Volumetric and cortical brain development and outcome in children born extremely preterm

Abstract

Children born extremely preterm (EPT) survive at an increasing rate. But they continue to have an increased risk for neurodevelopmental impairments. Magnetic resonance imaging (MRI) is used in a clinical setting, but can also be used as a research tool to detect differences in growth patterns between studied groups. The aim of this thesis was to explore differences in brain volumes and cortical thickness of children born EPT compared to term-born controls up into childhood, and to relate these to language and cognitive outcomes.

We included 51 children born EPT and 38 term-born controls with high-quality MRI scans at 10 years of age. Out of these, more than half also had volumetric data from term age. Out of the included children with MRI assessments at 10 years of age there were 42 children born EPT and 29 term-born controls with cognitive follow-up data at 12 years of age.

Imaging softwares, Statistical Parametric Mapping (SPM) and Freesurfer, were used to calculate global and regional brain volumes and cortical thickness.

In Study I the children born EPT had similar global brain volumes at term age as compared to term-born controls, but at 10 years of age their total brain tissue volume was reduced. After correction for total intracranial volume, we found a relative decrease of grey matter volume at term age and a relative decrease of white matter volume at 10 years of age.

In Study II, regions important for higher-order cognitive functions were found to be especially affected when children born EPT were compared to term-born controls at 10 years of age. A pattern with both volumetric increases and decreases was detected. Children born EPT with low-grade intraventricular hemorrhages and that were operated for patent ductus arteriosus had small, but persistent volumetric alterations.

In Study III the aim was to explore pre-selected language-related brain regions, and we found that their volume and cortical thickness were generally reduced at 10 years of age for children born EPT compared to term-born controls. In the children born EPT the brain volume of language-related regions was related to language scores, prior to adjustments for general cognition. Volumetric asymmetry or cortical thickness of language-related regions at 10 years were not related to language outcomes when children born EPT reached 12 years of age.

In Study IV we found that larger volumes of both grey and white matter corresponded to better cognitive performance. Conversely, increased thickness in the right cortex was linked to lower cognitive function in children born EPT. These relationships were consistent with those observed in term-born children. Growth in the brain volume from term age to 10 years of age did not appear to influence cognitive abilities at 12 years of age. However, for the children born EPT, the volume of the insula at age 10 years showed a connection to cognitive outcome.