Hypoxic-ischemic Encephalopathy Group Research Articles

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.

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.

Human Placenta-Derived Mesenchymal Stem Cells Improve Neurological Function in Rats with Intrauterine Hypoxic-Ischaemic Encephalopathy by Reducing Apoptosis and Inflammatory Reactions.

Hypoxic-ischaemic encephalopathy (HIE) is a major cause of neonatal disability and mortality. Although hypothermia therapy offers some neuroprotection, the recovery of neurological function is limited. Therefore, new synergistic therapies are necessary to improve the prognosis. Mesenchymal stem cell-based therapy is emerging as a promising treatment option for HIE. In this study, we studied the therapeutic efficacy of human placenta-derived mesenchymal stem cells (PD-MSCs) in the HIE rat model and analyzed the underlying therapeutic mechanisms. Rats were divided into 6 groups (n = 9 for each) as follows: control, HIE model, HIE + normal saline, and HIE + PD-MSC transplantation at days 7, 14 and 28 postpartum. Following PD-MSC transplantation, neurological behavior was evaluated using rotarod tests, traction tests, and the Morris water maze test. The degree of brain tissue damage was assessed by histological examination and Nissl staining. Expression levels of apoptosis-related proteins and inflammatory factors were quantified by Western blotting and enzyme-linked immunosorbent assays. Immunofluorescence was used to investigate the ability of PD-MSCs to repair the morphology and function of hippocampal neurons with hypoxic-ischaemic (HI) injury. PD-MSC transplantation enhanced motor coordination and muscle strength in HIE rats. This treatment also improved spatial memory ability by repairing pathological damage and preventing the loss of neurons in the cerebral cortex. The most effective treatment was observed in the HIE + PD-MSC transplantation at day 7 group. Expression levels of microtubule-associated protein-2 (MAP-2), B-cell lymphoma-2 (BCL-2), interleukin (IL)-10, and transforming growth factor (TGF -β1) were significantly higher in the HIE + PD-MSC treatment groups compared to the HIE group, whereas the levels of BCL-2-associated X protein (BAX), BCL-2-associated agonist of cell death (BAD), IL-1β and tumour necrosis factor α (TNF-α) were significantly lower. We demonstrated that intravenous injection of PD-MSC at 7, 14 and 28 days after intrauterine HI damage in a rat model could improve learning, memory, and motor function, possibly by inhibiting apoptosis and inflammatory damage. These findings indicate that autologous PD-MSC therapy could have potential application for the treatment of HIE.

Bone Marrow Nucleated Cells and Bone Marrow-Derived CD271+ Mesenchymal Stem Cell in Treatment of Encephalopathy and Drug-Resistant Epilepsy.

The broad spectrum of brain injuries in preterm newborns and the plasticity of the central nervous system prompts us to seek solutions for neurodegeneration to prevent the consequences of prematurity and perinatal problems. The study aimed to evaluate the safety and efficacy of the implantation of autologous bone marrow nucleated cells and bone marrow mesenchymal stem cells in different schemes in patients with hypoxic-ischemic encephalopathy and immunological encephalopathy. Fourteen patients received single implantation of bone marrow nucleated cells administered intrathecally and intravenously, followed by multiple rounds of bone marrow mesenchymal stem cells implanted intrathecally, and five patients were treated only with repeated rounds of bone marrow mesenchymal stem cells. Seizure outcomes improved in most cases, including fewer seizures and status epilepticus and reduced doses of antiepileptic drugs compared to the period before treatment. The neuropsychological improvement was more frequent in patients with hypoxic-ischemic encephalopathy than in the immunological encephalopathy group. Changes in emotional functioning occurred with similar frequency in both groups of patients. In the hypoxic-ischemic encephalopathy group, motor improvement was observed in all patients and the majority in the immunological encephalopathy group. The treatment had manageable toxicity, mainly mild to moderate early-onset adverse events. The treatment was generally safe in the 4-year follow-up period, and the effects of the therapy were maintained after its termination.

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.

