Clinical trial NCT01789268: Impact of Respiratory Pathogens in Infants
Official title: Impact of Respiratory Virus Infections and Bacterial Microbiome Shifts on Lymphocyte and Respiratory Function in Infants Born Prematurely or Full Term
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Respiratory Tract Infection
Keywords: acute
adaptive cellular immune phenotypes
infants
Lymphocyte
premature
respiratory viral infections
Lead sponsor: University of Rochester
Sponsor class: OTHER
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2013-02-12
Enrollment: 267
Sex: ALL
Minimum age (years): 0
Maximum age (years): 3
Standard ages: CHILD
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Study subjects were enrolled from sequential preterm and full term births at the University of Rochester

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Calculate presence of at/near term gestation cellular immune response to mitogen and antigen specific responses to > /=1 viral pathogens isolated over 1st 2yrs CGA via lymphocyte assessment
timeFrame: 2 years CGA
measure: Degree of adaptive immune system maturation utilizing flow cytometric analysis of lymphocytes in blood
timeFrame: From 41 weeks gestation through 3 years CGA
measure: Degree of immune system maturation utilizing flow cytometric analysis of lymphocytes in umbilical cord blood and peripheral blood
timeFrame: From 41 weeks gestation through 3 years CGA
measure: Etiology of symptomatic viral respiratory infections as assessed by TLDA PCR Assays of biospecimens
timeFrame: 2 years CGA
measure: Number of respiratory tract symptomatic and asymptomatic viral infections weekly.
timeFrame: 41weeks gestation
measure: Number of symptomatic viral respiratory infections
timeFrame: 2 years CGA
measure: Occurrence of respiratory tract viral infections (asymptomatic and symptomatic)
timeFrame: From 37- 41 weeks gestation, through the first 1 and 2 years CGA, respectively
measure: Patterns of respiratory and gut bacterial microbiome as they develop weekly
timeFrame: 41 weeks gestation
measure: Pulmonary function via Respiratory Inductive Plethysmography (RIP) with Bronchodilator Response (BDR)
timeFrame: 41 weeks gestation
measure: Rate of adaptive immune system maturation utilizing flow cytometric analysis of lymphocytes in blood
timeFrame: From 37- 41 weeks, through the first 1 and 3 years CGA
measure: Rate of immune system maturation utilizing flow cytometric analysis of lymphocytes in umbilical cord blood and peripheral blood
timeFrame: 41 weeks gestation
measure: Severity of illness due to viral respiratory tract infections
timeFrame: 2 years CGA
measure: Severity of respiratory tract viral infections (asymptomatic and symptomatic) as assessed by the COAST Respiratory Symptom Scale.
timeFrame: 2 years CGA
measure: Viral load of respiratory pathogens in the nasopharynx of infants with symptomatic RTIs
timeFrame: 2 years CGA
Secondary outcomes:
measure: Patterns of respiratory and gut bacterial microbiome as they change monthly from hospital discharge at term or near term gestation
timeFrame: Through the first 1 year CGA
measure: Presence of cord blood antigen-neutralizing antibodies correlates with the presence of specific antigen responses in lymphocytes
timeFrame: At term or near term gestation
measure: Pulmonary function via RIP with BDR
timeFrame: At 1 year CGA and 3 years CGA
measure: Titers of neutralizing antibodies in cord blood to isolated viral pathogens
timeFrame: Through the first 2 years CGA
Other outcomes:
Locations:
city: Rochester
country: United States
facility: University of Rochester Medical Center - Strong Memorial Hospital - Infectious Diseases
state: New York
Study officials:
References:
citation: McDavid A, Corbett AM, Dutra JL, Straw AG, Topham DJ, Pryhuber GS, Caserta MT, Gill SR, Scheible KM, Holden-Wiltse J. Eight practices for data management to enable team data science. J Clin Transl Sci. 2020 Jun 23;5(1):e14. doi: 10.1017/cts.2020.501.
citation: Caserta MT, Yang H, Bandyopadhyay S, Qiu X, Gill SR, Java J, McDavid A, Falsey AR, Topham DJ, Holden-Wiltse J, Scheible K, Pryhuber G. Measuring the Severity of Respiratory Illness in the First 2 Years of Life in Preterm and Term Infants. J Pediatr. 2019 Nov;214:12-19.e3. doi: 10.1016/j.jpeds.2019.06.061. Epub 2019 Jul 31.