Autism Spectrum Disorder (ASD) affects 1 in 68 U.S. children. Early identification and prevention are key to reducing the population burden of ASD. Growing evidence supports fetal or even preconception origins of ASD yet existing findings are mostly derived from case-control or retrospective studies. No adequately powered birth cohort studies have prospectively ascertained early life risk factors and biomarkers for ASD in US minorities.
Goals and objectives:
This proposal aims to address the areas of interest outlined by HRSA- 17- 014 (Autism Longitudinal Data Project): 'Genomic metabolic and inflammatory markers for screening'; 'minority population'; and 'maternal and perinatal origins'. We will leverage the exceptional resources of the Boston Birth Cohort (BBC) to accomplish the following aims in a time and cost-efficient fashion: Aim 1. Examine the role of maternal and cord blood metabolomes in ASD; Aim 2. Examine placental histological findings in relation to the risk of ASD; Aim 3. Examine in utero fetal growth patterns in relation to the risk of ASD; Aim 4. Integrate multi-dimensional data to develop early prediction models and test interventions; and Aim 5. Provide leadership in education training and dissemination. Methods: We will apply cutting-edge metabolomic technologies which allow for a highthroughput and comprehensive characterization of all major circulating metabolites reflecting the biological state of genetic and environmental interactions. In addition we will examine placental histological findings as assessed by highly experienced placental pathologists and fetal longitudinal growth patterns as assessed by a series of prenatal ultrasound exams. We will also use a novel approach that combines computational systems modeling with empirical data from the BBC to understand the complex interplay of pre- peri- and post-natal factors in ASD; determine key modifiable factors that most impact the subsequent development of ASD; and test the intervention effects by modifying these factors to different degrees under a variety of scenarios in a computer environment. Healthy People 2020 Objective(s): To our knowledge this will be by far the largest prospective birth cohort study on ASD and associated developmental disabilities in a U.S. urban predominantly low-income minority population. This study is unprecedented due to the integration of maternal and cord blood metabolome with a prospective birth cohort and has a high likelihood to discover novel maternal and cord blood biomarkers which in turn will be much useful to develop screening algorithms to identify newborns at higher risk for ASD. By integrating a myriad of multi-level longitudinal data and dissecting the complex causal pathways that contribute to ASD at critical early developmental windows this study may lead to a transformation in the way in which clinical and public health services are organized and delivered. This will ultimately lead to the development of cost-effective interventions to halt or reverse the ASD risk trajectory during early developmental periods when interventions may have the greatest life-long impact. The establishment of these novel approaches amongst high-risk urban U.S. populations will be of key importance for lowering the population burden of ASD.
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