Do Probiotics Reduce The Risk Of Severe Necrotising Enterocolitis (NEC) In Infants Born Before 32 Weeks Gestation?

May 4, 2025 updated by: Cheryl Battersby, Imperial College London

Do Probiotics Reduce The Risk Of Severe Necrotising Enterocolitis (NEC) In Infants Born Before 32 Weeks Gestation? An Observational Study Using Routinely Collected Data.

Necrotising enterocolitis (NEC) is one of the leading causes of mortality and morbidity in very preterm infants. This study aims to determine whether NEC rates are different between infants who receive probiotics versus infants who do not receive probiotics. The study has a retrospective cohort design and will utilise routinely collected data from the UK National Neonatal Research Database (NNRD). The cohort will comprise all infants born before 32 weeks gestation and cared for in neonatal units in England and Wales between 2016 and 2022. A propensity score matched approach will be used to conduct two comparisons: i) the risk of necrotising enterocolitis (NEC) between who do and those who do not receive probiotics in the first 14 days of life ii) the risk of NEC between babies who receive the two most common probiotic products used in UK units, (Labinic and Proprems).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Enrolling by invitation

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
48000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Child

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Infants born very preterm i.e. before 32 weeks gestation

Description

Inclusion Criteria:

  • Eligible infants must have been born at less than 32 weeks gestation and be cared for in a English or Welsh unit which contributes data to the National Neonatal Research Database (this includes all NHS neonatal units in England and Wales).
  • Infants born in the period January 1st, 2016, to December 31st, 2022 (7 years) will be included.

Exclusion Criteria:

  • They have missing data for any of: gestational age at birth, birth weight, year of birth and date of death (for those that died).
  • Their NNRD record does not include details of their first admission or begins after Day 3 of life.
  • The absolute value of their recorded birthweight for gestational age z score exceeds 4 or is missing.
  • They die in the first two postnatal days of life.
  • They have a major congenital abnormality

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Exposed to probiotics

Receipt of any probiotic in the first 14 days of life. Probiotics to include: Labinic, Proprems probiotic, Acidophillus, Bifidobacterium, Bio-kult, Infloran, LB2.

To address potential recording error, infants whose NNRD records show minimal (one day) of probiotic exposure will only be classed as exposed if they are cared for in a probiotic unit. Probiotic units are defined as:

  • units who have confirmed that a guideline was in place to provide probiotics to infants born before 32 weeks gestation and that the guideline was in place at any point in the year that the infant was born OR
  • units where more than 50% of the infants eligible to be part of the cohort received probiotics in the six months after the infant was born.
Dietary supplement: Probiotics
Any exposure to probiotics in first 14 days of life
Other Names:
  • Infloran
  • Bifidobacterium
  • Labinic
  • Proprems
  • Acidophillus
  • Bio-kult
  • LB2
No probiotic exposure
Did not receive any probiotic in the first 14 days of life.
Dietary supplement: Probiotics
Any exposure to probiotics in first 14 days of life
Other Names:
  • Infloran
  • Bifidobacterium
  • Labinic
  • Proprems
  • Acidophillus
  • Bio-kult
  • LB2

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Severe necrotising enterocolitis (NEC)
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
NEC confirmed at surgery or postmortem or listed as a cause of death
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Necrotising enterocolitis (NNAP definition)
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
NEC diagnosed at postmortem or NEC diagnosed during surgery or NEC diagnosed using clinical and radiographic features (where the infant has at least one clinical feature (bilious gastric aspirate or emesis, abdominal distension, occult, gross blood in stool) and at least one radiographic feature (pneumatosis, hepato-biliary gas, pneumoperitoneum)).
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Pragmatically defined NEC
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Infants who had a recorded diagnosis of necrotising enterocolitis and received at least 5 consecutive days of antibiotics whilst also nil by mouth
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Late onset sepsis
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
HQIP NNAP case definition
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Pragmatically defined late onset sepsis
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Growth of any organisms that appear in the NNAP lists of "Clearly pathogenic organisms" and "Other organisms"
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Survival to discharge home
Time Frame: On date of discharge from final neonatal unit, assessed up to 24 months
On date of discharge from final neonatal unit, assessed up to 24 months
Survival without severe NEC or late onset sepsis (LOS)
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
LOS is defined according to the Healthcare Quality Improvement Partnership (HQIP) National Neonatal Audit Programme (NNAP) case definition i.e. blood stream or cerebrospinal fluid confirmed pure growth in culture after first three days of life
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Survival without any NEC
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
NEC is defined as per the NNAP definition
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Brain injury
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Either left or right grade 3 or higher intra-ventricular haemorrhage or cystic periventricular leukomalacia
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Treated retinopathy of prematurity
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Defined as cryotherapy, laser therapy or injection of anti-vascular endothelial growth factor therapy for ROP in either or both eyes
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Stage of retinopathy of prematurity
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Bronchopulmonary dysplasia
Time Frame: 36 weeks postmenstrual age
Defined as any respiratory or ventilatory support or supplemental oxygen at 36 weeks postmenstrual age
36 weeks postmenstrual age
Severe bronchopulmonary dysplasia
Time Frame: 36 weeks postmenstrual age
Defined as ventilation via endotracheal tube or trachestomy, and excluding non-invasive support or CPAP, at 36 weeks postmenstrual age
36 weeks postmenstrual age
Length of stay
Time Frame: From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Number of days between first neonatal unit admission and final neonatal unit discharge for surviving infants
From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Time to full feeds
Time Frame: Before discharge from final neonatal unit
Defined as the number of days until an infant is recorded as not requiring any parenteral nutrition or fluid (i.e. no parenteral nutrition or intravenous dextrose)
Before discharge from final neonatal unit
Growth
Time Frame: 36 weeks corrected gestational age
Weight for post-menstrual age standard deviation score
36 weeks corrected gestational age

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Imperial College London

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
University of Nottingham
Queen Mary University of London
Newcastle University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 30, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 30, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 24, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 21, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 7, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 4, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRAS323099

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

IPD Plan Description

Study protocol available now. Analysis code will be available after publication of results.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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