“新生儿脑病”比“缺氧缺血性脑病”更合适吗?——美国妇产科学会和儿科学会发布的新生儿脑病工作组报告介绍

已经广泛使用30多年的“新生儿缺氧缺血脑病”,作为标准术语越来越受到质疑,大多推荐用“新生儿脑病”代替“缺氧缺血性脑病”.2014年美国妇产科学会和儿科学会分别发布新生儿脑病工作组报告《新生儿脑病和神经系统结果(第2版)》,对“新生儿脑病”的定义、诊治相关内容进行更新,推荐对新生儿脑病作综合性多维评估.该文将介绍关于“新生儿脑病”与“缺氧缺血性脑病”的争议和新生儿脑病工作组报告的内容.     

别嘌呤醇对缺氧缺血性脑损伤的保护作用

别嘌呤醇为次黄嘌呤异构体,是临床上治疗痛风的主要用药.随着氧自由基学说的不断拓展,别嘌呤醇的抗氧化作用越来越受到重视.近年来新生儿缺氧缺血性脑病的危害受到高度重视,抗氧化治疗成为一种新的治疗方法.该文主要探讨了别嘌呤醇的药理作用及其对新生儿缺氧缺血性脑病保护作用的可能机制,包括减少氧自由基的产生、直接清除氧自由基、改善脑血管内皮细胞功能、抑制缺氧缺血性脑细胞凋亡、扩张血管改善脑血流等途径,为临床上应用别嘌呤醇治疗新生儿缺氧缺血性脑病提供参考.     

脑活素治疗新生儿缺氧缺血性脑病38例疗效分析

新生儿缺氧缺血性脑病(简称HIE)是新生儿死亡及儿童神经系统发育障碍的重要原因,已越来越受到儿科医师的重视。本文对38例缺氧缺血性脑病新生儿在常规治疗基础上加用脑活素治疗,取得     

新生儿缺氧缺血性脑病神经干细胞的研究进展

随着干细胞基础与临床研究的进展,干细胞具有的自我更新和多向分化潜能为新生儿缺氧缺血性脑病的治疗提供了一种新的方法.缺氧缺血性脑损伤后可以激活内源性神经干细胞,诱导其增殖、迁移、分化和凋亡,参与损伤后结构修复和功能重建.联合外源性的因素如干细胞移植术和神经营养因子等,将对干细胞应用于临床,治疗新生儿缺氧缺血性脑病具有重要意义.     

新生儿缺氧缺血性脑病神经干细胞的研究进展

随着干细胞基础与临床研究的进展,干细胞具有的自我更新和多向分化潜能为新生儿缺氧缺血性脑病的治疗提供了一种新的方法.缺氧缺血性脑损伤后可以激活内源性神经干细胞,诱导其增殖、迁移、分化和凋亡,参与损伤后结构修复和功能重建.联合外源性的因素如干细胞移植术和神经营养因子等,将对干细胞应用于临床,治疗新生儿缺氧缺血性脑病具有重要意义.     

新生儿缺氧缺血性脑病神经干细胞的研究进展

随着干细胞基础与临床研究的进展,干细胞具有的自我更新和多向分化潜能为新生儿缺氧缺血性脑病的治疗提供了一种新的方法.缺氧缺血性脑损伤后可以激活内源性神经干细胞,诱导其增殖、迁移、分化和凋亡,参与损伤后结构修复和功能重建.联合外源性的因素如干细胞移植术和神经营养因子等,将对干细胞应用于临床,治疗新生儿缺氧缺血性脑病具有重要意义.     

新生儿缺氧缺血性脑病神经干细胞的研究进展

随着干细胞基础与临床研究的进展,干细胞具有的自我更新和多向分化潜能为新生儿缺氧缺血性脑病的治疗提供了一种新的方法.缺氧缺血性脑损伤后可以激活内源性神经干细胞,诱导其增殖、迁移、分化和凋亡,参与损伤后结构修复和功能重建.联合外源性的因素如干细胞移植术和神经营养因子等,将对干细胞应用于临床,治疗新生儿缺氧缺血性脑病具有重要意义.     

