogen sulfide (H2S) in the development of hypoxic-ischemic encephalopathy (HIE). We investigated the relationship between CBS, H2S, and miR-377 in both humans with HIE and animals with hypoxic-ischemic insult. An animal model of fetal rats with hypoxic-ischemic brain injury was established, and the fetal rats were randomly assigned to control and hypoxic-ischemic groups for 15min (mild) and 30min (moderate) groups. Human samples were collected from children diagnosed with HIE. Healthy or non-neurological disease children were selected as the control group. Hematoxylin-eosin (HE) staining, quantitative real-time polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot were used to conduct this study. Hypoxia-ischemia induced pathological alterations in brain tissue changes were more severe in groups with severe hypoxic insult. miRNA-377 expression levels were upregulated in brain tissue and serum of fetal rats and human samples with HIE compared to controls. Conversely, CBS and H2S expression levels were significantly decreased in both human and animal samples compared to controls. Our findings suggest that CBS is a target gene of miR-377 which may contribute to the development of HIE by regulating CBS/H2S. H2S has a protective effect against hypoxic damage in brain tissue. The study provides new insights into the potential mechanisms underlying the protective role of H2S in hypoxic brain damage and may contribute to the development of novel therapies for HIE.

The Association of Different Genetic Variants with the Development of Hypoxic-Ischemic Encephalopathy.

The aim of this study is to investigate the frequency of six tag SNPs (single nucleotide polymorphisms) within specific genes (F2, F5, F7, MTHFR, NOS2A, PAI 2-1, PAI 2-2, and PAI 3-3): F2 (rs1799963), F5 (rs6025), F7 (rs6046), NOS 2 (rs1137933), PAI 2 (SERPINB2) (rs6103), MTHFR (rs1801133). The study also investigates their association with the development and severity of HIE. The genes F2, F5, and F7 code for proteins involved in blood clotting. MTHFR is a gene that plays a significant role in processing amino acids, the fundamental building blocks of proteins. NOS2A, PAI 2-1, PAI 2-2, and PAI 3-3 are genes involved in the regulation of various physiological processes, such as the relaxation of smooth muscle, regulation of central blood pressure, vasodilatation, and synaptic plasticity. Changes in these genes may be associated with brain injury. This retrospective study included 279 participants, of which 132 participants had Hypoxic-Ischemic Encephalopathy (HIE) and 147 subjects were in the control group. Our study found that certain genetic variants in the rs61103 and rs1137933 polymorphisms were associated with hypoxic-ischemic encephalopathy (HIE) and the findings of the magnetic resonance imaging. There was a correlation between Apgar scores and the degree of damage according to the ultrasound findings. These results highlight the complex relationship between genetic factors, clinical parameters, and the severity of HIE.

Serum Vitamin D status in full term neonates with severe perinatal depression.

Severe perinatal depression is a significant cause of mortality and morbidity in neonates. Vitamin D levels were observed to be low in mothers and their neonates with hypoxic ischemic encephalopathy in some studies, owing to its neuroprotective properties. Primary objective was to compare vitamin D deficiency state in full term neonates with severe perinatal depression and healthy term controls. Secondary objectives were to determine sensitivity and specificity of serum 25(OH)D<12 ng/mL in predicting mortality, development of hypoxic ischemic encephalopathy, abnormal neurological examination at discharge, and developmental outcome at 12 weeks of age. Serum 25(OH)D levels in full term neonates with severe perinatal depression and healthy controls were compared. Serum 25(OH)D levels in severe perinatal depression and controls (n = 55 each group) were significantly different (7.50 ± 3.53 ng/mL vs 20.23 ± 12.70 ng/mL). At cut-off of < 12 ng/mL, serum 25(OH)D could predict mortality with 100% sensitivity and 17% specificity and poor developmental outcomes with sensitivity of 100% and specificity of 50%. Vitamin D deficiency status at birth can serve as an effective screening tool and poor prognostic markers in term neonates with severe perinatal depression.

