Epigenetic Markers of B-Cell Function in Low Birth Weight Infants

NCT00925925 | Completed

• 1 other identifier: 35580
• Study Type: observational
• Target: 64
• Locations: 1 country
• Sites: 1

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.

Conditions

Low Birth Weight; Small for Gestational Age; Immunodeficiency

Keywords

Low birth weight; small for gestational age; B-cell function; epigenetics; B1a; B1b; CD19; CD5

Outcome Measures

Primary Outcomes (1)

• Characterize and compare the Low Birth Weight(LBW) B lymphocyte subtype B1b with that of Normal Birth Weight(NBW) infants.

  2 years

Secondary Outcomes (1)

• Characterize CD19 and CD5 epigenetic regulation in LBW infants as compared to NBW infants.

  2 years

Study Arms (2)

Normal Birth Weight (NBW)

Term, healthy infants born at normal birth weights

Other: Cord blood collection 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

Interventions

Cord blood collection for analysis OTHER

Cord blood will be collected from the placentas at delivery for analysis

Low Birth Weight (LBW); Normal Birth Weight (NBW)

Eligibility Criteria

• Age: Up to 2 Hours
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

Term or near-term infants born at less than or equal to 10% normal birth weight for gestation.

You may qualify if:

• Infants delivered at University of Utah Health Sciences Center
• For LBW group:
• Gestational age \> or = to 34 0/7 weeks
• Birth weight \< or = to 10% for gestational age
• For NBW group:
• Term infant controls delivered without complication
• Adequate cord blood sample obtained directly after birth
• Parents or guardians must have signed informed consent

You may not qualify if:

• Infants with major congenital anomalies will be excluded

Sponsors & Collaborators

• University of Utah: lead
• Department of Health and Human Services: collaborator

Study Sites (1)

University of Utah

Salt Lake City, Utah, 84108, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood will be stored as frozen mRNA isolates if parents consent to tissue banking.

MeSH Terms

Conditions

Immunologic Deficiency Syndromes

Condition Hierarchy (Ancestors)

Immune System Diseases

Study Officials

• Christian C Yost, M.D.

  University of Utah

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 18, 2009
• First Posted: June 22, 2009
• Study Start: June 1, 2009
• Primary Completion: May 1, 2012
• Study Completion: May 1, 2012
• Last Updated: May 12, 2015

Record last verified: 2012-06

Locations

US (1)