2/4: Investigation of Opioid Exposure and Neurodevelopment (iOPEN)

2/4：阿片类药物暴露和神经发育的调查 (iOPEN)

• 批准号: 9898919
• 负责人: Elizabeth E Krans
• 金额: $ 27.57万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-30 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9898919
• 关键词: 2 year old; Acceleration; Address; Adolescence; Affect; Age; Alcohol or Other Drugs use; Assessment tool; Attitude; Behavioral; Biological; Birth; Brain; Characteristics; Child; Childhood; Cognitive; Collection; Communities; Complex; Data; Data Collection; Data Quality; Data Set; Deposition; Development; Disadvantaged; Dropout; Drops; Early Intervention; Elements; Emotional; Enrollment; Environmental Risk Factor; Family; Fathers; Fetal Structures; Foundations; Funding; Health Sciences; Human; Image; Image Analysis; Infant Health; Institutes; Investigation; Iron; Knowledge; Learning; Link; Logistics; Long-Term Effects; Longitudinal Studies; Longitudinal Surveys; Longitudinal cohort study; Longitudinal prospective study; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Measurement; Measures; Medical center; Meta-Analysis; Methodology; Methods; Modeling; Monitor; Motion; Movement; Multimodal Imaging; Neonatal; Neonatal Abstinence Syndrome; Neurocognitive; New York; Opioid user; Oregon; Outcome; Participant; Personal Satisfaction; Persons; Phase; Phase II Clinical Trials; Population; Positioning Attribute; Pregnancy; Pregnant Women; Prevalence; Probability; Prospective cohort study; Protocols documentation; Psychosocial Assessment and Care; Recording of previous events; Research; Research Design; Research Personnel; Resources; Risk Factors; Role; Savings; Site; Standardization; Structure; Techniques; Testing; Third Pregnancy Trimester; Time; Toddler; United States National Institutes of Health; Universities; Validation; Variant; Vermont; Work; age related; biobehavior; cognitive neuroscience; critical period; data acquisition; data collection methodology; data sharing; demographics; design; efficacy testing; experience; fetal; fetal drug exposure; fetal opioid exposure; flexibility; health assessment; high risk population; improved; in utero; incentive strategies; innovation; lifestyle factors; multidisciplinary; multimodality; neonatal magnetic resonance imaging; neurodevelopment; neuroimaging; neuromechanism; novel; opioid exposure; opioid use; opioid use disorder; opioid use in pregnancy; phase 2 study; postnatal; preference; pregnant; prenatal; prospective; protective factors; recruit; research study; resilience; response; retention rate; social; success; tool; usability; young mother

PROJECT SUMMARY/ABSTRACT While the rate of neonatal abstinence syndrome has reached a staggering 6.5 per 1,000 births nationwide, the short- and long-term effects of in-utero opioid exposure are far from clear. We lack fundamental knowledge of neurotypical neonatal development and struggle to disentangle the effect of opioid exposure from other protective and risk factors impacting infant health. The fetal stage of brain development is a critical period when foundational aspects of brain structure and function are being established. In addition, postnatal brain development and specialization are shaped by environmental experiences thus allowing maturation to be influenced by lifestyle factors associated with opioid use. This Phase I project will plan for a large scale, multi- site research study to prospectively examine human brain, cognitive, behavioral, social, and emotional development beginning prenatally through childhood. The University of Pittsburgh is one of four linked sites including Oregon Health and Sciences University, New York University and the University of Vermont that will address key challenges critical to the success of the planned Phase II study. Aim 1 will develop, implement and evaluate innovative recruitment and retention strategies for high-risk populations through a longitudinal survey of 150 pregnant women per site (n=600 across sites), half of whom are opioid using. Aim 2 will implement a multi-site, standardized, longitudinal research protocol by enrolling 20 pregnant women per site (n=80 across sites), half of whom are opioid using. This prospective longitudinal study will collect fetal and neonatal multimodal MRI, biospecimens, and maternal psychosocial and health assessments. Aim 3 will evaluate data acquisition, processing, and statistical considerations to maximize data quality, usability, and integration across sites. We will test the efficacy of (A) real-time motion monitoring/quality assessment for improving overall data quality and (B) time-savings versus MRI quality using new acceleration sequence protocols. This approach will inform and set a strong foundation for a comprehensive and effective Phase II research plan. The University of Pittsburgh site is led by a highly productive, NIH-funded investigative team with multidisciplinary expertise in substance use (Krans, Bogen), pregnancy (Krans), and fetal, neonatal, and pediatric neuroimaging (Luna, Panigrahy). Specifically, our team has established study protocols that yield excellent recruitment (~76%) and retention (~74%) rates among opioid using pregnant women, has substantial experience with imaging the immature brain (fetal/neonatal) and is a leader in developmental cognitive neuroscience using multimodal imaging to investigate neural mechanisms underlying neurocognitive development through adolescence. We will leverage our on-going, NIH-funded, multi-center neuroimaging studies to provide imaging harmonization techniques and assist with the development of structural fetal brain and placental imaging pipeline for all linked sites to assistant with development of Phase II protocol. Further, we will pilot innovative studies of age-related Iron deposition and quantitative fetal MR spectroscopy.

