Clinical trial NCT01815385: Epigenetic and Developmental Effects of In Utero Exposure to Environmental Toxicants
Official title: Early Life Exposure to Polycyclic Aromatic Hydrocarbons: Metabolic Perturbations and Epigenetic Biomarkers
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Full Term Infants
Environmental Exposures
Adiposity
Keywords: Term gestation
Environmental exposure
Benzo(a)pyrene
Polycyclic aromatic hydrocarbons
Adiposity
Cytosine methylation
Lead sponsor: Montefiore Medical Center
Sponsor class: OTHER
Collaborators: name: American Diabetes Association
First posted: 2013-03-21
Enrollment: 110
Sex: ALL
Minimum age (years): 1
Maximum age (years): 72
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Mother-baby pairs will be recruited.

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.


Eligibility criteria: 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

Primary outcomes:
measure: Measure indices of adiposity in enrolled patients
timeFrame: up to 24 months
measure: Measure benzo(a)pyrene levels in blood samples
timeFrame: up to 12 months of age
measure: Measure tobacco by-products in blood samples
timeFrame: up to 12 months of age
measure: Characterize cytosine methylation changes in CD3+ T-lymphocytes
timeFrame: up to 12 months of age
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: Montefiore Medical Center - Jack D. Weiler Division
state: New York
Study officials:
affiliation: Montefiore Medical Center
name: Mamta Fuloria, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Albert Einstein College of Medicine
name: Maureen Charron, PhD
role: PRINCIPAL_INVESTIGATOR
References: