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Effect of Systemic Hydrocortisone on Brain Abnormalities and Regional Brain Volumes in Ventilator-dependent Infants
Nienke M Halbmeijer1, Wes Onland1, Jeroen Dudink2
1Department of Neonatology, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands; Amsterdam Reproduction and Development Research Institute, Amsterdam, the Netherlands.
Insights
High-dose systemic hydrocortisone in very preterm infants did not impact brain development compared to placebo. This study found no significant differences in brain injury scores or volumes in infants treated with hydrocortisone.
Area of Science:
- Neonatal neuroscience
- Developmental pediatrics
- Clinical pharmacology
Background:
- Systemic hydrocortisone is used in preterm infants to manage respiratory distress.
- Concerns exist regarding potential neurodevelopmental effects of high-dose steroids.
- This study investigates hydrocortisone's impact on brain development in very preterm infants.
Purpose of the Study:
- To determine if high cumulative doses of systemic hydrocortisone affect brain development.
- To compare brain development between infants receiving hydrocortisone and placebo.
- Initiation of treatment was between 7 and 14 days after birth in ventilated preterm infants.
Main Methods:
- A double-blind, placebo-controlled, randomized trial was conducted in 16 NICUs.
- Infants were born at <30 weeks gestation or with birth weight <1250g and were ventilator-dependent.
- MRI at term-equivalent age assessed brain injury (Kidokoro score) and volumes; multivariable regression analysis was used.
Main Results:
- 78 infants participated; 59 had acceptable MRI scans (31 hydrocortisone, 28 placebo).
- No significant difference in the median global brain abnormality score (Kidokoro) between groups (P=.92).
- No differences in adjusted mean total brain tissue volumes were observed between hydrocortisone and placebo groups (P=.80).
Conclusions:
- Systemic hydrocortisone initiated in the second week after birth did not show significant differences in brain development.
- The findings suggest no adverse neurodevelopmental impact from this hydrocortisone regimen in very preterm infants.
- Further research may explore long-term outcomes and different dosing strategies.
Objective:
To evaluate whether a high cumulative dose of systemic hydrocortisone affects brain development compared with placebo when initiated between 7 and 14 days after birth in ventilated infants born preterm.
Study Design:
A double-blind, placebo-controlled, randomized trial was conducted in 16 neonatal intensive care units among infants born at <30 weeks of gestation or with a birth weight of <1250 g who were ventilator-dependent in the second week after birth. Three centers performed MRI at term-equivalent age. Brain injury was assessed on MRI using the Kidokoro scoring system and compared between the 2 treatment groups. Both total and regional brain volumes were calculated using an automatic segmentation method and compared using multivariable regression analysis adjusted for baseline variables.
Results:
From the 3 centers, 78 infants participated in the study and 59 had acceptable MRI scans (hydrocortisone group, n = 31; placebo group, n = 28). Analyses of the median global brain abnormality score of the Kidokoro score showed no difference between the hydrocortisone and placebo groups (median, 7; IQR, 5-9 vs median, 8, IQR, 4-10, respectively; P = .92). In 39 infants, brain tissue volumes were measured, showing no differences in the adjusted mean total brain tissue volumes, at 352 ± 32 mL in the hydrocortisone group and 364 ± 51 mL in the placebo group (P = .80).
Conclusions:
Systemic hydrocortisone started in the second week after birth in ventilator-dependent infants born very preterm was not found to be associated with significant differences in brain development compared with placebo treatment.
Trial Registration:
The SToP-BPD study was registered with the Netherlands Trial Register (NTR2768; registered on 17 February 2011; https://www.trialregister.nl/trial/2640) and the European Union Clinical Trials Register (EudraCT, 2010-023777-19; registered on 2 November 2010; https://www.clinicaltrialsregister.eu/ctr-search/trial/2010-023777-19/NL).
