Published online June 29, 2009
PEDIATRICS Vol. 124 No. 1 July 2009, pp. 268-276 (doi:10.1542/peds.2008-1294)
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ARTICLE

The Association of Lung Disease With Cerebral White Matter Abnormalities in Preterm Infants

Mustafa Anjari, BSc, Serena J. Counsell, PhD, Latha Srinivasan, MRCPCH, MSc, Joanna M. Allsop, DCR, Joseph V. Hajnal, PhD, Mary A. Rutherford, FRCPCH, FRCR and A. David Edwards, FMedSci

Division of Clinical Sciences, Imperial College London and MRC Clinical Sciences Centre, London, United Kingdom

OBJECTIVE: Preterm infants have a high incidence of neurodevelopmental impairment associated with diffuse cerebral white matter abnormalities and also a high incidence of serious respiratory disease. However, it is unclear if lung disease and brain injury are related, and previous research has been impeded by confounding effects, including prematurity and infection. Using a new approach that permits multivariate statistical analysis, we tested the hypothesis that lung disease is associated with specific white matter abnormalities, detected as reduced fractional anisotropy (FA) in diffusion tensor imaging data.

METHODS: Fifty-three preterm infants with no evidence of focal abnormality on conventional MRI were studied at term-equivalent age by using tract-based spatial statistics, an automated observer-independent method for voxelwise analysis of major white matter pathways.

RESULTS: In several white matter tracts, FA decreased with a linear relation to the gestational age at birth. Independent of the confounding effects of prematurity and age at scan, respiratory disease was associated with specific white matter abnormalities in preterm infants; those infants receiving mechanical ventilation for >2 days in the perinatal period (n = 10) showed reduced FA in the genu of the corpus callosum, whereas subjects with chronic lung disease (n = 15) displayed a reduction in FA in the left inferior longitudinal fasciculus.

CONCLUSION: Independent of the degree of prematurity, respiratory disease is associated with cerebral white matter abnormalities.

Key Words: brain development • preterm • MRI • diffusion tensor imaging • DTI • white matter • ventilation • chronic lung disease • tract-based spatial statistics • TBSS

Abbreviations: DTI—diffusion tensor imaging • TBSS—tract-based spatial statistics • GA—gestational age • PMA—postmenstrual age • PROM—prolonged rupture of membranes • ADC—apparent diffusion coefficient • CLD—chronic lung disease • PLIC—posterior limb of the internal capsule • FA—fractional anisotropy • CI—confidence interval

Accepted Jan 7, 2009.


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