# Early Prophylactic Hydrocortisone and Bronchopulmonary Dysplasia–Free Survival in Extremely Preterm Infants

## TL;DR

Early use of hydrocortisone in extremely preterm infants in Sweden is linked to better survival without lung disease, with no major safety concerns.

## Contribution

This study provides real-world evidence supporting the benefits and safety of early prophylactic hydrocortisone in preterm infants.

## Key findings

- Hydrocortisone was associated with a 62% higher odds of survival without BPD.
- BPD occurred less frequently in the hydrocortisone group.
- No significant increase in severe neonatal morbidities was observed.

## Abstract

This cohort study evaluates the association between early prophylactic hydrocortisone and survival without bronchopulmonary dysplasia (BPD) in extremely preterm infants in Sweden.

After guideline implementation, has early prophylactic hydrocortisone improved survival without bronchopulmonary dysplasia (BPD) in extremely preterm infants born in Sweden, and is it safe to use?

In this cohort study using prospectively collected data from 1106 infants from a national register, introduction of prophylactic hydrocortisone was followed by an increased likelihood of survival without BPD. There was no significant increase in severe neonatal morbidities.

These findings, based on clinical implementation data, suggest alignment with previous similar studies supporting the benefits and safety of early prophylactic hydrocortisone treatment.

In randomized trials, early prophylactic hydrocortisone improved survival without bronchopulmonary dysplasia (BPD) with few adverse effects in extremely preterm infants. Large scale implementation data are needed to evaluate clinical effects and safety.

To examine the association between early prophylactic hydrocortisone and survival without BPD at 36 weeks’ postmenstrual age (PMA) in extremely preterm infants in Sweden after guideline implementation and to assess treatment safety.

A national historical cohort study with prospectively collected data from the Swedish Neonatal Quality register from 4 Swedish centers where hydrocortisone prophylaxis was implemented. The study included infants born between 22 and 27 weeks’ gestation between 2018 and 2023. Infants were divided into exposed and nonexposed groups according to the intention-to-treat principle.

Hydrocortisone, 1 mg/kg/d, for the first 7 days of life, followed by 0.5 mg/kg/d from days 8 through 10.

The primary outcome was survival without BPD at 36 weeks’ PMA. A predefined statistical analysis plan with logistic regression was used to calculate unadjusted and adjusted odds ratios.

Among 1106 infants (median [IQR] gestational age, 25 weeks, 6 days [24 weeks, 3 days to 27 weeks]; median [IQR] birth weight, 780 [610-964] g), 474 received hydrocortisone prophylaxis and 632 did not. Survival without BPD occurred in 154 of 474 exposed (32.5%) and 185 of 632 nonexposed (29.3%) infants (adjusted odds ratio, 1.62; 95% CI, 1.16-2.27). BPD occurred in 233 exposed (49.2%) and 345 nonexposed (54.6%) infants (adjusted odds ratio, 0.65; 95% CI, 0.49-0.86). Death before 36 weeks’ PMA occurred in 87 exposed (18.4%) and 102 nonexposed (16.1%) infants. Late-onset bacterial infection was more common in exposed infants, but not significant after adjustment. No other severe neonatal morbidities differed significantly between the 2 groups.

In this cohort study of extremely preterm infants, the introduction of prophylactic hydrocortisone was associated with increased survival without BPD, after adjusting for covariates. There was no significant increase in severe neonatal morbidities, except that late-onset bacterial infection was more common in the exposed group before adjustments.