ECHO Consortium on Perinatal Programming of Neurodevelopment

Project: Research project

Project Details

Description

The Icahn School of Medicine at Mount Sinai will form a new ECHO (Environmental Influences on Child Health Outcomes) Consortium on Perinatal Programming of Neurodevelopment. This initiative will build on our internationally recognized research expertise in children’s environmental health and leverages Mount Sinai’s recently established Exposome Laboratory and designation as the Data Coordinating Center and one of six national laboratory hubs in the National Institutes of Enviornmental Health Sciences CHEAR (Children’s Health & Environmental Assessment Resource) network. Our mission will be to determine how the environment affects children’s brain development across childhood and adolescence.
Environmental influences on neurodevelopment are extraordinarily complex. Environmental interactions with genes, co-occurring environmental factors, sex, and life stage define normal variations and altered developmental trajectories over the life course. This complexity has fostered the “exposome” concept which considers temporal variation in multiple exposures (e.g., chemical, non-chemical or social) as well as consequences of exposures indexed via biomarkers of response over the lifespan. While individual prospective cohorts have provided insight into environmental programming, exposomal research will need larger samples and methods development to address its inherent complexities. These include methodological advances that model the physical environment, assess higher order mixtures of chemicals, assess interactions of chemicals with social stressors, and objectively assess how exposure timing impacts brain development. Our transdisciplinary team is uniquely poised to address many of these issues by leveraging the ECHO initiative.
Although many mechanisms contribute to toxicant-elicited disruption of neurodevelopment, much evidence underscores a central role for oxidative stress (OS) in the prenatal and early childhood periods. In our consortium, we will characterize oxidative stress (OS) as a key component of the fetal/early childhood exposome in evaluating perinatal exposures and children’s neurodevelopment. We will examine three paradigm pro-oxidants chosen to illustrate key exposome related methods: 1) the external exposure of physical / social toxicants estimated by integrating geographical information systems (GIS) and spatial analysis, 2) the internal dose of chemical mixtures through biomarkers, and 3) repeated measurement of psychosocial stress and biological correlates. We will also assess biomarkers of cumulative OS, i.e., mitochondrial DNA (mtDNA) damage and telomere length over early development. We will prospectively assess 4275 children in a harmonized cohort consortium with extensive environmental assessments and biobanked samples, including placenta, from the prenatal and childhood periods up to age 7-10 years. Our long-term goal is to develop and apply methods to study the exposome and children’s health more broadly, and our extensive biobanked tissue archives, novel laboratory-based technologies and advanced computational methods will be available to expand the scope of our work to others who use ECHO. Our aims are:

Aim 1: Harmonize variables and evaluate the heterogeneity of characteristics of existing longitudinal epidemiological data within 5 prenatally enrolled cohorts.
Aim 2: Derive GIS-based environmental exposure estimates of (a) criterion pollutants (PM2.5, SO2, NO2, O3) and (b) built environment using a satellite-based spatio-temporal resolved model.
Aim 3: Identify pre-/postnatal exposure windows in w
StatusActive
Effective start/end date9/23/168/31/21

Funding

  • Icahn School of Medicine at Mount Sinai (0255-2294-4609//5UG3OD023337-04)
  • Office of the Director, National Institutes of Health (0255-2294-4609//5UG3OD023337-04)

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