Effect of Early Hydrocortisone on Risk of Gastrointestinal Perforations in Extremely Preterm Infants
NCT Number: NCT06515405
Status: NOT_YET_RECRUITING
Study Type: OBSERVATIONAL
Conditions: Intestinal Perforation
Interventions: DRUG: Hydrocortisone
Sponsor: Imperial College London
Collaborators: Guy's and St Thomas' NHS Foundation Trust
Sex: ALL
Age: CHILD, ADULT, OLDER_ADULT
Enrollment: 16000
Study Design: Observational Model: |Time Perspective: p
Start Date: 2024-07-30
Completion Date: 2025-08-30

Summary:
A large, randomised control trial, the PREMILOC trial, has established that giving low dose hydrocortisone prophylactically in the first ten days of life reduces the risk of bronchopulmonary dysplasia in babies born before 32 weeks' gestation. However, the PREMILOC trial was underpowered to investigate rarer side effects, such as gastrointestinal perforation. This study aims to establish whether the odds of gastrointestinal perforation increase when extremely preterm infants are given prophylactic hydrocortisone in the first ten days of life.

This retrospective cohort study will use routinely collected data from the U.K. National Neonatal Research Database. We will examine the records of all infants born before 28 weeks' gestation and cared for in English and Welsh neonatal units between 2016 and 2023. Infants will be considered exposed if they received hydrocortisone for at least eight consecutive days, beginning on postnatal day 1 or 2. The primary outcome will be gastrointestinal perforation, as recorded in the infant's neonatal unit record. This outcome will be validated with the original care teams for a sample of babies. Data will be analysed using a propensity score matched approach to reduce the impact of confounding.

Primary Outcome Measures: Gastrointestinal (GI) perforation, A baby will be considered to have had a gastrointestinal perforation if their National Neonatal Research Database record includes a record of a GI perforation in the diagnoses field., From date of birth until day 14 of life
Secondary Outcome Measures: Survival without gastrointestinal perforation, Baby survived to discharge from neonatal unit without a gastrointestinal perforation, From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months|Mortality before discharge home, Baby died before discharge from neonatal unit, From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months|Total length of stay, Length of stay in neonatal care, From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months|Proportion of days on unit being mechanically ventilated, From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months|Bronchopulmonary dysplasia, any respiratory or ventilatory support or supplemental oxygen at 36 weeks' postmenstrual age (PMA), From date of birth until 36 weeks' postmenstrual age (PMA)|Bronchopulmonary dysplasia, Using an adapted Jensen criteria based on the highest level of respiratory support at 36 weeks PMA, From date of birth until 36 weeks' postmenstrual age (PMA)
Other Outcome Measures: Necrotising enterocolitis, UK National Neonatal Audit Programme definition, From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months|Severe necrotising enterocolitis, Necrotising enterocolitis confirmed at surgery or post-mortem or stated as cause of death, From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months|Pragmatically defined necrotising enterocolitis, 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, One or more episodes of a positive blood or cerebrospinal fluid culture with either a pure or mixed growth of a known pathogenic organism after the first three days following birth, From postnatal day 3 until the date of discharge from final neonatal unit, assessed up to 24 months|Brain injury occurring at or soon after birth, Intracranial haemorrhage, perinatal stroke, central nervous system infection, kernicterus (bilirubin encephalopathy), periventricular leukomalacia or any recorded seizure, From date of birth until the date of discharge from final neonatal unit, assessed up to 24 months|Treated retinopathy of prematurity, 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