Association between prophylactic hydrocortisone and focal intestinal perforations in preterm infants born before 28 weeks gestation: an observational propensity matched population study in England and Wales
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Objective
To examine the association between prophylactic hydrocortisone, given to prevent bronchopulmonary dysplasia, and the risk of focal intestinal perforation in preterm infants.
Design
Retrospective cohort study using routinely-collected data from infants born between 2016 and 2023.
Setting
All English and Welsh neonatal units
Patients
15,746 infants born at less than 28 weeks’ gestation and admitted to a neonatal unit. Infants were matched (exposed vs unexposed) using a propensity score comprising 17 variables.
Exposure
Exposed infants received hydrocortisone for at least eight consecutive days beginning on postnatal day one or two. Unexposed infants did not receive hydrocortisone in line with this definition.
Main outcome measures
Primary outcome was focal intestinal perforation (FIP). Secondary outcomes included mortality, survival without FIP, bronchopulmonary dysplasia.
Results
6.3% (999/15,746) infants were exposed to early hydrocortisone, and 4.6% (722/15,746) had FIP. 2,815 infants (988 exposed and 1,827 unexposed) were included in the matched analysis; 47% girls, median gestational age of 26.0 weeks (IQR 24.6-26.9) and median birthweight of 815 grams (IQR 674-965). There was no significant difference in risk of FIP (4.9% (48/988) exposed vs 6.1% (111/1827) unexposed, OR 0.79, 95% CI 0.55- 1.14); findings were consistent in the sensitivity analyses. Early hydrocortisone was associated
with increased mortality (21.3% (210/988) exposed vs 16.2% (295/1827) unexposed, OR 1.40, 95% CI 1.14-1.72).
Conclusions
Early prophylactic hydrocortisone from the first postnatal week was not associated with FIP. The observed association with higher mortality was a secondary finding in this observational study and requires cautious interpretation and further investigation.
To examine the association between prophylactic hydrocortisone, given to prevent bronchopulmonary dysplasia, and the risk of focal intestinal perforation in preterm infants.
Design
Retrospective cohort study using routinely-collected data from infants born between 2016 and 2023.
Setting
All English and Welsh neonatal units
Patients
15,746 infants born at less than 28 weeks’ gestation and admitted to a neonatal unit. Infants were matched (exposed vs unexposed) using a propensity score comprising 17 variables.
Exposure
Exposed infants received hydrocortisone for at least eight consecutive days beginning on postnatal day one or two. Unexposed infants did not receive hydrocortisone in line with this definition.
Main outcome measures
Primary outcome was focal intestinal perforation (FIP). Secondary outcomes included mortality, survival without FIP, bronchopulmonary dysplasia.
Results
6.3% (999/15,746) infants were exposed to early hydrocortisone, and 4.6% (722/15,746) had FIP. 2,815 infants (988 exposed and 1,827 unexposed) were included in the matched analysis; 47% girls, median gestational age of 26.0 weeks (IQR 24.6-26.9) and median birthweight of 815 grams (IQR 674-965). There was no significant difference in risk of FIP (4.9% (48/988) exposed vs 6.1% (111/1827) unexposed, OR 0.79, 95% CI 0.55- 1.14); findings were consistent in the sensitivity analyses. Early hydrocortisone was associated
with increased mortality (21.3% (210/988) exposed vs 16.2% (295/1827) unexposed, OR 1.40, 95% CI 1.14-1.72).
Conclusions
Early prophylactic hydrocortisone from the first postnatal week was not associated with FIP. The observed association with higher mortality was a secondary finding in this observational study and requires cautious interpretation and further investigation.
Date Acceptance
2026-08-17
Citation
Archives of Disease in Childhood: Fetal and Neonatal Edition
ISSN
1359-2998
Publisher
BMJ Publishing Group
Journal / Book Title
Archives of Disease in Childhood: Fetal and Neonatal Edition
Copyright Statement
Copyright This paper is embargoed until publication. Once published the author’s accepted manuscript will be made available under a CC-BY License in accordance with Imperial’s Research Publications Open Access policy (www.imperial.ac.uk/oa-policy).
License URL
Publication Status
Accepted