Association between postnatal dexamethasone for treatment of bronchopulmonary dysplasia and brain volumes at adolescence in infants born very preterm

Jeanie L Y Cheong, Alice C Burnett, Katherine J Lee, Gehan Roberts, Deanne K Thompson, Stephen J Wood, Alan Connelly, Peter J Anderson, Lex W Doyle, Victorian Infant Collaborative Study Group, Catherine Callanan, Esther Hutchinson, Marion McDonald, Karissa Searle, Cinzia R De Luca, Carly Molloy, Michelle Wilson-Ching, Elaine Kelly, Elizabeth Carse, Margaret P Charlton, Marie Hayes, Gillian Opie, Andrew Watkins, Amanda Williamson, Heather Woods, Colin Robertson, Jeanie L Y Cheong, Alice C Burnett, Katherine J Lee, Gehan Roberts, Deanne K Thompson, Stephen J Wood, Alan Connelly, Peter J Anderson, Lex W Doyle, Victorian Infant Collaborative Study Group, Catherine Callanan, Esther Hutchinson, Marion McDonald, Karissa Searle, Cinzia R De Luca, Carly Molloy, Michelle Wilson-Ching, Elaine Kelly, Elizabeth Carse, Margaret P Charlton, Marie Hayes, Gillian Opie, Andrew Watkins, Amanda Williamson, Heather Woods, Colin Robertson

Abstract

Objectives: To compare brain volumes in adolescents who were born extremely preterm (<28 weeks gestation) who had received postnatal dexamethasone, and to determine if there was a postnatal dexamethasone dose-response effect on brain volumes.

Study design: Geographical cohort study of extremely preterm adolescents born in 1991-1992 in Victoria, Australia. T1-weighted magnetic resonance imaging was performed at 18 years of age. Segmented and parcellated brain volumes were calculated using an automated segmentation method (FreeSurfer) and compared between groups, with and without adjustment for potential confounders. The relationships between total postnatal dexamethasone dose and brain volumes were explored using linear regression.

Results: Of the 148 extremely preterm participants, 55 (37%) had received postnatal dexamethasone, with a cumulative mean dose of 7.7 mg/kg. Compared with participants who did not receive postnatal dexamethasone, those who did had smaller total brain tissue volumes (mean difference -3.6%, 95% CI [-7.0%, -0.3%], P value = .04) and smaller white matter, thalami, and basal ganglia volumes (all P < .05). There was a trend of smaller total brain and white matter volumes with increasing dose of postnatal dexamethasone (regression coefficient -7.7 [95% CI -16.2, 0.8] and -3.2 [-6.6, 0.2], respectively).

Conclusions: Extremely preterm adolescents who received postnatal dexamethasone in the newborn period had smaller total brain tissue volumes than those who did not receive postnatal dexamethasone, particularly white matter, thalami, and basal ganglia. Vulnerability of brain tissues or structures associated with postnatal dexamethasone varies by structure and persists into adolescence.

Copyright © 2014 Mosby, Inc. All rights reserved.

Figures

Figure 1
Figure 1
Mean differences (95% CI) in cortical white matter volume in preterm infants who received postnatal dexamethasone compared with preterm infants who did not receive postnatal dexamethasone at 18 years of age. All estimates are adjusted for corrected age at the time of the scan, sex, and hemisphere, allowing the effect of group, sex, and hemisphere to vary by region. Adjusted estimates are also adjusted for gestational age at birth, small for gestational age, bronchopulmonary dysplasia, neonatal brain injury, and intracranial volume.
Figure 2
Figure 2
Relationship between total brain tissue volume and cumulative postnatal dexamethasone dose. Regression coefficient −7.7 (95% CI −16.2, 0.8), R2 0.06, P value = .08.

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