Is Low-Grade Intraventricular Hemorrhage in Very Preterm Infants an Innocent Condition? Structural and Functional Evaluation of the Brain Reveals Regional Neurodevelopmental Abnormalities

There is increasing evidence of abnormal neurodevelopmental outcomes in very preterm infants with low-grade intraventricular hemorrhage grades I and II. Our purpose was to evaluate the effects of low-grade intraventricular hemorrhage on gray and white matter integrity. MR imaging at around term-equivalent age was performed in 16 very preterm infants (mean gestational age, 28.8 ± 5.3 weeks) with mild intraventricular hemorrhage on brain sonography and 13 control subjects (mean gestational age, 29.6 ± 4.1 weeks) without intraventricular hemorrhage. Structural and functional evaluation of the cortex was performed using regional measurements of surface area, thickness and volume, and resting-state fMRI, respectively, and of WM microstructural integrity, applying Tract-Based Spatial Statistics to diffusion tensor imaging data. Compared with the control infants, the infants with low-grade intraventricular hemorrhage had decreases in the following: 1) GM surface area in Brodmann areas 19 left and 9 and 45 right, and GM volume in Brodmann areas 9 and 10 right; 2) fractional anisotropy bilaterally in major WM tracts; and 3) brain activity in the left lower lateral and in the right higher medial somatosensory cortex. Very premature infants with low-grade intraventricular hemorrhage at around term-equivalent age may present with regional abnormalities, appearing on imaging studies as cortical underdevelopment, functional impairment, and microstructural immaturity of major WM tracts.