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

Study Overview
=================
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.

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

Conditions
-----------------
Low Birth Weight, Small for Gestational Age, Immunodeficiency

Intervention / Treatment
-----------------
* Other: Cord blood collection for analysis


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Maximum Age: 2 Hours

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal Birth Weight (NBW)<br>Term, healthy infants born at normal birth weights | Other: Cord blood collection for analysis<br>* Cord blood will be collected from the placentas at delivery for analysis<br>|
| Low Birth Weight (LBW)<br>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<br>* Cord blood will be collected from the placentas at delivery for analysis<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize CD19 and CD5 epigenetic regulation in LBW infants as compared to NBW infants. |  | 2 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Low birth weight, small for gestational age, B-cell function, epigenetics, B1a, B1b, CD19, CD5