Epigenetic and Developmental Effects of In Utero Exposure to Environmental Toxicants

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

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.

Study Overview

• Status: Completed
• Conditions: Adiposity; Environmental Exposures; Full Term Infants

• Study Type: Observational
• Enrollment (Actual): 110

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10461
      • Montefiore Medical Center - Jack D. Weiler Division

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 hour to 3 days (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Mother-baby pairs will be recruited.

Description

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

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Collaborators: American Diabetes Association
• Investigators: Principal Investigator: Mamta Fuloria, MD, Montefiore Medical Center; Principal Investigator: Maureen Charron, PhD, Albert Einstein College Of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2013
• Primary Completion (Actual): December 1, 2018
• Study Completion (Actual): March 28, 2020

Study Registration Dates

• First Submitted: March 19, 2013
• First Submitted That Met QC Criteria: March 20, 2013
• First Posted (Estimate): March 21, 2013

Study Record Updates

• Last Update Posted (Actual): February 11, 2021
• Last Update Submitted That Met QC Criteria: February 10, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Adiposity; Environmental exposure; Benzo(a)pyrene; Polycyclic aromatic hydrocarbons; Term gestation; Cytosine methylation
• Additional Relevant MeSH Terms: Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity
• Other Study ID Numbers: 12-12-428; 1-13-CE-06 (Other Grant/Funding Number: American Diabetes Association)