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

Smedbäck, Veronica ; Björklund, Lars J. LU ; Flisberg, Anders ; Wróblewska, Jolanta ; Baud, Olivier ; Wejryd, Erik and Ådén, Ulrika LU (2026) In JAMA Network Open 9(2).
Abstract

Importance 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. Objective 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. Design, Setting, and Participants 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... (More)

Importance 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. Objective 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. Design, Setting, and Participants 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. Exposure Hydrocortisone, 1 mg/kg/d, for the first 7 days of life, followed by 0.5 mg/kg/d from days 8 through 10. Main outcomes and measures 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. Results 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. Conclusions and relevance 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.

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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
JAMA Network Open
volume
9
issue
2
article number
e2560146
publisher
American Medical Association
external identifiers
  • pmid:41712209
  • scopus:105030633153
ISSN
2574-3805
DOI
10.1001/jamanetworkopen.2025.60146
language
English
LU publication?
yes
additional info
Publisher Copyright: © 2026 Smedbäck V et al.
id
12c7a62f-33bb-471a-ae35-bd47cf04f729
date added to LUP
2026-04-16 15:40:03
date last changed
2026-04-17 03:00:02
@article{12c7a62f-33bb-471a-ae35-bd47cf04f729,
  abstract     = {{<p>Importance 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. Objective 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. Design, Setting, and Participants 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. Exposure Hydrocortisone, 1 mg/kg/d, for the first 7 days of life, followed by 0.5 mg/kg/d from days 8 through 10. Main outcomes and measures 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. Results 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. Conclusions and relevance 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.</p>}},
  author       = {{Smedbäck, Veronica and Björklund, Lars J. and Flisberg, Anders and Wróblewska, Jolanta and Baud, Olivier and Wejryd, Erik and Ådén, Ulrika}},
  issn         = {{2574-3805}},
  language     = {{eng}},
  month        = {{02}},
  number       = {{2}},
  publisher    = {{American Medical Association}},
  series       = {{JAMA Network Open}},
  title        = {{Early Prophylactic Hydrocortisone and Bronchopulmonary Dysplasia–Free Survival in Extremely Preterm Infants}},
  url          = {{http://dx.doi.org/10.1001/jamanetworkopen.2025.60146}},
  doi          = {{10.1001/jamanetworkopen.2025.60146}},
  volume       = {{9}},
  year         = {{2026}},
}