Comparison between selective head cooling and whole-body cooling in neonatal therapeutic hypothermia / Comparação entre resfriamento seletivo da cabeça e resfriamento de corpo inteiro na hipotermia terapêutica neonatal

INTRODUCTION: Experimental evidence, as well as improved clinical studies of the reduction of brain injury and, improves the neurological outcome, in newborns with hypoxic-ischemic encephalopathy (HIE) occurring in therapeutic hypothermia (TH). OBJECTIVE: To verify the potential of hypothermic hypoxic-ischemic encephalopathy (HIE) therapy in neonatal asphyxia, based on literature data, comparing the benefits between selective head cooling (SHC) and whole-body cooling (WBC), see that the use of TH as a standard treatment in newborns with moderate or severe HIE has been adopted. METHODS: A search was performed in the PubMed and SciELO databases of human studies, using the keywords "Therapeutic Hypothermia", "Induced Hypothermia", and "Hypoxic-Ischemic Encephalopathy", "Selective cooling of the head", "Total body cooling" and its variables. RESULTS: Eleven articles were selected to compose the review, after detailed reading. There is a consensus, that the reduction of the risk of death or disability at 18 months of life in neonates with moderate to severe HIE, occurs to TH through the techniques of WBC or SHC. It was found in the studies that there is no difference in terms of adverse effects between the two methods. As for radiological changes, such as hypoxic-ischemic injuries and the incidence of seizures after cooling, they are more frequent with SHC. CONCLUSION: Both WBC and SHC demonstrated neuroprotective properties, although WBC provides a broader area of brain protection. However, no significant differences were found between the methods in terms of adverse effects and beneficial short or long-term results.

INTRODUÇÃO: Evidências experimentais, assim como estudos clínicos, sugerem a redução da lesão cerebral e melhora do desfecho neurológico, em recém-nascidos com encefalopatia isquêmica hipóxica (EHI) submetidos à hipotermia terapêutica (HT). OBJETIVO: Verificar a potencialidade da terapia hipotérmica de encefalopatia hipóxico-isquêmica (EHI) na asfixia neonatal, com base em dados da literatura, comparando os benefícios entre o resfriamento seletivo da cabeça (RSC) e o resfriamento de corpo inteiro (RCI), visto que o uso de hipotermia terapêutica (HT) como tratamento padrão em recém-nascidos com EHI moderada ou grave tem sido amplamente adotada. MÉTODOS: Foi realizada uma busca nas bases de dados PubMed e SciELO de estudos em humanos, utilizando-se as palavras-chave "Therapeutic Hypothermia", "Induced Hypothermia", "Hypoxic-Ischemic Encephalopathy", "selective head cooling", "whole body cooling" e suas respectivas variáveis. RESULTADOS: Foram selecionados 11 artigos para compor a revisão, após leitura detalhada. É consenso, a redução do risco de morte ou incapacidade aos 18 meses de vida nos neonatos com EHI moderado a grave, submetidos à HT através das técnicas de RCI ou RSC. Constatou-se diante dos estudos que não há diferença em termos de efeitos adversos entre os dois métodos. Quanto às alterações radiológicas, as lesões hipóxico-isquêmicas e incidência de convulsões após o resfriamento são mais frequentes com o RSC. CONCLUSÃO: Tanto RCI quanto o RSC demonstraram propriedades neuroprotetoras, embora o RCI proporcione uma área de proteção cerebral mais ampla. No entanto, não foram constatadas diferenças significativas entre os métodos quanto a efeitos adversos e a resultados benéficos em curto e longo prazo.

Research progress of ferroptosis in hypoxia-associated brain injury / 生理学报

Cerebral hypoxia often brings irreversible damage to the central nervous system, which seriously endangers human health. It is of great significance to further explore the mechanism of hypoxia-associated brain injury. As a programmed cell death, ferroptosis mainly manifests as cell death caused by excessive accumulation of iron-dependent lipid peroxides. It is associated with abnormal glutathione metabolism, lipid peroxidation and iron metabolism, and is involved in the occurrence and development of various diseases. Studies have found that ferroptosis plays an important role in hypoxia-associated brain injury. This review summarizes the mechanism of ferroptosis, and describes its research progress in cerebral ischemia reperfusion injury, neonatal hypoxic-ischemic brain damage, obstructive sleep apnea-induced brain injury and high-altitude hypoxic brain injury.

A novel method for electroencephalography background analysis in neonates with hypoxic-ischemic encephalopathy / 中国当代儿科杂志

OBJECTIVES@#To explore a new method for electroencephalography (EEG) background analysis in neonates with hypoxic-ischemic encephalopathy (HIE) and its relationship with clinical grading and head magnetic resonance imaging (MRI) grading.@*METHODS@#A retrospective analysis was performed for the video electroencephalography (vEEG) and amplitude-integrated electroencephalography (aEEG) monitoring data within 24 hours after birth of neonates diagnosed with HIE from January 2016 to August 2022. All items of EEG background analysis were enrolled into an assessment system and were scored according to severity to obtain the total EEG score. The correlations of total EEG score with total MRI score and total Sarnat score (TSS, used to evaluate clinical gradings) were analyzed by Spearman correlation analysis. The total EEG score was compared among the neonates with different clinical gradings and among the neonates with different head MRI gradings. The receiver operating characteristic (ROC) curve and the area under thecurve (AUC) were used to evaluate the value of total EEG score in diagnosing moderate/severe head MRI abnormalities and clinical moderate/severe HIE, which was then compared with the aEEG grading method.@*RESULTS@#A total of 50 neonates with HIE were included. The total EEG score was positively correlated with the total head MRI score and TSS (rs=0.840 and 0.611 respectively, P<0.001). There were significant differences in the total EEG score between different clinical grading groups and different head MRI grading groups (P<0.05). The total EEG score and the aEEG grading method had an AUC of 0.936 and 0.617 respectively in judging moderate/severe head MRI abnormalities (P<0.01) and an AUC of 0.887 and 0.796 respectively in judging clinical moderate/severe HIE (P>0.05). The total EEG scores of ≤6 points, 7-13 points, and ≥14 points were defined as mild, moderate, and severe EEG abnormalities respectively, which had the best consistency with clinical grading and head MRI grading (P<0.05).@*CONCLUSIONS@#The new EEG background scoring method can quantitatively reflect the severity of brain injury and can be used for the judgment of brain function in neonates with HIE.

