Effect of Blood Transfusion Practices on Cerebral and Somatic Oximetry

描述(申请人提供)：早产在美国是一个严重的健康问题，给社会造成了巨大的经济负担，并对幸存者及其家人的生活质量产生了重大影响。出生体重低于1000克的极低出生体重(ELBW)婴儿存活下来，神经发育迟缓的比率很高。在新生儿期，由于频繁采血和骨髓反应不成熟，极低出生体重儿需要输血。输血的理想血红蛋白水平尚不清楚，对于是否以较高的血红蛋白为靶点是否能改善神经发育结果，存在相互矛盾的数据。在缺乏有关风险和收益的令人信服的数据的情况下，做法仍然大相径庭。早产儿输血(TOP)(1U01HL112776-1)目前正在NICHD新生儿研究网络(NRN)的18个临床中心进行，这是一项随机临床试验，旨在确定22至26个月幸存者死亡或严重神经发育障碍(NDI)的主要结局在维持较高血红蛋白水平的早产儿中是否较少见。以下建议是针对Valerie Chock的临床试验辅助研究RFA提出的，Valerie Chock医学博士是一位在早产儿使用近红外光谱(NIRS)方面具有专业知识的早期研究员。NIRS是一种非侵入性床边技术，能够可靠地测量脑组织和肠系膜组织的局部组织氧合。局部组织氧饱和度测定可能比单独使用血红蛋白更好地衡量终末器官氧合，并可提供NDI和坏死性小肠结肠炎(NEC)的生理学数据预测，NEC是可能与ELBW婴儿输血有关的不良后果。这项建议的一个目标是确定在红细胞输注过程中高和低血红蛋白阈值组之间脑氧合和近红外光谱(NIRS)部分组织氧提取(目标1)的差异。我们还建议确定脑NIRS测量异常是否比单独使用血红蛋白更好地预测NDI(目标2)，以及肠系膜NIRS测量异常是否与输血后48小时内NEC的发生有关(目标3)。参加顶级试验的合格婴儿将在生命的头7天和随后的输血期间进行大脑和肠系膜NIRS监测。据估计，样本大小为490名婴儿，纵向分析将确定近红外光谱测量与输血阈值组之间的关联。分类和回归树(CART)分析将确定异常近红外光谱测量对死亡或NDI和输血相关NEC结果的预测能力。通过与顶级私人投资机构的合作以及自然资源中心的参与承诺，这项提议的可行性和成功程度得到了提高。局部组织血氧测定仪的新应用将提供对了解顶级试验结果差异至关重要的生理指标。这项辅助研究将显著提高对早产儿输血的益处和风险的认识，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.