Defining the Intestinal Microbiota in Premature Neonates

The Microbiota of the Premature Neonatal Gastrointestinal Tract: Its Development and Relation to Necrotizing Enterocolitis and Bloodstream Infection

The investigators will collect daily faecal samples from premature (<32 weeks) infants in the intensive care unit from the day of birth until they are discharged. By using newly developed molecular detection techniques the investigators aim to define more precisely than has ever previously been attempted, all the species of bacteria present in the faeces. This will enable comparison of the pre-morbid and post-morbid intestinal microbiota (all the bacteria in the gut) in premature neonates.

Study Overview

• Status: Completed
• Conditions: Necrotizing Enterocolitis; Premature Intestinal Microbiota; Late Onset Bloodstream Infection

Detailed Description

Highly premature infants are susceptible to serious infections such as necrotizing enterocolitis (NEC) and late-onset blood stream infections (BSIs).

NEC is a poorly understood, potentially life-threatening bowel disorder. It is thought that bacteria proliferating abnormally in the bowel may play an important part in its cause, but no single pathogen has yet been identified.

BSIs are commonly caused by gut bacteria. As the highly premature gut is fragile and has increased permeability, poor motility and decreased immune defences, localised inflammation caused by abnormal bacterial growth may allow 'bystander' microbes to translocate through the gut into the blood stream leading to systemic infection.

In a small proportion of infants who develop NEC, surgery will be required as part of treatment of the condition. In these infants the investigators will seek consent to collect a small part of the diseased bowel which has been removed. Similar analysis will be performed on these samples. The analysis of the tissue samples will give us an indication of how well the faeces act as a proxy for the intestinal microbiota.

In this ecological study of the evolution of the intestinal microbiota in preterm infants, by comparing samples from babies who develop NEC or late-onset BSI with those of well babies the investigators will be able to look for differences characteristic of the conditions. This information will help aid design of prevention or treatment strategies.

• Study Type: Observational
• Enrollment (Actual): 369

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, W21PG
    • Imperial College London
  • London, United Kingdom
    • Queen Charlotte's and Chelsea Hospital - NICU
  • London, United Kingdom
    • St. Mary's Hospital - Winnicott Baby Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 7 months (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Premature babies born at less than 32 completed weeks gestation

Description

Inclusion Criteria:

• All premature babies born at less than 32 completed weeks gestation who are admitted to an Imperial College NHS Healthcare Trust Neonatal Intensive Care Unit (St. Mary's Hospital or Queen Charlotte's & Chelsea Hospital), and whose parents/guardians have given their consent will be eligible to enter the study.

Exclusion Criteria:

• All babies born at more than 32 completed weeks gestation will be excluded from the study.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Premature babies (<32 weeks); All premature babies born at less than 32 completed weeks gestation who are admitted to an Imperial College NHS Healthcare Trust Neonatal Intensive Care Unit (St. Mary's Hospital or Queen Charlotte's & Chelsea Hospital), and whose parents/guardians have given their consent will be eligible to enter the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The Composition of Bacteria Present, Established by Ultra-deep RNA Gene Sequencing, in Pre-morbid Faecal Samples From Neonates With Necrotizing Enterocolitis and Late-onset Bacterial Sepsis.	Faecal samples were analysed using 16S rRNA gene sequencing to determine the bacterial content present in faecal samples collected from pre term infants prior to the onset of necrotising enterocolitis. Bacteria were identified and relative proportions reported for each faecal sample analysed.	Maximum of 6 months - serial samples collected from each infant (maximum admission duration 6 months), recruitment opened for 24 months.

Collaborators and Investigators

• Sponsor: Imperial College London
• Collaborators: Chelsea and Westminster NHS Foundation Trust; National Heart and Lung Institute; The Winnicott Foundation
• Investigators: Principal Investigator: J Simon Kroll, MA BM FRCP, Imperial College London

Publications and helpful links

General Publications

• Shaw AG, Cornwell E, Sim K, Thrower H, Scott H, Brown JCS, Dixon RA, Kroll JS. Dynamics of toxigenic Clostridium perfringens colonisation in a cohort of prematurely born neonatal infants. BMC Pediatr. 2020 Feb 18;20(1):75. doi: 10.1186/s12887-020-1976-7.
• Sim K, Shaw AG, Randell P, Cox MJ, McClure ZE, Li MS, Haddad M, Langford PR, Cookson WO, Moffatt MF, Kroll JS. Dysbiosis anticipating necrotizing enterocolitis in very premature infants. Clin Infect Dis. 2015 Feb 1;60(3):389-97. doi: 10.1093/cid/ciu822. Epub 2014 Oct 23. Erratum In: Clin Infect Dis. 2015 Jun 15;60(12):1879.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2011
• Primary Completion (Actual): January 1, 2013
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: March 31, 2010
• First Submitted That Met QC Criteria: April 12, 2010
• First Posted (Estimate): April 13, 2010

Study Record Updates

• Last Update Posted (Actual): May 1, 2020
• Last Update Submitted That Met QC Criteria: April 30, 2020
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: Necrotizing Enterocolitis; Premature intestinal microbiota
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Systemic Inflammatory Response Syndrome; Inflammation; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Sepsis; Infections; Premature Birth; Enterocolitis; Enterocolitis, Necrotizing
• Other Study ID Numbers: CR01542

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No