Component A: NC Study to Explore Early Development Phase 3 (SEED 3)

摘要 自闭症谱系障碍(ASD)是一种严重的终生神经发育障碍，与 对个人造成相当大的损害，给他们的家庭和社区带来很大的负担。小才是 了解ASD的原因或相关因素。虽然诊断实践正在改善ASD的识别， 关于ASD的风险和保护因素以及表型变异，仍有许多有待发现 以及合并症的流行。为了回应日益增长的关切，2000年的《儿童健康法》 授权疾控中心建立ASD监测和研究计划，以解决ASD的规模、发病率、 以及自闭症和相关发育障碍的原因。自闭症与发展中心 残疾研究和流行病学(CADDRE)在六个国家站点(加利福尼亚州、 科罗拉多州、佐治亚州、马里兰州、北卡罗来纳州和宾夕法尼亚州)履行这一任务，目前 开展研究的第二阶段以探索早期发育(SEED)，这是一个以人口为基础的病例- 对照研究。SEED提出的假设包括：ASD表型变异，包括核心聚集性 症状、认知状态和合并症的存在；胃肠道特征；遗传变异和 基因-环境相互作用(GxE)；感染、免疫功能和自身免疫因子；以及激素 影响因素和母体生殖特征。数据收集包括发展评估和 产前和围产期健康和环境，通过面谈、病历审查、自我管理 问卷和生物样本。截至2015年12月，种子1和2已完成数据收集 4652个家庭-1341个患有自闭症，1722个患有其他发育障碍，1589个对照组。在这颗种子中3 北卡罗来纳州种子公司提议为每组125名儿童进行新的招募和数据收集， 为网络作出贡献，每个SEED 3学习小组总共有625名儿童。这是增加后的组合样本 规模将使种子假说的评估变得更加有力，特别是对表型亚群和GxE 互动。考虑到SEED 1和SEED 2的经验以及每个CADDRE站点的基础设施，SEED 3可以快速实施，创建临床、风险因素和生物学的组合种子样本 6500多个家庭的标本和数据。Seed将是此类ASD最大的研究，使 对我们理解复杂的自闭症表型和识别潜在风险有重大贡献 ASD的保护因素。

ABSTRACT Autism Spectrum Disorder (ASD) is a severe, life-long neurodevelopmental disorder that is associated with considerable impairment for individuals and a substantial burden to their families and communities. Little is known about the causes or correlates of ASD. While diagnostic practices are improving ASD identification, much remains to be discovered about risk and protective factors for ASD and about the phenotypic variation and prevalence of co-morbid conditions. In response to growing concerns, the Children's Health Act of 2000 mandated CDC to establish ASD surveillance and research programs that address the magnitude, incidence, and causes of ASD and related developmental disabilities. The Centers for Autism and Developmental Disabilities Research and Epidemiology (CADDREs) were established at six national sites (California, Colorado, Georgia, Maryland, North Carolina, and Pennsylvania) to fulfill this mandate and are currently carrying out the second phase of the Study to Explore Early Development (SEED), a population-based case- control study. SEED addresses hypotheses including: ASD phenotypic variation, including clustering of core symptoms, cognitive status, and presence of co-morbidities; gastrointestinal features; genetic variation and gene-environment interaction (GxE); infection, immune function, and autoimmunity factors; and hormonal factors and maternal reproductive characteristics. Data collection includes developmental assessments and pre- and perinatal health and environment via interviews, medical record review, self-administered questionnaires, and biologic samples. As of December 2015, SEED 1 & 2 had completed data collection on 4652 families - 1341 with ASD, 1722 with other developmental disorders, and 1589 controls. In this SEED 3 proposal, North Carolina SEED proposes new recruitment and data collection for 125 children in each group, to contribute to the Network total of 625 children per SEED 3 study group. This increased, combined sample size will enable well-powered assessment of SEED hypotheses, particularly for phenotypic subgroups and GxE interactions. Given the experience of SEED 1 & 2 and the infrastructure in place at each CADDRE site, SEED 3 can be quickly implemented, creating a combined SEED sample of clinical, risk factor, and biological specimens and data on over 6500 families. SEED would be the largest study of ASD of this kind, making significant contributions to our understanding of the complex autism phenotype and identifying potential risk and protective factors for ASD.