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

项目摘要 新生儿禁欲综合症的发病率在全国范围内达到了惊人的每1,000名新生儿中6.5人， 迫切需要确定宫内暴露于阿片类药物和相关风险因素如何影响 大脑发育对这一主题进行严格的科学调查需要解决缺乏基础知识的问题。 神经发育的知识。然而，从胎儿时期开始描述大脑发育 特别是在受药物使用影响的边缘化人群中， 提出了无数的挑战。该提案汇集了一个具有所有专业知识的多学科团队， 经验和机构支持，以解决这些挑战，在俄勒冈州，一个国家特别严重的打击， 阿片类药物流行病通过与佛蒙特大学、纽约大学和 匹兹堡大学医学中心，这个拟议的第一阶段项目的影响显着增强， 并将提供关键信息，以支持国家一级的努力，第二阶段的健康大脑和儿童 发展研究。目标1将制定、实施和评估创新的招聘和留用办法 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 通过对150名孕妇的纵向调查，分析了不同招募方法的相关特征 每个研究中心的妇女人数（各研究中心n=600），其中一半在怀孕期间使用阿片类药物。目标2将解决 通过实施和评价多中心， 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态MRI， 生物标本收集和物质使用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个母婴配对的纵向样本中进行评估 （各研究中心N=80，其中一半在妊娠期间使用阿片类药物），以及5个24个月的横断面样本， 有产前阿片类药物暴露史的大龄儿童（各研究中心N=20）。目标3将评估数据采集， 处理和统计考虑，以最大限度地提高数据质量，可用性和跨站点的集成。我们 将：（1）检查不同发育阶段MRI实时运动监测的功效;（2）测试 使用新的加速序列节省时间和提高数据质量;以及（3）协调数据和处理 将胎儿、新生儿和儿童MRI管道整合到基于通用脑成像的通用框架中 数据结构（BIDS）。该项目以OHSU的几条非常强有力的研究路线为基础， 物质使用和阿片类药物流行（NIDA临床试验网络），产前和产后暴露的影响 对大脑和行为发育（ECHO）、胎盘和胎儿发育（UO 1 Frias/Kroenke）以及儿童 青少年大脑发育（ABCD）我们与主要政府机构的现有和发展中关系 机构、治疗机构和非营利组织为解决重要的法律的和 道德问题，并为该奖项的第二阶段建立招募和留住家庭的网络。

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.