Effect of Blood Transfusion Practices on Cerebral and Somatic Oximetry

描述（由申请人提供）：早产在美国是一个严重的健康问题，给社会造成巨大的经济负担，并对幸存者及其家庭的生活质量产生重大影响。出生时体重低于1000克的极低出生体重（ELBW）婴儿的存活率很高，神经发育迟缓。在新生儿期，ELBW婴儿由于频繁的血液采样和不成熟的骨髓反应而需要输血。输血的理想血红蛋白水平尚不清楚，关于是否以更高的血红蛋白为目标改善神经发育结果，存在相互矛盾的数据。由于缺乏关于风险和效益的令人信服的数据，各种做法仍然大相径庭。早产儿输血（TOP）（1U 01 HL 112776 -1），目前正在NICHD的新生儿研究网络（NRN）的18个临床中心进行，是一项随机临床试验，旨在确定在22至26个月的存活者中死亡或显著神经发育障碍（NDI）的主要结局在维持较高血红蛋白水平的早产儿中是否不太常见。以下提案是为了回应Valerie Chock（医学博士和医学硕士）的临床试验RFA辅助研究而提交的，Valerie Chock是一位在早产儿中使用近红外光谱（NIRS）方面具有专业知识的早期研究者。NIRS是一种无创床边技术，能够可靠地测量大脑和肠系膜组织的局部组织氧合。局部组织血氧测定可能是比单独血红蛋白更好的终末器官氧合指标，并可提供预测NDI以及坏死性小肠结肠炎（NEC）的生理数据，这是一种可能与ELBW婴儿输血相关的不良结局。本提案的一个目的是确定红细胞输注期间高血红蛋白阈值组和低血红蛋白阈值组之间的脑氧合和NIRS组织氧提取分数（目的1）的差异。我们还建议确定异常的脑NIRS测量是否是比单独的血红蛋白更好的NDI预测因子（目的2），以及异常的肠系膜NIRS测量是否与输血后48小时内NEC的发展相关（目的3）。入组TOP试验的合格婴儿将在出生后前7天和随后的输血期间进行脑和肠系膜NIRS监测。估计样本量为490名婴儿，纵向分析将确定NIRS指标与输血阈值组之间的关联。分类和回归树（CART）分析将确定异常NIRS指标对死亡或NDI结局以及输血相关NEC结局的预测能力。通过与TOP PI的合作以及NRN中心参与的承诺，该提案的可行性和成功性得到了加强。局部组织血氧测定的新用途将为了解TOP试验中的结局差异提供关键的生理指标。这项辅助研究将显著提高对早产儿输血益处和风险的认识，从而优化输血实践。

DESCRIPTION (provided by applicant): Preterm birth is a significant health problem in the U.S. resulting in a large economic burden to society and a major impact on quality of life for survivors and their families. Surviving extremely low birth weight (ELBW) infants born at less than 1000 grams have a high rate of neurodevelopmental delay. During the neonatal period, ELBW infants require blood transfusions due to frequent blood sampling and an immature bone marrow response. The ideal hemoglobin level at which to transfuse is not known and there are conflicting data as to whether targeting a higher hemoglobin improves neurodevelopmental outcome. Practices remain widely divergent in the absence of compelling data regarding risks and benefits. Transfusion of Prematures (TOP) (1U01HL112776-1), currently underway at the 18 clinical centers of NICHD's Neonatal Research Network (NRN), is a randomized clinical trial designed to determine whether the primary outcome of death or significant neurodevelopmental impairment (NDI) in survivors at 22 to 26 months is less common among preterm infants maintained at a higher hemoglobin level. The following proposal is submitted in response to the Ancillary Studies in Clinical Trials RFA by Valerie Chock, MD MS, an early stage investigator with expertise in the use of near infrared spectroscopy (NIRS) in preterm infants. NIRS is a non-invasive bedside technology able to reliably measure regional tissue oxygenation of both cerebral and mesenteric tissues. Regional tissue oximetry may be a better measure of end-organ oxygenation than hemoglobin alone and may provide physiologic data predictive of NDI as well as necrotizing enterocolitis (NEC), an adverse outcome potentially related to transfusion in ELBW infants. One objective of this proposal is to determine differences in cerebral oxygenation and fractional tissue oxygen extraction with NIRS (Aim 1) between high and low hemoglobin threshold groups during red blood cell transfusions. We also propose to determine whether abnormal cerebral NIRS measures are a better predictor of NDI than hemoglobin alone (Aim 2) and whether abnormal mesenteric NIRS measures are associated with the development of NEC within the 48 hours following a transfusion (Aim 3). Eligible infants enrolled in the TOP trial will have cerebral and mesenteric NIRS monitoring during the first 7 days of life and during subsequent transfusions. With an estimated sample size of 490 infants, longitudinal analyses will determine the association between NIRS measures and transfusion threshold group. Classification and Regression Tree (CART) analyses will determine the predictive capability of abnormal NIRS measures for the outcome of death or NDI and the outcome of transfusion-associated NEC. The feasibility and success of this proposal is enhanced by collaboration with the TOP PIs and commitment by NRN centers to participate. The novel use of regional tissue oximetry will provide physiologic measures critical to understanding outcome differences in the TOP trial. This ancillary study will significantly improve knowledge of the benefits and risks of transfusions in the preterm neonate, resulting in optimized transfusion practices.