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.

项目概要/摘要 先天性心脏病 (CHD) 影响着 40-50% 的唐氏综合症 (DS) 患者，最常见的是 完全性房室间隔缺损（CAVSD）。尽管婴儿期围手术期危险因素的影响 心脏手术在一般人群中得到了充分研究，DS 患者几乎被排除在所有人群之外。 关于婴儿心脏手术后神经发育（ND）结果决定因素的前瞻性研究。我们的 总体目标是分析婴儿期修复的 CHD 对总体 ND 和行为结果的影响 DS 人口。我们提出的研究是 NHLBI 资助的前瞻性儿科心脏网络的辅助研究 (PHN) 残余病变评分 (RLS) 研究，招募了 207 名患有 CAVSD 的 DS 患者。父 RLS 研究正在评估婴儿心脏手术后修复技术的充分性对早期和中期的影响 结果，包括围手术期发病率和死亡率，并随访 12 个月。在这里，我们将 在带有 DS 的 RLS 研究样本中调查 ND 和 3-5 岁时行为结果的决定因素 与年龄匹配的 DS 且无 CHD 的样本相比，他们在生命的第一年接受了 CAVSD 修复 相同的 PHN 站点。在目标 1（主要）中，我们将比较患有以下疾病的儿童之间的 ND 和行为结果： 接受过 CAVSD 修复的 DS 以及来自同一临床中心的患有 DS 但未患 CHD 的儿童。主要结果 将是 (i) 源自马伦早期学习量表的语言和非语言智商比率，以及 (ii) 适应性 Vineland 适应行为量表第三版的综合分数，次要结果是 (i) 语言分数源自学前语言量表 - 第五版，(ii) 情感和行为 儿童行为检查表的功能得分，以及 (iii) 注意力和执行功能得分 执行功能行为评定量表，学前版。在目标 2 中，我们将调查 ND 的预测因子和目标 1 中测量的行为，对于接受 CAVSD 修复和未修复的 DS 儿童 CHD，利用结构方程模型探索预测变量之间的关系和可能的中介 变量。在目标 3 中，我们将建立一系列生物材料，用于未来探索遗传的研究 影响 DS 中广泛的 ND 能力的因素。我们将纳入家长咨询 小组负责研究问题、设计学习材料以及向 DS 社区传播。此外 创建了一大群患有 DS 和 CAVSD 修复的儿童以及年龄匹配的对照组，这 研究解决了一个重要的知识空白，即需要婴儿心脏手术的先天性心脏病是否会发挥作用 DS 儿童的 ND 和行为结果中发挥着重要作用。如果是这样，则应从 术后早期可以针对这一弱势群体进行设计。无论是积极还是消极，这项研究都将 为产前咨询提供关于 CAVSD 对后期 ND 影响的宝贵数据。最后是生物样本库 将利用我们研究人群精致的 ND 表型分析，为未来提供样本 确定 ND 的分子标记和遗传决定因素以及 DS 儿童行为的研究。