Respiratory Distress Syndrome (RDS) in Newborns with Hypoxic-Ischemic Encephalopathy (HIE).

Respiratory distress syndrome (RDS) and hypoxic-ischemic encephalopathy (HIE) are frequent causes of death and disability in neonates. This study included newborns between January 2021 and July 2022 at the University Clinic for Gynecology and Obstetrics, Skopje. Up to date criteria for HIE/RDS for term and for preterm infants as well for the severity of HIE/RDS were used in a comprehensive analysis of cranial ultrasonography, neurological status, neonatal infections, Apgar score, bradycardia and hypotension, X-ray of the lungs, FiO2, acid-base status, assisted ventilation and use of surfactant. Three groups were created: HIE with RDS (42 babies), HIE without RDS (30 babies) and RDS without HIE in 38 neonates. All newborns with severe (third) degree of HIE died. Intracranial bleeding was found in 35.7% in the first group and 30% in the second group, and in the third group in 53.3%. The need for surfactant in the HIE group with RDS is 59.5%, and in the RDS group without HIE 84.2%. DIC associated with sepsis was found in 13.1-50% in those groups. In newborns with HIE and bradycardia, the probability of having RDS was on average 3.2 times higher than in those without bradycardia. The application of the surfactant significantly improved the pH, pO2, pCO2, BE and chest X-ray in children with RDS. An Apgar score less than 6 at the fifth minute increases the risk of RDS by 3 times. The metabolic acidosis in the first 24 hours increases the risk of death by 23.6 times. The combination of HIE/ RDS significantly worsens the disease outcome. The use of scoring systems improved the early detection of high risk babies and initiation of early treatment increased the chances for survival without disabilities.

CGAS Deficiency Regulates the Phenotypic Polarization and Glycolysis of Microglia Through Lactylation in Hypoxic-Ischemic Encephalopathy Cell Model.

Promoting the M2 phenotype polarization of microglia is of great significance in alleviating hypoxic-ischemic encephalopathy (HIE). The umbilical artery blood sample was collected to evaluate the expression of cGAS, and the aberrant expressed cGAS was verified in the oxygen glucose deprivation (OGD) microglia which was established to mimic HIE in vitro. Then the regulating role of cGAS on the transformation of microglia M2 phenotype polarization and glycolysis was investigated. Moreover, the lactylation of cGAS in OGD treated microglia was evaluated by western blot. cGAS was found to be highly expressed in umbilical artery blood of HIE group, and OGD treated microglia. OGD interference activated microglia into M1 phenotype by enhancing CD86 and suppressing CD206 levels; meanwhile, the microglia in OGD group highly expressed IL-1β, iNOS and TNF-α, and lowly expressed IL-4, IL-10, and Arg-1. Inhibition of cGAS promotes the transformation of microglia from M1 to M2 phenotype. Meanwhile, OGD increased ECAR and decreased OCR to regulate glycolysis, cGAS deficiency inhibits glycolysis in OGD treated microglia. Moreover, the pan lysine lactylation (Pan-Kla) levels and lactated cGAS levels in microglia were upregulated in the OGD group. Lactate reversed the effects of cGAS knockdown on microglia polarization and glycolysis. The present study reveals that the cGAS-mediated neuron injury is associated with high level of cGAS lactylation. Inhibition of cGAS promotes the M2 phenotype polarization of microglia and suppress glycolysis. Thereby, targeting cGAS provides a new strategy for the development of therapeutic agents against HIE.

Inflammatory and Hematologic Liver and Platelet (HALP) Scores in Hypothermia-Treated Hypoxic-Ischemic Encephalopathy (HIE).

