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Brain Advance Access published online on September 28, 2006
Brain, doi:10.1093/brain/awl277
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© The Author (2006). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org
Received January 28, 2006
Revised August 30, 2006
Accepted September 1, 2006

Article

Perinatal risk factors altering regional brain structure in the preterm infant

Deanne K. Thompson 1, Simon K. Warfield 2, John B. Carlin 3, Masa Pavlovic 4, Hong X. Wang 4, Merilyn Bear 3, Michael J. Kean 5, Lex W. Doyle 6, Gary F. Egan 4, and Terrie E. Inder 7 *

1 Howard Florey Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Australia; Department of Pediatrics, St Louis Children's Hospital, Washington University, St Louis, MO, USA
2 Departments of Radiology, Brigham and Women's Hospital and Children's Hospital, Harvard Medical School, Boston, MA, USA
3 Murdoch Children's Research Institute, Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Australia
4 Howard Florey Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Australia
5 Department of Medical Imaging, Royal Children's Hospital, University of Melbourne, Melbourne, Australia
6 Royal Women's Hospital, University of Melbourne, Melbourne, Australia
7 Howard Florey Institute, Royal Children's Hospital, University of Melbourne, Melbourne, Australia; Murdoch Children's Research Institute, Department of Paediatrics, Royal Children's Hospital, University of Melbourne, Melbourne, Australia; Department of Pediatrics, St Louis Children's Hospital, Washington University, St Louis, MO, USA

* To whom correspondence should be addressed.
Terrie E. Inder, E-mail: inder_t{at}kids.wustl.edu


  Abstract

Neuroanatomical structure appears to be altered in preterm infants, but there has been little insight into the major perinatal risk factors associated with regional cerebral structural alterations. MR images were taken to quantitatively compare regional brain tissue volumes between term and preterm infants and to investigate associations between perinatal risk factors and regional neuroanatomical alterations in a large cohort of preterm infants. In a large prospective longitudinal cohort study of 202 preterm and 36 term infants, MR scans at term equivalent were undertaken for volumetric estimates of cortical and deep nuclear grey matter, unmyelinated and myelinated white matter (WM) and CSF within 8 parcellated regions for each hemisphere of the brain. Perinatal correlates analysed in relation to regional brain structure included gender, gestational age, intrauterine growth restriction, bronchopulmonary dysplasia, white matter injury (WMI) and intraventricular haemorrhage. Results revealed region-specific reductions in brain volumes in preterm infants compared with term controls in the parieto-occipital (preterm mean difference: -8.1%; 95% CI = -13.8 to -2.3%), sensorimotor (-11.6%; -18.2 to -5.0%), orbitofrontal (-30.6%; -49.8 to -11.3%) and premotor (-7.6%; -14.2 to -0.9%) regions. Within the sensorimotor and orbitofrontal regions cortical grey matter and unmyelinated WM were most clearly reduced in preterm infants, whereas deep nuclear grey matter was reduced mainly within the parieto-occipital and subgenual regions. CSF (ventricular and extracerebral) was doubled in volume within the superior regions in preterm infants compared with term controls. Cerebral WMI and intrauterine growth restriction were both associated with a more posterior reduction in brain volumes, whereas bronchopulmonary dysplasia was associated with a more global reduction across all regions. In contrast degree of immaturity was not related to regional brain structure among preterm infants. In summary, preterm birth is associated with regional cerebral tissue reductions, with the adverse pattern varying between risk factors. These findings add to our understanding of the potential pathways leading to altered brain structure and outcome in the preterm infant.

Keywords: cerebral development; preterm infant; volumetric MRI; white matter injury.
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