A neonatal intelligent regulation system based on the combination of mild hypothermia mattress and hyperbaric oxygen chamber: introduction to a patent / 中国当代儿科杂志

Neonatal hypoxic-ischemic encephalopathy (HIE) is a common disease that affects brain function in neonates. At present, mild hypothermia and hyperbaric oxygen therapy are the main methods for the treatment of neonatal HIE; however, they are independent of each other and cannot be combined for synchronous treatment, without monitoring of brain function-related physiological information. In addition, parameter setting of hyperbaric oxygen chamber and mild hypothermia mattress relies on the experience of the medical practitioner, and the parameters remain unchanged throughout the medical process. This article proposes a new device for the treatment of neonatal HIE, which has the modules of hyperbaric oxygen chamber and mild hypothermic mattress, so that neonates can receive the treatment of hyperbaric oxygen chamber and/or mild hypothermic mattress based on their conditions. Meanwhile, it can realize the real-time monitoring of various physiological information, including amplitude-integrated electroencephalogram, electrocardiogram, and near-infrared spectrum, which can monitor brain function, heart rate, rhythm, myocardial blood supply, hemoglobin concentration in brain tissue, and blood oxygen saturation. In combination with an intelligent control algorithm, the device can intelligently regulate parameters according to the physiological information of neonates and give recommendations for subsequent treatment.

Effect of ligustrazine on hypoxic-ischemic encephalopathy in neonatal rats by regulating autophagy through the PINK1/Parkin pathway / 中国当代儿科杂志

OBJECTIVES@#To study the effect of ligustrazine injection on mitophagy in neonatal rats with hypoxic-ischemic encephalopathy (HIE) and its molecular mechanism.@*METHODS@#Neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group with 8 rats, a model group with 12 rats, and a ligustrazine group with 12 rats. The rats in the model group and the ligustrazine group were used to establish a neonatal rat model of HIE by ligation of the left common carotid artery followed by hypoxia treatment, and blood vessels were exposed without any other treatment for the rats in the sham-operation group. The rats in the ligustrazine group were intraperitoneally injected with ligustrazine (20 mg/kg) daily after hypoxia-ischemia, and those in the sham-operation group and the model group were intraperitoneally injected with an equal volume of normal saline daily. Samples were collected after 7 days of treatment. Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of neurons in brain tissue; immunohistochemical staining was used to observe the positive expression of PINK1 and Parkin in the hippocampus and cortex; TUNEL staining was used to measure neuronal apoptosis; Western blotting was used to measure the expression levels of the mitophagy pathway proteins PINK1 and Parkin and the autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (P62).@*RESULTS@#Compared with the sham-operation group, the model group had a significant reduction in the number of neurons, an increase in intercellular space, loose arrangement, lipid vacuolization, and a reduction in Nissl bodies. The increased positive expression of PINK1 and Parkin, apoptosis rate of neurons, and protein expression levels of PINK1, Parkin, Beclin1 and LC3 (P<0.05) and the decreased protein expression level of P62 in the hippocampus were also observed in the model group (P<0.05). Compared with the model group, the ligustrazine group had a significant increase in the number of neurons with ordered arrangement and an increase in Nissl bodies, significant reductions in the positive expression of PINK1 and Parkin, the apoptosis rate of neurons, and the protein expression levels of PINK1, Parkin, Beclin1, and LC3 (P<0.05), and a significant increase in the protein expression level of P62 (P<0.05).@*CONCLUSIONS@#Ligustrazine can alleviate hypoxic-ischemic brain damage and inhibit neuronal apoptosis in neonatal rats to a certain extent, possibly by inhibiting PINK1/Parkin-mediated autophagy.

Clinical efficacy of mild therapeutic hypothermia with different rewarming time on neonatal hypoxic-ischemic encephalopathy: a prospective randomized controlled study / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical efficacy of mild therapeutic hypothermia (MTH) with different rewarming time on neonatal hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A prospective study was performed on 101 neonates with HIE who were born and received MTH in Zhongshan Hospital, Xiamen University, from January 2018 to January 2022. These neonates were randomly divided into two groups: MTH1 group (n=50; rewarming for 10 hours at a rate of 0.25°C/h) and MTH2 group (n=51; rewarming for 25 hours at a rate of 0.10°C/h). The clinical features and the clinical efficacy were compared between the two groups. A binary logistic regression analysis was used to identify the factors influencing the occurrence of normal sleep-wake cycle (SWC) on amplitude-integrated electroencephalogram (aEEG) at 25 hours of rewarming.@*RESULTS@#There were no significant differences between the MTH1 and MTH2 groups in gestational age, 5-minute Apgar score, and proportion of neonates with moderate/severe HIE (P>0.05). Compared with the MTH2 group, the MTH1 group tended to have a normal arterial blood pH value at the end of rewarming, a significantly shorter duration of oxygen dependence, a significantly higher proportion of neonates with normal SWC on aEEG at 10 and 25 hours of rewarming, and a significantly higher Neonatal Behavioral Neurological Assessment score on days 5, 12, and 28 after birth (P<0.05), while there was no significant difference in the incidence rate of rewarming-related seizures between the two groups (P>0.05). There were no significant differences between the two groups in the incidence rate of neurological disability at 6 months of age and the score of Bayley Scale of Infant Development at 3 and 6 months of age (P>0.05). The binary logistic regression analysis showed that prolonged rewarming time (25 hours) was not conducive to the occurrence of normal SWC (OR=3.423, 95%CI: 1.237-9.469, P=0.018).@*CONCLUSIONS@#Rewarming for 10 hours has a better short-term clinical efficacy than rewarming for 25 hours. Prolonging rewarming time has limited clinical benefits on neonates with moderate/severe HIE and is not conducive to the occurrence of normal SWC, and therefore, it is not recommended as a routine treatment method.