The Maternal Risk Factor for HIE Progression in Infants

Background: Perinatal asphyxia, or more accurately, hypoxic-ischemic encephalopathy (HIE), remains a devastating illness, producing considerable death and long-term morbidity despite great breakthroughs with sophisticated monitoring technologies and understanding of fetal and neonatal pathology. Objective: In this study our main goal is to evaluate the maternal risk factor for HIE progression in infants. Method: This case control study was conducted in the Department of the Paediatrics, Jalalabad Ragib Rabeya Medical College Hospital, Sylhet during the period from 1 st January 2014 to 30 th June 2014. Ninety-six normal birth weight term babies with HIE were selected as case; Ninety six sex and birth weight matched, term singleton baby without HIE born in Jalalabad Ragib Rabeya Medical College Hospital, Sylhet were taken as control. Results: Maternal age (&lt;20 years) [15 (15.6%) versus 6 (6.2%); OR=3.165; 95% of CI=1.176-8.518; p=0.037]; maternal height (&lt;145 cm) [37 (38.5%) versus 24 (25.0%); OR=1.881; 95% of CI=1.014-3.492; p=0.044), primiparity [45 (46.9%) versus 31 (32.3%); OR=1.850; 95% of CI=1.029-3.325; p=0.039], irregular or no antenatal care [41 (42.7%) versus 27 (28.1%); OR=1.905; 95% of CI=1.044-3.476; p=0.035]; pregnancy induced hypertension [38 (39.6%) versus 22 (22.9%);OR=2.204; 95% of CI=1.777-4.128; p=0.013]. Conclusion: Maternal risk factors of development of hypoxic ischemic encephalopathy are maternal age (&amp; lt;20 years), primigravida mother, absence or irregular antenatal care, pregnancy induced hypertension is associated with HIE.

Myricetin attenuates hypoxic-ischemic brain damage in neonatal rats via NRF2 signaling pathway.

Introduction: Hypoxic-ischemic encephalopathy (HIE) is a crucial cause of neonatal death and neurological sequelae, but currently there is no effective therapy drug for HIE. Both oxidative stress and apoptosis play critical roles in the pathological development of HIE. Myricetin, a naturally extracted flavonol compound, exerts remarkable effects against oxidative stress, apoptosis, and inflammation. However, the role and underlying molecular mechanism of myricetin on HIE remain unclear. Methods: In this study, we established the neonatal rats hypoxic-ischemic (HI) brain damage model in vivo and CoCl2 induced PC12 cell model in vitro to explore the neuroprotective effects of myricetin on HI injury, and illuminate the potential mechanism. Results: Our results showed that myricetin intervention could significantly reduce brain infarction volume, glia activation, apoptosis, and oxidative stress marker levels through activating NRF2 (Nuclear factor-E2-related factor 2) and increase the expressions of NRF2 downstream proteins NQO-1 and HO-1. In addition, the NRF2 inhibitor ML385 could significantly reverse the effects of myricetin. Conclusion: This study found that myricetin might alleviate oxidative stress and apoptosis through NRF2 signaling pathway to exert the protective role for HI injury, which suggested that myricetin might be a promising therapeutic agent for HIE.

The relationship between miRNA-210 and SCN1B in fetal rats with hypoxic-ischemic brain injury.

Hypoxic-ischemic brain injury contributes to major neurodevelopmental disorders and is one of the leading causes of seizures, which substantially results in neurodevelopmental impairments with long-lasting outcomes and is one of the main causes of death in neonates. We aimed to investigate the correlation between miRNA-210 and SCN1B, a voltage-gated sodium channel gene, in brain tissue of fetal rats with hypoxic-ischemic brain injury. We found that after 10 min of hypoxia-ischemia, all reperfusion groups showed different degrees of damage. The degree of the injury increased in all the groups after 30 min of hypoxia-ischemia. Those changes include changes in the pericellular lumen, capillaries in the cortex, erythrocytes, enlarged pericellular lumen, the enlarged pericapillary lumen in the cortex, edema around glial cells, enlarged gap to form multiple necrotic foci, deformation of neurons, and loss of cell structure. The expression levels of HIF-1α, miRNA-210, and HIF-1α mRNA were higher in the hypoxic-ischemic groups than that in the control groups, among which the expression levels in the severe group were higher than that in mild group. SCN1B is down-regulated in both the mild and severe groups, and the lowest level was found at 30 min after hypoxia in both groups. MiRNA-210 plays a role in the development of hypoxic-ischemic encephalopathy (HIE) by regulating the expression changes of SCN1B. The brain tissue of fetal rats in the hypoxic-ischemic animal model showed pathological changes of brain injury.

