Impact of Congenital Heart Disease Surgery on Neurodevelopment and Behavior in Children with Down Syndrome - Admin Supp

先天性心脏病手术对唐氏综合症儿童神经发育和行为的影响 - Admin Supp

• 批准号: 10409121
• 负责人: Nicole Baumer
• 金额: $ 30.82万
• 依托单位: NEW ENGLAND RESEARCH INSTITUTES, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-07-01 至 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10409121
• 关键词: 5 year old; Adaptive Behaviors; Address; Affect; Age; Attention; Behavior; Behavioral; Biocompatible Materials; Cardiac Surgery procedures; Child; Child Behavior Checklist; Childhood; Collection; Communities; Counseling; Data; Development; Down Syndrome; Emotional; Enrollment; Equation; Equipment and supply inventories; Funding; Future; General Population; Genetic; Genetic Determinism; Goals; Heart; Individual; Infant; Intervention; Knowledge; Language; Learning; Lesion; Life; Measures; Mediation; Modeling; Molecular Genetics; National Heart, Lung, and Blood Institute; Nursery Schools; Operative Surgical Procedures; Outcome; Parents; Patients; Perioperative; Phenotype; Play; Population; Postoperative Period; Prospective Studies; Research; Residual state; Risk Factors; Role; Sampling; Sampling Studies; Site; Structure; Vulnerable Populations; atrioventricular septal defect; behavioral outcome; biobank; clinical research site; cohort; comparison group; congenital heart disorder; design; executive function; follow-up; infancy; molecular marker; neurodevelopment; perioperative morbidity; perioperative mortality; prenatal; primary outcome; prospective; repaired; secondary outcome; study population; virtual

PROJECT SUMMARY/ABSTRACT Congenital heart disease (CHD) affects 40-50% of individuals with Down syndrome (DS), most commonly complete atrioventricular septal defect (CAVSD). Although the impact of perioperative risk factors during infant heart surgery are well studied in the general population, DS patients have been excluded from virtually all prospective studies on determinants of neurodevelopmental (ND) outcomes after infant heart surgery. Our overarching goal is to analyze the impact of CHD repaired in infancy on overall ND and behavioral outcomes in the DS population. Our proposed study is ancillary to the NHLBI-funded, prospective, Pediatric Heart Network (PHN) Residual Lesion Score (RLS) Study, which enrolled 207 DS patients with CAVSD. The parent RLS Study is evaluating the effect of technical adequacy of repair after infant heart surgery on early and mid-term outcomes, including perioperative morbidity and mortality, with follow-up through 12 months. Here, we will investigate determinants of ND and behavioral outcomes at 3-5 years of age in the RLS Study sample with DS who had CAVSD repair in the first year of life compared to an age-matched sample with DS without CHD from the same PHN sites. In Aim 1 (primary), we will compare ND and behavioral outcomes between children with DS who had CAVSD repair and children from the same clinical sites with DS without CHD. Primary outcomes will be (i) verbal and non-verbal ratio IQs derived from the Mullen Scales of Early Learning and (ii) adaptive composite scores from the Vineland Adaptive Behavior Scales-3rd edition, and secondary outcomes will be (i) language scores derived from the Preschool Language Scales-5th edition, (ii) emotional and behavioral functioning scores on the Childhood Behavior Checklist, and (iii) attention and executive functioning scores on the Behavior Rating Inventory of Executive Functioning, Preschool Version. In Aim 2, we will investigate predictors of ND and behavior as measured in Aim 1 in children with DS with CAVSD repair and those without CHD, utilizing structural equation modeling to explore relationships and possible mediation among predictor variables. In Aim 3, we will establish a collection of biological material for future studies exploring genetic factors contributing to the wide spectrum of ND abilities seen in DS. We will incorporate a parent advisory group for research questions, design of study materials, and dissemination to the DS community. In addition to creating a large cohort of children with DS and CAVSD repair and an age-matched comparison group, this study addresses an important knowledge gap about whether CHD requiring infant heart surgery plays an important role in ND and behavioral outcomes in children with DS. If so, targeted interventions beginning in the early postoperative period could be designed for this vulnerable population. Positive or negative, this study will provide invaluable data for prenatal counseling on the impact of CAVSD on later ND. Finally, the biorepository will leverage the exquisite ND phenotyping of our study population by making samples available for future studies to identify molecular markers and genetic determinants of ND and behavior in children with DS.

项目摘要/摘要 先天性心脏病（CHD）影响40-50％的唐氏综合症患者（DS），最常见 完成室内间隔缺陷（CAVSD）。虽然围手术期风险因素在婴儿中的影响 心脏手术在一般人群中进行了很好的研究，DS患者几乎被排除在外 婴儿心脏手术后神经发育（ND）结局的决定因素的前瞻性研究。我们的 总体目标是分析冠心病期维修对整体ND和行为结果的影响 DS人口。我们拟议的研究是NHLBI资助的，前瞻性，小儿心脏网络的辅助 （PHN）残留病变评分（RLS）研究，该研究招募了207例CAVSD患者。父rls 研究正在评估婴儿心脏手术后修复技术充足性对早期和中期的影响 结局，包括围手术期的发病率和死亡率，并进行了12个月的随访。在这里，我们会的 在RLS研究样本中，研究ND和行为结果的决定因素和行为结果 与没有CHD的年龄匹配的样本相比，他在生命的第一年进行了CAVSD维修 相同的PHN站点。在AIM 1（主要）中，我们将比较ND和儿童之间的行为结果 具有CAVSD修复的DS和来自无冠心病的DS的同一临床部位的儿童。主要结果 将是（i）从早期学习和（ii）自适应的言语和非语言比率智商 Vineland自适应行为量表-3rd Edition的综合分数和次要结果将是（i） 语言得分从幼儿园语言量表-5版，（ii）情感和行为 儿童行为清单上的功能分数，以及（iii）注意力和执行功能分数 执行功能的行为评级清单，学前班版本。在AIM 2中，我们将调查 在具有CAVSD修复的DS儿童中，在AIM 1中测量的ND和行为的预测因素和行为的预测因素，而没有 CHD，利用结构方程建模来探索预测指标之间的关系和可能的调解 变量。在AIM 3中，我们将建立一系列生物学材料，用于探索遗传的未来研究 有助于DS中看到的ND能力广泛的因素。我们将合并父母咨询 研究材料的研究问题，设计材料的设计以及向DS社区传播。此外 创建一大批具有DS和CAVSD维修的儿童，以及一个年龄匹配的比较组， 研究解决了关于需要婴儿心脏手术是否发挥的重要知识差距 DS儿童在ND和行为结果中的重要作用。如果是这样，则从 术后早期可以为这个脆弱的人群设计。正面或负面，这项研究将 提供有关CAVSD后来ND影响的产前咨询的宝贵数据。最后，生物位 将通过使样本可用于未来来利用我们研究人群的精美ND表型 鉴定DS儿童中ND和行为的分子标记和遗传决定因素的研究。