Clinical trial NCT00925925: Epigenetic Markers of B-Cell Function in Low Birth Weight Infants
Official title: Epigenetic Markers of B-Cell Function in Low Birth Weight Infants
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: Department of Health and Human Services
First posted: 2009-06-22
Enrollment: 64
Sex: ALL
Maximum age (years): 2
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
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.

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.


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

Primary outcomes:
measure: Characterize and compare the Low Birth Weight(LBW) B lymphocyte subtype B1b with that of Normal Birth Weight(NBW) infants.
timeFrame: 2 years
Secondary outcomes:
measure: Characterize CD19 and CD5 epigenetic regulation in LBW infants as compared to NBW infants.
timeFrame: 2 years
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Christian C Yost, M.D.
role: PRINCIPAL_INVESTIGATOR
References: