Source: de Baat T, van de Loo M, Aarnoudse-Moens, et al. Effect of systemic hydrocortisone in ventilated infants born preterm: mortality and 5.5-year neurodevelopmental outcomes of a randomized clinical trial. J Pediatr. 2026:290:114954; doi: 10.1016/j.jpeds.2025.114954.Investigators from multiple institutions conducted a follow-up study to assess the association between treatment with hydrocortisone (HC) in premature infants and mortality and neurodevelopmental outcomes at 5.5 years corrected age. Study participants were born at <30 weeks’ gestation and were considered to be at risk for development of bronchopulmonary dysplasia (BPD) when they were enrolled in the original randomized controlled trial. These infants were randomized to treatment with HC or placebo when they were 7–14 days of age. For the current study, surviving children had a comprehensive neurodevelopmental assessment when they were approximately 5.5 years corrected age. The assessment included the Wechsler Preschool and Primary Scale of Intelligence-III (WPPSI), a detailed neurologic examination, and evaluation of functional disabilities, eg, need for hearing aids. Based on the assessment, participants were classified as having no neurodevelopmental impairment (NDI) or mild, moderate, or severe NDI. The primary study outcome was a composite of death or moderate-to-severe NDI. Moderate-to-severe NDI was defined as ≥1 of the following: full scale IQ (FSIQ) ≤70, functionally impaired vision or hearing, or cerebral palsy with a Gross Motor Function Classification System of 2 or worse. Secondary outcomes included death or moderate-to-severe NDI, assessed separately, and individual components of WPPSI. These outcomes were compared among children in the HC or placebo groups using a variety of statistical tests.Of the 371 participants in the original randomized controlled trial, 277 (75%) survived to 5.5 years old. A neurodevelopmental assessment was completed in 213 (78%) of the survivors, including 111 in the HC group and 102 who had been randomized to placebo. The primary outcome (death or moderate-to-severe NDI) occurred in 64/181 (35.4%) of children assigned to the HC group and 80/190 (42.1%) for those randomized to placebo (P = 0.18). Among those in the HC group, 38 (21.0%) had died by the corrected age of 5.5 years, compared to 56 (29.5%) of those in the placebo group (P = 0.06). A classification of moderate-to-severe NDI was made in 18.2% of children randomized to HC and 17.7% of placebo recipients (P = 0.94). There also was no difference between treatment groups in proportion of children with no, mild, moderate, or severe NDI (P = 0.66). The mean FSIQ was 90.4 ±14.9 for those in the HC group and 90.8 ±16.3 for children randomized to placebo (P = 0.86). There also were no significant differences between groups in proportion of children with a FSIQ <85 or <70, or in scores for the verbal and performance domains in the WPPSI.The authors conclude that treatment with HC for premature infants at risk for BPD did not affect the risk of death or moderate-to-severe NDI at 5.5 years of corrected age.Dr King has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.The current trial provides useful long-term data on the safety of postnatal late HC. Among ventilator-dependent very preterm infants treated between 7 and 14 days, HC was not associated with worse cognitive or neurosensory outcomes at school age. This follow-up is important because assessments beyond 2 years may detect later-emerging difficulties in cognition, behavior, and functional performance that are not fully captured in earlier evaluations.1The findings, however, should be interpreted alongside earlier trial results. In the original trial, HC did not improve the primary outcome of death or BPD at 36 weeks’ postmenstrual age or neurodevelopmental outcomes at 2-year follow-up.2,3 The present report therefore strengthens the longer-term safety profile of late HC but does not materially change the uncertainty regarding clinical efficacy. A similar conclusion emerged from the US-based NRN trial, in which late hydrocortisone did not result in significantly higher survival without moderate or severe BPD than placebo.4 Taken together, the randomized trial evidence suggests that late hydrocortisone may be acceptable from a neurodevelopmental perspective, but has not yet demonstrated a clear benefit on the outcomes that would justify adoption.The Cochrane review of late systemic corticosteroids found reductions in mortality and BPD overall, but the clearest efficacy signal was observed with dexamethasone rather than HC.4 Doyle and colleagues similarly showed that the balance between benefit and harm depends on baseline risk of BPD, with the greatest benefit, including potentially improved neurodevelopmental outcomes, seen in infants at highest risk receiving dexamethasone.5 The 2022 AAP clinical report reflects the persistent uncertainty in this field. It acknowledges that late systemic low-dose corticosteroids may be considered for infants at the highest risk of BPD, but concludes that the evidence remains insufficient to recommend routine postnatal corticosteroid use in preterm infants.6Current evidence continues to support a selective, risk-based approach to postnatal corticosteroid use in preterm infants at risk for BPD, favoring low-dose dexamethasone for late treatment.
A Wed, study studied this question.