新生儿缺氧缺血性脑病神经干细胞的研究进展

随着干细胞基础与临床研究的进展,干细胞具有的自我更新和多向分化潜能为新生儿缺氧缺血性脑病的治疗提供了一种新的方法.缺氧缺血性脑损伤后可以激活内源性神经干细胞,诱导其增殖、迁移、分化和凋亡,参与损伤后结构修复和功能重建.联合外源性的因素如干细胞移植术和神经营养因子等,将对干细胞应用于临床,治疗新生儿缺氧缺血性脑病具有重要意义.     

新生儿缺氧缺血性脑病神经干细胞的研究进展

随着干细胞基础与临床研究的进展,干细胞具有的自我更新和多向分化潜能为新生儿缺氧缺血性脑病的治疗提供了一种新的方法.缺氧缺血性脑损伤后可以激活内源性神经干细胞,诱导其增殖、迁移、分化和凋亡,参与损伤后结构修复和功能重建.联合外源性的因素如干细胞移植术和神经营养因子等,将对干细胞应用于临床,治疗新生儿缺氧缺血性脑病具有重要意义.     

新生儿缺氧缺血性脑病神经干细胞的研究进展

随着干细胞基础与临床研究的进展,干细胞具有的自我更新和多向分化潜能为新生儿缺氧缺血性脑病的治疗提供了一种新的方法.缺氧缺血性脑损伤后可以激活内源性神经干细胞,诱导其增殖、迁移、分化和凋亡,参与损伤后结构修复和功能重建.联合外源性的因素如干细胞移植术和神经营养因子等,将对干细胞应用于临床,治疗新生儿缺氧缺血性脑病具有重要意义.     

Current management of the infant who presents with neonatal encephalopathy

Neonatal encephalopathy after perinatal hypoxic-ischemic insult is a major contributor to global child mortality and morbidity. Brain injury in term infants in response to hypoxic-ischemic insult is a complex process evolving over hours to days, which provides a unique window of opportunity for neuroprotective treatment interventions. Advances in neuroimaging, brain monitoring techniques, and tissue biomarkers have improved the ability to diagnose, monitor, and care for newborn infants with neonatal encephalopathy as well as predict their outcome. However, challenges remain in early identification of infants at risk for neonatal encephalopathy, determination of timing and extent of hypoxic-ischemic brain injury, as well as optimal management and treatment duration. Therapeutic hypothermia is the most promising neuroprotective intervention to date for infants with moderate to severe neonatal encephalopathy after perinatal asphyxia and has currently been incorporated in many neonatal intensive care units in developed countries. However, only 1 in 6 babies with encephalopathy will benefit from hypothermia therapy; many infants still develop significant adverse outcomes. To enhance the outcome, specific diagnostic predictors are needed to identify patients likely to benefit from hypothermia treatment. Studies are needed to determine the efficacy of combined therapeutic strategies with hypothermia therapy to achieve maximal neuroprotective effect. This review focuses on important concepts in the pathophysiology, diagnosis, and management of infants with neonatal encephalopathy due to perinatal asphyxia, including an overview of recently introduced novel therapies.     

Neurodevelopmental outcome of infants with birth asphyxia treated with magnesium sulfate

BACKGROUND: A neuroprotective effect of MgSO(4) has been shown in some animal models of perinatal hypoxic-ischemic brain damage. The aim of the present paper was to determine whether postnatal MgSO(4) infusion (250 mg/kg per day i.v. for 3 days, in combination with dopamine) is safe in infants with severe birth asphyxia, and also observe effects on neurodevelopmental outcome at 18 months. METHODS: Inclusion criteria were clinical history consistent with perinatal asphyxia; gestational age at least 37 weeks; 5 min Apgar score < or =6; failure to initiate spontaneous respiration within 10 min after birth; and symptoms of encephalopathy. On each day MgSO(4) was infused over 1 h in combination with dopamine (5 microg/kg per min). Changes in vital signs, clinical course of encephalopathy, laboratory variables, and adverse events were monitored. Infants were followed for 18 months. RESULTS: Thirty infants were studied. Mean birthweight was 2878 g; mean gestational age, 39.6 weeks, and median 5 min Apgar score, 3. All required endotracheal intubation for resuscitation. Median age at MgSO(4) initiation was 5 h. All infants had moderate or severe hypoxic-ischemic encephalopathy. Mean serum Mg(2+) concentration remained at least 1.3 mmol/L. MgSO(4) caused no change in physiological variables including mean arterial pressure. Two infants died as neonates, while six of 28 survivors had severe neurodevelopmental disability at 18 months; the remaining 22 had no neurodevelopmental disability. CONCLUSION: Postnatal infusion of MgSO(4) with dopamine caused no change in physiological variables. Deaths and severe sequelae were less frequent than in reported cases with the same grade of hypoxic-ischemic encephalopathy severity, and this treatment may improve neurodevelopmental outcome in infants with severe birth asphyxia.     

