A long-term follow-up cohort study of the multicenter Neonatal Research Network (NRN) Hydrocortisone for BPD (bronchopulmonary dysplasia) trial, which was published by DeMauro et al in JAMA Pediatrics, found no difference in rates of functional impairment—or its components, including cognitive, motor, or academic delays and poor functional exercise capacity—at early school age between preterm-born children who were treated with hydrocortisone vs placebo for the prevention of bronchopulmonary dysplasia.

“We previously reported that hydrocortisone, using the dosing strategy evaluated in this trial, did not have significant impacts on either in-hospital survival without moderate or severe bronchopulmonary dysplasia or survival without moderate or severe neurodevelopmental impairment at corrected age 2 years,” the investigators commented. “Together, these results suggest that the hydrocortisone regimen tested in this trial does not provide benefits but also does not cause any evident harms in preterm infants with early evolving lung disease.”

Study Details

This study followed participants from the abovementioned trial, which was conducted across 19 centers within the Eunice Kennedy Shriver National Institute of Child Health and Human Development NRN. From August 2011 to February 2018, the trial enrolled intubated infants born before 30 weeks’ gestation who required mechanical ventilation for at least 7 days by postnatal day 14 to 28. They were randomly assigned to receive either a 10-day tapering course of hydrocortisone (n = 398; 18 mg/kg total dose) or a placebo (n = 402) starting between postnatal days 14 and 28.

Participants between the corrected ages of 5 and 7 years were invited to a single, in-person follow-up assessment. The primary outcome, functional impairment, was defined as the presence of any cognitive, motor, or academic delay, or poor functional exercise capacity. Of 674 eligible children, 545 (80.9%) had available primary outcome data, including 272 treated with hydrocortisone (55.9% female; mean gestational age = 24.9 weeks) and 273 who received placebo (39.6% female; mean gestational age = 24.8 weeks). Their mean ages at follow-up were 5.3 and 5.4 years, respectively.

Key Findings

The rate of functional impairment did not appear to differ between participants who received hydrocortisone vs placebo (71.3% vs 73.3%; adjusted relative risk = 0.99, 95% confidence interval [CI] = 0.89–1.10); no differences in the rates of the individual components of this composite outcome were reported. Motor delay was found to be the most common impairment (n = 308 of 510 [60.4%]), followed by poor functional exercise capacity (n = 175 of 484 [36.2%]).

The investigators concluded, “These data will be valuable to benchmark functional outcomes of very preterm infants exposed to mechanical ventilation in the first few weeks after birth and to inform future evaluations of postnatal steroid therapies and novel therapeutic interventions. Interpreted together with the lack of evidence for short-term benefit, this study demonstrates that the hydrocortisone regimen evaluated in this trial should not be used to prevent bronchopulmonary dysplasia or to improve long-term functional outcomes of ventilated, very preterm infants.”

Sara B. DeMauro, MD, MSCE, of the Children’s Hospital of Philadelphia, is the corresponding author of the article in JAMA Pediatrics.

Disclosure: This study was funded by grants from the National Heart, Lung, and Blood Institute, the National Institute of Child Health and Human Development, and the National Center for Advancing Translational Sciences. For full disclosures of the study authors, visit jamanetwork.com.

Source: JAMA Pediatrics