This study examined systemic inflammatory indices and "Hemoglobin, Albumin, Lymphocyte, Platelet (HALP) scores" in neonates with hypoxic-ischemic encephalopathy (HIE). A total of 43 neonates with moderate-to-severe HIE at 36 weeks' gestation were assessed. Systemic inflammatory markers were measured before HT commenced within 0-6 h after birth and between 60 and 72 h during and after therapy or before adjusting for hypothermia. Platelet counts, hemoglobin levels, and platelet indices in the HIE group were significantly lower at both time points (p = 0.001). Both the neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) decreased in the HIE group after hypothermia therapy (p = 0.001). Seizures, PVL, and kidney injuries were associated with higher HALP scores. The AUCs of NLR, PLR, MLR, SII, SIRI, and platelet, neutrophil, monocyte, and lymphocyte Index (PIV) showed significant sensitivity and specified HIE, with area under the curve (AUC) values of 0.654, 0.751, 0.766, 0.700, 0.722, and 0.749, respectively. A significant difference in systemic inflammatory markers was found between the HIE and control groups after hypothermia treatment, with significant reductions in the MLR and NLR. These markers, particularly MLR, were significant predictors of adverse clinical outcomes including seizures, PVL, and kidney damage.

Neonatal Hypoxic-Ischemic Encephalopathy Spectrum: Severity-Stratified Analysis of Neuroimaging Modalities and Association with Neurodevelopmental Outcomes

To compare hypoxic-ischemic injury on early cranial ultrasonography (cUS) and post-rewarming brain magnetic resonance imaging (MRI) in newborn infants with hypoxic-ischemic encephalopathy (HIE) and to correlate that neuroimaging with neurodevelopmental outcomes. This was a retrospective cohort study of infants with mild, moderate, and severe HIE treated with therapeutic hypothermia and evaluated with early cUS and postrewarming MRI. Validated scoring systems were used to compare the severity of brain injury on cUS and MRI. Neurodevelopmental outcomes were assessed at 18months of age. Among the 149 included infants, abnormal white matter (WM) and deep gray matter (DGM) hyperechogenicity on cUS in the first 48hours after birth were more common in the severe HIE group than the mild HIE group (81% vs 39% and 50% vs 0%, respectively; P<.001). In infants with a normal cUS, 95% had normal or mildly abnormal brain MRIs. In infants with severely abnormal cUS, none had normal and 83% had severely abnormal brain MRIs. Total abnormality scores on cUS were higher in neonates with near-total brain injury on MRI than in neonates with normal MRI or WM-predominant injury pattern (adjusted P<.001 for both). In the multivariable model, a severely abnormal MRI was the only independent risk factor for adverse outcomes (OR: 19.9, 95% CI: 4.0-98.1; P<.001). The present study shows the complementary utility of cUS in the first 48hours after birth as a predictive tool for the presence of hypoxic-ischemic injury on brain MRI.

Long-term effect of indomethacin on a rat model of neonatal hypoxia ischemic encephalopathy through behavioral tests.

Many medical experts prescribe indomethacin because of its anti-inflammatory, analgesic, tocolytic, and duct closure effects. This article presents an evaluation of the enduring impact of indomethacin on neonatal rats with hypoxic-ischemic (HI) insults, employing behavioral tests as a method of assessment. The experiment was conducted on male Wistar-Albino rats weighing 10 to 15 g, aged between seven and 10 days. The rats were divided into three groups using a random allocation method as follows: hypoxic ischemic encephalopathy (HIE) group, HIE treated with indomethacin group (INDO), and Sham group. A left common carotid artery ligation and hypoxia model was applied in both the HIE and INDO groups. The INDO group was treated with 4mg/kg intraperitoneal indomethacin every 24 h for 3days, while the Sham and HIE groups were given dimethylsulfoxide (DMSO). After 72 h, five rats from each group were sacrificed and brain tissue samples were stained with 2,3,5-Triphenyltetrazolium chloride (TCC) for infarct-volume measurement. Seven rats from each group were taken to the behavioral laboratory in the sixth postnatal week (PND42) and six from each group were sacrificed for the Evans blue (EB) experiment for blood-brain barrier (BBB) integrity evaluation. The open field (OF) test and Morris water maze (MWM) tests were performed. After behavioral tests, brain tissue were obtained and stained with TCC to assess the infarct volume. The significant increase in the time spent in the central area and the frequency of crossing to the center in the INDO group compared with the HIE group indicated that indomethacin decreased anxiety-like behavior (p < 0.001, p < 0.05). However, the MWM test revealed that indomethacin did not positively affect learning and memory performance (p > 0.05). Additionally, indomethacin significantly reduced infarct volume and neuropathological grading in adolescence (p < 0.05), although not statistically significant in the early period. Moreover, the EB experiment demonstrated that indomethacin effectively increased BBB integrity (p < 0.05). In this study, we have shown for the first time that indomethacin treatment can reduce levels of anxiety-like behavior and enhance levels of exploratory behavior in a neonatal rat model with HIE. It is necessary to determine whether nonsteroidal anti-inflammatory agents, such as indomethacin, should be used for adjuvant therapy in newborns with HIE.