Artesunate alleviates hypoxic-ischemic brain damage in neonatal rats by inhibiting NLRP3 inflammasome activation and inflammatory cytokine secretion / 细胞与分子免疫学杂志

Objective To investigate the protective effect of artesunate on hypoxic-ischemic brain damage (HIBD) and its mechanism in neonatal rats. Methods 7-day-old neonatal SD rats were randomly divided into sham operation group, model group, artesunate 5 mg/kg group, artesunate 10 mg/kg group, artesunate 20 mg/kg group and dexamethasone 6 mg/kg group, with 18 rats in each group. HIBD models were established in groups except for the sham operation group. The sham operation group only needed to separate the left common carotid artery without ligation and nitrogen-oxygen mixed gas ventilation. Each group was injected with drug intraperitoneally right after surgery and the rats in the sham operation group and the model group were injected with an equal volume of normal saline (once a day for a total of 5 times). One hour after the last injection, the rats in each group were scored for neurological defects. After the rats were sacrificed, the brain water content was measured and the pathological changes of the brain tissues of rats were observed. Terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) was used to detect the neuronal cell apoptosis, and ELISA was applied to detect the levels of IL-1β, IL-6 and TNF-α in brain tissues and peripheral blood of each group of rats. Western blot analysis was adopted to detect the protein expression levels of NLR family pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing CARD (ASC) and caspase-1 in the rats brain tissues of each group. Results Compared with the model group, the neurological deficit score was decreased; the pathological damage of brain tissues was relieved; the brain water content was significantly reduced; the apoptosis number of hippocampal neurons was decreased significantly; the levels of IL-1β, IL-6 and TNF-α in brain tissues and peripheral blood were significantly reduced; the protein expression levels of NLRP3, ASC and caspase-1 were significantly lowered in the middle-dose and high-dose artesunate groups and the dexamethasone group. Conclusion Artesunate can improve the neurological function, relieve the brain damage, and alleviate the brain edema in neonatal rats with HIBD. It can protect the HIBD, which may be related to the inhibition of NLRP3 inflammasome activation and reduction of inflammatory cytokine secretion.

Impacto de uma intervenção educativa no manejo da hipotermia terapêutica neonatal: estudo quase experimental / Impact of an educational intervention in the management of neonatal therapeutic hypothermia: a quasi-experimental study

Introdução: A hipotermia terapêutica é o tratamento indicado para encefalopatia moderada a grave em recém-nascidos. A terapia requer uma equipe de enfermagem capacitada e integrada, visando um cuidado qualificado, efetivo e seguro. Modelos teóricos têm sido desenvolvidos para auxiliar a incorporação de evidências científicas à prática dos enfermeiros, representando um desafio na área da saúde. A implementação de uma intervenção educativa, guiada pela estrutura i-PARIHS (Estrutura Integrada de Promoção da Ação na Implementação de Pesquisa em Serviços de Saúde), poderá preencher a lacuna entre a teoria e a prática, beneficiando a assistência e tornando os sujeitos ativos no manejo do recém-nascido em hipotermia terapêutica. Objetivo geral: avaliar o impacto de uma intervenção educativa, guiada pelo referencial teórico i-PARIHS, sobre o manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica na unidade intensiva neonatal no conhecimento, atitudes e práticas de enfermeiros. Objetivos específicos: analisar o conhecimento, atitude e prática dos enfermeiros sobre o manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica pré e pós-intervenção educativa; identificar as barreiras e facilitadores percebidos pelos enfermeiros sobre o manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica na unidade intensiva neonatal; implementar uma intervenção educativa, guiada pelo referencial i-PARIHS, para melhorar o conhecimento, a atitude e a prática dos enfermeiros sobre o manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica na unidade intensiva neonatal; comparar o conhecimento, atitude e prática dos enfermeiros após a intervenção educativa e os indicadores quanto ao manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica. Método: trata-se de um estudo de intervenção, do tipo quase-experimental, realizado com 29 enfermeiros de uma unidade intensiva neonatal, referência no Rio de Janeiro. O desfecho principal: conhecimento, atitudes e práticas dos enfermeiros no manejo do recém-nascido com asfixia perinatal em hipotermia terapêutica na unidade intensiva neonatal A intervenção compreendeu três fases: pré-intervenção - intervenção educativa- pós-intervenção. A intervenção educativa contou com cinco encontros: "Asfixia Perinatal x Hipotermia Terapêutica", "Controle da temperatura", "Cuidados de enfermagem na HT: avaliação de dor", "Monitoramento neurológico" e "Cuidado Centrado na Família". Para a análise estatística utilizou-se de análise descritiva e aplicação dos testes Wilcoxon-Mann-Whitney e Mc Nemar, sendo o nível de significância adotado de 0,05. Resultados: a análise dos resultados do pré e pós-teste demonstrou um incremento no escore de acertos das questões sobre conhecimento, atitude e prática dos enfermeiros no manejo do recém-nascido submetido à hipotermia terapêutica na unidade intensiva neonatal, apresentando significância estatística para a maioria dos itens. Para a inovação foram construídos lembretes, fluxo de admissão para recém-nascido da instituição e uma cartilha para os pais como produto da intervenção com os enfermeiros. Conclusão: O resultado das auditorias realizadas, após a implementação das evidências, constatou uma transformação positiva da prática dos enfermeiros. A utilização da estrutura i-PARIHS evidenciou a necessidade e o valor de investir no engajamento das partes interessadas, na avaliação colaborativa do contexto e na cocriação de inovação usando facilitação qualificada. A intervenção educativa, guiada pela estrutura i-PARIHS, mostrou ter impacto no manejo do recém-nascido submetido à hipotermia terapêutica por enfermeiros.

