Brief Title
Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies
Official Title
Prematurity and Respiratory Outcome Program: Single Center Study of Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies
Brief Summary
This is an observational study that proposes to collect clinical, physiological, cellular and
molecular information in an attempt to identify a set of factors that may predict the risk
for persistent lung disease in babies born prematurely.
Detailed Description
Approximately 550,000 babies born prematurely each year in the United States suffer from
birth at a time in development when the respiratory tract and immune system would normally be
protected and maintained in a naïve state. This project is a component of the NIH Prematurity
and Respiratory Outcomes Program (PROP) whose goals are the identification of disease
mechanisms and biomarkers to stratify premature infants, at the time of discharge, for their
risk of subsequent pulmonary morbidity. This Clinical Research Center (CRC) project will
investigate prematurity-dependent alterations in cellular innate and adaptive immune systems
resulting in increased susceptibility to respiratory infections and environmental irritants,
and leading to respiratory morbidity in the first year of life. Prior studies have
established developmental (maturity) and disease-related changes in circulating and pulmonary
lymphocyte populations but a comprehensive assessment of their relationship to disease
risk/outcome has not been undertaken. We hypothesize that cellular and molecular
immuno-maturity is altered due to intrinsic and extrinsic factors presented by premature
birth in such a way as to reduce resistance to viral infections and to promote cytotoxic
damage to the lung. We will evaluate immunologic maturity by comprehensively phenotyping
lymphocyte populations in peripheral blood sampled at premature delivery, at the time of
discharge from the hospital and at twelve months corrected age. The lymphocytic phenotype
will be analyzed particularly in the context of gestational age and maternal-fetal stressors
capable of modulating oxidative stress (oxygen exposure, infection and environmental tobacco
smoke exposure). Additionally, we will assess changes in the molecular phenotype of isolated
CD8 lymphocytes, a cell type preferentially recruited to the lungs of premature infants and
capable of contributing to disease pathogenesis, by genome-wide expression profiling, in
order to uncover novel disease pathways and define a gene expression signature associated
with disease risk. Finally, we propose to build a statistical model, using cellular and
molecular phenotypes and additional clinical variables, for stratifying risk of lung
morbidity within the first year of life.
Study Type
Observational
Primary Outcome
Symptomatic Respiratory Disease (SRD)
Secondary Outcome
Assessment of T lymphocyte numbers, subsets (CD4, CD8) and functional phenotype determined by flow cytometry.
Condition
Prematurity
Study Arms / Comparison Groups
Premature Infant
Description: Infants born 23 0/7 weeks gestation to 35 6/7 weeks gestation.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Estimated Enrollment
277
Start Date
August 2011
Completion Date
July 2015
Primary Completion Date
July 2015
Eligibility Criteria
Inclusion Criteria:
1. Premature infants born at gestational age 24 0/7 to 35 6/7 week and admitted to the
Neonatal Intensive Care Unit or normal newborn nursery at URMC or UB
2. Healthy term infants 37 0/7 to 41 6/7 recruited from the birthing centers or Ob/Gyn
floors (3-1200 at URMC) prior to discharge
3. Infants who are less than or equal to 7 days old
Exclusion Criteria:
1. The infant is not considered to be viable (therapies limited due to futility decision
made by clinical care team)
2. Congenital heart disease (not including PDA and hemodynamically insignificant VSD or
ASD)
3. Structural abnormalities of the upper airway, lungs or chest wall
4. Other congenital malformations or syndromes that adversely affect life expectancy or
cardio-pulmonary development
5. Family is unlikely to be available for long-term follow-up as determined by the site
investigators dependent on the distance of the infant's residence from the follow-up
center and/or family plans to move out of the region
6. Family does not speak or understand English
Gender
All
Ages
N/A - 7 Days
Accepts Healthy Volunteers
No
Contacts
Gloria Pryhuber, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT01607216
Organization ID
37933
Secondary IDs
U01HL101813
Responsible Party
Principal Investigator
Study Sponsor
University of Rochester
Collaborators
National Institutes of Health (NIH)
Study Sponsor
Gloria Pryhuber, MD, Principal Investigator, University of Rochester
Verification Date
January 2020