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.

项目总结