Introduction: Therapeutic hypothermia is the currently indicated treatment for moderate to severe encephalopathy in newborns. Therapy requires a trained and integrated nursing team, aiming at qualified, effective and safe care. Theoretical models have been developed to help the incorporation of scientific evidence into nurses' practice, representing a challenge in the health area. The implementation of an educational intervention, guided by the i-PARIHS (Integrated Promoting Action on Research Implementation in Health Services Framework) framework, can fill the gap between theory and professional practice, benefiting care and making subjects active in the management of newborns with therapeutic hypothermia. General objective: to evaluate the impact of an educational intervention guided by the theoretical framework i-PARIHS, on the management of newborns with perinatal asphyxia in therapeutic hypothermia in the neonatal intensive care unit on the knowledge, attitudes and practices of nurses. Specific objectives: to analyze the knowledge, attitude and practice of nurses on the management of newborns with perinatal asphyxia in pre- and post-educational therapeutic hypothermia; to identify barriers and facilitators perceived by nurses on the management of newborns with perinatal asphyxia in therapeutic hypothermia in the neonatal intensive care unit; implement an educational intervention, guided by the i-PARIHS framework, to improve nurses' knowledge, attitude and practice on the management of newborns with perinatal asphyxia in therapeutic hypothermia in the neonatal intensive care unit and compare the knowledge, attitude and practice of nurses after the participatory educational intervention program and indicators regarding the management of newborns with perinatal asphyxia in therapeutic hypothermia. Method: this is a quasi-experimental intervention study carried out with 29 nurses from a neonatal intensive care unit, a reference in Rio de Janeiro. The main outcome: knowledge, attitudes and practices of nurses in the management of newborns with perinatal asphyxia in therapeutic hypothermia in the neonatal intensive unit The intervention comprised three phases: pre-intervention - educational intervention - post-intervention. The educational intervention had five meetings: "Perinatal Asphyxia x Therapeutic Hypothermia", "Temperature control", "Nursing care in HT: pain assessment", "Neurological monitoring" and "Family-Centered Care". For the statistical analysis, descriptive analysis and application of the Wilcoxon-Mann-Whitney and Mc Nemar tests were used, with the adopted significance level of 0.05. Results: the analysis of pre- and post-test results showed an increase in the correct score of questions about nurses' knowledge and practices in the management of newborns submitted to therapeutic hypothermia in the neonatal intensive care unit, showing statistical significance for most items. For innovation, reminders, admission flow for newborns at the institution and a booklet for parents were created as a product of the intervention with nurses. Conclusion: The result of the audits carried out, after the implementation of the evidence, found a positive transformation of the nurses' practice. Using the i-PARIHS framework highlighted the need and value of investing in stakeholder engagement, collaborative context assessment, and co-creation of innovation using qualified facilitation. The educational intervention guided by the i-PARIHS framework was shown to have an impact on the management of newborns with perinatal asphyxia in therapeutic hypothermia by nurses.

South African neonates with mild and moderate hypoxic-ischaemic encephalopathy

Background. Clear risk profiles of neonates with mild and moderate hypoxic-ischaemic encephalopathy (HIE) are lacking.Objective. To describe and compare factors associated with mild and moderate HIE in South African neonates. Methods.A prospective, comparative design was used to describe factors among South African neonates with mild (n=13) and moderate (n=33) HIE in an urban tertiary academic hospital. HIE diagnosis and encephalopathy grading were conducted using the modified Sarnat stages. Thompson scores were recorded. Participants' clinical records were reviewed to identify factors. Descriptive data were obtained. Chi-square and Fisher's exact tests were used to compare categorical data, and Mann-Whitney tests were used to compare continuous data between groups. Results. Significant differences were found between groups' admission (p<0.001) and highest Thompson scores (p<0.001). The mild group's APGAR scores were significantly higher than those of the moderate group at five (p=0.012) and ten minutes (p=0.022). Duration of resuscitation (p=0.011) and time to spontaneous respiration (p=0.012) also differed significantly between groups. Significantly more moderate than mild participants received therapeutic hypothermia(TH) (p<0.001).Conclusion. Clinical tests and management factors differed significantly between groups. The findings provided the multidisciplinary team with an increased understanding of the heterogeneous HIE population and add to existing evidence for identifying neonates eligible for TH in resource-limited settings

Expert consensus on the clinical practice of neonatal brain magnetic resonance imaging / 中国当代儿科杂志

