Perinatal Assessment of At-Risk Populations

我们项目的总体目标与我们最初的应用程序保持不变：开展一项研究计划，以开发基于已知生理机制的非侵入性评估工具，用于有SID和其他发育障碍风险的婴儿。为了继续这一使命，我们扩大了我们的方法和我们的多学科围产期研究团队，以便在胎儿和婴儿的生活中尽早开发新的风险指数。在接下来的几年里，我们将在北部平原地区每年评估大约80名婴儿，在纽约市每年评估100名受试者，从胎儿晚期到新生儿早期。在这些研究中，我们建议纳入更直接的睡眠期间中枢神经系统成熟的测量，以及在健康和高危人群中对胎儿和婴儿自主神经系统调节的更复杂的分析。 我们的生理学研究重点是测试健康的足月儿和高危早产儿，以应对与睡眠状态变化、俯卧与仰卧睡姿和立位倾斜相关的生理挑战。这些研究是在小岛屿发展中国家最脆弱的年龄段之前和期间进行的。除了我们现有的呼吸、心率、血压、运动、脑电和温度测量组件外，我们还建议采用新的最先进的静脉回流和组织灌注测量方法，因为我们相信这些参数将提供关于驱动对倾斜和睡眠位置变化的反应的生理力的更直接信息。 此外，我们将扩大胎儿心电监测的使用范围，以更全面地评估晚期胎儿的自主神经和心脏功能。具体地说，我们将使用Monica腹式胎心电信号设备研究母婴心电相互作用、子宫活动对胎儿心率的影响、胎儿心律失常的发生率和变异、胎儿运动和心率耦合、心率变异性和胎儿心率对声音的反应模式。这项新技术还将允许访问围产期自主神经功能的时域和频域标记物，以前只有婴儿才能访问。 我们还建议增加我们的自主挑战，包括对唤醒和学习的调查 我们已经发现了一个重要的皮质成分来倾斜，皮质力量和同步性与受孕后年龄和后来的结果有很强的关系。我们还开发了分析性的嘟嘟声，可以量化觉醒，即大脑皮质的激活，对感觉刺激的反应，以及在睡眠中学习的时候。我们建议扩大我们对健康早产儿和高危早产儿在出院前和一个月大时睡眠中反应和学习的皮质和小脑标志物的研究。我们预测，在早产儿和来自北部平原的高危样本中，皮质同步性的改变模式将与不利的产前暴露相关。在这些人群中，我们将继续测量局部和远端相干性，以及高频频谱功率，我们已经证明这些参数在倾斜过程中会发生变化，并且会受到睡眠姿势的影响。额外的脑电测量将对不良暴露后的个人生理轨迹提供更全面的估计。 与我们最初的提议一致，我们将出口哥伦比亚实验室开发的新的全面评估技术，以评估脆弱人口(北部平原的土著阿曼坎人)。这项工作过去几年是在南达科他州的松岭印第安人保护区进行的，由于我们上次申请的预算削减，这项工作被削减了。然而，我们现在计划将我们的努力与另一项由南达科他州拉皮特城的PASS网络进行的NICHD/NIAAA研究相结合：在这些研究中，我们将测量一个月大婴儿在俯卧和仰卧位睡眠以及应对倾斜挑战时的脑电和自主神经活动作为产前风险因素的函数。 综上所述，我们的主要假设集中在测试已知的SID风险因素(早产、睡眠姿势、产前暴露)如何改变胎儿和婴儿的生理功能。我们的长期目标是阐明SID背后的生理机制，并开发适合年龄的非侵入性检测方法，以确定哪些婴儿面临最大的风险。这些主要假设和目标仍与我们最初的申请中所述相同。

The overall goals of our project remain unchanged from our original application: to carry out a program of research to develop non-invasive assessment tools, grounded in known physiological mechanisms, in infants at risk for SIDS and other developmental disorders. To continue this mission we have expanded our approach and our multidisciplinary team of perinatal researchers in order to develop new risk indices as early as possible in the life of the fetus and young infant. Over the next Ave years we will be assessing approximately 80 infants/year In the Northern Plains and 100 subjects/year in NYC from the late fetal through the early newborn period. In these studies we propose to incorporate more direct measures of CNS maturation during sleep, as well as more sophisticated analyses of autonomic nervous system regulation in both the fetus and infant in healthy and at-risk populations. Our physiological studies focus on testing both healthy term and at-risk, prematurely born infants in response to physiological challenges associated with changes in sleep state, prone vs supine sleep positions, and orthostatic tilt. These studies are conducted prior to and during the age range of greatest vulnerability for SIDS. In addition to our battery of existing measurements of respiration, heart rate, blood pressure, movement, EEG and temperature, we propose to incorporate new state of the art measures of venous return and tissue perfusion, as we believe these parameters will provide more direct information about the physiological forces that drive responses to alterations in tilt and sleep position. In addition, we will expand our use of fetal ECG monitoring to more comprehensively assess autonomic and cardiac function in the late term fetus. Specifically, with the Monica abdominal fECG device we will investigate maternal/fetal ECG interactions, the effect of uterine activity on fetal heart rate, incidence and variation in fetal arrhythmias, fetal movement and heart rate coupling, patterns of heart rate variability and fetal heart rate response to sound. This new technology will also allow access to-markers of perinatal autonomic function in both time and frequency domains, previously only accessible in the infant. We also propose to augment our autonomic challenges to include investigation of arousal and learning We have found an important cortical component to tilt and a strong relationship of cortical power and synchrony with postconceptional age and later outcome. We have also developed analytic toots that can quantify arousal, i.e., cortical activation, in response to sensory stimulation and while learning during Sleep. We propose to extend our investigations of cortical and cerebellar markers of reactivity and learning during sleep in both healthy and high risk premature infants prior to discharge from the hospital and at one month of age. We predict that altered patterns of electrocortical synchrony will be associated with adverse prenatal exposures, both in premature infants and in the high risk sample from the Northern Plains. In these populations we will continue to measure local and distal coherence, as well as high frequency spectral power, parameters we have shown to be altered during tilts and which are affected by sleep positions. The additional EEG measures will provide more comprehensive estimates of individual physiological trajectories following adverse exposures. Consistent with our initial proposal we will export new comprehensive assessment techniques developed in our Columbia laboratories to assess a vulnerable population (Native Amencans in the Northern Plains). This work, which in past years was conducted on the Pine Ridge Indian Reservation in South Dakota, was curtailed due to budget cuts in our last application. However, we now plan to merge our efforts with those of another NICHD/NIAAA study being conducted by the PASS network in Rapid City, S.D: In these studies, we will measure EEG and autonomic activity as a function of prenatal risk factors In one month old Infants during sleep in both prone and supine positions and in response to a tilt challenge. In summary, our primary hypotheses focus on testing how known risk factors for SIDS premature birth, sleep position, prenatal exposures) alter physiological function in the fetus and infant Our long-term objectives are to elucidate physiologic mechanisms that underlie SIDS and to develop, age-appropriate, non-invasive tests that will identify infants who are at the greatest risk. These primary hypotheses and goals remain as stated in our original application.