Impact of Respiratory Pathogens in Infants

This clinical study will investigate the relationships between sequential respiratory viral
infections, patterns of intestinal and respiratory bacterial colonization, and adaptive
cellular immune phenotypes which are associated with increased susceptibility to respiratory
infections and long term respiratory morbidity in preterm and full term infants. This is a
prospective, cohort study, enrolling at a single center via two sites (URMC and
URMC-affiliated Highland Hospital and Rochester General Hospital). Enrollment will be
accomplished in approximately 15 - 36 months. The study will enroll 280 subjects, 150
pre-term and 130 full-term. This protocol does not study an agent or intervention. However,
the bronchodilator, albuterol, a beta 2 agonist, will be administered as part of the
Respiratory Inductive Plethysmography (RIP) pulmonary function assessments. All infants will
remain in the study up to 3 years plus 17 weeks, depending on gestational age at birth. The
full-term infants are expected to be typically developing newborns and generally healthy.
Enrolled newborns will have a sample of cord blood (CB) for evaluation of lymphocyte
phenotype and baseline neutralizing antibody titers. Maternal saliva samples will be
collected to test exposure to environmental tobacco smoke. A nose, throat and rectal swab
will be obtained for the assessment of the respiratory and gut microbiome and testing for
known respiratory pathogens and pathogen discovery. Prior to hospital discharge, infants will
have an evaluation of lymphocyte phenotype and function, and will undergo a respiratory
assessment via RIP prior to and after a bronchodilator. Co-morbidities, familial and
environmental risk factors for atopy, asthma and respiratory symptoms will be assessed.
Following hospital discharge, all babies (full-term and former preterm infants) will be
followed longitudinally through 3 years CGA as outpatients. During the first year of
follow-up, all infants will have rectal and nose, throat swabs obtained monthly. Screening
for symptomatic respiratory dysfunction and illnesses will also occur during the time of
follow-up as per schedule.

Inclusion Criteria:

Inclusion Criteria for Preterm Cohort: - Signed Informed Consent from parent(s) or legal
guardian(s) - Preterm infants born at gestational age 23 0/7 to 35 6/7 weeks - Preterm
infants admitted to the URMC NICU or Normal Newborn Nursery - Infants less than or equal to
7 days old - Attending physician agreement Inclusion Criteria for Full Term Cohort: -
Healthy term infants 37 0/7 to 41 6/7 weeks gestation - Recruited prior to delivery, or
from the birthing centers and labor and delivery floor at URMC and Highland Hospital -
Infants less than or equal to 7 days old - Signed Informed Consent from parent(s) or legal
guardian(s)

Exclusion Criteria:

- Considered to be non-viable (decision made by clinical care team to not provide
life-saving therapies) - Known congenital heart disease, not including patent ductus
arteriosus (PDA), hemodynamically insignificant ventricular septal defect (VSD) or atrial
septal defect (ASD) - Known structural abnormalities of the upper airway, lungs, or chest
wall - Known other congenital malformations or syndromes that adversely affect life
expectancy or cardiopulmonary development (i.e., neuromuscular disease, trisomy 21) - Known
to be born to women who are human immunodeficiency virus (HIV) positive (HIV testing is not
required prior to study entry but is available for most mothers-to-be and is performed on
all newborns in NY state) - Known congenital or acquired immune deficiency - Family is
unlikely to be available for long-term follow-up as determined by the site investigators -
No legal guardian who speaks and reads English - Specifically for the term Infants, as
healthy infants, they will not have been admitted to the URMC NICU prior to consent. - Any
infant with a diagnosis of hypertension, hyperthyroidism, seizures, arrhythmias, or
sensitivity to sympathomimetic amines will be excluded from the BDR assessment. - Any
infant with hypersensitivity to any of components of albuterol sulfate will be excluded
from the BDR assessment. An infant or child with such history may remain eligible for the
remainder of the study if they qualify by other inclusion and exclusion criteria.