Do Probiotics Reduce The Risk Of Severe Necrotising Enterocolitis (NEC) In Infants Born Before 32 Weeks Gestation?
- Conditions
- Enterocolitis, Necrotizing
- Interventions
- Dietary Supplement: Probiotics
- Registration Number
- NCT06422988
- Lead Sponsor
- Imperial College London
- Brief 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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ENROLLING_BY_INVITATION
- Sex
- All
- Target Recruitment
- 48000
- 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.
- 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 & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description No probiotic exposure Probiotics Did not receive any probiotic in the first 14 days of life. Exposed to probiotics 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.
- Primary Outcome Measures
Name Time Method Severe necrotising enterocolitis (NEC) 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
- Secondary Outcome Measures
Name Time Method Pragmatically defined NEC 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
Survival without severe NEC or late onset sepsis (LOS) 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
Late onset sepsis From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months HQIP NNAP case definition
Pragmatically defined late onset sepsis 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"
Survival without any NEC 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
Treated retinopathy of prematurity 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
Necrotising enterocolitis (NNAP definition) 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)).
Brain injury 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
Stage of retinopathy of prematurity From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months Bronchopulmonary dysplasia 36 weeks postmenstrual age Defined as any respiratory or ventilatory support or supplemental oxygen at 36 weeks postmenstrual age
Survival to discharge home On date of discharge from final neonatal unit, assessed up to 24 months Severe bronchopulmonary dysplasia 36 weeks postmenstrual age Defined as ventilation via endotracheal tube or trachestomy, and excluding non-invasive support or CPAP, at 36 weeks postmenstrual age
Length of stay 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
Time to full feeds 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)
Growth 36 weeks corrected gestational age Weight for post-menstrual age standard deviation score
Trial Locations
- Locations (1)
Imperial College
🇬🇧London, United Kingdom