In recent years, magnetic resonance imaging (MRI) has been widely used in evaluating neonatal brain development, diagnosing neonatal brain injury, and predicting neurodevelopmental prognosis. Based on current research evidence and clinical experience in China and overseas, the Neonatologist Society of Chinese Medical Doctor Association has developed a consensus on the indications and standardized clinical process of neonatal brain MRI. The consensus has the following main points. (1) Brain MRI should be performed for neonates suspected of hypoxic-ischemic encephalopathy, intracranial infection, stroke and unexplained convulsions; brain MRI is not considered a routine in the management of preterm infants, but it should be performed for further evaluation when cranial ultrasound finds evidence of brain injury; as for extremely preterm or extremely low birth weight infants without abnormal ultrasound findings, it is recommended that they should undergo MRI examination at term equivalent age once. (2) Neonates should undergo MRI examination in a non-sedated state if possible. (3) During MRI examination, vital signs should be closely monitored to ensure safety; the necessity of MRI examination should be strictly evaluated for critically ill neonates, and magnetic resonance compatible incubator and ventilator can be used. (4) At present, 1.5 T or 3.0 T equipment can be used for neonatal brain MRI examination, and the special coil for the neonatal head should be used to improve signal-to-noise ratio; routine neonatal brain MRI sequences should at least include axial T1 weighted image (T1WI), axial T2 weighted imaging (T2WI), diffusion-weighted imaging, and sagittal T1WI or T2WI. (5) It is recommended to use a structured and graded reporting system, and reports by at least two reviewers and multi-center collaboration are recommended to increase the reliability of the report.

The impact of therapeutic hypothermia on peripheral blood cell in newborns with hypoxic ischemic encephalopathy

Abstract The effect of hypothermia treatment on white blood cell (WBC), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR) and platelet-to-lymphocyte ratio (PLR) values as an indicator of inflammation was evaluated in newborns with hypoxic ischemic encephalopathy (HIE). The study was performed that the before-therapeutic hypothermia (TH) and after-TH WBC, lymphocytes, neutrophils, monocytes and NLR, LMR and PLR values of the complete blood cell count were retrospectively evaluated. The results of the patient group were compared with the results of healthy newborns. A total of 78 patients who underwent TH were evaluated in our study. Mean values before and after TH were NLR3.8/2.7, LMR 5.6/8.6, and PLR 60.3/67.1 respectively. A statistical significance was present for NLR values before and after TH in those with seizure in our study (4.15±2.95/3.01±2.54) but no statistical significance was found for LMR or PLR. In neonates with HIE, effect of TH on complete blood cell count and inflammatory mechanisms (mediated neutrophil and lymphocyte) may be minimal.

Inserción "velamentosa", encefalopatía hipóxico-isquémica y rehabilitación neurológica: reporte de caso / Velamentous cord insertion, ischemic-hypoxic encephalopathy, and neurological rehabilitation: A case report

Resumen. La encefalopatía hipóxico-isquémica es una causa frecuente e importante de daño neurológico en recién nacidos a término y prematuros. Un evento centinela de esta condición es la vasa previa, específicamente cuando existe anormalidad de la placenta como la inserción "velamentosa" del cordón umbilical. Algunos reportes evidencian la asociación entre estas dos condiciones, pero son escasos los que dan cuenta del proceso de recuperación y del pronóstico neurológico de los niños afectados por ellas. Se presenta el caso de un paciente, con antecedentes de inserción "velamentosa" del cordón umbilical y encefalopatía hipóxico-isquémica, que recibió hipotermia terapéutica (cool cap). Se describe su proceso de rehabilitación neurológica y se calculó el porcentaje de probabilidad de presentar esta condición frente a la población sin estos factores. El niño tenía cinco años y el puntaje en su prueba de Apgar fue de 0 al minuto y de 2 a los 15 minutos. Desarrolló encefalopatía hipóxico-isquémica grave secundaria a una inserción "velamentosa" del cordón umbilical sin diagnóstico prenatal, con gran compromiso neurológico y multisistémico inicial. El proceso de recuperación incluyó el manejo inicial multidisciplinario en la unidad de cuidados intensivos neonatales y el inicio temprano de habilitación neurológica. Hoy el niño está escolarizado y en terapia integral, no presenta deficiencias motoras ni sensoriales en el examen físico, aunque la prueba neuropsicológica sugiere un riesgo de trastorno por déficit de atención e hiperactividad. Habitualmente, los niños con encefalopatía hipóxico-isquémica grave presentan discapacidad por deficiencias motoras, cognitivas o conductuales. El haber recibido hipotermia terapéutica y un manejo estructurado de rehabilitación redujo en gran medida las deficiencias esperadas y ha promovido un satisfactorio desarrollo físico y neurológico.

Abstract. Hypoxic-ischemic encephalopathy is a frequent and important cause of neurological problems in term and preterm newborns. A sentinel event of this entity is the vasa previa, specifically when there is an abnormality of the placenta such as a velamentous cord insertion. Some reports have shown the association between these two entities, but those regarding the recovery process and the neurological prognosis of children with both conditions are scarce. We present the case of a patient with a history of velamentous cord insertion and hypoxic-ischemic encephalopathy who received therapeutic hypothermia (cool cap). We describe his neurological rehabilitation process and we calculated the percentage of probability of presenting this condition compared to the population without these factors. The patient was a five-year-old boy with an Apgar index at birth equal to zero at one minute and equal to two at fifteen minutes who developed severe hypoxic-ischemic encephalopathy secondary to a velamentous cord insertion without prenatal diagnosis and a marked initial neurological and multisystemic compromise. The recovery process included early multidisciplinary management in the neonatal intensive care unit and a focus on early neurological habilitation. The patient is currently in school and he undergoes comprehensive therapies; on physical examination, he presents no motor or sensory deficiencies. His neuropsychological test suggests the risk of attention deficit hyperactivity disorder. Children with severe hypoxic-ischemic encephalopathy usually have disabilities due to motor, cognitive, and/or behavioral deficiencies. Having received therapeutic hypothermia and a structured rehabilitation process greatly reduced the expected deficiencies according to prognosis and have promoted satisfactory physical and neurological development.

