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Impaired cerebral cortical gray matter growth after treatment with dexamethasone for neonatal chronic lung disease
B P Murphy1, T E Inder, P S Huppi
1Division of Newborn Medicine, Harvard Medical School and Brigham & Women's Hospital, Boston, Massachusetts, USA.
Insights
Postnatal dexamethasone treatment for premature infants with chronic lung disease may impair brain growth, particularly cerebral cortical gray matter. This finding suggests a potential negative impact on neonatal brain development and neurodevelopmental outcomes.
Area of Science:
- Neonatal neuroscience
- Pediatric pharmacology
- Developmental biology
Background:
- Neonatal chronic lung disease (CLD) is a common complication in premature infants.
- Systemic corticosteroids, such as dexamethasone, are used to manage CLD.
- Concerns exist regarding the potential neurodevelopmental effects of postnatal dexamethasone exposure.
Purpose of the Study:
- To quantify the impact of postnatal systemic dexamethasone on brain growth in premature infants at term.
- To assess the influence of dexamethasone on specific brain tissue volumes, including gray matter and white matter.
- To compare brain development in treated premature infants with untreated premature infants and healthy term infants.
Main Methods:
- Quantitative volumetric 3D MRI was used to measure cerebral tissue volumes in premature infants (23-31 weeks gestation) at term (38-41 weeks).
- Infants were categorized into groups: treated with dexamethasone (n=7) and untreated (n=11).
- Healthy term infants (n=14) served as controls. Image processing algorithms segmented MRI data into gray matter, white matter, and cerebrospinal fluid volumes.
Main Results:
- Cerebral cortical gray matter volume was significantly reduced by 35% in dexamethasone-treated premature infants compared to untreated infants.
- Total cerebral tissue volume was reduced by 30% in treated premature infants compared to both untreated premature infants and healthy term controls.
- No significant differences were observed in subcortical gray matter or myelinated/unmyelinated white matter volumes between treated and untreated premature infants.
Conclusions:
- Postnatal systemic dexamethasone therapy appears to impair brain growth, primarily affecting cerebral cortical gray matter in premature infants.
- These findings suggest a potentially deleterious effect of dexamethasone on neonatal brain development and subsequent neurodevelopmental outcomes.
- Clinicians should consider these risks when balancing the benefits and risks of dexamethasone for infants with CLD.
Objective:
The specific aim of this study was to quantify at term the influence of postnatal systemic dexamethasone treatment for neonatal chronic lung disease on subsequent brain growth and development in premature infants without evidence of severe intraventricular hemorrhage or white matter injury.
Methods:
Eighteen premature (23 to 31 weeks) infants, 7 treated with dexamethasone and 11 not treated, were studied at term, ie, 38 to 41 postconceptional weeks, by an advanced quantitative volumetric 3-dimensional magnetic resonance imaging (MRI) technique to quantify cerebral tissue volumes. Fourteen healthy term infants also were studied for comparison. A sequence of image processing algorithms was used to segment each of the MRI slices into the following separate tissue classes: cerebral cortical gray matter, basal ganglia/thalami, unmyelinated white matter, myelinated white matter, and cerebrospinal fluid, all classified based on magnetic resonance signal intensity and anatomic location. A final summing of voxels for each tissue class was performed to compute absolute volumes in milliliters.
Results:
Cerebral cortical gray matter volume in premature infants treated with dexamethasone was reduced 35% when compared with gray matter volume in premature infants not treated with dexamethasone (mean +/- standard deviation, 130.3 +/- 54.0 vs 200.6 +/- 35.1 mL, respectively). Subcortical gray matter volumes (basal ganglia and thalami) and myelinated and unmyelinated white matter volumes were not significantly different among the treated and untreated groups. However, premature infants treated with dexamethasone exhibited a reduction (30%) in total cerebral tissue volume compared with total cerebral tissue volume in both the premature infants not treated with dexamethasone and the control term infants (312.7 +/- 43.7 vs 448.2 +/- 50.2 and 471.6 +/- 36.4 mL respectively). This latter finding relates primarily to the decrease in cerebral cortical gray matter volume.
Conclusions:
The data suggest an impairment in brain growth, principally affecting cerebral cortical gray matter, secondary to systemic dexamethasone therapy. Although the premature infants who received dexamethasone were smaller with more severe respiratory disease, these findings are consistent with growing evidence of a potential deleterious effect of dexamethasone on neonatal brain and subsequent neurodevelopmental outcome. This apparent deleterious effect should be taken into consideration by clinicians when weighing the potential risks and benefits of this therapy for low birth weight infants with neonatal chronic lung disease.
