Epigenetic and Developmental Effects of In Utero Exposure to Environmental Toxicants

NCT01815385 | Completed

• 2 other identifiers: 12-12-4281-13-CE-06
• Study Type: observational
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Full Term Infants; Environmental Exposures; Adiposity

Keywords

Term gestation; Environmental exposure; Benzo(a)pyrene; Polycyclic aromatic hydrocarbons; Adiposity; Cytosine methylation

Outcome Measures

Primary Outcomes (4)

• 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

Eligibility Criteria

• Age: 1 Hour - 72 Hours
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Mother-baby pairs will be recruited.

You may qualify if:

• Infants whose mothers were followed by the Obstetric Department at MMC, and
• Deliver a single healthy live term infant

You may not qualify if:

• 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

Sponsors & Collaborators

• Montefiore Medical Center: lead
• American Diabetes Association: collaborator

Study Sites (1)

Montefiore Medical Center - Jack D. Weiler Division

The Bronx, New York, 10461, United States

Location

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

MeSH Terms

Conditions

Obesity

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Mamta Fuloria, MD

  Montefiore Medical Center

  PRINCIPAL INVESTIGATOR

• Maureen Charron, PhD

  Albert Einstein College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: ECOLOGIC OR COMMUNITY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Pediatrics

Study Record Dates

• First Submitted: March 19, 2013
• First Posted: March 21, 2013
• Study Start: March 1, 2013
• Primary Completion: December 1, 2018
• Study Completion: March 28, 2020
• Last Updated: February 11, 2021

Record last verified: 2021-02

Locations

US (1)