Late Onset Bloodstream Infection, Necrotizing Enterocolitis, Premature Intestinal Microbiota
Conditions
Keywords
Premature intestinal microbiota, Necrotizing Enterocolitis
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.
Interventions
None listed
Sponsors
The Winnicott Foundation
National Heart and Lung Institute
Chelsea and Westminster NHS Foundation Trust
Imperial College London
Study design
Observational model
ECOLOGIC_OR_COMMUNITY
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 32 Weeks
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Maximum of 6 months - serial samples collected from each infant (maximum admission duration 6 months), recruitment opened for 24 months. | 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 369 |
| Total | 369 |
Baseline characteristics
| Characteristic | Premature Babies (<32 Weeks) |
|---|---|
| Age, Categorical <=18 years | 369 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 2 days |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 339 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 28 Participants |
| Region of Enrollment United Kingdom | 369 participants |
| Sex: Female, Male Female | 171 Participants |
| Sex: Female, Male Male | 198 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 30 / 369 |
| other Total, other adverse events | 0 / 369 |
| serious Total, serious adverse events | 0 / 369 |
Outcome results
Primary
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.
Time frame: Maximum of 6 months - serial samples collected from each infant (maximum admission duration 6 months), recruitment opened for 24 months.
Population: Faecal samples and clinical data were collected from all participants (369 infants) recruited into the study. Samples were only analysed from infants who developed NEC (n=12) and 3 matched controls (n=36).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Premature Babies (<32 Weeks) | 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. | Klebsiella OTU associated NEC | 7 Participants |
| Premature Babies (<32 Weeks) | 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. | Clostridium associated NEC | 4 Participants |
| Premature Babies (<32 Weeks) | 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. | Non Klebsiella or Clostridium associated NEC | 1 Participants |
| Premature Babies (<32 Weeks) | 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. | Controls | 36 Participants |