Epigenetic Markers of B-Cell Function in Low Birth Weight Infants
Study Details
Study Description
Brief Summary
Low birth weight (LBW) status (< 10% for gestational age at birth) is associated with increased risk for diseases such as type II diabetes mellitus, hypertension, chronic obstructive pulmonary disease and coronary artery disease in adults, and represents one example of the "fetal onset of adult disease" hypothesis. Recent data strongly associates LBW status with impaired innate and adaptive immunity leading to increased risk for severe infections during adolescence or early adulthood. Animal studies suggest that the ratio of certain B lymphocyte subpopulations, the B1a and B1b cells, determines whether deficits in immunity occur.
This study will determine the ratio of B1b to B1a lymphocyte subpopulations in the cord blood of infants born LBW in the late preterm to term gestations (> 34 weeks at birth) and compare those ratios with those of normal birth weight (NBW) controls in a nested case control study design.
Furthermore, animal studies suggest that the expression patterns of CD5 and CD19 proteins determines the cellular phenotype of the B lymphocyte, that of a B1a or a B1b cell, and that the regulatory regions controlling their expression are epigenetically vulnerable. The investigators will therefore isolate DNA and RNA from both B lymphocyte subpopulations and determine whether epigenetic changes to the regulatory regions of the genes coding for CD5 and CD19 protein expression occur in LBW lymphocyte subpopulations as compared to the lymphocytes from NBW infants.
This proposal will be the first human study to examine epigenetic determination of a maladaptive phenotype following LBW status at birth in a specific cell type leading to a specific impairment of innate and adaptive immunity.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Normal Birth Weight (NBW) Term, healthy infants born at normal birth weights |
Other: Cord blood collection for analysis
Cord blood will be collected from the placentas at delivery for analysis
|
| Low Birth Weight (LBW) Infants born at > or equal to 34 0/7 weeks with a birth weight at < or equal to 10% for gestational age at birth (Small for Gestational Age, SGA) |
Other: Cord blood collection for analysis
Cord blood will be collected from the placentas at delivery for analysis
|
Outcome Measures
Primary Outcome Measures
- Characterize and compare the Low Birth Weight(LBW) B lymphocyte subtype B1b with that of Normal Birth Weight(NBW) infants. [2 years]
Secondary Outcome Measures
- Characterize CD19 and CD5 epigenetic regulation in LBW infants as compared to NBW infants. [2 years]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Infants delivered at University of Utah Health Sciences Center
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For LBW group:
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Gestational age > or = to 34 0/7 weeks
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Birth weight < or = to 10% for gestational age
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For NBW group:
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Term infant controls delivered without complication
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Adequate cord blood sample obtained directly after birth
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Parents or guardians must have signed informed consent
Exclusion Criteria:
- Infants with major congenital anomalies will be excluded
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Utah | Salt Lake City | Utah | United States | 84108 |
Sponsors and Collaborators
- University of Utah
- Department of Health and Human Services
Investigators
- Principal Investigator: Christian C Yost, M.D., University of Utah
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 35580