Epigenetic and Developmental Effects of In Utero Exposure to Environmental Toxicants
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.
Full Term Infants
|Study Design:||Observational Model: Ecologic or Community
Time Perspective: Prospective
|Official Title:||Early Life Exposure to Polycyclic Aromatic Hydrocarbons: Metabolic Perturbations and Epigenetic Biomarkers|
- Measure indices of adiposity in enrolled patients [ Time Frame: up to 24 months ] [ Designated as safety issue: No ]Assessments will be performed within 72 hours of birth and at 1 and 2 years of age.
- Measure benzo(a)pyrene levels in blood samples [ Time Frame: up to 12 months of age ] [ Designated as safety issue: No ]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.
- Measure tobacco by-products in blood samples [ Time Frame: up to 12 months of age ] [ Designated as safety issue: No ]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.
- Characterize cytosine methylation changes in CD3+ T-lymphocytes [ Time Frame: up to 12 months of age ] [ Designated as safety issue: No ]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.
Biospecimen Retention: Samples With DNA
Maternal blood sample Cord blood sample Infant saliva Peripheral blood sample from enrolled patients at 12 and 24 months of age
|Study Start Date:||March 2013|
|Estimated Study Completion Date:||August 2016|
|Estimated Primary Completion Date:||August 2016 (Final data collection date for primary outcome measure)|
|Contact: Mamta Fuloria, MDfirstname.lastname@example.org|
|Contact: Deborah Campbell, MDemail@example.com|
|United States, New York|
|Montefiore Medical Center - Jack D. Weiler Division||Recruiting|
|Bronx, New York, United States, 10461|
|Contact: Mamta Fuloria, MD 718-904-4105 firstname.lastname@example.org|
|Contact: Deborah Campbell, MD 718-904-4105 email@example.com|
|Principal Investigator: Mamta Fuloria, MD|
|Principal Investigator: Maureen Charron, PhD|
|Sub-Investigator: Francine Einstein, MD|
|Sub-Investigator: Deborah Campbell, MD|
|Principal Investigator:||Mamta Fuloria, MD||Montefiore Medical Center|
|Principal Investigator:||Maureen Charron, PhD||Albert Einstein College of Medicine of Yeshiva University|