Longitudinal Assessment of Cerebrovascular Autoregulation (CA) and Associations to Neurodevelopmental Delays in Infants and Toddlers with and without Congenital Heart Disease (CHD)

意义先天性心脏病(CHD)是美国主要的出生缺陷之一，影响 每年约有40,000名新生儿。1，2尽管努力预防和及早发现贫穷 神经发育结局(NDO)，许多CHD儿童的神经功能缺陷将持续到 4、5手术因素只能解释20%的不良核素，6、7导致因素检查 冠心病的内在原因是导致不良结局的原因。一个没有得到广泛检验的假设是， 脑血管自身调节(CA)与先天性心脏病婴儿较差的神经营养不良有关。 目标我的总体目标是成为一名独立的学术调查员，制定战略和干预措施，以 减少或防止易受伤害的儿科人群，例如患有冠心病的人群的发育迟缓，从而 提高他们的生活质量。这一目标与美国国家护理研究所的“症状”一致 科学“战略计划，因为它寻求理解发展的机制路径 先天性心脏病儿童的延迟。我的职业发展计划是：提高我对心血管和 CHD和健康婴儿的脑生理学；学习如何利用平均动脉血的相关性来分析CA 压力与近红外光谱测量；熟悉复杂的统计分析， 多层次、依赖时间的模式；提高赠款和手稿写作技能。位于的环境 洛杉矶儿童医院和南加州大学得到了支持和基础设施 完成我的培训和项目所必需的。K23的指导和培训计划将帮助我发现 损伤的机制，并可能导致改善CA的治疗，这将防止或减弱 高危儿童的发育迟缓。这项研究旨在评估患有和不患有CA的婴儿和幼儿的CA CHD，并评估出生时、6个月、9个月和18个月龄时间点CA与NDO的相关性。目标1： 通过4个发育时间点比较CHD患儿与健康对照儿童CA的差异。目标2：评估 冠心病儿CA与NDOS的相关性以及CA与NDOS的相关性是否在不同的婴儿中有所不同 诊断组(冠心病组与对照组)。方法本研究采用前瞻性、纵向、2组队列设计。 我们将招募出生时[±2周]的婴儿(32名冠心病患者和32名年龄和性别匹配的健康对照组)。 在18个月的随访中，约20%的自然减员后有完整数据的50人)。CA将使用姿势进行测量- 引起脑氧合的变化。将使用适合年龄的标准工具来衡量NDO，例如 贝利婴幼儿发展量表IV.如果本研究的假设得到支持， CA受损将被证明是冠心病较差的NDO的重要决定因素，它们将成为新的 未来预防性干预的目标，以改善这些高危儿童的发展结果。两者都有 对冠脉受损的高危CHD婴儿和早期干预时间点的了解将会提高 在这一脆弱的人群中终生不能幸免。

Significance Congenital heart disease (CHD) is one of the leading birth defects in the United States, affecting approximately 40,000 newborns annually.1,2 Despite efforts aimed at prevention and early detection of poor neurodevelopmental outcomes (NDO), many children with CHD will have neurologic deficits lasting into adulthood.4,5 Surgical factors explain only 20% of these poor NDOs,6,7 leading to the examination of factors intrinsic to CHD as the cause for poor outcomes. A hypothesis not extensively examined is whether impaired cerebrovascular autoregulation (CA) is responsible for poorer NDOs in infants with CHD.8 Career Development Goals My overall goal is to be an independent academic investigator creating strategies and interventions to reduce or prevent developmental delays in vulnerable pediatric populations, such as those with CHD, thereby improving their quality of life. This goal aligns with the National Institute of Nursing Research’s “Symptoms Science” strategic plan because it seeks to understand the mechanistic pathways underlying developmental delay in children with CHD. My career development plan is to: improve my knowledge of cardiovascular and brain physiology in CHD and healthy infants; learn how to analyze CA using correlations of mean arterial blood pressures with Near-Infrared Spectroscopy measures; acquire familiarity of statistical analyses of complex, multilevel, time-dependent models; and enhance grant and manuscript writing skills. The environment at Children’s Hospital Los Angeles and the University of Southern California have the support and infrastructure necessary to complete my training and project. The mentoring and training plan of the K23 will help me discover the mechanism of injury and may lead to treatments that improve CA, which will prevent or attenuate developmental delays in high-risk children. Study Aims To assess CA in infants and toddlers with and without CHD, and to evaluate the association of CA with NDOs at birth, 6, 9, and 18-months of age time points. Aim #1: Compare CA between CHD infants and healthy controls through 4 developmental time points. Aim #2: Assess the association of CA with NDOs in CHD infants and whether the association of CA with NDOs varies across diagnostic groups (CHD vs controls). Methods This study is a prospective, longitudinal, 2-group cohort design. We will enroll 64 infants at birth [± 2 weeks] (32 with CHD and 32 age- and sex-matched healthy controls to yield 50 with complete data after ~20% attrition over the 18-month follow-up). CA will be measured using posture- induced changes in brain oxygenation. NDOs will be measured using standard age-appropriate tools, e.g., the Bayley Scales of Infant and Toddler Development IV. Impact If the hypotheses of this study are supported, impaired CA will be shown to be important determinants of poorer NDOs in CHD, and they will serve as new targets for future preventive interventions to improve developmental outcomes in these high-risk children. Both the knowledge of CHD infants at higher-risk for impaired CA and the early time points to intervene, will improve lifelong NDOs in this vulnerable population.