Enterocolitis, Necrotizing
Conditions
Keywords
Probiotics
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).
Interventions
DIETARY_SUPPLEMENTProbiotics
Any exposure to probiotics in first 14 days of life
Sponsors
University of Nottingham
Newcastle University
Queen Mary University of London
Imperial College London
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
No minimum to 32 Weeks
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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)). |
| 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 |
| 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 to discharge home | On date of discharge from final neonatal unit, assessed up to 24 months | — |
| 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 |
| Bronchopulmonary dysplasia | 36 weeks postmenstrual age | Defined as any respiratory or ventilatory support or supplemental oxygen at 36 weeks postmenstrual age |
| 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 |
| 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 |
| Stage of retinopathy of prematurity | From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months | — |
| 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 |
| 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 |
Countries
United Kingdom
Outcome results
None listed