Changes in white matter diffusion anisotropy in adolescents born prematurely.

Being born with very low birth weight (VLBW, birth weight<or=1500 g) or small for gestational age (SGA) carries an increased risk of cerebral white matter damage. The reduced cognitive and motor skills these two groups exhibit suggest that the early injuries to white matter persist into adolescence. White matter integrity was assessed using voxel-wise statistical analysis of fractional anisotropy (FA) maps between three groups of adolescents at age 15; the VLBW group (n=34), the SGA group (n=42) and a control group with normal birth weight (n=47). The FA maps were normalized to a study specific template and group differences were assessed using an analysis of covariance with gender as a confounder (FDR-corrected P<0.05). The main finding is that the VLBW group has significantly reduced FA values in several white matter regions, including the corpus callosum, internal capsule and superior fasciculus compared to the control group. Some of the observed reduction in anisotropy, particularly that observed in the corpus callosum, may have been caused by inaccurate spatial normalization, but this can only explain 30% of the area with reduced anisotropy. Analysis of the eigenvalues of the diffusion tensor show that the reduced FA values in the VLBW group is primarily due to an increase in the two lowest eigenvalues of the diffusion tensor. We speculate that this may be caused by reduced myelination. For the SGA group, we find no statistically significant differences in anisotropy compared to the control group.