Examining Prenatal Inflammation and Neurodevelopment in a Longitudinal Fetal-to-Age 9 Imaging Study

在胎儿至 9 岁纵向影像学研究中检查产前炎症和神经发育

• 批准号: 10369041
• 负责人: CHRISTOPHER J TRENTACOSTA
• 金额: $ 71.37万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-14 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10369041
• 关键词: Address; Adolescent; Affect; Age; Anatomy; Animals; Attention deficit hyperactivity disorder; Behavior; Behavioral; Belief; Biological; Biological Assay; Biological Markers; Birth; Brain; C-reactive protein; Child; Child Rearing; Childhood; Conceptions; Data; Data Collection; Dependence; Development; Diffusion Magnetic Resonance Imaging; Disease; Disease Pathway; Early Diagnosis; Enrollment; Environment; Etiology; Event; Fetal Development; Fetal Neurobehavioral Development; Foundations; Functional Magnetic Resonance Imaging; Future; Health; Human; Immune; Impairment; Inflammation; Inflammatory; Interleukin-1; Intervention; Lead; Life; Link; Long-Term Effects; Longitudinal cohort; Magnetic Resonance Imaging; Measures; Mental disorders; Modeling; Mothers; Neighborhoods; Neurocognitive; Neurodevelopmental Disorder; Neurologic; Neurological outcome; Outcome; Participant; Pathologist; Pathway interactions; Pregnancy; Prevention; Property; Protocols documentation; Research; Rest; Risk; Sampling; Schizophrenia; Stress; Sum; Support System; System; TNF gene; Techniques; Testing; Third Pregnancy Trimester; Time; Tooth structure; Trauma; United States National Institutes of Health; Validation; Work; autism spectrum disorder; base; behavioral outcome; cognitive development; cohort; connectome; contextual factors; course development; deciduous tooth; developmental disease; fetal; imaging study; immune activation; in utero; indexing; inflammatory marker; innovation; interest; intrauterine environment; intrauterine inflammation; nervous system disorder; neural circuit; neural correlate; neurobehavioral; neurodevelopment; neuroimaging; offspring; postnatal; prenatal; protective factors; psychologic; public health relevance; relating to nervous system; resilience; response; sleep behavior; social; systemic inflammatory response; temporal measurement

PROJECT SUMMARY The association between early inflammation and altered child neurobehavioral development is indisputable, but understanding of neurological phenomena underlying this association is almost entirely lacking. Studies in animals suggest that, even before birth, inflammation acts on developing neural connections to alter the course of development. However, these critical associations remain to be tested in the human brain. Here, we will examine prenatal inflammation, fetal neural programming effects, and child neurodevelopment in a unified framework. We will leverage an existing longitudinal cohort to evaluate whether inflammation in the prenatal period exerts influence over the developing fetal neural connectome, and subsequently increases risk for childhood disorders. We will pair advances in fetal resting-state functional connectivity (RSFC) MRI with innovations in tooth-biomarker assays to address prenatal neural-immune interactions, and using advanced modeling techniques will rigorously investigate protective and resilience factors in early life that mitigate maladaptive childhood outcomes. To achieve these objectives, we will attain deciduous tooth samples from children enrolled in a longitudinal neurodevelopmental protocol that included fetal brain RSFC MRI. A new wave of data collection, partially harmonized with the NIH’s Adolescent Brain Cognitive Development (ABCD) study protocol, will be conducted at age 9 and will include MRI on the same scanner used prenatally. In these participants, associations between fetal systemic inflammation, fetal brain functional connectivity, and child neurobehavioral development will be examined. Our technique involves high temporal resolution sampling of five inflammatory markers, C reactive protein, Interleukin (IL) 1, 6, 10, TNF-a, across post conception week 15 through postnatal week 12, enabling isolation of sensitive periods and interactive effects. The primary aims of this project are to (i) identify fetal brain connectome abnormalities associated with heightened prenatal inflammation, (ii) characterize long-term brain and behavioral consequences of heightened prenatal inflammation, and (iii) isolate protective factors in the postnatal environment that predict advantageous long- term outcomes. We will thus be able to meaningfully evaluate whether and how prenatal inflammatory events affect functional neurocircuitry of the developing fetal brain, and the long-term neurobehavioral consequences of those associations. Such work would constitute a substantial advance in our understanding of not only the long-term effects of prenatal inflammation, but also the origins of child neurological disorders.

项目摘要 早期炎症与儿童神经行为变化之间的关联是无可争议的，但是 对这种关联的基础神经现象的理解几乎完全缺乏。研究 动物建议，即使在出生前，感染也会作用于开发神经联系以改变过程 发展。但是，这些关键关联在人脑中仍有待测试。在这里，我们会的 检查统一的产前感染，胎儿神经编程效应和儿童神经发育 框架。我们将利用现有的纵向队列来评估产前炎症是否 时期对发育中的胎儿神经连接仪产生影响，随后增加了风险 儿童期疾病。我们将将胎儿静止状态功能连通性（RSFC）MRI的进步与 牙齿生物标志物测定的创新，以解决产前神经免疫相互作用，并使用高级 建模技术将严格研究早期生命的保护和弹性因素 适应不良的童年结果。为了实现这些目标，我们将从 参加纵向神经发育方案的儿童包括胎儿脑RSFC MRI。一个新 数据收集浪潮，部分与NIH的青少年脑认知发展（ABCD）协调 研究方案将在9岁时进行，并将在产前使用的同一扫描仪上包括MRI。在这些 参与者，胎儿全身炎症，胎儿脑功能连通性与儿童之间的关联 将检查神经行为的发展。我们的技术涉及高临时分辨率抽样 五个炎症标记，C反应蛋白，白介素（IL）1、6、10，TNF-A，遍布概念后第15周 通过产后第12周，可以隔离敏感时期和互动效果。主要目的 该项目是（i）识别与产前增长有关的胎儿脑连接异常 炎症，（ii）表征长期大脑和产前增强的行为后果 炎症，（iii）在产后环境中孤立的受保护因素，这些因素预测有利的长长 术语成果。因此，我们将能够有意义地评估产前炎症事件是否以及如何 影响发育中胎儿大脑的功能性神经记录，以及长期神经行为的后果 这些关联。这项工作将不仅了解 产前感染的长期作用，也是儿童神经系统疾病的起源。