Newborns with Favourable Outcomes after Perinatal Asphyxia Have Upregulated Glucose Metabolism-Related Proteins in Plasma.

Hypoxic-ischaemic encephalopathy (HIE) is an important cause of morbidity and mortality globally. Although mild therapeutic hypothermia (TH) may improve outcomes in selected babies, the mechanism of action is not fully understood. A proteomics discovery study was carried out to analyse proteins in the plasma of newborns with HIE. Proteomic analysis of plasma from 22 newborns with moderate-severe HIE that had initially undergone TH, and relative controls including 10 newborns with mild HIE who did not warrant TH and also cord blood from 10 normal births (non-HIE) were carried out using the isobaric Tandem Mass Tag (TMT®) 10plexTM labelling with tandem mass spectrometry. A total of 7818 unique peptides were identified in all TMT10plexTM samples, translating to 3457 peptides representing 405 proteins, after applying stringent filter criteria. Apart from the unique protein signature from normal cord blood, unsupervised analysis revealed several significantly regulated proteins in the TH-treated moderate-severe HIE group. GO annotation and functional clustering revealed various proteins associated with glucose metabolism: the enzymes fructose-bisphosphate aldolase A, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate mutase 1, phosphoglycerate kinase 1, and pyruvate kinase PKM were upregulated in newborns with favourable (sHIE+) outcomes compared to newborns with unfavourable (sHIE-) outcomes. Those with favourable outcomes had normal MR imaging or mild abnormalities not predictive of adverse outcomes. However, in comparison to mild HIE and the sHIE- groups, the sHIE+ group had the additional glucose metabolism-related enzymes upregulated, including triosephosphate isomerase, α-enolase, 6-phosphogluconate dehydrogenase, transaldolase, and mitochondrial glutathione reductase. In conclusion, our plasma proteomic study demonstrates that TH-treated newborns with favourable outcomes have an upregulation in glucose metabolism. These findings may open new avenues for more effective neuroprotective therapy.

Long-chain omega-3 polyunsaturated fatty acids are reduced in neonates with substantial brain injury undergoing therapeutic hypothermia after hypoxic-ischemic encephalopathy.

Hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal morbidity and mortality. Although therapeutic hypothermia is an effective treatment, substantial chronic neurological impairment often persists. The long-chain omega-3 polyunsaturated fatty acids (PUFAs), docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids, offer therapeutic potential in the post-acute phase. To understand how PUFAs are affected by HIE and therapeutic hypothermia we quantified for the first time the effects of HIE and therapeutic hypothermia on blood PUFA levels and lipid peroxidation. In a cross-sectional approach, blood samples from newborns with moderate to severe HIE, who underwent therapeutic hypothermia (sHIE group) were compared to samples from newborns with mild HIE, who did not receive therapeutic hypothermia, and controls. The sHIE group was stratified into cerebral MRI predictive of good (n = 10), or poor outcomes (n = 10; nine developed cerebral palsy). Cell pellets were analyzed for fatty acid content, and plasma for lipid peroxidation products, thiobarbituric acid reactive substances and 4-hydroxy-2-nonenal. Omega-3 Index (% DHA + EPA) was similar between control and HIE groups; however, with therapeutic hypothermia there were significantly lower levels in poor vs. good prognosis sHIE groups. Estimated Δ-6 desaturase activity was significantly lower in sHIE compared to mild HIE and control groups, and linoleic acid significantly increased in the sHIE group with good prognosis. Reduced long-chain omega-3 PUFAs was associated with poor outcome after HIE and therapeutic hypothermia, potentially due to decreased biosynthesis and tissue incorporation. We speculate a potential role for long-chain omega-3 PUFA interventions in addition to existing treatments to improve neurologic outcomes in sHIE.

