Premature Infants Receiving Cord Milking Or Delayed Cord Clamping

接受脐带挤奶或延迟断脐的早产儿

• 批准号: 9914830
• 负责人: Anup C Katheria
• 金额: $ 57.25万
• 依托单位: SHARP MEMORIAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9914830
• 关键词: Age; American College of Obstetricians and Gynecologists; Area; Autologous Blood Transfusion; Bilirubin; Birth; Blood; Blood Transfusion; Blood Volume; Blood flow; Brain; Budgets; Cardiac; Cesarean section; Cessation of life; Closure by clamp; Critical Illness; Data; Guidelines; Hemorrhage; Hospitalization; Hour; Human; Hypotension; Incidence; Infant; International; Intervention; Life; Meta-Analysis; Methods; Milk; Morbidity - disease rate; Neonatal; Neurodevelopmental Impairment; Newborn Infant; Operative Surgical Procedures; Organ; Outcome; Perfusion; Phase; Physiological; Placenta; Polycythemia; Premature Infant; Preterm brain injury; Public Health; Randomized; Reporting; Research; Resuscitation; Risk; Safety; Sample Size; Sampling; Solid; Techniques; Testing; Time; Transfusion; Translating; Umbilical cord structure; Vaginal delivery procedure; blood perfusion; cerebral hemodynamics; cerebral oxygenation; cost; design; expectation; follow-up; grasp; improved; intraventricular hemorrhage; neonatal outcome; optimal treatments; pilot trial; preterm newborn; side effect; trial comparing; trial design

BACKGROUND: Preterm brain injury from intraventricular hemorrhage (IVH) is a pressing worldwide public health problem. Over 12,000 premature newborns develop IVH every year in the US alone. Delaying clamping the umbilical cord at birth for 30-60 seconds provides the newborn with a significant autologous transfusion of blood from the placenta and has been shown to reduce IVH. Delayed cord clamping (DCC) has been shown to reduce overall IVH (mainly lower grades 1 and 2) by 50 percent, but has not reduced the incidence of severe IVH or death. This may reflect inadequate placental transfusion for newborns delivered by Cesarean section (C/S), the most common mode of delivery for very preterm infants. In 3 DCC trials an increased placental transfusion was evident in infants born by vaginal delivery (V/D), but no or minimal transfusion in infants delivered by C/S. We evaluated a technique – umbilical cord milking (UCM) – which provides a placental transfusion by grasping the unclamped umbilical cord and pushing blood towards the newborn several times before the cord is clamped. Our Phase 1 pilot trial (PREMOD) compared UCM to DCC in premature newborns delivered by C/S and V/D. Results were equivalent for V/D. UCM improved blood flow and organ perfusion in C/S infants. SPECIFIC AIMS: The specific aims of this trial are: Aim 1. To compare the incidence of severe IVH and/or death in premature newborns <32 weeks GA delivered by C/S receiving UCM to those receiving DCC. Aim 2. To compare the safety and efficacy profiles of premature newborns <32 weeks GA delivered by C/S receiving UCM vs. DCC during their hospitalization and at 24 months corrected age. Aim 3. To compare the outcomes of premature newborns <32 weeks GA delivered by C/S (from Aims 1 and 2) with those born by V/D receiving UCM or DCC. DESIGN: This trial has a 2-tiered approach that will first demonstrate that the incidence of severe IVH and/or death in premature newborns <32 weeks delivered by C/S with UCM is equivalent to DCC (non-inferiority), and then test whether there is a decreased incidence of severe IVH and/or death with UCM (superiority). This approach is being used in other neonatal trials, is endorsed by the FDA, and can be done within the scope and sample of the proposed trial. DCC: The obstetrician will wait at least 60 seconds to clamp the cord. UCM: The obstetrician will milk about 20 cm of umbilical cord four times over 2 seconds each. Brain oxygenation will be recorded for the first 72 hours of life. Outcomes will include resuscitation interventions and neurodevelopmental follow-up at 2 years. UCM is simple and allows resuscitation of the most critical infants without delay, which justifies its use, even if UCM is equivalent to DCC. Optimal umbilical cord management in premature newborns is an area that urgently needs scientific evidence to establish clear guidelines worldwide.

背景：脑室内出血（IVH）引起的早产脑损伤是全球公众关注的一个紧迫问题 仅在美国，每年就有超过 12,000 名早产儿患上 IVH。 出生时脐带留存 30-60 秒为新生儿提供大量自体输血 延迟脐带结扎 (DCC) 已被证明可以减少胎盘血液。 将总体 IVH（主要是较低的 1 级和 2 级）降低 50%，但并未降低严重的发生率 脑内出血或死亡可能反映出剖腹产新生儿的胎盘输血不足。 (C/S)，这是极早产儿最常见的分娩方式。在 3 项 DCC 试验中，胎盘增多。 阴道分娩（V/D）的婴儿有明显的输血，但分娩的婴儿没有或很少有输血 我们评估了一种技术——脐带挤奶（UCM）——它通过以下方式提供胎盘输血： 在脐带被松开之前，多次抓住松开的脐带并将血液推向新生儿。 我们的 1 期试点试验 (PREMOD) 在 C/S 分娩的早产儿中比较了 UCM 和 DCC。 V/D 的结果与 V/D 改善 C/S 婴儿的血流量和器官灌注相同。 具体目标：本试验的具体目标是： 目标 1. 比较 GA 分娩 32 周以下的早产儿严重 IVH 和/或死亡的发生率 由接收 UCM 的 C/S 到接收 DCC 的 C/S。 目标 2. 比较 C/S 分娩 <32 周 GA 早产儿的安全性和有效性 住院期间和 24 个月校正年龄时接受 UCM 与 DCC 比较。 目标 3. 比较 C/S 分娩的 GA 32 周以下早产儿的结局（来自目标 1 和 2） 那些由 V/D 出生的人接受 UCM 或 DCC。 设计：本试验采用 2 层方法，首先证明严重 IVH 和/或 采用 UCM 的 C/S 分娩的 <32 周早产儿的死亡相当于 DCC（非劣效性），并且 然后测试 UCM 是否会降低严重 IVH 和/或死亡的发生率（优越性）。 该方法正在其他新生儿试验中使用，得到 FDA 的认可，并且可以在以下范围内进行： DCC 提议的试验样本：产科医生将等待至少 60 秒来夹紧脐带。 产科医生将挤奶约 20 厘米的脐带四次，每次持续 2 秒。 记录生命最初 72 小时的结果将包括复苏干预和神经发育。 2 年随访很简单，可以立即对最危重的婴儿进行复苏。 即使 UCM 相当于早产儿的最佳脐带管理，也证明了其使用的合理性。 这是一个迫切需要科学证据来在全世界范围内建立明确指导方针的领域。