Neurological Outcome of Glycemia in Neonatal Encephalopathy

新生儿脑病血糖的神经系统结局

• 批准号: 10640859
• 负责人: Emily Wing Yun Tam
• 金额: $ 17.95万
• 依托单位: HOSPITAL FOR SICK CHLDRN (TORONTO)
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-19 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640859
• 关键词: 5 year old; Acute; Adult; Age; Altered Level of Consciousness; American; Behavioral; Blood Glucose; Brain; Brain Hypoxia-Ischemia; Brain Injuries; Breathing; Child; Clinical; Cognitive; Continuous Glucose Monitor; Data; Death Rate; Diagnosis; Early Diagnosis; Early identification; Encephalopathies; Enrollment; Glucose; Hyperglycemia; Hypoglycemia; Impairment; Incidence; Intervention; Intervention Trial; Investigation; Knowledge; Language; Link; Literature; Live Birth; Magnetic Resonance Imaging; Magnetoencephalography; Methods; Monitor; Motor; Neonatal Hypoglycemia; Neurodevelopmental Impairment; Neurodevelopmental Problem; Neurologic; Neurological outcome; Neuropsychological Tests; Neuropsychology; Newborn Infant; Outcome; Parents; Prospective, cohort study; Questionnaires; Reflex action; Research; Rest; Risk; School-Age Population; Seizures; Severities; Standardization; Syndrome; Testing; Therapeutic; Translating; Vision; Visual; Visual Cortex; adverse outcome; brain circuitry; brain dysfunction; cognitive function; cohort; design; disability; effective therapy; feeding; follow-up; improved; improved outcome; innovation; natural hypothermia; neonatal encephalopathy; neonatal hypoxic-ischemic brain injury; neonatal period; neonate; neuroprotection; new technology; newborn brain injury; outcome prediction; social; visual processing

Hypoxic-ischemic encephalopathy (HIE) is one of the most significant causes of neurodevelopmental problems in American children, with high rates of death and major disability. The understanding of the impacts of glucose in these newborns has been limited to date by intermittent testing. The NOGIN study (Neurological Outcome of Glycemia in Neonatal Encephalopathy), using continuous glucose monitoring, has demonstrated that hyperglycemia occurs in more than 50% of HIE. While hypoglycemia was expected to be associated with brain injury, the surprising discovery has been that hyperglycemia, and not hypoglycemia, is associated with worse immediate brain function, brain injury on MRI, and motor and cognitive function at 18-month follow-up, despite adjusting for HIE severity. Standardized questionnaires also suggest increased risk for behavioural diagnoses. With the high incidence of hyperglycemia in neonatal encephalopathy and the strong evidence suggesting major additive impacts on long- term outcomes, it is now critical to clarify (1) how the findings of posterior- predominant brain injury translate to difficulties in cortical visual processing and (2) how the early findings of cognitive and behavioural concerns translate to later diagnoses by early school age. The overall objective for this study is to determine how hyperglycemia, in the context of neonatal encephalopathy, independently predicts outcomes by early school age. The specific aims include: 1. Assess how hypo- and hyperglycemia in neonatal encephalopathy impact cortical visual processing by early school age. 2. Assess how hypo- and hyperglycemia in neonatal encephalopathy impact cognitive, language, social, and behavioral function by early school age. The NOGIN study, a prospective cohort study originally aiming to determine what degree of low glucose results in hypoglycemic brain injury, with enrolment to complete in the next few months. The first subject turns 5 years old in September 2019. To achieve the current research objectives, children will be asked to return at 5 years of age for neuropsychological assessment (including WPPSI-IV, NEPSY-II, MCHAT, CBCL) and magnetoencephalography (vision tasks, resting brain network circuitry) to understand how specific levels of hyperglycemia translate to ongoing long-term deficits. By correlating specific levels of hyperglycemia in HIE in neonates with the degree of neurodevelopmental impairment, this study will help to target the management and control of hyperglycemia to decrease brain injury and improve outcomes for these newborns. The data generated will also help with early identification of newborns at greatest risk for adverse outcomes, enabling more targeted early adjunctive therapies to improve outcomes after HIE.

