4:4 Investigation of opioid exposure and neurodevelopment (iOPEN)

项目总结 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 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。纽约大学是四个相互关联的申请之一 与俄勒冈健康与科学大学、匹兹堡大学医学院的研究人员合作 佛蒙特州中心和佛蒙特州大学。我们将共同应对关键挑战，这些挑战对 计划中的第二阶段研究。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将实施多个 站点，标准化的纵向研究方案，每个站点招募20名孕妇(跨站点n=80)， 其中一半人在怀孕期间使用阿片类药物。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、生物成像以及产妇心理社会和健康评估。AIM 3将评估 旨在解决关键问题的创新磁共振成像获取和处理策略和统计考虑因素 第二阶段目标，包括最佳计量战略和跨地点协调。具体来说，我们会：(A) 评估交叉扫描仪和跨时间图像协调的策略；(B)测试MRI的实时评估 采集过程中的数据质量/运动；(C)测试加速图像采集序列的效果；和(D) 建设胎儿和新生儿磁共振成像处理管道。我们的纽约调查团队广泛贡献了 对阿片成瘾患者、暴露于阿片类药物的胎儿和纵向队列的领先研究经验 研究对象为孕妇、幼儿和难以接触到的人群。我们已经执导了多部 进行了大规模的人群研究，并进行了多模式核磁共振、脑电和超声波 对胎儿、新生儿和儿童的研究。我们先前在婴儿MRI数据和纵向建模方面的专业知识 磁共振成像方法学的发展非常适合于引导AIM 3‘S图像的协调和胎儿/新生儿 加工流水线开发。此外，纽约市的人口带来了亟需的多样性 从种族、民族、原籍和社会经济地位到相互关联的协作应用程序。

PROJECT SUMMARY 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 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. New York University is one of four linked applications collaborating with investigators at Oregon Health and Sciences University, University of Pittsburgh Medical Center and University of Vermont. Together, we will address key challenges that are 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. 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 implement a multi- site, standardized, longitudinal research protocol by enrolling 20 pregnant women per site (n=80 across sites), half of whom use opioids during pregnancy. This prospective longitudinal study will collect fetal and neonatal multi-modal MRI, biospecimens, and maternal psychosocial and health assessments. Aim 3 will evaluate innovative MRI acquisition and processing strategies and statistical considerations intended to address key Phase II goals, including optimal measurement strategies and cross-site harmonization. Specifically, we will (a) evaluate strategies for cross-scanner and cross-time image harmonization; (b) test real-time evaluation of MRI data quality/motion during acquisition; (c) test the efficacy of accelerated image acquisition sequences; and (d) build fetal and neonatal MRI processing pipelines. Our New York investigative team contributes extensive experience leading studies in patients with opioid addiction, fetuses exposed to opioids, and longitudinal cohort studies in pregnant patients, young children, and difficult to reach populations. We have directed multiple consortia, performed large-scale population studies, and conducted multimodal MRI, EEG, and ultrasound studies in fetuses, neonates, and children. Our prior expertise in longitudinal modelling of infant MRI data and MRI methodology development suits us well to lead Aim 3's image harmonization and fetal/neonatal processing pipeline development. Additionally, the New York City population brings much-needed diversity across race, ethnicity, nativity, and socioeconomic status to the linked collaborative applications.