Research advances in the role of ferroptosis in neonatal hypoxic-ischemic brain damage / 中国当代儿科杂志

Neonatal hypoxic-ischemic brain damage (HIBD) remains an important cause of neonatal death and disability in infants and young children, but it has a complex mechanism and lacks specific treatment methods. As a new type of programmed cell death, ferroptosis has gradually attracted more and more attention as a new therapeutic target. This article reviews the research advances in abnormal iron metabolism, glutamate antiporter dysfunction, and abnormal lipid peroxide regulation which are closely associated with ferroptosis and HIBD.

Effect of astragaloside IV on the expression of NOD-like receptor protein 3 inflammasome in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

OBJECTIVE@#To study the effect of astragaloside IV (AS-IV) on NOD-like receptor protein 3 (NLRP3) inflammasome in neonatal rats with hypoxic-ischemic brain damage (HIBD).@*METHODS@#A total of 24 Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group, an HIBD group, and an AS-IV treatment group, with 8 rats in each group. After 24 hours of modeling, brain tissue was collected for hematoxylin-eosin staining, yo-PRO-1 staining, and EthD-2 immunofluorescent staining in order to observe the cerebral protection effect of AS-IV in vivo. HT22 cells were used to prepare a model of oxygen-glycogen deprivation (OGD), and a concentration gradient (50-400 μmol/L) was established for AS-IV. CCK-8 assay was used to measure the viability of HT22 cells. RT-PCR and Western blot were used to observe the effect of different concentrations of AS-IV on the mRNA and protein expression of NLRP3, gasdermin D (GSDMD), caspase-1, and interleukin-1β (IL-1β).@*RESULTS@#Yo-Pro-1 and EthD-2 staining showed that compared with the sham-operation group, the HIBD group had an increase in pyroptotic cells with a small number of necrotic cells, and the AS-IV group had reductions in both pyroptotic and necrotic cells. Compared with the sham-operation group, the HIBD group had significantly higher protein expression levels of NLRP3, IL-1β, caspase-1, and GSDMD (@*CONCLUSIONS@#AS-IV may alleviate HIBD in neonatal rats by inhibiting the expression of NLRP3, GSDMD, caspase-1, and IL-1β.

Effect of different melatonin treatment regimens on white matter damage in neonatal rats with hypoxic-ischemic brain damage / 中国当代儿科杂志

OBJECTIVE@#To study the effect of different melatonin treatment regimens on long-term behavior and white matter damage in neonatal rats with hypoxic-ischemic brain damage (HIBD), and to seek an optimal melatonin treatment regimen.@*METHODS@#Healthy Sprague-Dawley rats, aged 7 days, were randomly divided into four groups: sham-operation, HIBD, single-dose immediate treatment (SDIT), and 7-day continuous treatment (7DCT), with 8 rats in each group. A neonatal rat model of HIBD was prepared according to the classical Rice-Vannucci method. On day 21 after HIBD, the Morris water maze test was used to evaluate spatial learning and memory abilities. On day 70 after HIBD, immunofluorescence assay was used to measure the expression of neuronal nuclear antigen (NeuN) in the cerebral cortex and the hippocampal CA1 region of neonatal rats, and double-label immunofluorescence was used to measure the expression of myelin basic protein (MBP) and neurofilament 200 (NF200) in the corpus striatum and the corpus callosum.@*RESULTS@#The results of the Morris water maze test showed that the SDIT and 7DCT groups had a significantly shorter mean escape latency than the HIBD group, and the 7DCT group had a significantly shorter mean escape latency than the SDIT group (@*CONCLUSIONS@#Both SDIT and 7DCT can improve long-term behavior and reduce white matter damage in neonatal rats with HIBD, and 7DCT is more effective than SDIT.

Impact of mild hypothermia therapy on hemodynamics during the induction stage in neonates with moderate to severe hypoxic-ischemic encephalopathy / 中国当代儿科杂志

OBJECTIVE@#To study the changes in hemodynamics during the induction stage of systemic mild hypothermia therapy in neonates with moderate to severe hypoxic-ischemic encephalopathy (HIE).@*METHODS@#A total of 21 neonates with HIE who underwent systemic mild hypothermia therapy in the Department of Neonatology, Dongguan Children's Hospital Affiliated to Guangdong Medical University, from July 2017 to April 2020 were enrolled. The rectal temperature of the neonates was lowered to 34℃ after 1-2 hours of induction and maintained at this level for 72 hours using a hypothermia blanket. The impedance method was used for noninvasive hemodynamic monitoring, and the changes in heart rate (HR), mean arterial pressure (MAP), stroke volume (SV), cardiac output (CO), cardiac index (CI), and total peripheral resistance (TPR) from the start of hypothermia induction to the achievement of target rectal temperature (34℃). Blood lactic acid (LAC) and resistance index (RI) of the middle cerebral artery were recorded simultaneously.@*RESULTS@#The 21 neonates with HIE had a mean gestational age of (39.6±1.1) weeks, a mean birth weight of (3 439±517) g, and a mean 5-minute Apgar score of 6.8±2.0. From the start of hypothermia induction to the achievement of target rectal temperature (34℃), there were significant reductions in HR, CO, and CI (@*CONCLUSIONS@#The systemic mild hypothermia therapy may have a significant impact on hemodynamics in neonates with moderate to severe HIE, and continuous hemodynamic monitoring is required during the treatment.