Urinary metabotypes of newborns with perinatal asphyxia undergoing therapeutic hypothermia.

Perinatal asphyxia (PA) still occurs in about three to five per 1,000 deliveries in developed countries; 20% of these infants show hypoxic-ischemic encephalopathy (HIE) on brain magnetic resonance imaging (MRI). The aim of our study was to apply metabolomic analysis to newborns undergoing therapeutic hypothermia (TH) after PA to identify a distinct metabotype associated with the development of HIE on brain MRI. We enrolled 53 infants born at >35 weeks of gestation with PA: 21 of them showed HIE on brain MRI (the "HIE" group), and 32 did not (the "no HIE" group). Urine samples were collected at 24, 48 and 72 hours of TH. Metabolomic data were acquired using high-resolution mass spectrometry and analyzed with univariate and multivariate methods. Considering the first urines collected during TH, untargeted analysis found 111 relevant predictors capable of discriminating between the two groups. Of 35 metabolites showing independent discriminatory power, four have been well characterized: L-alanine, Creatine, L-3-methylhistidine, and L-lysine. The first three relate to cellular energy metabolism; their involvement suggests a multimodal derangement of cellular energy metabolism during PA/HIE. In addition, seven other metabolites with a lower annotation level (proline betaine, L-prolyl-L-phenylalanine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E, 2,6 dimethylheptanoyl carnitine, Octanoylglucuronide, 19-hydroxyandrost-4-ene-3,17-dione) showed biological consistency with the clinical picture of PA. Moreover, 4 annotated metabolites (L-lysine, L-3-methylhistidine, 2-methyl-dodecanedioic acid, S-(2-methylpropionyl)-dihydrolipoamide-E) retained a significant difference between the "HIE" and "no HIE" groups during all the TH treatment. Our analysis identified a distinct urinary metabotype associated with pathological findings on MRI, and discovered 2 putative markers (L-lysine, L-3-methylhistidine) which may be useful for identifying neonates at risk of developing HIE after PA.

Asphyxia of newborns: new ideas about risk factors and pathogenetic mechanisms of the condition

Intrauterine hypoxia and asphyxia during childbirth are among the leading causes of neonatal deaths in the structure of «Separate conditions arising in the perinatal period» according to the Ministry of Health of the Russian Federation. The main causes of asphyxia are chronic intrauterine hypoxia and acute fetal hypoxia (most often in the intrapartum period). The article observes current data on antenatal and intrapartum risk factors for the development of asphyxia in newborns. Risk factors (modifiable and non-modifiable) triggering intrauterine hypoxia are discussed, as well as methods of management and prevention of asphyxia to prevent the subsequent development of hypoxic-ischemic encephalopathy. The importance of the problem under consideration is due to the need to find promising «tools» for managing neonatal and infant mortality, as well as preventing the long-term consequences of hypoxic brain damage.

Atorvastatin inhibits neuronal apoptosis via activating cAMP/PKA/p-CREB/BDNF pathway in hypoxic-ischemic neonatal rats.

Neuronal apoptosis is one of the main pathological processes of hypoxic-ischemic brain damage (HIBD) and is involved in the development of hypoxic-ischemic encephalopathy (HIE) in neonates. Atorvastatin has been found to have neuroprotective effects in some nervous system diseases, but its role in regulating the pathogenesis of neonatal HIBD remains elusive. Thus, this study aimed to explore the effects and related mechanisms of atorvastatin on the regulation of neuronal apoptosis after HIBD in newborn rats. The rat HIBD model and the neuronal oxygen glucose deprivation (OGD) model were established routinely. Atorvastatin, cAMP inhibitor (SQ22536), and BDNF inhibitor (ANA-12) were used to treat HIBD rats and OGD neurons. Cerebral infarction, learning and memory ability, cAMP/PKA/p-CREB/BDNF signaling molecules, and apoptosis-related indicators (TUNEL, cleaved caspase-3, and Bax/Bcl2) were then examined. In vivo, atorvastatin reduced cerebral infarction, improved learning and memory ability, decreased the number of TUNEL-positive neurons, inhibited the expression of cleaved caspase-3 and Bax/Bcl2, and activated the cAMP/PKA/p-CREB/BDNF pathway in the cerebral cortex after HIBD. In vitro, atorvastatin also decreased the apoptosis-related indicators and activated the cAMP/PKA/p-CREB/BDNF pathway in neurons after OGD. Furthermore, inhibition of cAMP or BDNF attenuated the effect of atorvastatin on the reduction of neuronal apoptosis, suggesting that atorvastatin inhibits HIBD-induced neuronal apoptosis and alleviates brain injury in neonatal rats mainly by activating the cAMP/PKA/p-CREB/BDNF pathway. In conclusion, atorvastatin may be developed as a potential drug for the treatment of neonatal HIE.

