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Pilot randomized trial of hydrocortisone in ventilator-dependent extremely preterm infants: effects on regional brain
Nehal A Parikh1, Kathleen A Kennedy, Robert E Lasky
1Department of Pediatrics, Neonatal-Perinatal Medicine, University of Texas Medical School at Houston, Houston, TX, USA. Nehal.Parikh@NationwideChildrens.org
Insights
Hydrocortisone treatment did not improve brain volumes in high-risk, ventilator-dependent extremely low birth weight infants. This study found no significant differences in brain tissue volume or pulmonary outcomes.
Area of Science:
- Neonatalogy
- Pediatric Neurology
- Critical Care Medicine
Background:
- Extremely low birth weight (ELBW) infants are at high risk for neurodevelopmental impairments.
- Ventilator-dependent ELBW infants often experience respiratory challenges and may benefit from early interventions.
- Hydrocortisone has been explored as a potential neuroprotective agent in this vulnerable population.
Purpose of the Study:
- To evaluate the effect of a 7-day course of hydrocortisone on total brain tissue volume in high-risk, ventilator-dependent ELBW infants.
- To determine if hydrocortisone administration influences regional brain volumes and pulmonary outcomes.
- To test the hypothesis that hydrocortisone increases total brain tissue volume compared to placebo.
Main Methods:
- A randomized controlled trial involving 64 ventilator-dependent ELBW infants (birth weight ≤1000 g) aged 10-21 days.
- Infants were randomized to receive either systemic hydrocortisone (17 mg/kg cumulative dose) or saline placebo over 7 days.
- Total brain tissue volume was assessed using volumetric magnetic resonance imaging at 38 weeks postmenstrual age; secondary outcomes included regional brain volumes and bronchopulmonary dysplasia.
Main Results:
- No significant difference was observed in total brain tissue volume between the hydrocortisone group (N=23) and the placebo group (N=21) (adjusted mean difference: 6.35 cm³, P = .64).
- Survival without severe bronchopulmonary dysplasia was similar between groups (3/31 in hydrocortisone arm vs. 5/33 in placebo arm).
- No significant differences were found in secondary outcomes, including regional brain volumes or days on respiratory support; no adverse effects were noted.
Conclusions:
- Low-dose hydrocortisone administered for 7 days in high-risk, ventilator-dependent infants did not demonstrate a discernible effect on regional brain volumes.
- The treatment also showed no significant impact on pulmonary outcomes before neonatal intensive care unit discharge.
- Further research may be needed to explore alternative or prolonged therapeutic strategies for neuroprotection in ELBW infants.
Objective:
To test the hypothesis that high-risk ventilator-dependent extremely low birth weight (birth weight ≤1000 g) infants treated with 7 days of hydrocortisone will have larger total brain tissue volumes than placebo treated infants.
Study Design:
A predetermined sample size of 64 extremely low birth weight infants, between 10-21 days old and ventilator-dependent with a respiratory index score ≥2, were randomized to systemic hydrocortisone (17 mg/kg cumulative dose) or saline placebo. Primary outcome was total brain tissue volume. Volumetric magnetic resonance imaging was performed at 38 weeks postmenstrual age; brain tissue regions were segmented and quantified automatically with a high degree of accuracy and 9 structures were segmented manually. All analyses of regional brain volumes were adjusted by postmenstrual age at magnetic resonance imaging scan.
Results:
The study groups were similar at baseline and 8 infants died in each arm. Unadjusted total brain tissue volume (mean ± SD) in the hydrocortisone (N = 23) and placebo treated infants (N = 21) was 272 ± 40.3 cm(3) and 277.8 ± 59.1 cm(3), respectively (adjusted mean difference: 6.35 cm(3) (95% CI: (-20.8, 32.5); P = .64). Three of the 31 hydrocortisone treated infants and 5 of the 33 placebo treated infants survived without severe bronchopulmonary dysplasia (relative risk 0.62, 95% CI: 0.13, 2.66; P = .49). No significant differences were noted in prespecified secondary outcomes of regional structural volumes or days on respiratory support. No adverse effects of hydrocortisone were observed.
Conclusions:
Low dose hydrocortisone in high-risk ventilator-dependent infants after a week of age had no discernible effect on regional brain volumes or pulmonary outcomes prior to neonatal intensive care unit discharge.
