Epigenetic and Developmental Effects of In Utero Exposure to Environmental Toxicants

Study Overview
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Brief Summary
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Metabolic diseases such as obesity and diabetes are modern day epidemics. Early life exposure to an adverse developmental environment, including environmental toxins, are linked to increased susceptibility to obesity, metabolic syndrome and type 2 diabetes. Although the mechanisms underlying the fetal origins of metabolic disease are poorly understood, strong evidence suggests that alterations in the epigenome play a critical role in this process. The central hypothesis of this proposal is that intrauterine exposure to benzo[a]pyrene leads to epigenetic changes which will have functional consequences and may be a marker for, or may contribute to, increased susceptibility to adverse outcomes in childhood including increased adiposity and the subsequent development of obesity, metabolic syndrome or diabetes. The goals of this proposal are to: 1) determine benzo[a]pyrene levels in umbilical cord blood of newborns, 2) determine whether benzo[a]pyrene exposure during pregnancy correlates with early onset of obesity and metabolic disease by examining the children at 12 and 24 months of age, 3) determine whether in utero benzo[a]pyrene exposure programs metabolic disease through alterations in DNA methylation and gene expression, and 4) determine the plasticity of the DNA methylation patterns in the same offspring at 12 months of age. The long-term goal of this project is to define biomarkers that identify neonates at high-risk for diminished attainment of full health potential, who can then be targeted for preventative measures.

Official Title
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Early Life Exposure to Polycyclic Aromatic Hydrocarbons: Metabolic Perturbations and Epigenetic Biomarkers

Conditions
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Full Term Infants, Environmental Exposures, Adiposity

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Infants whose mothers were followed by the Obstetric Department at MMC, and Deliver a single healthy live term infant Exclusion Criteria: Multiple gestation, Maternal depression, History of maternal smoking in the 3rd trimester of pregnancy, Infants in extremis, Apgar score <7 at 5 min and umbilical artery pH ≤7.25, Chromosomal/congenital abnormalities, Congenital infections, and Inborn errors of metabolism

Ages Eligible for Study
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Minimum Age: 1 Hour
Maximum Age: 72 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measure indices of adiposity in enrolled patients | Assessments will be performed within 72 hours of birth and at 1 and 2 years of age. | up to 24 months | 
| Measure benzo(a)pyrene levels in blood samples | Benzo(a)pyrene levels will be measured in cord blood samples obtained at birth and in peripheral blood samples obtained at 12 months of age. | up to 12 months of age | 
| Measure tobacco by-products in blood samples | Levels of tobacco by-products will be measured in cord blood samples obtained at birth and in peripheral blood samples obtained at 12 months of age. | up to 12 months of age | 
| Characterize cytosine methylation changes in CD3+ T-lymphocytes | Cytosine methylation changes in CD3+ T-lymphocytes will be characterized in cord blood and in a peripheral blood sample obtained at 12 months of age. | up to 12 months of age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Term gestation, Environmental exposure, Benzo(a)pyrene, Polycyclic aromatic hydrocarbons, Adiposity, Cytosine methylation