Oxygen for intrauterine resuscitation: Investigating the role of oxidative stress

宫内复苏的氧气：研究氧化应激的作用

• 批准号: 10197177
• 负责人: Nandini Raghuraman
• 金额: $ 15.2万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-17 至 2023-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10197177
• 关键词: 4 hydroxynonenal; Address; Adult; Air; American College of Obstetricians and Gynecologists; Blood; Categories; Cell Death; Cerebral Palsy; Cesarean section; Clinical; Clinical Trials; Cohort Studies; Country; Data; Delivery Rooms; Dose; Exposure to; Fetal Monitoring; Fetus; Free Radicals; Functional disorder; Funding; Generations; Goals; Hyperoxia; Hypoxia; Infant; Inflammatory Response; Knowledge; Link; Lipid Peroxidation; Lipids; Malondialdehyde; Mediating; Mothers; Neonatal Nursing; Nucleic Acids; Observational Study; Obstetrical Nursing; Outcome; Outcome Study; Oxidative Stress; Oxygen; Oxygen Therapy Care; Pathway interactions; Patients; Pattern; Perinatal; Proteins; Randomized; Randomized Controlled Trials; Reactive Oxygen Species; Resuscitation; Retinal Diseases; Risk; Role; Safety; Schedule; Serum; Serum Markers; Structure of umbilical artery; Supplementation; Techniques; Testing; Time; Time trend; Tissues; Umbilical cord structure; United States; Urine; Woman; Women' s Health; Work; adverse outcome; animal data; base; cell injury; clinical practice; design; evidence base; fetal; fetus hypoxia; in utero; intrapartum; maternal serum; neonatal hypoxic-ischemic brain injury; neonatal morbidity; neonatal resuscitation; neonate; neurodevelopment; pilot trial; prevent; randomized controlled design; supplemental oxygen; trend; trial comparing

Project Summary/Abstract Approximately 2/3 of laboring women receive supplemental oxygen (O2) in an attempt to reverse perceived fetal hypoxia on electronic fetal monitoring (EFM). O2 supplementation is most commonly used in patients with Category II EFM, a class of EFM patterns designed in part to identify fetal acidemia. This liberal use of O2 in laboring patients is concerning because hyperoxygenation in infants is associated with adverse outcomes including retinopathy and abnormal neurodevelopment. Furthermore, excess O2 exposure is linked to free radical generation and subsequent oxidative cell damage. This calls for a closer look at the safety of intrauterine O2 exposure. The proposed project explores potential mechanisms for harm with maternal O2 supplementation in laboring patients with Category II EFM. Specifically, this project will determine the effect of O2, compared to room air (RA), on umbilical cord and maternal serum levels of malondialdehyde (MDA) and 4-hydroxynonenal (4- HNE), markers of free radical-induced oxidative stress. The study will also explore the feasibility of using urine markers of oxidative stress as a less invasive alternative to serum markers and to establish temporal trends in oxidative stress throughout labor. This project will employ a randomized controlled design based on a recently completed pilot trial that demonstrated feasibility of such an approach. The expected outcome of this study is high-quality, mechanistic, pilot data on the pathophysiology of in-utero O2 exposure. If the central hypothesis that intrauterine exposure to O2 during labor is less safe than RA is confirmed, the findings will impact the intrapartum management of millions of patients who labor and deliver each year in the United States. Ultimately, this work will lead to evidence-based intrauterine resuscitation during labor that minimizes neonatal morbidity.

项目概要/摘要 大约 2/3 的临产妇女接受补充氧气 (O2)，以试图逆转胎儿的感知 胎儿电子监护 (EFM) 缺氧。 O2 补充最常用于患有以下疾病的患者 II 类 EFM，一类 EFM 模式，部分设计用于识别胎儿酸血症。这种对 O2 的大量使用 临产患者令人担忧，因为婴儿的过度氧合与不良后果相关 包括视网膜病变和神经发育异常。此外，过量的氧气暴露与自由基有关 的产生和随后的氧化细胞损伤。这需要仔细研究宫内吸氧的安全性 接触。拟议的项目探讨了孕产妇补充氧气造成伤害的潜在机制。 II 类 EFM 的临产患者。具体来说，该项目将确定 O2 与房间相比的效果 空气（RA）对脐带和母体血清中丙二醛（MDA）和4-羟基壬烯醛（4- HNE），自由基诱导的氧化应激的标志物。该研究还将探索利用尿液的可行性 氧化应激标记物作为血清标记物侵入性较小的替代品，并建立氧化应激标记物的时间趋势 整个分娩过程中的氧化应激。该项目将采用基于最近的一项随机对照设计 完成了试点试验，证明了这种方法的可行性。这项研究的预期结果是 关于宫内 O2 暴露病理生理学的高质量、机械性试验数据。如果中心假设 确认分娩期间宫内暴露于 O2 的安全性低于 RA，该发现将影响 每年在美国对数百万临产和分娩的患者进行产时管理。最终， 这项工作将导致分娩期间基于证据的宫内复苏，从而最大限度地减少新生儿发病率。