PHYSIOLOGICAL DISTURBANCES ASSOCIATED WITH NEONATAL INTRAVENTRICULAR HEMORRHAGE

该子项目是利用 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。列出的机构是 中心，不一定是研究者的机构。 在美国，每年约有5，000名极低出生体重（ELBW，出生体重d1000 g; d2 lbs，3盎司）婴儿发生严重脑室内出血（IVH），与智力迟钝、脑瘫和学习障碍相关。由于这些婴儿的终身护理费用超过30亿美元，ELBW婴儿的IVH是一个主要的公共卫生问题。不幸的是，在过去的十年中，ELBW婴儿中严重IVH的发生率保持不变，并且很难准确识别处于发展IVH的最高风险的ELBW婴儿。因此，我们以患者为导向的临床研究的长期目标是确定与IVH相关的干扰生理现象的影响，以预测那些风险最大的婴儿，并制定可能限制严重脑损伤的最佳护理临床实践。我们假设，减少二氧化碳、血压和心率的变化和极端，这些影响ELBW婴儿脑血流量和脑自动调节的因素，可能会减轻IVH的发展，并作为ELBW婴儿最有IVH发展风险的重要预测因素。这将通过一系列临床研究进行调查，这些研究将解决：1）正常碳酸通气与传统高碳酸通气相比是否会通过将IVH的发生率降低至较低级别或无IVH来减少重度IVH的发生（随机对照试验），2）当血压正常化时，膨胀的ELBW婴儿是否恢复了完整的脑自动调节或持续的压力被动脑血流，以及使用我们新的连续生理监测系统，出生后发育的脑自动调节模式在发育迟缓的婴儿中是如何改变的，以及3）改变的分形心律动力学是否可以作为即将发生IVH的准确预测因子。我们将使用我们在K23研究中开发的连续生理监测系统来确定低血压治疗期间的脑自动调节能力以及出生后第一周内脑自动调节的发育模式。将测定出生后第一天的心律动力学，并评价其作为即将发生IVH的预测因子的价值。如果成功，我们提出的临床研究将通过开发更好的护理临床实践和提供即将发生IVH的新的准确预测因子来减少新生儿ELBW婴儿神经系统疾病的负担，从而可以识别高危婴儿并进行干预以限制IVH的发展。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Almost 5,000 extremely low birth weight (ELBW, birth weight d1000 g; d2 lbs, 3 ounces) infants per year in the US develop severe intraventricular hemorrhage (IVH) that is associated with mental retardation, cerebral palsy, and learning disabilities. As lifetime care costs in these infants exceed $3 billion, IVH in ELBW infants is a major public health problem. Unfortunately, the incidence of severe IVH in ELBW infants has remained constant over the last decade, and accurately identifying the ELBW infants at highest risk of developing IVH has been difficult. Therefore, the long-term goal of our patient-oriented clinical research is to determine the effects of disturbed physiological phenomena associated with IVH in order to predict those infants most at risk and to develop best care clinical practices that may limit severe brain injury. We hypothesize that reducing alterations and extremes of carbon dioxide, blood pressure, and heart rate, factors that influence cerebral blood flow and cerebral autoregulation in ELBW infants, may mitigate the development of IVH and serve as important predictors of ELBW infants most at risk of developing IVH. This will be investigated through a series of clinical studies that will address: 1) whether normocapnic ventilation vs. traditional hypercapnic ventilation will reduce the develop of severe IVH by shifting the incidence to lower grade or no IVH (randomized controlled trial), 2) whether hypotensive ELBW infants have restored intact cerebral autoregulation or continued pressure-passive cerebral blood flow when blood pressure is normalized, and how the postnatal pattern of development of cerebral autoregulation is altered in hypotensive infants, using our novel continuous physiological monitoring system, and 3) whether altered fractal heart rhythm dynamics will serve as an accurate predictor of impending IVH. We will use our continuous physiological monitoring system developed during our K23 studies to determine cerebral autoregulatory capacity during treatment of hypotension and the developmental pattern of cerebral autoregulation during the first week of life. Heart rhythm dynamics on the first day of life will be determined and its value at a predictor of impending IVH will be evaluated. If successful, our proposed clinical studies will reduce the burden of neurological disease in newborn ELBW infants by developing better care clinical practices and by providing a new accurate predictor of impending IVH, so that high risk infants may be identified and interventions applied to limit the development of IVH.