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

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 - 行政补充

基本信息

批准号：
10818776
负责人：
CHRISTOPHER J TRENTACOSTA
金额：
$ 12.68万
依托单位：
NEW YORK UNIVERSITY SCHOOL OF MEDICINE
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-08-06 至 2025-02-28
项目状态：
未结题

项目摘要

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.

项目概要早期炎症与儿童神经行为发育改变之间的关联是无可争议的，但是对这种关联背后的神经学现象的理解几乎完全缺乏。研究于动物表明，即使在出生之前，炎症也会影响神经连接的发育，从而改变过程的发展。然而，这些重要的关联仍有待在人脑中进行测试。在这里，我们将以统一的方式检查产前炎症、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月经周期会对胎儿神经连接组的发育产生影响，从而增加患上这种疾病的风险儿童期疾病。我们将胎儿静息态功能连接 (RSFC) MRI 的进展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，并使用先进的建模技术将严格研究早期生活中的保护性和复原力因素，这些因素会减轻适应不良的童年结果。为了实现这些目标，我们将从以下位置获取乳牙样本：儿童参加了纵向神经发育方案，其中包括胎儿大脑 RSFC MRI。一个新的数据收集浪潮，部分与 NIH 的青少年大脑认知发展 (ABCD) 一致研究方案将于 9 岁时进行，其中包括在产前使用的同一台扫描仪上进行 MRI 检查。在这些参与者，胎儿全身炎症、胎儿大脑功能连接和儿童之间的关联将检查神经行为发育。我们的技术涉及高时间分辨率采样受孕后第 15 周的五种炎症标志物：C 反应蛋白、白细胞介素 (IL) 1、6、10、TNF-a 到产后第 12 周，能够隔离敏感期和交互效应。主要目标该项目的目的是 (i) 识别与产前升高相关的胎儿大脑连接组异常炎症，(ii) 是产前升高的长期大脑和行为后果的特征炎症，以及（iii）分离产后环境中预测有利的长期生存的保护因素。期限结果。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发生影响发育中的胎儿大脑的功能神经回路，以及长期的神经行为后果这些协会。这样的工作不仅会极大地增进我们对产前炎症的长期影响，也是儿童神经障碍的根源。