Patterns of neurobehavioral functioning in school-aged survivors of neonatal jaundice and hypoxic-ischemic encephalopathy in Kilifi, Kenya: A cross-sectional study

Background: Studies in high-income countries have reported that school-aged children who survive neonatal jaundice (NNJ) and hypoxic-ischemic encephalopathy (HIE) develop long-term neurocognitive problems. However, less is known about the patterns of functioning in school-aged survivors of NNJ and HIE in sub-Saharan Africa. This study examined patterns of functioning in school-aged children who survived NNJ and HIE in Kilifi, Kenya. Methods: This is a cross-sectional study that included 107 survivors of NNJ/HIE (64 with NNJ, 43 with HIE), aged 6-12 years, admitted to Kilifi County Hospital on the Kenyan Coast. The Gross Motor Function Classification System (GMFCS), Adapted Communication Profile, Raven’s Coloured Progressive Matrices (RCPM) and an epilepsy screening tool were used to assess gross motor function, communication function, intellectual functioning, and epilepsy, respectively. Results: Most of the survivors of NNJ (95.2%) and HIE (95.3%) had no impairments in gross motor functioning. A small percentage of the children in the NNJ and HIE groups had profound problems in their communication (4.7% and 4.7%); expressive communication function (4.7% and 4.7%); social functions (3.1% and 2.3%); receptive communication (4.7% and 2.3%); and communicative effectiveness (4.7% and 2.3%). Cognitive impairment was reported in 10.9% and 11.9% for NNJ and HIE survivors, respectively. Active epilepsy was detected in 1.6% of survivors of NNJ and 2.3% of survivors of HIE. A subgroup of severe NNJ and HIE survivors without co-occurring conditions had the worst intellectual and active epilepsy outcomes. All children had normal hearing and visual functioning except one participant who presented with mild visual acuity problems. Conclusions: Most school-aged children who survive with NNJ and HIE have normal motor and communication function; however, one in ten are likely to present with lowered intellectual functioning compared to the normative sample.

Subcortical brain volumes in neonatal hypoxic-ischemic encephalopathy.

Despite treatment with therapeutic hypothermia, hypoxic-ischemic encephalopathy (HIE) is associated with adverse developmental outcomes, suggesting the involvement of subcortical structures including the thalamus and basal ganglia, which may be vulnerable to perinatal asphyxia, particularly during the acute period. The aims were: (1) to examine subcortical macrostructure in neonates with HIE compared to age- and sex-matched healthy neonates within the first week of life; (2) to determine whether subcortical brain volumes are associated with HIE severity. Neonates (n = 56; HIE: n = 28; Healthy newborns from the Developing Human Connectome Project: n = 28) were scanned with MRI within the first week of life. Subcortical volumes were automatically extracted from T1-weighted images. General linear models assessed between-group differences in subcortical volumes, adjusting for sex, gestational age, postmenstrual age, and total cerebral volumes. Within-group analyses evaluated the association between subcortical volumes and HIE severity. Neonates with HIE had smaller bilateral thalamic, basal ganglia and right hippocampal and cerebellar volumes compared to controls (all, p < 0.02). Within the HIE group, mild HIE severity was associated with smaller volumes of the left and right basal ganglia (both, p < 0.007) and the left hippocampus and thalamus (both, p < 0.04). Findings suggest that, despite advances in neonatal care, HIE is associated with significant alterations in subcortical brain macrostructure. Compared to their healthy counterparts, infants with HIE demonstrate significant alterations in subcortical brain macrostructure on MRI acquired as early as 4 days after birth. Smaller subcortical volumes impacting sensory and motor regions, including the thalamus, basal ganglia, and cerebellum, were seen in infants with HIE. Mild and moderate HIE were associated with smaller subcortical volumes.

