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

Objective To examine the association between prophylactic hydrocortisone, given to prevent bronchopulmonary dysplasia, and the risk of focal intestinal perforation (FIP) 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 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. 2815 infants (988 exposed and 1827 unexposed) were included in the matched analysis; 47% girls, median gestational age of 26.0 weeks (IQR 24.6–26.9) and median birth weight of 815 g (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 to 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 to 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.