Evaluation of risk factors for neonatal hypoxic ischemic encephalopathy

Aim: Hypoxic ischemic encephalopathy (HIE) is a serious condition in neonates and is associated with neuromuscular dysfunction and death. In this study, we aimed to investigate potential risk factors for neonatal HIE.Methods: A retrospective case–control study was conducted on infants admitted to our neonatal intensive care unit between 2015 and 2020. Infants born at ≥36 weeks of gestation and diagnosed with HIE were included in the case group. For each case, 4 gestational agematched infants without HIE were selected and included in the control group. The groups were compared in terms of maternal demographic characteristics, pregnancy characteristics, and birth-related factors.Results: The study included 75 infants with HIE and 300 controls. Nulliparity, history of antenatal care, medical complications during pregnancy, prolonged difficult birth, abnormal fetal heart rate, mode of delivery, and acute birth complications were found to be significantly associated with HIE in univariate analysis. In multivariate logistic analysis, the lack of antenatal care, abnormal fetal heart rate (FHR), and acute birth complication were the strongest factors associated with neonatal HIE.Conclusion: Our findings demonstrated that the lack of antenatal care, abnormal FHR, and acute birth complications were risk factors for the development of HIE. Ensuring that pregnant women receive adequate antenatal care and applying necessary obstetric measures may help to reduce the HIE incidence.

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.

Predictive modelling of hypoxic ischaemic encephalopathy risk following perinatal asphyxia

Hypoxic Ischemic Encephalopathy (HIE) remains a major cause of neurological disability. Early intervention with therapeutic hypothermia improves outcome, but prediction of HIE is difficult and no single clinical marker is reliable. Machine learning algorithms may allow identification of patterns in clinical data to improve prognostic power. Here we examine the use of a Random Forest machine learning algorithm and five-fold cross-validation to predict the occurrence of HIE in a prospective cohort of infants with perinatal asphyxia. Infants with perinatal asphyxia were recruited at birth and neonatal course was followed for the development of HIE. Clinical variables were recorded for each infant including maternal demographics, delivery details and infant's condition at birth. We found that the strongest predictors of HIE were the infant's condition at birth (as expressed by Apgar score), need for resuscitation, and the first postnatal measures of pH, lactate, and base deficit. Random Forest models combining features including Apgar score, most intensive resuscitation, maternal age and infant birth weight both with and without biochemical markers of pH, lactate, and base deficit resulted in a sensitivity of 56-100% and a specificity of 78-99%. This study presents a dynamic method of rapid classification that has the potential to be easily adapted and implemented in a clinical setting, with and without the availability of blood gas analysis. Our results demonstrate that applying machine learning algorithms to readily available clinical data may support clinicians in the early and accurate identification of infants who will develop HIE. We anticipate our models to be a starting point for the development of a more sophisticated clinical decision support system to help identify which infants will benefit from early therapeutic hypothermia.

Alzheimer's Disease Associated Presenilin 1 and 2 Genes Dysregulation in Neonatal Lymphocytes Following Perinatal Asphyxia.

Perinatal asphyxia is mainly a brain disease leading to the development of neurodegeneration, in which a number of peripheral lesions have been identified; however, little is known about the expression of key genes involved in amyloid production by peripheral cells, such as lymphocytes, during the development of hypoxic-ischemic encephalopathy. We analyzed the gene expression of the amyloid protein precursor, β-secretase, presenilin 1 and 2 and hypoxia-inducible factor 1-α by RT-PCR in the lymphocytes of post-asphyxia and control neonates. In all examined periods after asphyxia, decreased expression of the genes of the amyloid protein precursor, β-secretase and hypoxia-inducible factor 1-α was noted in lymphocytes. Conversely, expression of presenilin 1 and 2 genes decreased on days 1–7 and 8–14 but increased after survival for more than 15 days. We believe that the expression of presenilin genes in lymphocytes could be a potential biomarker to determine the severity of the post-asphyxia neurodegeneration or to identify the underlying factors for brain neurodegeneration and get information about the time they occurred. This appears to be the first worldwide data on the role of the presenilin 1 and 2 genes associated with Alzheimer’s disease in the dysregulation of neonatal lymphocytes after perinatal asphyxia.