Adrenal congestion in perinatal hypoxia: Sonographic assessment and relationship with hypoxic ischemic encephalopathy

BackgroundDuring hypoxia, blood flow to the brain, myocardium, and adrenal glands is preserved or even increased to maintain homeostasis. Adrenal congestion occurs when venous return remains insufficient. Several different ultrasound measurements of adrenal glands in neonates have been reported in the literature. However, there is no data related on adrenal gland size in neonates with perinatal hypoxia. AimsTo evaluate the adrenal congestion using by ultrasound (US) measurements in perinatal hypoxia, and to reveal the relationship of adrenal congestion with hypoxic-ischemic encephalopathy (HIE) grades and magnetic resonance imaging (MRI) findings. Study designProspective cohort study. SubjectsInfants with perinatal hypoxia who met therapeutic hypothermia criteria and were being cooled were included in the present study. The control group was established from healthy neonates admitted to our center during the recruitment. Outcome measuresThe gland area was measured by tracing, and both the corpus and crura widths were measured. ResultsWe reported adrenal gland area data of 110 newborns with HIE and compared them with 56 normal neonates. The adrenal size was significantly higher in the HIE group than in the control group (p<0,01). The frequency of adrenal congestion was 72.7% based on the selected cut-off values. The adrenal gland measurements were increased in the patients with perinatal hypoxia than those of the controls. ConclusionsIn the systemic evaluation of newborns with perinatal hypoxia, additional care should be taken regarding adrenal congestion. The measurement of adrenal size with 2D US will help us to diagnose or confirm adrenal congestion and possible hemorrhagic changes. The morphological data and cut-off values given in our study will be useful for neonatologists and pediatric radiologists to evaluate the patient while managing perinatal hypoxia.

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

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

Clinical Characteristics and Risk Factors of Neonatal Hypoxic-Ischaemic Encephalopathy and Its Associated Neurodevelopmental Outcomes During the First Two Years of Life: A Retrospective Study in Saudi Arabia.

This study aimed to determine the clinical characteristics and factors associated with neonatal hypoxic-ischaemic encephalopathy (HIE) and its neurodevelopmental outcomes. We conductedretrospective case-control researchto investigate the clinical and labour-related risk factors for HIE. In addition, a single-centre cohort study was conducted on infants with HIE to describe their neurodevelopment from birth to 24 months. For this investigation, cases with a diagnosis of HIE who were born at King Abdullah Children's Specialist Hospital (KASCH), Riyadh, Saudi Arabia, between 2015 and 2019 were identified and matched with controls from the same facility (1:4). Each case's clinical information was extracted using electronic medical records. In addition,24-monthfollow-up HIE cases were included in a cohort study to describe their neurodevelopmental outcomes. The sample includes 60 infants diagnosed with HIE and 234 infants serving as controls, with a mean gestational age of 38.8 weeks (SD 1.6)and a predominance of males (56.4%). Around one-thirdof the HIE cases (36.6%) had moderate HIE (stage 2), whereas 35.1% of infants had severe HIE (stage 3), according to Sarnat staging. Compared to the control group, children with HIE were twice as likely to be born to mothers with maternal comorbidities and more likely to have prepartum and intrapartum complications. A 24-month follow-up of neurodevelopmental outcomes for HIE babies revealed that approximately 24% exhibited delays in gross motor skill development, 22% in fine motor skill development, 33% in language skill development, and 22% in social skill development. In the HIE group, maternal comorbidities and prepartumor intrapartum complications were more common. The severity grade of HIE can be used to predict neurodevelopmental consequences. Enhancing patient care and rehabilitation requires a minimum of 24 months of neurodevelopmental follow-up.

