Clinical trial NCT01102738: Defining the Intestinal Microbiota in Premature Neonates
Official title: The Microbiota of the Premature Neonatal Gastrointestinal Tract: Its Development and Relation to Necrotizing Enterocolitis and Bloodstream Infection
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Premature Intestinal Microbiota
Necrotizing Enterocolitis
Late Onset Bloodstream Infection
Keywords: Premature intestinal microbiota
Necrotizing Enterocolitis
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: The Winnicott Foundation
name: National Heart and Lung Institute
name: Chelsea and Westminster NHS Foundation Trust
First posted: 2010-04-13
Enrollment: 369
Sex: ALL
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: yes
Observational model: ECOLOGIC_OR_COMMUNITY
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Premature babies born at less than 32 completed weeks gestation

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Maximum of 6 months - serial samples collected from each infant (maximum admission duration 6 months), recruitment opened for 24 months.
Secondary outcomes:
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College London
city: London
country: United Kingdom
facility: Queen Charlotte's and Chelsea Hospital - NICU
city: London
country: United Kingdom
facility: St. Mary's Hospital - Winnicott Baby Unit
Study officials:
affiliation: Imperial College London
name: J Simon Kroll, MA BM FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.