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Brain Advance Access originally published online on December 3, 2007
Brain 2008 131(1):205-217; doi:10.1093/brain/awm282
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© The Author (2007). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome

Chiara Nosarti1, Elena Giouroukou1, Elaine Healy1, Larry Rifkin1, Muriel Walshe1, Abraham Reichenberg1, Xavier Chitnis2, Steven C. R. Williams2 and Robin M. Murray1

1Department of Psychiatry, King's College London Institute of Psychiatry and 2Centre for Neuroimaging Sciences, King's College London Institute of Psychiatry and South London and Maudsley NHS Trust, London, UK

Correspondence to: Dr Chiara Nosarti, Department of Psychiatry, PO Box 63, King's College London Institute of Psychiatry, 16 De Crespigny Park, Denmark Hill, London SE5 8AF, UK E-mail: c.nosarti{at}iop.kcl.ac.uk

Very preterm (VPT) birth is associated with altered cortical development and long-term neurodevelopmental sequelae. We used voxel-based morphometry to investigate white (WM) and grey matter (GM) distribution in VPT adolescents and controls, and the association with gestational age and neonatal ultrasound findings in the VPT individuals. GM and WM volumes were additionally investigated in relation to adolescent neurodevelopmental outcome. Structural MRI data were acquired with a 1.5 Tesla machine in 218 VPT adolescents (<33 weeks, gestation) and 128 controls aged 14–15 years, and analysed using SPM2 software. VPT individuals compared to controls showed reduced GM in temporal, frontal, occipital cortices and cerebellum, including putamen, insula, cuneus, fusiform gyrus, thalamus and caudate nucleus, and increased GM predominantly in temporal and frontal lobes, including cingulate and fusiform gyri and cerebellum. WM loss was concentrated in the brainstem, internal capsule, temporal and frontal regions and the major fasciculi. WM excesses were observed in temporal, parietal and frontal regions. Investigation of the inter-relationships between brain regions and changes revealed that all selected areas where between-group increased and decreased WM and GM volumes differences were observed, were structurally associated, highlighting the influence that abnormalities in one brain area may exert over others. VPT individuals with evidence of periventricular haemorrhage and ventricular dilatation on neonatal ultrasound exhibited the greatest WM and GM alterations. VPT adolescents obtained lower scores than controls on measures of language and executive function and were more likely to show cognitive impairment compared to controls (27% versus 14%, respectively). Several areas where VPT individuals demonstrated decreased GM and WM volume were linearly associated with gestational age and mediated cognitive impairment. To summarize, our data demonstrates that VPT birth is associated with altered brain structure in adolescence. GM and WM alterations are associated with length of gestation and mediate adolescent neurodevelopmental impairment. Thus, anatomical brain changes may contribute to specific cognitive deficits associated with VPT birth and could be used in the identification of those individuals who may be at increased risk for cognitive impairment.

Key Words: preterm birth; magnetic resonance; neurocognition; neural plasticity

Abbreviations: GM, grey matter; LBW, low birth weight; VPT, very preterm; WM, white matter

Received August 15, 2007. Revised September 20, 2007. Accepted October 19, 2007.


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