Deformation-based morphometry enables the automatic quantification of neuroanatomical differences by measuring regional shape and volume differences between a reference space and the population under investigation. In this paper we use deformation-based morphometric methods to study volumetric differences between preterm infants at term equivalent age and term born controls using high-resolution MR imaging, and we investigate the influence of the choice of reference image on results obtained. We constructed mean atlases of preterm infants at term equivalent age and term born infants using three different reference spaces, and used them to compare the brains of the two groups. A non-rigid registration algorithm was used to map all 3 atlases into a common coordinate system and volumetric differences were extracted. Our results demonstrate significant volume differences between preterm infants at term equivalent age and the control group in the ventricular system, the interhemispheric fissure anteriorly, and the globus pallidus and thalamus. Morphometric changes are consistent between all three maps of volume change and indicate that the results obtained using deformation-based morphometry are largely independent of the choice of the reference space.