Differential vulnerability of gray matter and white matter to intrauterine growth restriction in preterm infants at 12 months corrected age

Abstract

Intrauterine growth restriction (IUGR) is associated with a high risk of abnormal neurodevelopment. Underlying neuroanatomical substrates are partially documented. We hypothesized that at 12 months preterm infants would evidence specific white-matter microstructure alterations and gray-matter differences induced by severe IUGR. Twenty preterm infants with IUGR (26-34 weeks of gestation) were compared with 20 term-born infants and 20 appropriate for gestational age preterm infants of similar gestational age. Preterm groups showed no evidence of brain abnormalities. At 12 months, infants were scanned sleeping naturally. Gray-matter volumes were studied with voxel-based morphometry. White-matter microstructure was examined using tract-based spatial statistics. The relationship between diffusivity indices in white matter, gray matter volumes, and perinatal data was also investigated. Gray-matter decrements attributable to IUGR comprised amygdala, basal ganglia, thalamus and insula bilaterally, left occipital and parietal lobes, and right perirolandic area. Gray-matter volumes positively correlated with birth weight exclusively. Preterm infants had reduced FA in the corpus callosum, and increased FA in the anterior corona radiata. Additionally, IUGR infants had increased FA in the forceps minor, internal and external capsules, uncinate and fronto-occipital white matter tracts. Increased axial diffusivity was observed in several white matter tracts. Fractional anisotropy positively correlated with birth weight and gestational age at birth. These data suggest that IUGR differentially affects gray and white matter development preferentially affecting gray matter. At 12 months IUGR is associated with a specific set of structural gray-matter decrements. White matter follows an unusual developmental pattern, and is apparently affected by IUGR and prematurity combined.

Keywords: AD; AGA; Appropriate for gestational age; Axial diffusivity; Brain development; CA; Corrected age; DARTEL; DTI; Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra; Diffusion tensor imaging; FA; FWE; GM; Gray matter development; IUGR; MD; MRI; Prematurity; RD; SGA; TBSS; VBM; Voxel-based morphometry; WM; White matter development; diffusion tensor imaging; family-wise error; fractional anisotropy; gray matter; intrauterine growth restriction; magnetic resonance imaging; mean diffusivity; radial diffusivity; small for gestational age; tract-based spatial statistics; voxel-based morphometry; white matter.