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

项目摘要/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 完全性房室间隔缺损(CAVSD)尽管围术期危险因素对婴幼儿的影响 心脏手术在普通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。我们的 总体目标是分析婴儿期修复的CHD对儿童整体ND和行为结局的影响 DS人群。我们建议的研究是NHLBI资助的未来儿科心脏网络的辅助研究 (PHN)残留病变评分(RLS)研究，纳入207例合并CAVSD的DS患者。父RLS 一项研究正在评估婴儿心脏手术后修复的技术充分性对早中期的影响 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 在患有DS的RLS研究样本中调查3-5岁儿童ND和行为结果的决定因素 谁在生命的第一年接受了CAVSD修复，与年龄匹配的没有冠心病的DS样本进行了比较 相同的PHN站点。在目标1(初级)中，我们将比较患有ND和行为障碍的儿童 接受CAVSD修补术的DS和来自相同临床部位的无CHD的DS儿童。主要结果 将是(I)从马伦早期学习量表得出的语言和非语言比例智商和(Ii)适应性 Vineland适应行为量表的综合分数-第三版，次要结果将是(I) 学龄前语言量表第5版的语言分数(II)情感和行为 儿童行为检查表上的功能分数，以及(Iii)注意力和执行功能的分数 执行功能行为评定量表，学龄前版本。在目标2中，我们将调查 CAVSD修复术和未修复者DS患儿的ND和AIM 1测试中行为的预测因素 CHD，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 变量。在目标3中，我们将建立一个生物材料集合，用于未来探索基因的研究 在DS中看到的ND能力广谱的因素。我们将合并家长咨询 研究问题小组，研究材料的设计，并向DS社区传播。除了……之外 建立了一个患有DS和CAVSD修复术的儿童和年龄匹配的对照组的大量队列，这 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是否会对 在DS儿童ND和行为结局中的重要作用。如果是这样的话，从 术后早期可为这一弱势人群设计手术时间。无论是积极的还是消极的，这项研究将 为产前咨询CAVSD对后期ND的影响提供有价值的数据。最后，生物库 将利用我们研究人群的精致ND表型，为未来提供样本 DS儿童ND和行为的分子标记和遗传决定因素的研究

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.