Delayed Cord Clamping with Oxygen In Extremely Low Gestational Age Infants (DOXIE)

极低胎龄婴儿延迟供氧断脐 (DOXIE)

• 批准号: 10373881
• 负责人: Anup C Katheria
• 金额: $ 7.72万
• 依托单位: SHARP MEMORIAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-01-15 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10373881
• 关键词: Advocate; Air; Alveolar; Animals; Birth; Blinded; Blood; Blood flow; Brain; Breathing; Cardiac; Cerebrovascular Circulation; Cerebrum; Cessation of life; Clinical; Closure by clamp; Continuous Positive Airway Pressure; Data; Delivery Rooms; Discipline of obstetrics; Disease; Double-Blind Method; Duct (organ) structure; Echocardiography; Enrollment; Extremely low gestational age newborn; Gases; Gestational Age; Head; Heart Rate; Hemorrhage; Hour; Hypoxemia; Hypoxia; Incidence; Infant; Infant Care; Intervention; Legal patent; Life; Lung; Masks; Measurement; Measures; Meta-Analysis; Methods; Milk; Morbidity - disease rate; Movement; Multicenter Trials; Nature; Near-Infrared Spectroscopy; Neonatal; Newborn Infant; Organ; Outcome; Oxygen; Oxygen Therapy Care; Oxygen saturation measurement; Partial Pressure; Peripheral; Physiological; Pilot Projects; Pregnancy; Premature Infant; Protocols documentation; Randomized; Randomized Controlled Trials; Respiration; Resuscitation; Safety; Stream; Tidal Volume; Time; Trachea; Ultrasonography; Umbilical cord structure; Venous; Video Recording; Work; arm; design; disability; face mask; feasibility testing; glottis; hemodynamics; improved; intraventricular hemorrhage; mortality; organ injury; oxygen toxicity; pilot trial; positive airway pressure; postnatal; pressure; preterm newborn; prevent; respiratory; safety and feasibility; supplemental oxygen; trial comparing; ventilation

Background: Current newborn care practice is to delay clamping and cutting the umbilical cord to allow for hemodynamic stabilization. Supported by numerous randomized controlled trials and meta-analyses, delayed cord clamping (DCC) is endorsed by both neonatal and obstetrical governing bodies. Limited oxygenation data on DCC in extremely preterm infants suggests they remain hypoxic immediately after birth. This may be due to differences in how infants transition during DCC. Immediately after delivery, extremely preterm infants attempt to initiate lung aeration and gas exchange. Animal studies have demonstrated that delaying clamping of the umbilical cord until breathing is established avoids adverse cerebral and cardiac hemodynamics, which may reduce bleeding in the brain, including severe intraventricular hemorrhage (sIVH). In a multicenter trial comparing DCC to umbilical cord milking, 76 percent of preterm newborns between 230-276 weeks gestation who received DCC without respiratory support initiated respirations prior to cord clamping, yet still had relative hypoxia demonstrated by a low 5-minute arterial oxygen saturation (SpO2 73 percent (95% CI 71.4, 75.6)). Two recent analyses found that preterm infants with a 5-minute SpO2 < 80 percent were more likely to have sIVH or death. Supplemental oxygen provided during DCC with resultant lung aeration may decrease significant morbidities and death in extremely preterm infants. A pilot study with detailed assessments of hemodynamics and organ function immediately after birth is needed to determine the efficacy and safety of providing 100 percent oxygen during DCC. Design: This randomized double-blinded pilot trial will enroll 140 extremely low gestational age infants (230- 276 weeks gestation) who receive DCC of at least 60 seconds with carefully detailed hemodynamic assessments and simultaneous video recordings. The study will evaluate infants providing continuous positive airway pressure (CPAP) and/or positive pressure ventilation (PPV) by face mask with an inspired fractional oxygen (FiO2) of 1.0 (HI Group) during DCC compared to infants given mask CPAP/PPV with an inspired FiO2 of 0.30 during DCC (LO Group). Due to the nature of the intervention, both arms receive CPAP/PPV with identical cord clamping times and respiratory support, the study can be blinded by covering the oxygen blender, avoiding any postnatal treatment bias. Once the cord is clamped and cut, each infant is resuscitated as per usual protocol (CPAP/PPV with a starting FiO2 0.30) by the clinical team. We will collect physiological parameters from birth through the first 24 hours of life (including detailed breathing assessments from video recordings at birth/ resuscitation suite). If we reduce hypoxia in extremely preterm infants by providing supplemental oxygen during the period of delayed cord clamping, there may be a dramatic reduction in morbidity and mortality. Depending on the findings, results will be used to design a more definitive larger, multicenter R01 trial powered for important clinical outcomes such as severe IVH or death and neurodevelopmental outcomes.

背景：目前的新生儿护理做法是延迟夹住和切断脐带，以允许 血流动力学稳定。由大量随机对照试验和荟萃分析支持，延迟 脐带夹闭(DCC)得到了新生儿和产科管理机构的认可。极限氧合数据 极早产儿的DCC显示他们出生后立即处于低氧状态。这可能是由于 婴儿在DCC期间如何转变的差异。分娩后立即，极早产儿试图 以启动肺充气和气体交换。动物研究表明，延迟夹住 脐带直到呼吸建立，可以避免不利的脑和心脏血流动力学，这可能 减少脑出血，包括严重脑室出血(SIVH)。在一项多中心试验中比较 DCC到脐带挤奶，76%的早产儿在230-276周之间接受了 无呼吸支持的DCC在夹住脐带前开始呼吸，但仍有相对低氧 表现为低5分钟动脉血氧饱和度(SpO2 73%(95%CI 71.4，75.6))。最近的两个 分析发现，呼吸暂停5分钟的早产儿80%更有可能出现SIVH或 死亡。在DCC期间提供的补充氧气和由此产生的肺曝气可能会显著减少 极早产儿的发病率和死亡率。一项具有详细血流动力学评估的先导性研究 并需要在出生后立即进行器官功能检查，以确定100%提供 DCC过程中的氧气。 设计：这项随机、双盲的先导试验将招募140名极低胎龄儿(230- 妊娠276周)，接受至少60秒的DCC，并仔细进行详细的血流动力学评估 和同步录像。这项研究将评估提供持续气道正压的婴儿 (CPAP)和/或正压通风(PPV)，面罩吸入氧分压(FiO2)为1.0 (HI组)DCC期间与接受面罩CPAP/PPV的婴儿进行比较，DCC期间吸入氧饱和度为0.30 (LO集团)。由于干预的性质，两个手臂接受CPAP/PPV时使用相同的脐带夹闭 次数和呼吸支持，这项研究可以通过盖住氧气混合器来盲目，避免任何出生后 治疗偏向。一旦脐带被夹住并切断，每个婴儿都会按照通常的方案(CPAP/PPV)进行复苏 临床团队的起始血氧饱和度为0.30)。我们将收集从出生到第一次分娩的生理参数 24小时的生命(包括从出生/复苏套间的录像中进行详细的呼吸评估)。如果 我们通过在延迟期提供补充氧气来减少极早产儿的缺氧 如果夹住脐带，发病率和死亡率可能会显著降低。根据调查结果，结果 将用于设计更明确的更大规模的多中心R01试验，以获得重要的临床结果，如 作为严重的IVH或死亡和神经发育结果。