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.

项目总结/摘要 先天性心脏病（CHD）影响40-50%的唐氏综合征（DS）患者，最常见的是先天性心脏病（CHD）。 完全性房室间隔缺损（CAVSD）。虽然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很好的研究，DS患者几乎被排除在所有 婴儿心脏手术后神经发育（ND）结局决定因素的前瞻性研究。我们 总体目标是分析婴儿期CHD修复对总体ND和行为结局的影响， 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)残留病变评分（RLS）研究，入组了207例CAVSD DS患者。父RLS 研究评估了婴儿心脏手术后修复技术充分性对早期和中期的影响。 结局，包括围手术期发病率和死亡率，随访12个月。在这里，我们将 在患有DS的RLS研究样本中调查ND的决定因素和3-5岁时的行为结果 在出生后第一年接受CAVSD修复的患者与年龄匹配的无CHD的DS患者相比， 相同的PHN网站。在目标1（主要）中，我们将比较以下儿童的ND和行为结果： 接受CAVSD修复的DS和来自相同临床研究中心的DS儿童（无CHD）。主要结局 将是（i）从马伦早期学习量表中得出的语言和非语言比率智商和（ii）适应性智商。 Vineland适应性行为量表-第3版的综合评分，次要结局为（i） 来自学前语言量表的语言分数-第5版，（ii）情感和行为 儿童行为检查表上的功能评分，以及（iii）注意力和执行功能评分， 执行功能行为评定量表，学前版。在目标2中，我们将研究 目标1中测量的伴有CAVSD修复的DS儿童和未进行CAVSD修复的DS儿童中ND和行为的预测因素 冠心病，利用结构方程模型探索预测因素之间的关系和可能的中介作用 变量在目标3中，我们将建立一个生物材料库，用于未来探索遗传学的研究。 导致DS中所见的ND能力的广泛范围的因素。我们会在家长咨询中 小组的研究问题，设计学习材料，并传播到DS社区。除了 建立了一个大型的DS和CAVSD修复儿童队列和一个年龄匹配的对照组， 一项研究解决了一个重要的知识缺口，即需要婴儿心脏手术的CHD是否是 在ND和DS儿童行为结果中的重要作用。如果是这样的话， 对于这一脆弱人群，可设计早期术后期。无论是正面还是负面，这项研究将 为产前咨询CAVSD对后期ND的影响提供了宝贵的数据。最后，生物储存库 将通过提供样本供将来使用， 研究确定分子标记和遗传决定因素的ND和行为的儿童DS。