1/4 Investigation of opioid exposure and neurodevelopment (iOPEN)

项目总结摘要 在全国范围内，新生儿禁欲综合症的发生率达到了惊人的每1000名新生儿中有6.5人患有禁欲综合症，这创造了 迫切需要确定宫内阿片类药物暴露及其相关风险因素如何影响 发育中的大脑。对这一主题的严谨科学调查需要解决基础知识的缺乏 神经典型发育知识。然而，描述胎儿时期大脑发育的特征 通过婴儿期和幼儿期，特别是在受药物使用影响的边缘人群中， 带来了无数的挑战。这项提议汇集了一个拥有所有专业知识的多学科团队， 在俄勒冈州应对这些挑战的经验和机构支持，该州受到的打击尤其严重 阿片类药物泛滥。通过链接到其他三个站点，佛蒙特州大学、纽约大学和 匹兹堡大学医学中心，这一拟议的第一阶段项目的影响显著增强， 并将提供关键信息，以支持国家层面的健康大脑和儿童第二阶段工作 发展研究。目标1将开发、实施和评估创新的招聘和留用 针对高危人群的战略。我们将衡量可行性、吞吐量和人口统计 150例孕妇不同招募方式特征的纵向调查 每个地点有600名妇女(跨地点)，其中一半人在怀孕期间使用阿片类药物。Aim 2将针对 通过实施和评估多地点，规划的第二阶段研究的预期挑战， 标准化的研究方案包括胎盘、胎儿、新生儿和24个月大的大脑的多模式磁共振成像， 生物制品的收集，物质使用的评估，以及其他关键领域。可行性、数据质量和 不同评估方法的有效性将在20个母婴二人组的纵向样本中进行评估 (n=80个地点，其中一半人在怀孕期间使用阿片类药物)，以及5、24个月的横断面样本- 有产前阿片类药物暴露史的老年儿童(N=20个地点)。AIM 3将评估数据采集， 处理和统计方面的考虑，以最大限度地提高数据质量、可用性和跨站点集成。我们 将：(1)检查不同发育阶段MRI实时运动监测的效果；(2)测试 使用新的加速序列节省时间和数据质量；以及(3)协调数据和处理 基于通用脑成像的胎儿、新生儿和儿童磁共振成像流水线 数据结构(出价)。该项目与OHSU地址的几个非常强大的研究方向相吻合 药物使用和阿片类药物流行(NIDA临床试验网络)，出生前和出生后暴露的影响 关于大脑和行为发育(ECHO)、胎盘和胎儿发育(UO1 Frias/Kroenke)和儿童 和青少年大脑发育(ABCD)。我们现有的和发展中的与主要政府部门的关系 机构、治疗设施和非营利组织为解决重要的法律和社会问题提供了坚实的基础 道德问题，并扩大招募和留住家庭参加该奖项第二阶段的网络。

PROJECT SUMMARY ABSTRACT Rates of neonatal abstinence syndrome have reached a staggering 6.5 per 1,000 births nationwide, creating an urgent need to identify how in-utero exposure to opioids and associated risk factors influence the developing brain. Rigorous scientific investigation of this topic requires addressing the lack of foundational knowledge of neurotypical development. However, characterizing brain development from the fetal period through infancy and early childhood, and particularly in marginalized populations affected by substance use, presents myriad challenges. This proposal brings together a multidisciplinary team with all of the expertise, experience, and institutional support to address these challenges in Oregon, a state particularly hard hit by the opioid epidemic. Through linking with three other sites, University of Vermont, New York University, and University of Pittsburgh Medical Center, the impact of this proposed Phase I project is significantly enhanced, and will provide critical information to support a national level effort for Phase II of the HEALthy Brain and Child Development Study. Aim 1 will develop, implement and evaluate innovative recruitment and retention strategies for high-risk populations. We will measure the feasibility, throughput, and demographic characteristics associated with different recruitment methods through a longitudinal survey of 150 pregnant women per site (n=600 across sites), half of whom use opioids during pregnancy. Aim 2 will address anticipated challenges of the planned Phase II study by implementing and evaluating a multi-site, standardized, research protocol including multimodal MRI of placenta, fetus, neonate and 24-month-old brain, biospecimen collection, and asessment of substance use, and other key domains. Feasibility, data quality, and efficacy of different assessment methods will be evaluated in a longitudinal sample of 20 mother-infant dyads (N=80 across sites, half of whom use opioids during pregnancy), and a cross-sectional sample of 5, 24-month- old children with a history of prenatal opioid exposure (N=20 across sites). Aim 3 will evaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, and integration across sites. We will: (1) examine the efficacy of real-time motion monitoring for MRI at different developmental stages; (2) test time savings and data quality using new acceleration sequences; and (3) harmonize data and processing pipelines for fetal, neonatal and child MRI into a common framework based on the universal Brain Imaging Data Structure (BIDS). This project dovetails with several very strong lines of research at OHSU addressing substance use and the opioid epidemic (NIDA Clinical Trials Network), effects of pre- and postnatal exposures on brain and behavioral development (ECHO), placental and fetal development (UO1 Frias/Kroenke), and child and adolescent brain development (ABCD). Our existing and developing relationships with key governmental agencies, treatment facilities and nonprofits provides a strong foundation for addressing important legal and ethical issues, and growing a network for recruiting and retaining families for Phase II of this award.