诱导型一氧化氮合酶和缺氧缺血脑损伤

缺氧缺血可导致严重的神经系统疾病,如脑卒中、新生儿缺氧缺血性脑病。诱导型一氧化氮合酶在缺氧、缺血过程中被诱导表达,产生过量一氧化氮,导致神经系统的炎症反应及神经元死亡,加重神经损伤。抑制诱导型一氧化氮合酶表达在体内体外实验及临床应用中显示了一定的神经保护作用。该文综述了诱导型一氧化氮合酶在中枢神经系统中的表达及与缺氧缺血脑损伤的相关性,展望了诱导型一氧化氮合酶抑制剂作为缺氧缺血脑损伤治疗策略的前景。     

�ǵ��¼�����������ȱ��ȱѪ���Բ����ٴ�Ӧ��

??Hypoxic ischemic encephalopathy??HIE?? is the most important reason for morbidity and mortality in term-born infants. Neonatal HIE is seen approximately in 2-3/1000 live births. Moreover?? in the developing countries?? its frequency has risen up to 26/1000 live births. Among the remaining living newborns?? cerebral palsy?? epilepsy?? autism?? visual and auditory problems are diagnosed. Therapeutic hypothermia is now well-established as standard treatment for infants with moderate to severe hypoxic-ischemic encephalopathy. In this review?? the clinical appilication of therapeutic hypothermia in neonatal hypoxic-ischemic encephalopathy will be discussed.     

Clinical trials of treatments after perinatal asphyxia

Following critical hypoxia-ischemia during labor and delivery, there is a window of therapeutic opportunity during hypoxic-ischemic encephalopathy. Meta-analysis of three randomized trials of prophylactic barbiturate therapy for neonatal hypoxic-ischemic encephalopathy showed no significant effect on death or disability. One randomized trial of allopurinol showed short-term benefits but was too small to test death or disability. No adequate trials of dexamethasone, calcium channel blockers, or magnesium sulphate have yet been completed, but pilot studies in infants have shown the cardiovascular risks of magnesium sulphate and calcium channel blockers. There is considerable evidence from animal studies that posthypoxic mild hypothermia reduces brain injury. One small randomized trial of mild hypothermia found no adverse effects but was too small to examine death or disability. One large randomized trial of selective head cooling has finished recruitment and a number of large trials of systemic mild hypothermia are ongoing. As time is critical with post-hypoxic interventions, the delay involved in obtaining informed parental consent for such trials might obscure a clinically important therapeutic effect.     

Seguimiento de los recién nacidos con encefalopatía hipóxico-isquémica

Hypothermia treatment for newborn infants with hypoxic-ischemic encephalopathy reduces the number of neonates who die or have permanent neurological deficits. Although this therapy is now standard of care, neonatal hypoxic-ischaemic encephalopathy still has a significant impact on the child's neurodevelopment and quality of life. Infants with hypoxic-ischaemic encephalopathy should be enrolled in multidisciplinary follow-up programs in order to detect impairments, to initiate early intervention, and to provide counselling and support for families.This article describes the main neurodevelopmental outcomes after term neonatal hypoxic-ischaemic encephalopathy. We offer recommendations for follow-up based on the infant's clinical condition and other prognostic indicators, mainly neonatal neuroimaging. Other aspects, such as palliative care and medico-legal issues, are also briefly discussed.     