Hipotermia terapêutica na encefalopatia hipóxico-isquêmica neonatal: revisão integrativa / Therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy: integrative review / Hipotermia terapéutica em la encefalopatía hipóxico-isquémica neonatal: revisión integrativa

Objetivo: identificar evidências acerca do uso seguro da hipotermia terapêutica em recém-nascidos. Método: revisão integrativa realizada entre junho e julho de 2018, em fontes eletrônicas da Biblioteca Virtual de Saúde e PubMed, por meio da pergunta:"Que evidências podem subsidiar o cuidado de enfermagem voltado para a redução de sequelas em recém-nascidos submetidos à hipotermia terapêutica?".Foram eleitos nove artigos para análise, sendo oito internacionais e um nacional. Resultados:o resfriamento deve acontecer por 72 horas, com hipotermia leve. As indicações para inclusão no protocolo foram: primeiras seis horas de vida, idade gestacional maior que 35 semanas e acidose na primeira hora de vida.São cuidados essenciais: monitoração hemodinâmica, observação da pele, controle térmico retal, vigilância do Eletroencefalograma de Amplitude Integrada. Conclusão: a terapêutica apresenta benefícios, porém sua aplicação depende de protocolo institucional e treinamento das equipes com foco nas potenciais complicações.

Objective: to identify the evidence on safe use of therapeutic hypothermia in newborns. Method: integrative review of the literature, conducted between June and July of 2018, in electronic sources from the Virtual Health Library and PubMed, through the question: "What evidence can support nursing care aimed at reducing sequelae in newborns undergoing therapeutic hypothermia?". Analysis was conducted for nine selected article, being eight from international literature and one from Brazilian national literature. Results: cooling should occur for 72 hours with mild hypothermia. Indications for inclusion in the protocol were: first six hours of life, gestational age greater than 35 weeks and acidosis in the first hour of life. Essential care includes hemodynamic monitoring, skin observation, rectal thermal control, Integrated Amplitude Electroencephalogram surveillance. Conclusion: the therapy has benefits, but its application depends on institutional protocol and team training focusing on potential complications.

Objetivo: identificar la evidencia sobre el uso seguro de la hipotermia terapéutica en recién nacidos. Método: revisión integradora de la literatura, realizada entre junio y julio de 2018, en fuentes electrónicas de la Biblioteca Virtual de Salud y PubMed, a través de la pregunta: "¿Qué evidencia puede apoyar la atención de enfermería dirigida a reducir las secuelas en los recién nacidos que sufren hipotermia terapéutica?". Se realizaron análisis para nueve artículos seleccionados, ocho de literatura internacional y uno de literatura nacional brasileña. Resultados: el enfriamiento debe ocurrir durante 72 horas con hipotermia leve. Las indicaciones para la inclusión en el protocolo fueron: primeras seis horas de vida, edad gestacional mayor de 35 semanas y acidosis en la primera hora de vida. El cuidado esencial incluye monitoreo hemodinámico, observación de la piel, control térmico rectal, vigilancia integrada de electroencefalograma de amplitud. Conclusión: la terapia tiene beneficios, pero su aplicación depende del protocolo institucional y del entrenamiento del equipo, enfocándose en posibles complicaciones.

Hipomagnesemia en recién nacidos con encefalopatía hipóxico isquémica en hipotermia corporal total / Hypomagnesemia in newborns with hypoxic ischemic encephalopathy and whole-body hypothermia

Resumen: Introducción: En recién nacidos (RN) con encefalopatía hipóxico isquémica (EHI) en hipotermia se describen alte raciones metabólicas que se asocian a pronóstico neurológico. La hipomagnesemia ha sido reportada en la literatura, pero no es medida ni corregida en todos los centros de atención neonatal. Objeti vo: Evaluar la frecuencia de hipomagnesemia e hipocalcemia en RN con EHI en tratamiento con hipotermia corporal total y evaluar la respuesta al aporte de sulfato de magnesio. Pacientes y Méto do: Estudio prospectivo, observational y descriptivo en RN con EHI sometidos a hipotermia corporal total, hospitalizados entre los años 2016-2017. Se realizó medición seriada en sangre de magnesemia (Mg) y calcemia (Ca). Con Mg menor o igual de 1,8 mg/dl se administró suplemento como sulfato de Mg para mantener niveles entre 1,9 y 2,8 mg/dl. Se describió la frecuencia de hipomagnesemia e hipocalcemia y su presentación en el tiempo. Se realizó registro prospectivo de evolución clínica. Se hizo un análisis estadístico descriptivo, con medidas de tendencia central. Resultados: Se incluyeron 16 pacientes. Presentaron hipomagnesemia 13/16 (81,3%), la que fue precoz (6-36 h de vida), nor malizándose con aporte de sulfato de magnesio, requiriendo 2a dosis 4 de ellos. Presentaron hipo- calcemia 6/16 (37,5%). Conclusiones: La hipomagnesemia es frecuente (80%), similar a lo descrito en la literatura. Dado su importancia fisiológica debe controlarse y corregirse, de igual manera que el calcio.

