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

Completed

• Conditions: Low Birth Weight; Small for Gestational Age; Immunodeficiency
• Interventions: Other: Cord blood collection for analysis

• Registration Number: NCT00925925
• Lead Sponsor: University of Utah

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2009-06
• Study First Submitted: 2009-06-18
• Study First Submitted QC: 2009-06-19
• Study First Posted: 2009-06-22
• Primary Completion: 2012-05
• Study Completion: 2012-05
• Status Verified: 2012-06
• Last Update Submitted: 2015-05-11
• Last Update Posted: 2015-05-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 64

Inclusion Criteria

• 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

Exclusion Criteria

• Infants with major congenital anomalies will be excluded

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Normal Birth Weight (NBW)	Cord blood collection for analysis	Term, healthy infants born at normal birth weights
Low Birth Weight (LBW)	Cord blood collection for analysis	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)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
Characterize CD19 and CD5 epigenetic regulation in LBW infants as compared to NBW infants.	2 years

Trial Locations

Locations (1)

University of Utah; 🇺🇸 Salt Lake City, Utah, United States