Early Prophylactic Hydrocortisone and Survival Without BPD in Extremely Preterm Infants

Importance In randomized trials, early prophylactic low-dose hydrocortisone improved survival without bronchopulmonary dysplasia (BPD) and had few adverse effects in extremely preterm infants. Large scale implementation data are needed to estimate effect size and safety.

To examine the association between early prophylactic hydrocortisone and survival without BPD at 36 weeks postmenstrual age in extremely preterm infants in Sweden after implementation, and to assess the safety of this treatment. Design A national historical cohort study with prospectively collected data. Setting Data was collected from the Swedish Neonatal Quality register from four Swedish regions where prophylactic hydrocortisone was implemented. Participants The study included 1140 infants born before 28 weeks gestation between 2018 and 2023. A total of 1106 infants met inclusion criteria. Infants were divided into exposed and non-exposed groups based on the intention-to-treat principle. Exposure Hydrocortisone 1 mg/kg/day for the first 7 days of life, followed by 0.5 mg/kg/day from days 8 to 10. Main outcomes and measures The primary outcome was survival without BPD at 36 weeks’ postmenstrual age. Logistic regression was used to present odds ratios (OR), both unadjusted and after adjustment for covariates.

Among 1106 infants (median [IQR] gestational age, 25+6 [24+3-27+0] weeks; median [IQR] birth weight, 780 [610-964] g), 474 received prophylactic hydrocortisone and 632 did not. Survival without BPD occurred in 154 of 474 exposed infants (32.5%) and in 185 of 632 unexposed infants (29.3%). Adjusted OR was 1.62 (95% CI, 1.16–2.27). The reduction in BPD, rather than mortality, primarily drove this effect. The strongest association was observed in infants born at 24–25 weeks’ gestation. Late-onset bacterial infection was more common in the exposed group, but the difference was not significant after adjustment. No other severe neonatal morbidities differed significantly between the two groups.

and relevance Exposure to prophylactic hydrocortisone in extremely preterm infants was associated with increased survival without BPD, significant after adjustments. There was no significant increase in severe neonatal morbidities, except that late-onset bacterial infection was more common in the exposed group before adjustments. Question Does early prophylactic hydrocortisone improve survival without bronchopulmonary dysplasia in extremely preterm infants born in Sweden, and is it safe to use? Findings Using prospectively collected data from a national register, this study found that exposure to prophylactic hydrocortisone was associated with increased likelihood of survival without BPD. There was no significant increase in severe neonatal morbidities. Meaning This study, investigating real-world data, aligns with previous similar studies supporting the potential benefits and safety of early prophylactic hydrocortisone treatment. Competing Interest Statement The authors have declared no competing interest. Funding Statement This study was funded by the Cocozza foundation and research grant from ALF region Ostergotland Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the Swedish Ethical Review Authority (Dnr 2024-05118). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors