Functional and Lymphocytic Markers of Respiratory Morbidity in Hyperoxic Preemies

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.

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

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