Objectives-To more precisely examine regional and subregional microstructural brain changes associated with preterm birth.Study design-We obtained brain volumes from 29 preterm children, age 12 years, with no ultrasound scanning evidence of intraventricular hemorrhage or cystic periventricular leukomalacia in the newborn period, and 22 age-and sex-matched term control subjects.Results-Preterm male subjects demonstrated significantly lower white matter volumes in bilateral cingulum, corpus callosum, corticospinal tract, prefrontal cortex, superior and inferior longitudinal fasciculi compared with term male subjects. Gray matter volumes in prefrontal cortex, basal ganglia, and temporal lobe also were significantly reduced in preterm male subjects. Brain volumes of preterm female subjects were not significantly different from those of term female control subjects. Voxel-based morphometry results were not correlated with perinatal variables or cognitive outcome. Higher maternal education was associated with higher cognitive performance in preterm male subjects.
Conclusions-Pretermmale children continue to demonstrate abnormal neurodevelopment at 12 years of age. However, brain morphology in preterm female children may no longer differ from that of term female children. The neurodevelopmental abnormalities we detected in preterm male subjects appear to be relatively diffuse, involving multiple neural systems. The relationship between aberrant neurodevelopment and perinatal variables may be mediated by genetic factors, environmental factors, or both reflected in maternal education level.Children born prematurely are at risk for cognitive impairments with deficits in executive functioning, language, visual-motor integration, attention, and scholastic performance. 1 Although neuroimaging studies have begun to provide an initial picture of the neural correlates of preterm birth, 2-7 additional studies are needed to more precisely elucidate the functional neuroanatomy underlying cognitive dysfunction in affected children. In this study, we aimed to more precisely examine regional and subregional microstructural changes associated with this injury to the developing brain by using our 12-year-old prematurely born cohort. We hypothesized that preterm birth would result in long-lasting changes in brain development. Extending our earlier studies, this analysis used voxel-based Several VBM studies of preterm birth have been conducted. 9-12 However, we used VBM analyses as part of a unique, multimodal study of neurodevelopment in preterm children that included semi-automated volumetric and manual region of interest measurements on the basis of specific gyral boundaries to confirm our VBM findings.
METHODS
SubjectsAll subjects were enrolled in the follow-up component of the Multicenter Randomized Indomethacin IVH Prevention Trial. 13 The preterm subjects were sequentially recruited for the MRI study when they reached 12 years of age. The preterm cohort consisted of children with no ultrasound scanning evidence of intraven...