3/5 The Cumulative Risk of Substance Exposure and Early Life Adversity on Child Health Development and Outcomes

项目概要/描述 宫内阿片类药物暴露和早期逆境如何影响儿童的神经发育和健康结果？ 这个问题的简单性掩盖了人类神经发育的复杂性和多面性， 各种环境影响可加剧或缓解宫内物质暴露的影响。 从怀孕到10岁，我们的大脑经历了显着的结构和功能变化。过程 包括髓鞘形成和突触形成在整个年龄段处于高峰，有助于 几乎所有认知和行为技能的出现，以及对早期物质暴露和 环境刺激在胎儿阿片类药物暴露的背景下，这通常与其他母体物质同时发生 使用（酒精、烟草、大麻），以及产前和产后相关因素，包括产妇的精神 健康问题，支持或不利的家庭环境，低社会经济地位（SES），伴侣间 暴力，以及质量和数量的冲突。尽管越来越多的努力来了解神经发育 宫内阿片类药物和其他物质暴露对长期行为、认知和社会影响的后遗症 结果，重要的问题仍然存在，具体来说，1。胎儿物质是如何干扰大脑生长的， 相关的产前和产后暴露;以及2.这些被破坏的生长模式是如何与后来的 认知和行为结果这项建议旨在制定我们的方法，以解决这些关键问题， 问题，并破译这些交织在一起的产前和产后暴露的个体和累积效应 对儿童神经发育的影响通过汇集儿童发展和逆境方面的顶尖专家， 神经影像学，孕产妇，胎儿和儿童虐待医学，纵向和功能统计，以及公共卫生， 我们将在战略上位于受当前阿片类药物危机打击最严重的美国各州和县， 更大的健康大脑和儿童发展研究，并奠定了基础，我们参与三个 渐进的步骤。首先，我们将解决法律的，伦理，和母亲-儿童照顾和支持的关注隐含 在这项研究中，通过利用我们团队过去在家庭逆境、虐待儿童和胎儿物质方面的经验， 暴露研究。下一步，我们将整合我们的神经影像专业知识领域，以开发，实施， 并协调多模态MRI和EEG协议，以评估成熟的大脑结构，功能， 连通性。这项神经成像方案将与广泛的神经认知，社会人口统计学， 身体健康，家庭和病史，人体测量和生物标本数据收集，以量化 儿童的物质和环境对其整体健康的个体、累积和交互影响， 神经发育最后，我们将开发和测试先进的统计方法来建模和分析这一点 多维和纵向数据，同时考虑到 测量.总之，这些步骤为广泛和大规模的研究奠定了基础， 暴露于物质和早期逆境对儿童神经、身体和行为发育的影响。

PROJECT SUMMARY / DESCRIPTION How do in utero opioid exposure and early adversity affect a child’s neurodevelopmental and health outcomes? The simplicity of this question masks the complex and multifaceted nature of human neurodevelopment, and the variety of environmental influences that can exacerbate or moderate the effects of in utero substance exposure. From conception to age 10, our brain undergoes remarkable structural and functional change. Processes including myelination and synaptogenesis are at their peak throughout this age span, contributing to the emergence of nearly all cognitive and behavioral skills, and responsive to both early substance exposures and environmental stimuli. In the context of fetal opioid exposure, this often co-occurs with other maternal substance use (alcohol, tobacco, marijuana), as well as related pre- and post-natal factors including maternal mental health concerns, supportive or adverse family environments, low socioeconomic status (SES), inter-partner violence, and caregiving quality and quantity. Despite increased efforts to understand the neurodevelopmental sequela of in utero opioid and other substance exposure on long-term behavioral, cognitive, and societal outcomes, important questions remain, specifically, 1. How is brain growth is disrupted by fetal substance and related pre and post-natal exposures; and 2. How are these disrupted growth patterns causally related to later cognitive and behavioral outcomes? This proposal seeks to formulate our approach to addressing these key questions, and decipher the individual and cumulative effect of these intertwined pre- and post-natal exposures on child neurodevelopment. By bringing together leading experts in child development and adversity, pediatric neuroimaging, maternal, fetal, and child abuse medicine, longitudinal and functional statistics, and public health, strategically located US states and counties hardest hit by the current opioid crisis, we will articulate our vision of the larger HEALthy Brain & Child Development study, and lay the foundation for our participation in three incremental steps. First, we will address the legal, ethical, and mother-child care and support concerns implicit in this study by leveraging our team’s past experience in family adversity, child abuse, and fetal substance exposure research. Next, we will integrate across our areas of neuroimaging expertise to develop, implement, and harmonize a multi-modal MRI and EEG protocol to assess maturing brain structure, function, and connectivity. This neuroimaging protocol will be paired with extensive neurocognitive, sociodemographic, physical health, family and medical history, anthropometric, and biospecimen data collection to quantify the individual, cumulative, and interactive effects of a child’s substance and environment on their overall health and neurodevelopment. Finally, we will develop and test advanced statistical approaches to model and analyze this multidimensional and longitudinal data, taking into account the likely sparse and unbalanced nature of the measurements. Together, these steps lay the foundation for a broad and large-scale study to examine the impact of exposure to substances and early adversity on a child’s neural, physical, and behavioral development.