Oxygen for intrauterine resuscitation: Investigating the role of oxidative stress

项目总结/摘要 大约2/3的分娩妇女接受补充氧气（O2），试图扭转胎儿感觉 电子胎儿监护（EFM）。O2补充最常用于以下患者： II类EFM，一类EFM模式，部分用于识别胎儿酸血症。氧气的大量使用 分娩患者是令人担忧的，因为婴儿的过度氧合与不良后果有关 包括视网膜病和异常神经发育。此外，过量的O2暴露与自由基有关。 生成和随后的氧化性细胞损伤。这就需要更仔细地研究宫内O2的安全性 exposure.拟议的项目探讨了产妇补充O2的潜在危害机制， 患有II类EFM的分娩患者。具体来说，该项目将确定O2的效果，与室内相比， 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。这项研究还将探讨使用尿液的可行性 氧化应激标志物作为血清标志物的侵入性较小的替代品，并建立 氧化应激在整个劳动。本项目将采用随机对照设计，根据最近的 已完成的试点试验证明了这种方法的可行性。本研究的预期结果是 关于宫内O2暴露的病理生理学的高质量、机制性、试验性数据。如果中心假设 分娩期间宫内暴露于O2比RA更不安全，这一发现将影响 在美国，每年有数百万分娩和分娩的患者接受产时管理。最后， 这项工作将导致在分娩过程中以证据为基础的宫内复苏，最大限度地减少新生儿发病率。

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.