The Opioid in Pregnancy: Imaging of Oxygenation, Inflammation, and Development in Brain & Placenta Project (OPIOID BPP)

怀孕期间的阿片类药物:氧合、炎症和大脑发育的成像

基本信息

  • 批准号:
    10750770
  • 负责人:
  • 金额:
    $ 233.77万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2023
  • 资助国家:
    美国
  • 起止时间:
    2023-09-01 至 2026-08-31
  • 项目状态:
    未结题

项目摘要

Abstract Maternal opioid use disorder (OUD) is rapidly increasing in prevalence, and is associated with severe morbidities in offspring, such as neonatal opioid withdrawal syndrome (NOWS), brain dysmaturation, and impaired neurodevelopment (ND). However, little is known regarding the mechanisms by which maternal OUD causes these outcomes, so our ability to mitigate the impact of prenatal opioid exposure (POE) on outcomes is poor. Here, we propose to test the central hypothesis that POE causes abnormal neurodevelopment through direct actions on the fetal brain. Additionally, we propose that POE causes abnormal neurodevelopment via moderation effects from the placenta through mechanisms of hypoxia and inflammation. Strikingly, our preliminary results from the placental pathology of 17 POE pregnancies confirm hypoxic lesions in every patient. Furthermore, our preliminary work using placental immune imaging (PII), an advanced diffusion magnetic resonance imaging (dMRI) technology, confirmed elevated placental inflammation and decreased oxygenation, both near the chorionic plate in a POE 36-week pregnancy compared to unexposed controls. Placental hypoxia and inflammation are two known etiologies that cause fetal WM injury and brain dysmaturation, and our own data show that fetuses with impaired cerebral oxygenation have the greatest reductions in brain volume and WM alterations. Importantly, we have demonstrated that fetal brain volume most consistently predicted 2-year ND (n=78, r=0.32-0.47; all p<0.05) across all domains. To test our hypothesis, we leverage the Clinic for Acceptance, Recovery, and Empowerment, one of the few wrap-around OUD prenatal clinics in the country, and our ongoing work on the Human Placenta Project (R01HD094381-04) with longitudinal imaging of placental inflammation from unexposed patients, as a respose to the HEAL Initiative: Opioid Exposure and Effects on Placenta Function, Brain Development, and Neurodevelopmental Outcomes (RFA-HD-23-030). We propose this R01 to define the longitudinal effects of POE on placental inflammation and oxygenation (Aim 1), fetal brain development and oxygenation (Aim 2), and the relationship between placental and fetal brain development markers with NOWS and early ND outcomes in infants with POE (Aim 3). Completion of these aims will explore and refine an innovative fetal pathway by which POE leads to adverse outcomes, and identify markers of immune response and oxygenation status in placenta and fetal brain that predict NOWS and ND. In the long term, this work will allow us to identify therapeutic targets to mitigate the adverse effects of maternal OUD on offspring.
摘要 母亲阿片类药物使用障碍(OUD)的患病率正在迅速上升,并与严重的发病率有关 在后代中,如新生儿阿片类药物戒断综合征(NOWS)、脑发育不成熟和受损 神经发育(ND)。然而,关于母体OUD引起的机制却知之甚少。 这些结果,所以我们减轻产前阿片类药物暴露(POE)对结果的影响的能力很差。 在这里,我们建议检验POE导致神经发育异常的中心假设 通过对胎儿大脑的直接作用。此外,我们认为POE会导致神经发育异常 通过胎盘的调节作用,通过缺氧和炎症机制。引人注目的是,我们的 17例POE妊娠的胎盘病理初步结果证实,每个患者都有缺氧性损害。 此外,我们的初步工作使用了胎盘免疫成像(PII),这是一种先进的扩散磁 磁共振成像(DMRI)技术,证实胎盘炎症增加和氧合减少, 在妊娠36周的POE患者中,两者均位于绒毛膜板附近,与未暴露的对照组相比。胎盘缺氧 和炎症是导致胎儿WM损伤和大脑发育不成熟的两个已知原因,而我们自己 数据显示,大脑氧合受损的胎儿大脑体积和WM的减少幅度最大 改装。重要的是,我们已经证明,胎儿脑体积最一致地预测了2年后的ND (n=78,r=0.32-0.47;均P&lt;0.05)。为了检验我们的假设,我们利用诊所的认可, 康复和赋权,是全国为数不多的综合性产前诊所之一,我们正在进行的 人类胎盘计划(R01HD094381-04)的工作与胎盘炎症的纵向成像 来自未暴露的患者,作为对治愈倡议的回应:阿片类药物的暴露和对胎盘功能的影响, 脑发育和神经发育结果(RFA-HD-23-030)。我们建议使用R01来定义 POE对胎盘炎症和氧合的纵向影响(目标1),胎儿大脑发育和 氧合作用(目标2)以及胎盘和胎儿脑发育标志物与NOWS的关系 和POE婴儿的早期ND结果(目标3)。完成这些目标将探索和完善一个 POE导致不良结局的创新胎儿途径,并确定免疫反应的标记物 胎盘和胎脑中的氧合状态预示着NOWS和ND。从长远来看,这项工作将 使我们能够确定治疗目标,以减轻母体OUD对后代的不利影响。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Jeannie Chen Kelly其他文献

Jeannie Chen Kelly的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Jeannie Chen Kelly', 18)}}的其他基金

Using the Transdermal Patch for Buprenorphine Induction during Pregnancy: A Pilot Randomized Controlled Trial
怀孕期间使用透皮贴剂诱导丁丙诺啡:一项随机对照试验
  • 批准号:
    10738154
  • 财政年份:
    2023
  • 资助金额:
    $ 233.77万
  • 项目类别:
Safety, Testing/Transmission, and Outcomes in Pregnancy with COVID-19 (STOP-COVID-19 study)
妊娠期感染 COVID-19 的安全性、检测/传播和结果(STOP-COVID-19 研究)
  • 批准号:
    10259118
  • 财政年份:
    2020
  • 资助金额:
    $ 233.77万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 233.77万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了