Early Prophylactic Hydrocortisone and Survival Without Bronchopulmonary Dysplasia in Extremely Preterm Infants.

ImportanceIn 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. ObjectiveTo 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. DesignA national historical cohort study with prospectively collected data. SettingData was collected from the Swedish Neonatal Quality register from four Swedish regions where prophylactic hydrocortisone was implemented. ParticipantsThe 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. ExposureHydrocortisone 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 measuresThe 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. ResultsAmong 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. Conclusion and relevanceExposure 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. Key pointsO_ST_ABSQuestionC_ST_ABSDoes early prophylactic hydrocortisone improve survival without bronchopulmonary dysplasia in extremely preterm infants born in Sweden, and is it safe to use? FindingsUsing 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. MeaningThis study, investigating real-world data, aligns with previous similar studies supporting the potential benefits and safety of early prophylactic hydrocortisone treatment.