Abstract: Introduction: In newborns with the diagnosis of hypoxic-ischemic encephalopathy (HIE) treated with hypother mia, metabolic alterations are observed, which are associated with neurological prognosis. Hypo magnesemia has been reported frequently in the literature in these patients, but it is not measured or corrected in all neonatal healthcare centers. Objective: To evaluate the frequency of hypomag nesemia and hypocalcemia in newborns with HIE treated with whole-body hypothermia and to evaluate the response to the magnesium sulfate administration. Patients and Method: Prospective, observational and descriptive study in hospitalized newborns with the diagnosis of HIE and trea ted with whole-body hypothermia between the years 2016 and 2017. Serial blood measurement of magnesemia (Mg) and calcemia (Ca) was performed. When presenting an Mg level < 1.8 mg/dl, supplementation with magnesium sulfate was administered to maintain levels between 1.9 and 2.8 mg/dl. The frecuency of hypomagnesemia, hypocalcemia and clinical evolution was registered. A descriptive statistical analysis was performed, with central tendency measures. Results: Sixteen ca ses were included, 13 of them presented hypomagnesemia (81.3%), with early-onset (6-36 hours of life), which was normalized with magnesium sulfate treatment, receiving a second dose 4 patients. Six of 16 patients presented hypocalcemia (37.5 %). Conclusions: Hypomagnesemia is frequent (80%), similar to that described in the literature, and should be controlled and corrected early, given its physiological role, in the same way that calcium is controlled.

Clinical neonatal hypoxic ischemic injury: Cranial ultrasound spectrum of findings in neonates admitted to a Newborn Unit in Nairobi, Kenya

Introduction: Birth asphyxia causes significant neurologic injury and neurodevelopmental delay in children. Cranial ultrasound (CUS) can be used for the diagnosis, early intervention, and prognostication of birth asphyxia. We determined the CUS findings among term neonates with clinical birth asphyxia and correlated sonographic findings with the modified Sarnat clinical grade.Materials and Methods: We conducted a prospective cross-sectional analytical study in Kenyatta National Hospital New Born Unit (KNH NBU) between June 2018 and October 2018. Term babies, older than 24 h with clinical birth asphyxia, were recruited and CUS was performed. Statistical analysis was done using proportions, means, and frequencies. Chi-square tests were used to assess correlation between imaging findings and the clinical Sarnat grading of asphyxia.Results: Periventricular deep white matter echogenicity and thalamus and/or basal ganglia deep gray matter was reported in 56.4% and 31.1%, respectively. Only 4.4% had cortical gray matter. Normal CUS findings were reported in 40.0% of the neonates. Prolonged labor and meconium-stained liquor were the predominant risk factors for perinatal asphyxia, seen in 58% of the neonates. Prolonged labor was independently reported in 43% of the neonates. Moderate and severe Sarnat grades correlated with abnormal sonographic changes of hypoxic ischemic encephalopathy (HIE) (Grades 2­8) (P = 0.038). There was a trend toward HIE severity with worsening Sarnat stages (trend test P= 0.039). Abnormal resistive indices (<0.5 and >0.8) were strongly associated with the presence of HIE brain changes (P = 0.003).Conclusion: The correlation between birth asphyxia severity and CUS was more robust in Doppler evaluation of the deep cerebral arteries

Effect of irisin on hypoxic-ischemic brain damage in neonatal rats / 中国当代儿科杂志

OBJECTIVE@#To study the effect and mechanism of action of irisin on hypoxic-ischemic brain damage in neonatal rats.@*METHODS@#A total of 248 7-day-old Sprague-Dawley rats were randomly divided into a sham-operation group, a model group, and low- and high-dose irisin intervention groups (n=62 each). The rats in the model and irisin intervention groups were given hypoxic treatment after right common carotid artery ligation to establish a model of hypoxic-ischemic brain damage. Those in the sham-operation group were given the separation of the right common carotid artery without ligation or hypoxic treatment. The rats in the high- and low-dose irisin intervention groups were given intracerebroventricular injection of recombinant irisin polypeptide at a dose of 0.30 µg and 0.15 µg respectively. Those in the model and sham-operation groups were given the injection of an equal volume of PBS. The water maze test was used to compare neurological behaviors between groups. TTC staining, hematoxylin-eosin staining and TUNEL staining were used to observe histopathological changes of the brain. Western blot was used to measure the expression of the apoptosis-related molecules cleaved-caspase-3 (CC3), BCL-2 and BAX.@*RESULTS@#Compared with the sham-operation group, the model group had a significant increase in latency time and a significant reduction in the number of platform crossings (P<0.05). Compared with the model group, the high-dose irisin intervention group had a significant reduction in latency time and a significant increase in the number of platform crossings (P<0.05). Compared with the sham-operation group, the model group had massive infarction in the right hemisphere, with significant increases in karyopyknosis and karyorrhexis. Compared with the model group, the high-dose irisin intervention group had a smaller infarct area of the right hemisphere, with reductions in karyopyknosis and karyorrhexis. The model group had a significantly higher apoptosis rate of cells in the right cerebral cortex and the hippocampus than the sham-operation group. The high-dose irisin intervention group had a significantly lower apoptosis rate than the model group (P<0.05). At 24 and 48 hours after modeling, the sham-operation group had a significantly lower level of CC3 than the model group (P<0.05). Compared with the model group, the high-dose irisin intervention group had a significantly lower level of CC3 and a significantly higher BCL-2/BAX ratio (P<0.05). The low-dose irisin intervention group had similar laboratory markers and histopathological changes of the brain to the model group.@*CONCLUSIONS@#Irisin can alleviate hypoxic-ischemic brain damage in neonatal rats in a dose-dependent manner, possibly by reducing cell apoptosis in the cerebral cortex and the hippocampus.