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

Enterocolitis, Necrotizing Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT06422988
• Other study ID #: IRAS323099
• Status: Enrolling by invitation
• Start date: May 30, 2024
• Est. completion date: December 30, 2024

Study information

• Verified date: May 2024
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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).

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 48000
• Est. completion date: December 30, 2024
• Est. primary completion date: July 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 32 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Enterocolitis
• Enterocolitis, Necrotizing

Intervention

Dietary Supplement:
• Probiotics
Any exposure to probiotics in first 14 days of life

Locations

Country	Name	City	State
United Kingdom	Imperial College	London

Sponsors (4)

Lead Sponsor	Collaborator
Imperial College London	Newcastle University, Queen Mary University of London, University of Nottingham

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Severe necrotising enterocolitis (NEC)	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	Necrotising enterocolitis (NNAP definition)	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
Secondary	Pragmatically defined NEC	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
Secondary	Late onset sepsis	HQIP NNAP case definition	From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Secondary	Pragmatically defined late onset sepsis	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
Secondary	Survival to discharge home		On date of discharge from final neonatal unit, assessed up to 24 months
Secondary	Survival without severe NEC or late onset sepsis (LOS)	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
Secondary	Survival without any NEC	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
Secondary	Brain injury	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
Secondary	Treated retinopathy of prematurity	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
Secondary	Stage of retinopathy of prematurity		From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months
Secondary	Bronchopulmonary dysplasia	Defined as any respiratory or ventilatory support or supplemental oxygen at 36 weeks postmenstrual age	36 weeks postmenstrual age
Secondary	Severe bronchopulmonary dysplasia	Defined as ventilation via endotracheal tube or trachestomy, and excluding non-invasive support or CPAP, at 36 weeks postmenstrual age	36 weeks postmenstrual age
Secondary	Length of stay	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
Secondary	Time to full feeds	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
Secondary	Growth	Weight for post-menstrual age standard deviation score	36 weeks corrected gestational age