Experimental Study on the Correlation between miRNA-373 and HIF-1α, MMP-9, and VEGF in the Development of HIE.

Introduction Microribonucleic acids (miRNAs) have short (approximately 18 to 25) nucleotides and are evolutionarily conserved and endogenously expressed RNAs belonging to a family of noncoding RNA molecules. miRNA-373 regulates cell proliferation, migration, apoptosis, invasion, and repairing damaged DNA after hypoxia stress. Neonatal hypoxic–ischemic encephalopathy (HIE) refers to perinatal asphyxia caused by partial or complete hypoxia, reduced or suspended cerebral blood flow, and fetal or neonatal brain damage. We aim to investigate the relationship between miRNA-373 and HIF-1α, between miRNA-373 MMP-9, and between miRNA-373 VEGF in the occurrence and development of HIE. Methods Human (children) samples were divided into four groups (n = 15 in each group) according to HIE severity. The patient group was divided into middle, moderate, and severe HIE groups. The control group included healthy children or children with nonneurological diseases. The expressions of miRNA-373, HIF-1α, MMP-9, and VEGF were assayed in the serum samples. Results Our study showed a strong relationship between miRNA-373 and HIF-1α, between miRNA-373 and MMP-9, and between miRNA-373 and VEGF. The expression levels of miRNA-373, HIF-1α, MMP-9, and VEGF in the HIE groups were much higher than those of the control group. Conclusion The increased change in miRNA-373 expression has a certain diagnostic significance on neonatal HIE. In the occurrence and development of HIE, miRNA-373 is positively correlated with HIF-1α, MMP-9, and VEGF.

Improvement in the Prediction of Neonatal Hypoxic-Ischemic Encephalopathy with the Integration of Umbilical Cord Metabolites and Current Clinical Makers

To validate our previously identified candidate metabolites, and to assess the ability of these metabolites to predict hypoxic-ischemic encephalopathy (HIE) both individually and combined with clinical data. Term neonates with signs of perinatal asphyxia, with and without HIE, and matched controls were recruited prospectively at birth from 2 large maternity units. Umbilical cord blood was collected for later batch metabolomic analysis by mass spectroscopy along with clinical details. The optimum selection of clinical and metabolites features with the ability to predict the development of HIE was determined using logistic regression modelling and machine learning techniques. Outcome of HIE was determined by clinical Sarnat grading and confirmed by electroencephalogram grade at 24hours. Fifteen of 27 candidate metabolites showed significant alteration in infants with perinatal asphyxia or HIE when compared with matched controls. Metabolomic data predicted the development of HIE with an area under the curve of 0.67 (95% CI, 0.62-0.71). Lactic acid and alanine were the primary metabolite predictors for the development of HIE, and when combined with clinical data, gave an area under the curve of 0.96 (95% CI, 0.92-0.95). By combining clinical and metabolic data, accurate identification of infants who will develop HIE is possible shortly after birth, allowing early initiation of therapeutic hypothermia.

The Function of the NMDA Receptor in Hypoxic-Ischemic Encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is one of the main forms of neonatal brain injury which could lead to neonatal disability or even cause neonatal death. Therefore, HIE strongly affects the health of newborns and brings heavy burden to the family and society. It has been well studied that N-methyl-D-aspartate (NMDA) receptors are involved in the excitotoxicity induced by hypoxia ischemia in adult brain. Recently, it has been shown that the NMDA receptor also plays important roles in HIE. In the present review, we made a summary of the molecular mechanism of NMDA receptor in the pathological process of HIE, focusing on the distinct role of GluN2A- and GluN2B-containing NMDA receptor subtypes and aiming to provide some insights into the clinical treatment and drug development of HIE.

ФАКТОРИ РИЗИКУ ГІПОКСИЧНО-ІШЕМІЧНОЇ ЕНЦЕФАЛОПАТІЇ НЕДОНОШЕНИХ НОВОНАРОДЖЕНИХ

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