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

项目总结 早期炎症和儿童神经行为发育改变之间的联系是毋庸置疑的，但 对这种联系背后的神经现象的了解几乎完全缺乏。研究项目： 动物表明，甚至在出生之前，炎症就会影响神经连接的发展，从而改变这一过程 关于发展的问题。然而，这些关键的联系仍然需要在人脑中进行测试。在这里，我们将 统一检查产前炎症、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 月经对胎儿神经连接体的发育产生影响，从而增加患 儿童期精神障碍。我们将把胎儿静息状态功能连接(RSFC)磁共振的进展与 牙齿生物标记物分析的创新，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命中的保护性和恢复力因素，这些因素 适应不良的童年结局。为了达到这些目标，我们将从以下地点获取乳牙样本 儿童参加了包括胎儿大脑RSFC MRI在内的纵向神经发育方案。一种新的 数据收集浪潮，与NIH的青少年大脑认知发展(ABCD)部分协调 研究方案将在9岁时进行，并将包括在产前使用的同一扫描仪上进行磁共振成像。在这些 参与者，胎儿全身炎症、胎儿脑功能连接和儿童之间的关系 将对神经行为发育进行检查。我们的技术涉及高时间分辨率的采样 妊娠15周后C反应蛋白、白介素1、6、10、肿瘤坏死因子-α5种炎症标志物 通过出生后12周，能够隔离敏感期和交互影响。的主要目标是 该项目旨在(I)确定与产前高度相关的胎儿大脑连接体异常。 炎症，(Ii)表征产前增高的长期大脑和行为后果 炎症，和(Iii)分离出生后环境中的保护因素，预测有利的长期- 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 这些协会中的。这样的工作将大大促进我们不仅对 胎儿期炎症的长期影响，也是儿童神经系统疾病的根源。

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.