Clinical trial NCT03229967: Gastrointestinal Microbiome Influence on the Development of Bronchopulmonary Dysplasia
Official title: Gastrointestinal Microbiota Influence on the Pathogenesis of Bronchopulmonary Dysplasia in Very Low Birthweight Neonates
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Bronchopulmonary Dysplasia
Keywords: Bronchopulmonary dysplasia
Microbiome
Microbiota
Premature infant
Observational cohort study
Lead sponsor: University of Tennessee
Sponsor class: OTHER
First posted: 2017-07-26
Enrollment: 197
Sex: ALL
Minimum age (years): 0
Maximum age (years): 7
Standard ages: CHILD
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Study Population will be composed of VLBW infants (birthweight less than 1500 grams) and their mothers (Including 40 term infants and their mothers)

Brief summary: The purpose of this study is to advance our knowledge of the factors that contribute to the development of bronchopulmonary dysplasia (BPD), a chronic lung affecting premature infants. Specifically, the investigators will determine the complexity of the gut microbiota, the genera of the bacteria that naturally live in the gut, and determine if the relative diversity of the gut bacteria is a prognostic indicator of BPD. To accomplish this, the investigators propose to characterize the microbiota of human premature newborns with BPD, then validate this potential mechanism in mice. The investigators will enroll very low birthweight premature infants admitted to the neonatal intensive care units (NICU) at Le Bonheur Children's Hospital and Regional One Health that are at high risk to develop BPD. A cohort of well full term newborns will also be enrolled. Non-invasive stool samples will be obtained weekly over the first month of life. Infants that eventually develop BPD will be paired with infants that did not develop BPD. Stool samples from these infants will be sent for analysis. The investigators expect that reduced complexity of the gut microbiome is associated with BPD. The investigators will model the contribution of reduced microbiome complexity to the risk to develop BPD or death, as well as the association with disease severity. The project investigates important factors leading to the development of BPD, and has the potential to directly translate to therapy for the most significant pulmonary complication of prematurity.


Eligibility criteria: Inclusion Criteria:

1. Newborn humans less than 1 week of age with a birthweight less than 1,500 g, or fetuses with impending delivery and estimated birthweight of less than 1,500 grams. No individuals will be excluded on the basis of sex or ethnicity.
2. Parents can understand and comply with planned study procedures.
3. Parents provide assent/permission prior to any study procedures.

Inclusion criteria mothers:

1. The mother's of infants meeting the infant inclusion criteria above.

Exclusion Criteria:

1. Diagnosed immunodeficiency disorder.
2. Currently receiving investigational immunomodulatory, probiotic or antiviral agent.
3. Infants whose mothers meet the exclusion criteria below.

Exclusion criteria mothers:

1. Diagnosed immunodeficiency disorder
2. Currently receiving investigational immunomodulatory, probiotic or antiviral agents
3. Lacking the mental capacity (e.g. due to pain, anesthesia, mental impairment) to provide informed consent for themselves or assent for the participation of their infant.
4. Having an infant that meets the infant exclusion criteria.

Primary outcomes:
measure: Bronchopulmonary dysplasia (BPD)
timeFrame: 36 weeks corrected gestational age, until the date of death or initial hospital discharge whichever occurs first, assessed up to up to 3 months
measure: Death
timeFrame: from the date of enrollment until the date of death or initial hospital discharge, whichever occurs first, assessed up to up to 3 months
Secondary outcomes:
measure: Necrotizing Enterocolitis (NEC)
timeFrame: from the date of enrollment until the date of initial hospital discharge or death, whichever occurs first, assessed up to up to 3 months
measure: Maternal Chorioamnionitis
timeFrame: presence on admission
Other outcomes:
measure: Maternal perinatal antibiotic exposure
timeFrame: from hospital admission until birth of infant
measure: Infant antibiotic exposure
timeFrame: birth until 36 weeks corrected gestational age
Locations:
city: Memphis
country: United States
facility: LeBonheur Children's Hospital
state: Tennessee
city: Memphis
country: United States
facility: Regional One Health
state: Tennessee
Study officials:
References:
citation: Willis KA, Purvis JH, Myers ED, Aziz MM, Karabayir I, Gomes CK, Peters BM, Akbilgic O, Talati AJ, Pierre JF. Fungi form interkingdom microbial communities in the primordial human gut that develop with gestational age. FASEB J. 2019 Nov;33(11):12825-12837. doi: 10.1096/fj.201901436RR. Epub 2019 Aug 31.