Project 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 childrens environmental health and leverages Mount Sinais 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 (Childrens Health & Environmental Assessment Resource) network. Our mission will be to determine how the environment affects childrens 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 childrens 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 childrens 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 which PM/metals are associated with outcomes (inhibitory control, cognitive flexibility & working memory).
Aim 4: Examine stress x environment interactions.
Aim 5: Assess oxidative stress as a mediation variable.
Our consortium will address novel research questions as well as illustrate how we will contribute more broadly to the larger national synthetic ECHO cohort goals. While we focus on neurodevelopment, phenotyping includes growth/anthropometrics, respiratory outcomes (asthma, allergy, lung function) and perinatal outcomes in our consortium. We also have extensive biobanking of hair, teeth, urine, saliva, venous and spot bloods, placenta and derivatives (DNA/RNA) that can be used for expanded exposure assessment and mechanistic studies (e.g., metabolomics, epigenomics, gene-environment interactions) in an expanded sample size.
