Gastrointestinal Microbiome Influence on the Development of Bronchopulmonary Dysplasia

NCT03229967 | Completed

• 1 other identifier: 17-05311-XP
• Study Type: observational
• Target: 197
• Locations: 1 country
• Sites: 2

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.

Conditions

Bronchopulmonary Dysplasia

Keywords

Bronchopulmonary dysplasia; Microbiome; Microbiota; Premature infant; Observational cohort study

Outcome Measures

Primary Outcomes (2)

• Bronchopulmonary dysplasia (BPD)

  National Institute of Child Health and Disease (NICHD) consensus definition

  36 weeks corrected gestational age, until the date of death or initial hospital discharge whichever occurs first, assessed up to up to 3 months

• Death

  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 (2)

• Necrotizing Enterocolitis (NEC)

  from the date of enrollment until the date of initial hospital discharge or death, whichever occurs first, assessed up to up to 3 months

• Maternal Chorioamnionitis

  presence on admission

Other Outcomes (2)

• Maternal perinatal antibiotic exposure

  from hospital admission until birth of infant

• Infant antibiotic exposure

  birth until 36 weeks corrected gestational age

Study Arms (3)

Exploration Cohort

Up to 150 VLBW (very low birthweight) infants enrolled from the Regional One Health NICU (neonatal intensive care unit). Weekly stool samples will be obtained. After 36 weeks infants diagnosed with BPD per NIH guidelines, will be matched with infants without BPD. Stool samples from these infants will be sent for 16s rRNA (ribosomal ribonucleic acid) sequencing after conclusion of initial enrollment period. ITS (internal transcribed spacer) DNA may also be used to characterize fungal communities.

Diagnostic Test: 16S rRNA stool microbiome sequencing.

Validation Cohort

Up to 10 VLBW infants enrolled from the Le Bonheur Children's Hospital NICU. Weekly stool samples will be obtained. After 36 weeks infants diagnosed with BPD per NIH guidelines willl be matched with infants without BPD. Stool samples from these infants will be sent for 16s rRNA sequencing after conclusion of initial enrollment period.

Diagnostic Test: 16S rRNA stool microbiome sequencing.

Well Baby Cohort

40 Well Baby Infants have been enrolled and may be used for secondary analysis of microbial community composition of the meconium.

Diagnostic Test: 16S rRNA stool microbiome sequencing.

Interventions

16S rRNA stool microbiome sequencing. DIAGNOSTIC_TEST

This is an observational cohort that will undergo gut microbiome sequencing.

Exploration Cohort; Validation Cohort; Well Baby Cohort

Eligibility Criteria

• Age: 0 Days - 7 Days
• Sex: all
• Age Groups: Child (0-17)
• 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)

You may qualify if:

• 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.
• Parents can understand and comply with planned study procedures.
• Parents provide assent/permission prior to any study procedures.

You may not qualify if:

• Diagnosed immunodeficiency disorder.
• Currently receiving investigational immunomodulatory, probiotic or antiviral agent.
• Diagnosed immunodeficiency disorder
• Currently receiving investigational immunomodulatory, probiotic or antiviral agents
• 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.

Sponsors & Collaborators

• University of Tennessee: lead

Study Sites (2)

LeBonheur Children's Hospital

Memphis, Tennessee, 38105, United States

Location

Regional One Health

Memphis, Tennessee, 38105, United States

Location

Related Publications (1)

• 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.

  PMID: 31480903 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Fecal Stool Sample (contains bacterial and fungal DNA)

MeSH Terms

Conditions

Bronchopulmonary Dysplasia; Premature Birth

Condition Hierarchy (Ancestors)

Ventilator-Induced Lung Injury; Lung Injury; Lung Diseases; Respiratory Tract Diseases; Infant, Premature, Diseases; Infant, Newborn, Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Neonatal-Perinatal Medicine Fellow

Study Record Dates

• First Submitted: July 11, 2017
• First Posted: July 26, 2017
• Study Start: July 5, 2017
• Primary Completion: December 30, 2020
• Study Completion: December 30, 2020
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)