Impaired Cerebral Cortical Gray Matter Growth After Treatment With Dexamethasone for Neonatal Chronic Lung Disease

Abstract

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.

Adverse Neurodevelopmental Effects of Dexamethasone Modeled in PC12 Cells: Identifying the Critical Stages and Concentration Thresholds for the Targeting of Cell Acquisition, Differentiation and Viability

“…Our results thus are in agreement with impaired neurite formation reported earlier at much higher concentrations (Unsicker et al, 1978) and as found more recently in our studies with DEX treatment in vivo, including doses below those in therapeutic use (Kreider et al, 2005a(Kreider et al, , 2006. Effects on this aspect of cell differentiation are likely to contribute to the observation that, even in brain regions that are largely finished with neurogenesis at the time of glucocorticoid therapy, DEX administration elicits reductions in volume (Murphy et al, 2001). Also, in this phase, as was true for undifferentiated cells, high DEX concentrations did not decrease cell viability and actually reduced the proportion of cells showing trypan blue staining.…”

“…The reduction in mitotic index thus contributes to an actual decline in the number of neural cells, just as observed anatomically with the use of antenatal steroids in animals and humans (Bohn, 1984;Kreider et al, 2005aKreider et al, , 2006Murphy et al, 2001). Furthermore, we did not observe any decrease in cell viability, effectively ruling out the possibility that DEX reduces cell number through cytotoxic actions.…”

“…Currently, 10% of all infants delivered in the US receive glucocorticoids, although only a small proportion are likely to have developed respiratory distress, so that hundreds of thousands of infants are treated unnecessarily (Matthews et al, 2002). Growing evidence indicates long-term liabilities from such treatment, including altered brain architecture (Murphy et al, 2001), and subsequent cognitive deficiencies (Doyle et al, 2000;Seckl, 2001;Yeh et al, 2004). Accordingly, recent reviews point out the drawbacks of the blanket use of glucocorticoids (Blackmon et al, 2002;Coe and Lubach, 2005;Newnham, 2001;Raff, 2004;Seckl, 2004), but nevertheless, the major comorbidities associated with preterm delivery make it difficult to assign a clear cause-and-effect relationship.…”

“…We evaluated three different critical neurodevelopmental stages: undifferentiated cells that are undergoing active mitosis, early stages of differentiation in which cells are still dividing but are undergoing the transition to neuritic development and phenotypic specialization, and mid-differentiation in which the same processes are further developed. Again, these are stages that are most likely to be targeted by DEX, based on biochemical and morphological criteria from in vivo studies (Bohn, 1984;Murphy et al, 2001).…”

Hydrocortisone vs. dexamethasone treatment for bronchopulmonary dysplasia and their effects on general movements in preterm infants

“…Furthermore, this study had limited data on MRI findings because in the late 90s, MRI was not yet a part of standard clinical care. Therefore, we were not able to associate our findings on GMs with detailed neuroimaging as found previously (23,24). Still, we do not expect to have missed major brain lesions that could have resulted in deterioration of GM quality, as cranial ultrasound is able to detect most abnormalities that are associated with abnormal neurodevelopmental outcome (26,27).…”