项目摘要/摘要 虽然新生儿禁欲综合症的发病率在全国范围内达到了惊人的千分之6.5， 子宫内阿片类药物暴露的短期和长期影响还远不清楚。我们缺乏基本的知识 神经典型的新生儿发育，并努力解开阿片类药物暴露的影响，从其他 影响婴儿健康的保护和风险因素。胎儿阶段是大脑发育的关键时期 当大脑结构和功能的基础方面正在建立时。此外，产后大脑 发展和专业化是由环境经验塑造的，因此允许成熟 与阿片类药物使用相关的生活方式因素的影响。该项目一期将规划一个大规模，多- 现场研究，前瞻性地检查人类大脑、认知、行为、社会和情感 从出生前到童年的发展。匹兹堡大学是四个链接网站之一 包括俄勒冈州健康与科学大学、纽约大学和佛蒙特大学， 解决对计划的II期研究成功至关重要的关键挑战。目标1将制定、实施 并通过纵向评估高风险人群的创新招募和保留策略， 每个研究中心调查150名孕妇（各研究中心n = 600），其中一半使用阿片类药物。目标2将 实施多中心、标准化、纵向研究方案，每个中心招募20名孕妇 （各研究中心n = 80），其中一半使用阿片类药物。这项前瞻性纵向研究将收集胎儿和 新生儿多模式MRI、生物样本和产妇心理社会和健康评估。目标3将 评估数据采集、处理和统计考虑因素，以最大限度地提高数据质量、可用性和 跨站点集成。我们将测试（A）实时运动监测/质量评估的有效性， 改善整体数据质量和（B）使用新的加速序列与MRI质量相比节省时间 协议.这一办法将为全面和有效的第二阶段提供信息并奠定坚实的基础 研究计划。匹兹堡大学的网站是由一个高生产力，国家卫生研究院资助的调查小组 在物质使用（克兰斯，博根），怀孕（克兰斯），胎儿，新生儿和 儿科神经影像学（Luna，Panigrahy）。具体来说，我们的团队已经建立了研究协议， 在使用阿片类药物的孕妇中，良好的招募率（~76%）和保留率（~74%）， 拥有对未成熟大脑（胎儿/新生儿）进行成像的经验，是发育认知领域的领导者 神经科学使用多模态成像来研究神经认知的神经机制 通过青春期的发展。我们将利用我们正在进行的，NIH资助的，多中心神经成像 研究提供成像协调技术，并协助胎儿大脑结构的发育 和胎盘成像管道，用于所有链接的站点，以协助制定第二阶段方案。此外，本发明还 我们将对年龄相关的铁沉积和定量胎儿磁共振波谱进行创新性研究。