Early Hydrocortisone and Survival Without BPD in Extremely Preterm Infants

A Swedish registry-based national historical cohort study reported a higher likelihood of survival without bronchopulmonary dysplasia among extremely preterm infants after implementation of early prophylactic hydrocortisone, while also reporting no significant increase in severe neonatal morbidities.

The report characterizes the findings as arising from prospectively collected routine-care register data evaluating outcomes after clinical guideline implementation at participating centers.

As background, the report notes that more than half of infants born extremely prematurely (before 28 weeks’ gestation) develop bronchopulmonary dysplasia. The outcome emphasized in the write-up is survival without bronchopulmonary dysplasia, described as improved survival without lung disease. The analysis is presented as examining whether early prophylactic hydrocortisone exposure was associated with surviving without lung disease at 36 weeks’ postmenstrual age.

The comparison is described as a historical cohort analysis tied to implementation of prophylactic hydrocortisone at four Swedish centers, using an intention-to-treat approach in which infants born before each center’s implementation date were classified as nonexposed and infants born on or after implementation were classified as exposed. Investigators analyzed Swedish Neonatal Quality Register data to compare infants born at 22–27 weeks’ gestation between 2018 and 2023. A total of 474 exposed infants were compared with 632 nonexposed infants in the main cohort, with additional sensitivity analyses including a broader national cohort (including centers that did not adopt prophylactic hydrocortisone) and propensity score–matched comparisons.

Within that setup, the authors report that early prophylactic hydrocortisone exposure was associated with a greater chance of surviving without BPD. The study also reported the components of the primary outcome: BPD occurred in 233 of 474 exposed (49.2%) vs 345 of 632 nonexposed (54.6%) infants (adjusted odds ratio 0.65), and death before 36 weeks’ postmenstrual age occurred in 87 exposed (18.4%) vs 102 nonexposed (16.1%) infants, with no significant difference in mortality after adjustment.

For short-term safety, the authors reported no significant differences in severe neonatal morbidities overall between exposed and nonexposed infants. Late-onset bacterial infection was more common in exposed infants in unadjusted analyses but was not statistically significant after adjustment, and other severe neonatal morbidities did not differ significantly. The report describes this work as limited to short-term neonatal outcomes and notes that longer-term follow-up, including neurodevelopmental outcomes, is being planned.

Key Takeaways:

• There was an association between early prophylactic hydrocortisone exposure and higher survival without BPD in extremely preterm infants.
• The analysis is presented as a national historical cohort study using Swedish Neonatal Quality Register data, comparing exposed (n=474) and nonexposed (n=632) infants defined by center-level implementation timing (intention-to-treat), with additional national and propensity score–matched sensitivity analyses.
• Authors describe no significant increase in severe neonatal morbidities overall; late-onset bacterial infection was higher in unadjusted analyses but not significant after adjustment, and longer-term outcomes, including neurodevelopment, are planned for evaluation.