Gastrointestinal Microbiome Influence on the Development of Bronchopulmonary Dysplasia

Completed

• Conditions: Bronchopulmonary Dysplasia
• Interventions: Diagnostic Test: 16S rRNA stool microbiome sequencing.

• Registration Number: NCT03229967
• Lead Sponsor: University of Tennessee

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-07-05
• Study First Submitted: 2017-07-11
• Study First Submitted QC: 2017-07-24
• Study First Posted: 2017-07-26
• Primary Completion: 2020-12-30
• Study Completion: 2020-12-30
• Status Verified: 2023-05
• Last Update Submitted: 2023-05-08
• Last Update Posted: 2023-05-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 197

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Well Baby Cohort	16S rRNA stool microbiome sequencing.	40 Well Baby Infants have been enrolled and may be used for secondary analysis of microbial community composition of the meconium.
Validation Cohort	16S rRNA stool microbiome sequencing.	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.
Exploration Cohort	16S rRNA stool microbiome sequencing.	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.

Primary Outcome Measures

Name	Time	Method
Bronchopulmonary dysplasia (BPD)	36 weeks corrected gestational age, until the date of death or initial hospital discharge whichever occurs first, assessed up to up to 3 months	National Institute of Child Health and Disease (NICHD) consensus definition
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 Outcome Measures

Name	Time	Method
Maternal Chorioamnionitis	presence on admission
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	Modified Bell's staging for NEC \> Stage 2

Trial Locations

Locations (2)

Regional One Health; 🇺🇸 Memphis, Tennessee, United States

LeBonheur Children's Hospital; 🇺🇸 Memphis, Tennessee, United States