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: 10019149
• 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 2021-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10019149
• 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比率在全国范围内达到了惊人的每1000名新生儿中有6.5人，但 宫内阿片类药物暴露的短期和长期影响远不清楚。我们缺乏基本的知识 典型的新生儿神经发育和努力将阿片类药物暴露的影响与其他 影响婴儿健康的保护性因素和风险因素。胎儿时期是大脑发育的关键时期 当大脑结构和功能的基本方面建立起来的时候。此外，出生后的大脑 发展和专业化是由环境经验塑造的，因此允许成熟 受与阿片类药物使用相关的生活方式因素的影响。该项目一期规划规模大、规模大。 对人类大脑、认知、行为、社交和情感进行前瞻性研究的现场研究 从胎儿期开始直到童年的发育。匹兹堡大学是四个链接网站之一 包括俄勒冈健康与科学大学、纽约大学和佛蒙特州大学 应对对计划中的第二阶段研究的成功至关重要的关键挑战。目标1将制定、实施 并通过纵向调查评估针对高危人群的创新招聘和保留战略 对每个地点150名孕妇的调查(跨地点600人)，其中一半使用阿片类药物。目标2将 实施多站点、标准化、纵向研究方案，每个站点招募20名孕妇 (n=80个地点)，其中一半使用阿片类药物。这项前瞻性的纵向研究将收集胎儿和 新生儿多模式核磁共振、生物显微镜检查，以及母亲心理社会和健康评估。目标3将 评估数据采集、处理和统计方面的注意事项，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)实时运动监控/质量评估的有效性 使用新的加速序列提高整体数据质量和(B)与MRI质量相比节省时间 协议。这一方法将为全面和有效的第二阶段奠定坚实的基础。 研究计划。匹兹堡大学的网站由一个高生产率的、由NIH资助的调查团队领导 在物质使用(Krans，Bogen)、怀孕(Krans)、胎儿、新生儿和 儿童神经成像(露娜，帕尼格拉希)。具体地说，我们的团队已经建立了研究方案， 在使用阿片类药物的孕妇中，优秀的招募(~76%)和保留(~74%)的比率，有很大的 对未成熟大脑(胎儿/新生儿)进行成像的经验，在发展认知方面处于领先地位 神经科学使用多模式成像研究神经认知的神经机制 青春期发育。我们将利用我们正在进行的、由NIH资助的多中心神经成像 提供成像协调技术并协助胎儿大脑结构发育的研究 以及所有链接部位的胎盘成像管道，以协助第二阶段方案的开发。此外， 我们将试点与年龄相关的铁沉积和定量胎儿磁共振波谱的创新研究。