Safety and efficacy of topiramate in neonates with hypoxic ischemic encephalopathy treated with hypothermia (NeoNATI)

ABSTRACT: BACKGROUND: Despite progresses in neonatal care, the mortality and the incidence of neuro-motor disability after perinatal asphyxia have failed to show substantial improvements. In countries with a high level of perinatal care, the incidence of asphyxia responsible for moderate or severe encephalopathy is still 2--3 per 1000 term newborns. Recent trials have demonstrated that moderate hypothermia, started within 6 hours after birth and protracted for 72 hours, can significantly improve survival and reduce neurologic impairment in neonates with hypoxic-ischemic encephalopathy. It is not currently known whether neuroprotective drugs can further improve the beneficial effects of hypothermia. Topiramate has been proven to reduce brain injury in animal models of neonatal hypoxic ischemic encephalopathy. However, the association of mild hypothermia and topiramate treatment has never been studied in human newborns. The objective of this research project is to evaluate, through a multicenter randomized controlled trial, whether the efficacy of moderate hypothermia can be increased by concomitant topiramate treatment. METHODS: Term newborns (gestational age >= 36 weeks and birth weight >= 1800 g) with precocious metabolic, clinical and electroencephalographic (EEG) signs of hypoxic-ischemic encephalopathy will be randomized, according to their EEG pattern, to receive topiramate added to standard treatment with moderate hypothermia or standard treatment alone. Topiramate will be administered at 10 mg/kg once a day for the first 3 days of life. Topiramate concentrations will be measured on serial dried blood spots. 64 participants will be recruited in the study. To evaluate the safety of topiramate administration, cardiac and respiratory parameters will be continuously monitored. Blood samplings will be performed to check renal, liver and metabolic balance. To evaluate the efficacy of topiramate, the neurologic outcome of enrolled newborns will be evaluated by serial neurologic and neuroradiologic examinations. Visual function will be evaluated by means of behavioural standardized tests. DISCUSSION: This pilot study will explore the possible therapeutic role of topiramate in combination with moderate hypothermia. Any favourable results of this research might open new perspectives about the reduction of cerebral damage in asphyxiated newborns. Trial registration Current Controlled Trials ISRCTN62175998; ClinicalTrials.gov Identifier NCT01241019; EudraCT Number 2010-018627-25.     

Subcutaneous fat necrosis after moderate therapeutic hypothermia in neonates

Therapeutic moderate hypothermia in newborns with hypoxic-ischemic encephalopathy is rapidly becoming standard clinical practice. We report here 12 cases of subcutaneous fat necrosis among 1239 cases registered with a national registry of newborns treated with moderate whole-body hypothermia. All the infants suffered from perinatal asphyxia and hypoxic-ischemic encephalopathy. Moderate-to-severe hypercalcemia was identified in 8 of 10 infants with blood calcium measurements. In all cases the skin lesions appeared after completion of the cooling treatment. Our data suggest that prolonged moderate hypothermia is an actual risk factor for subcutaneous fat necrosis. Because the lesions often develop several days after birth, physicians need to be aware of this condition as a possible complication in infants treated with moderate hypothermia after asphyxia. Blood calcium levels need to be monitored in affected infants.     

Insulin like growth factors axis and growth disorders

The growth hormone-insulin like growth factor (GH-IGF) axis plays a crucial role in the regulation of growth. Initially considered to be a mediator of growth hormone actions, IGF axis has been established as an independent endocrine system with wide array of actions. Recent advances have led to tremendous increase in the clinical utility of the IGF axis. IGF-based investigations (IGF1 and IGF binding protein 3) are now replacing GH-based investigations for evaluation and monitoring of disorders of the GH-IGF axis. IGF therapy has been successfully utilized in growth hormone insensitivity syndrome and GHD type 1B. The possibility of IGF axis as therapeutic options is being explored in wide variety of disorders like hypoxic-ischemic encephalopathy, Alzheimer's disease and psoriasis.     

New biomarkers of fetal-neonatal hypoxic stress

The complex pathophysiological mechanisms underlying perinatal hypoxia make it difficult to define early markers of severe hypoxia-ischemia encephalopathy. However, as progress in the development of neuroprotective therapeutic measures continues, the early identification of neonates at risk of severe hypoxic-ischemic encephalopathy is an important goal for appropriate decision making. Although the timing of perinatal hypoxic brain damage may vary and is sometimes unknown, high levels of non-protein-bound iron and high nucleated red blood cell counts in cord blood indicate an antepartum origin of neurological impairment, because they can occur only as a consequence of a pre-existing asphyxic event.
Conclusion : The combined assessment of nucleated red blood cells and non-protein-bound iron at birth seems extremely useful for the early identification of newborns at high risk of brain damage. Activin A also seems to be a reliable marker of perinatal hypoxia. Prospective long-term follow-up studies are needed to verify their predictive role.