The levels of postpartum depression, anxiety, and hopelessness of the mothers of infants receiving therapeutic hypothermia in NICU

ABSTRACT The aim of this study was to evaluate anxiety, postpartum depression (PPD), and hopelessness in the mothers of newborns receiving therapeutic hypothermia for hypoxic ischemic encephalopathy (HIE) in NICU. A total of 104 mothers and infants were analyzed as a study group with HIE (n = 52) and a control groups of non-HIE (n = 52). All the mothers completed The State-Trait Anxiety, Beck Hopelessness and Edinburgh Postpartum Depression Scales (EPDS). The EPDS scores, the rate of PPD, state-trait anxiety and hopelessness levels were similar in the two groups. In the HIE group, chest compression and persistent pulmonary hypertension in infants were associated with maternal anxiety, hopelessness, and PPD. The absence of a statistical difference between the two groups in the current study does not mean that these differences do not exist. These results demonstrate the need for further detailed studies on this subject.

Radiomics based of deep medullary veins on susceptibility-weighted imaging in infants: predicting the severity of brain injury of neonates with perinatal asphyxia

ObjectiveThis study aimed to apply radiomics analysis of the change of deep medullary veins (DMV) on susceptibility-weighted imaging (SWI), and to distinguish mild hypoxic-ischemic encephalopathy (HIE) from moderate-to-severe HIE in neonates.MethodsA total of 190 neonates with HIE (24 mild HIE and 166 moderate-to-severe HIE) were included in this study. All of them were born at 37 gestational weeks or later. The DMVs were manually included in the regions of interest (ROI). For the purpose of identifying optimal radiomics features and to construct Rad-scores, 1316 features were extracted. LASSO regression was used to identify the optimal radiomics features. Using the Red-score and the clinical independent factor, a nomogram was constructed. In order to evaluate the performance of the different models, receiver operating characteristic (ROC) curve analysis was applied. Decision curve analysis (DCA) was implemented to evaluate the clinical utility.ResultsA total of 15 potential predictors were selected and contributed to Red-score construction. Compared with the radiomics model, the nomogram combined model incorporating Red-score and urea nitrogen did not better distinguish between the mild HIE and moderate-to-severe HIE group. For the training cohort, the AUC of the radiomics model and the combined nomogram model was 0.84 and 0.84. For the validation cohort, the AUC of the radiomics model and the combined nomogram model was 0.80 and 0.79, respectively. The addition of clinical characteristics to the nomogram failed to distinguish mild HIE from moderate-to-severe HIE group.ConclusionWe developed a radiomics model and combined nomogram model as an indicator to distinguish mild HIE from moderate-to-severe HIE group.

Volumetric apparent diffusion coefficient (ADC) histogram analysis of the brain in paediatric patients with hypoxic ischaemic encephalopathy.

To evaluate the whole brain, hippocampus, thalamus, and lentiform nucleus by volumetric apparent diffusion coefficient (ADC) histogram analysis in paediatric patients with hypoxic-ischaemic encephalopathy (HIE). This retrospective study included 25 patients with HIE and 50 patients as the control group. Diffusion-weighted imaging was obtained at b-values of 1000 mm2/s. The histogram parameters of ADC values, including the mean, minimum, maximum, 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles, as well as skewness, kurtosis, and variance were determined. The interclass correlation coefficient (ICC) was used to assess the inter-observer agreement. ADCmin, ADCmean, and ADCmax, as well as the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles of ADC values for the HIE group were all lower than those of the control group (p < 0.001) in the volumetric histogram analysis of the hippocampus, thalamus, and lentiform nucleus. In the whole-brain histogram analysis, ADC min, and the 50th and 75th percentiles of ADC values did not differ significantly, while other parameters were lower in the HIE group. The ROC curve revealed that the ADC histogram parameters of the hippocampus provided the most accurate results for the diagnosis of HIE. The area under the curve (AUC) of the 95th percentile of ADC values was the highest (AUC = 0.915; cut-off 1.262 × 10-3 mm2/s; sensitivity 88% and specificity 84%). Volumetric ADC histogram analysis of the whole brain, hippocampus, thalamus, and lentiform nucleus with b-values of 1000 mm2/s can serve as an imaging marker for determining HIE.