缺氧缺血性脑病（HIE）是神经发育障碍的最重要原因之一 美国儿童面临的问题包括高死亡率和严重残疾。的理解 迄今为止，间歇性测试限制了葡萄糖对这些新生儿的影响。诺金 研究（新生儿脑病血糖的神经学结果），使用连续葡萄糖 监测显示，50%以上的HIE发生高血糖。尽管 低血糖被认为与脑损伤有关，但令人惊讶的发现是 高血糖而非低血糖与较差的即时脑功能、脑损伤有关 尽管根据 HIE 严重程度进行了调整，但在 18 个月的随访中仍对 MRI 以及运动和认知功能进行了检查。 标准化问卷还表明行为诊断的风险增加。随着高 新生儿脑病高血糖的发生率以及强有力的证据表明主要 由于对长期结果的附加影响，现在至关重要的是澄清（1）后验结果如何 主要的脑损伤会导致皮层视觉处理困难，以及（2）早期大脑如何 认知和行为问题的发现转化为学龄早期的诊断。 本研究的总体目标是确定新生儿中高血糖如何发生 脑病，独立预测学龄早期的结果。具体目标包括： 1. 评估新生儿脑病中的低血糖和高血糖如何影响皮质视觉处理 到了学龄初期。 2. 评估新生儿脑病中的低血糖和高血糖如何影响认知、语言、 学龄早期的社交和行为功能。 NOGIN 研究是一项前瞻性队列研究，最初旨在确定低水平的程度 血糖会导致低血糖性脑损伤，招募将在接下来的几个月内完成。这 第一个受试者将于 2019 年 9 月满 5 岁。为了实现当前的研究目标，儿童 将被要求在 5 岁时返回进行神经心理学评估（包括 WPPSI-IV、 NEPSY-II、MCHAT、CBCL）和脑磁图（视觉任务、静息大脑网络 电路）来了解特定水平的高血糖如何转化为持续的长期赤字。 通过将新生儿 HIE 的具体高血糖水平与 HIE 的程度相关联 神经发育障碍，这项研究将有助于有针对性地管理和控制 高血糖可以减少脑损伤并改善这些新生儿的预后。数据 生成的数据还将有助于及早识别最有不良后果风险的新生儿， 实现更有针对性的早期辅助治疗，以改善 HIE 后的预后。

项目成果

Hyperglycemia associated with acute brain injury in neonatal encephalopathy.

高血糖与新生儿脑病急性脑损伤相关。

• 发表时间: 2021
• 作者: Tam, Emily W Y;Kamino, Daphne;Shatil, Anwar S;Chau, Vann;Moore, Aideen M;Brant, Rollin;Widjaja, Elysa
• 通讯作者: Widjaja, Elysa

Abnormalities in evoked potentials associated with abnormal glycemia and brain injury in neonatal hypoxic-ischemic encephalopathy.

新生儿缺氧缺血性脑病中与异常血糖和脑损伤相关的诱发电位异常。

• 发表时间: 2021
• 作者: Kamino, Daphne;Almazrooei, Asma;Pang, Elizabeth W;Widjaja, Elysa;Moore, Aideen M;Chau, Vann;Tam, Emily W Y
• 通讯作者: Tam, Emily W Y

Early neonatal heart rate variability patterns in different subtypes of perinatal hypoxic-ischemic brain injury.

围产期缺氧缺血性脑损伤不同亚型的早期新生儿心率变异模式。

• 发表时间: 2022-12
• 影响因子: 3.6
• 作者: Goswami, Ipsita;Kamino, Daphne;Widjaja, Elysa;Paniccia, Melissa;Mitsakakis, Nicholas;Moore, Aideen;Tam, Emily W Y
• 通讯作者: Tam, Emily W Y

Nutrition and management of glycemia in neonates with neonatal encephalopathy treated with hypothermia.

低温治疗新生儿脑病新生儿的营养和血糖管理。

• 发表时间: 2021
• 作者: Pinchefsky, E F;Schneider, J;Basu, S;Tam, E W Y;Gale, C;Newborn Brain Society Guidelines and Publications Committee*
• 通讯作者: Newborn Brain Society Guidelines and Publications Committee*

Building an Open Source Classifier for the Neonatal EEG Background: A Systematic Feature-Based Approach From Expert Scoring to Clinical Visualization.

为新生儿脑电图背景构建开源分类器：从专家评分到临床可视化的基于系统特征的方法。

• 发表时间: 2021
• 作者: Moghadam, Saeed Montazeri;Pinchefsky, Elana;Tse, Ilse;Marchi, Viviana;Kohonen, Jukka;Kauppila, Minna;Airaksinen, Manu;Tapani, Karoliina;Nevalainen, Päivi;Hahn, Cecil;Tam, Emily W Y;Stevenson, Nathan J;Vanhatalo, Sampsa
• 通讯作者: Vanhatalo, Sampsa