Expanding the Value of the EARLI study: Small Cohort with Big Data

神经发育障碍（NDD），包括ASD，影响超过15%的美国儿童- 自闭症谱系障碍（ASD）影响了大约1.5%的美国儿童。识别 对潜在原因的了解可以导致初级和二级预防工作。大量证据 支持基因和环境的贡献，特别是产前暴露。 前瞻性研究，收集妊娠期间、症状出现前的暴露信息 尽管在一般人群中进行前瞻性研究是不可行的， 对于ASD来说，成本效益或效率。丰富的家庭风险设计，它利用了 在ASD儿童的兄弟姐妹中，ASD和NDD的复发风险很大， 用于实现具有合理结局事件的前瞻性数据收集。早期 自闭症风险纵向调查（EARLI）研究有助于开拓这种丰富的风险 队列方法。EARLI招募并跟踪了260多名已经怀孕的孕妇， ASD儿童，多次研究访视，儿童评估，生物采样和家庭环境 在怀孕期间和生命的前3年进行调查。总样本量有限; EARLI的价值是纵向数据的深度和跨多个 组织类型和早期发育窗口。到目前为止，已经有超过94亿个数据点 在多种表型、组织、暴露和组学测量中产生。当前 提案旨在维护和丰富这项有价值的研究，以充分实现其对 环境卫生。目标是：1.维护和扩展EARLI生物样品库 通过支持储存和回收工作以及增加和储存脱落的婴儿牙齿， 这将使纵向产前接触措施，在越来越多的有毒物质， 暴露。2.衡量学龄儿童新出现的并发症的频率和模式 以更好地表征共发生的NDD和数量性状的表型。3. 表征时间、家族成员和 包括母亲的血液和尿液以及脱落的婴儿牙齿。4.制定和应用方法 对于表型和使用潜在结构的暴露协调， 队列研究; 5.迁移、增强和提高EARLI研究的可重复性 数据，实现数据共享。EARLI的研究是研究早期生命环境的宝贵财富。 神经发育结果的流行病学。实现这些目标将使我们能够最大限度地 这项新研究对理解ASD和NDD病因的贡献。

Neurodevelopmental disorders (NDDs), including ASD, affect over 15 percent of US children – Autism Spectrum Disorder (ASD) alone affects approximately 1.5% of US children. Identification of underlying causes can lead to primary and secondary prevention efforts. Substantial evidence supports contribution of both genes and environment, particularly prenatal exposures. Prospective studies, with exposure information collected during pregnancy, prior to symptom onset, are sorely needed although prospective studies in the general population are not feasible, cost effective, or efficient for ASD. The enriched-familial-risk design, which capitalizes on the substantial recurrence risk of both ASD and NDD among siblings of children with ASD, has been employed to achieve prospective data collection with reasonable outcome events. The Early Autism Risk Longitudinal Investigation (EARLI) study has helped to trailblaze this enriched risk cohort approach. EARLI recruited and followed over 260 pregnant women who already had a child with ASD with multiple study visits, child assessments, biosampling, and home environment surveys over pregnancy and the first 3 years of life. While the total sample size was constrained; the value of EARLI is the depth of longitudinal data and molecular measurements across multiple tissue types and early developmental windows. To date, over 9.4 billion data points have been generated across multiple phenotypes, tissues, exposures, and -omic measures. The current proposal seeks to maintain and enrich this valuable study to fully realize its impact on environmental health. The goals are to: 1. Maintain and extend the EARLI Biosample Repository through support of the storage and retrieval efforts and addition and storage of shed baby teeth that will enable longitudinal prenatal exposure measures across a growing array of toxicant exposures. 2. Measure frequency and patterns of emerging co-occurring conditions at school age to better characterize phenotypes across co-occurring NDDs and quantitative traits. 3. Characterize variability of heavy metals measurement across timing, family members, and matrices including maternal blood and urine and shed baby teeth. 4. Develop and apply methods for phenotype and for exposure harmonization using latent constructs, enabling within and cross- cohort investigations; 5. Migrate, enhance, and increase the reproducibility of EARLI research data to enable data sharing. The EARLI study is a valuable asset to early life environmental epidemiology of neurodevelopmental outcomes. Conducting these aims will allow us to maximize the contribution of this novel study to the understanding of ASD and NDD etiology.