Maternal oxygen supplementation for Intrauterine Resuscitation: a Multicenter Randomized Trial

摘要 在美国，每年分娩的300万妇女中有80%以上经历了 分娩过程中的连续电子胎儿监护（EFM）。这种监测的目的是识别胎儿 缺氧和防止转变为酸血症、加速手术分娩和/或新生儿发病。 第二类EFM，最常见的胎儿心率特征组，与可变 酸血症的风险对第二类EFM的一个常见反应是母体氧气（O2）补充。的 给氧的理论依据是，它增加了氧气向缺氧胎儿的转移，从而逆转了缺氧胎儿的缺氧状态。 缺氧和防止酸血症。这种做法是如此普遍使用，三分之二的患者接受 在分娩过程中的某个时候补充氧气。然而，尽管有理论依据，但没有严格的数据 以支持其广泛使用。我们的试验性随机非劣效性试验发表在《美国医学会儿科杂志》上， 证明了室内空气在改善脐动脉乳酸方面不劣于O2， 胎儿酸血症和新生儿发病率。我们随后对研究O2的随机试验进行的荟萃分析 与剖腹产或阴道分娩时的室内空气相比，脐动脉pH值没有差异， 在室内空气组和O2组之间，酸血症和新生儿重症监护室入院率。重要的是， 没有一项试验研究新生儿或产妇发病率的重要临床指标， 研究了O2在第二类EFM的设置。目前的证据状况在几个方面受到限制。一是 现有的关于分娩中O2的研究在O2给药的剂量、持续时间和时间方面各不相同。第二，只有一个 一项初步试验研究了O2补充剂对ACOG推荐的II类适应症的效用 EFM。第三，所有的研究都使用了新生儿发病率的替代指标，如脐带气或 新生儿重症监护室入院。最后，没有一项研究能够评估O2 在子宫内缺氧或手术分娩的新生儿临床后遗症中施用。如果没有这些数据， 明确的结果，无法提出管理II类EFM的循证建议。 为了填补这一重要的知识空白，我们提出了一个大的，多中心，随机非劣效性试验的O2 补充剂与室内空气对分娩中II类EFM患者的影响。我们的核心假设是 临床相关的母亲和新生儿结局在两组之间没有显著差异。我们 将追求以下具体目标：1）确定室内空气的效果，与补充O2相比， 对II类EFM患者新生儿发病率的影响; 2）确定室内空气的影响， 与补充O2相比，手术分娩率。共2124例患者将接受随机化 提供足够的把握度来检测上述具有临床意义的非劣效性界值 结果。

Abstract More than 80% of the 3 million women who labor and deliver each year in the United States undergo continuous electronic fetal monitoring (EFM) during labor. The goal of such monitoring is to identify fetal hypoxia and prevent the transition to acidemia, expedited operative delivery, and/or neonatal morbidity. Category II EFM, the most commonly observed group of fetal heart rate features, is associated with variable risks for acidemia. One common response to Category II EFM is maternal oxygen (O2) supplementation. The theoretic rationale for O2 administration is that it increases O2 transfer to a hypoxic fetus, thereby reversing hypoxia and preventing acidemia. This practice is so commonly used that 2 out of 3 patients receive supplemental O2 at some point during labor. However, despite the theoretic rationale, there is no rigorous data to support its widespread use. Our pilot randomized noninferiority trial, published in JAMA Pediatrics, demonstrated that room air was noninferior to O2 for improving umbilical artery lactate, a surrogate marker of fetal acidemia and neonatal morbidity. Our subsequent meta-analysis of randomized trials investigating O2 versus room air at time of cesarean section or vaginal delivery found no differences in umbilical artery pH, rates of acidemia, and neonatal intensive care unit admissions between room air and O2 groups. Importantly, none of the trials studied important clinical measures of neonatal or maternal morbidity and only one trial studied O2 in the setting of Category II EFM. The current state of evidence is limited in several ways. First, the existing studies of O2 in labor vary in the dose, duration, and timing of O2 administration. Second, only one pilot trial investigated the utility of O2 supplementation for the ACOG-recommended indication of Category II EFM. Third, all of the studies have used surrogate measures of neonatal morbidity such as cord gases or neonatal intensive care unit admission. Finally, none of the studies were powered to assess the impact of O2 administration on neonatal clinical sequelae of in utero hypoxia or operative delivery. Without data on these definitive outcomes, evidence-based recommendations for managing Category II EFM cannot be made. To fill this important knowledge gap, we propose a large, multicenter, randomized noninferiority trial of O2 supplementation versus room air in patients with Category II EFM in labor. Our central hypothesis is that clinically relevant maternal and neonatal outcomes will not significantly differ between the two arms. We will pursue the following specific aims: 1) Determine the effect of room air, compared with supplemental O2, on neonatal morbidity among patients with Category II EFM and 2) Determine the effect of room air, compared with supplemental O2, on rates of operative delivery. A total of 2124 patients will be randomized to provide adequate power to detect clinically meaningful noninferiority margins for the above stated outcomes.