Language performance and brain volumes, asymmetry, and cortical thickness in children born extremely preterm.

BACKGROUND: Children born preterm are more prone to have language difficulties. Few studies focus on children born extremely preterm (EPT) and the structural differences in language-related regions between these children and children born at term. METHODS: Our study used T1-weighted magnetic resonance imaging (MRI) scans to calculate the brain volumetry, brain asymmetry, and cortical thickness of language-related regions in 50 children born EPT and 37 term-born controls at 10 years of age. The language abilities of 41 of the children born EPT and 29 term-born controls were then assessed at 12 years of age, using the Wechsler Intelligence Scale for Children, Fifth Edition and the Clinical Evaluations of Language Fundamentals, Fourth Edition. The differences between MRI parameters and their associations with language outcomes were compared in the two groups. RESULTS: Brain volume and cortical thickness of language-related regions were reduced in children born EPT, but volumetric asymmetry was not different between children born EPT and at term. In children born EPT the brain volume was related to language outcomes, prior to adjustments for full-scale IQ. CONCLUSIONS: These findings expand our understanding of the structural correlates underlying impaired language performance in children born with EPT. IMPACT: The article expands understanding of the structure-function relationship between magnetic resonance imaging measurements of language-related regions and language outcomes for children born extremely preterm beyond infancy. Most literature to date has focused on very preterm children, but the focus in this paper is on extreme prematurity and language outcomes. While the brain volume and cortical thickness of language-related regions were reduced in children born EPT only the volume, prior to adjustment for full-scale IQ, was associated with language outcomes. We found no differences in volumetric asymmetry between children born EPT and at term.

Extreme prematurity and perinatal risk factors related to extremely preterm birth are associated with complex patterns of regional brain volume alterations at 10 years of age: a voxel-based morphometry study.

Objective: Structural brain volumetric differences have been investigated previously in very preterm children. However, children born extremely preterm, at the border of viability, have been studied to a lesser degree. Our group previously analyzed children born extremely preterm at term using voxel-based morphometry. In this study, we aimed to examine regional gray and white matter differences for children born extremely preterm derived from the same cohort during childhood. We also aimed to explore the effect of perinatal risk factors on brain volumes in the same group. Methods: At 10 years of age, 51 children born extremely preterm (before 27 weeks and 0 days) and 38 term-born controls with high-quality 3.0 Tesla magnetic resonance images were included. Statistical analyses using voxel-based morphometry were conducted on images that were normalized using age-specific templates, modulated, and smoothed. Analyses were also performed in stratified groups of children born extremely preterm in the absence or presence of perinatal risk factors that have previously been shown to be associated with volumetric differences at term. Results: We found volumetric decreases in gray and white matter in the temporal lobes, gray matter decreases in the precuneus gyri, and white matter decreases in the anterior cingulum for children born extremely preterm (all p < 0.001, and pfwe < 0.05). Gray and white matter increases were predominantly observed in the right posterior cingulum and occipital lobe (all p < 0.001, and pfwe < 0.05). Of the examined perinatal risk factors, intraventricular hemorrhage grades I-II compared with no intraventricular hemorrhage and patent ductus arteriosus ligation compared with no treated patent ductus arteriosus or patent ductus arteriosus treated with ibuprofen led to volumetric differences at 10 years of age (all p < 0.001, and pfwe < 0.05). Conclusions: Children born extremely preterm exhibit volumetric alterations in a pattern overlapping that previously found at term, where many regions with differences are the main hubs of higher order networks. Some, but not all, risk factors known to be associated with structural alterations at term were associated with alterations at 10 years of age.

Discrete white matter abnormalities at age 8-11 years in children born extremely preterm are not associated with adverse cognitive or motor outcomes.

AIM: Little is known about the prevalence of discrete white matter abnormalities (WMA) beyond the first years in children born extremely preterm (EPT) and the relation to neurodevelopmental outcomes. Our aim was to investigate the prevalence of discrete WMA in children born EPT and the relationship to neonatal white matter injuries (WMI), white matter (WM) volume, WM diffusivity and neurodevelopment. METHODS: The study was a part of a longitudinal follow-up study of EPT neonates. All children were scanned at Karolinska University hospital 2004-2007 (neonates) and 2014-2015 (children at 8-11 years). WMA was qualitatively assessed by visual inspection. Developmental assessment was conducted at 12 years. RESULTS: In total, 112 children (median age 10.3 years, 56 girls) underwent MRI of the brain (68 EPT, 45 controls). In the EPT group, a subset had MRI around term equivalent age (n = 61). In the EPT group, the prevalence of discrete WMA at 8-11 years was 52%. There was a positive association between WMI at TEA and 8-11 years. There was no association between WMI and WM volumes or diffusivity at 8-11 years. Discrete WMA was not related to neurodevelopmental outcomes. CONCLUSION: Discrete WMA was prevalent in children born EPT at 8-11 years but were not related to neurodevelopmental outcomes.

Exploring the distribution of grey and white matter brain volumes in extremely preterm children, using magnetic resonance imaging at term age and at 10 years of age.

OBJECTIVES: To investigate differences in brain volumes between children born extremely preterm and term born controls at term age and at 10 years of age. STUDY DESIGN: Children born extremely preterm (EPT), up to 26 weeks and 6 days gestational age, in Stockholm between January 1 2004 to March 31 2007 were included in this population-based cohort study. A total of 45 EPT infants were included at term age and 51 EPT children were included at 10 years of age. There were 27 EPT children included at both time points. Two different control groups were recruited; 15 control infants were included at term age and 38 control children at 10 years of age. The primary outcomes were the grey and white matter volumes. Linear regression, adjusted for intracranial volume and sex, was used. RESULTS: At term age, the extremely preterm infants had significantly smaller grey matter volume compared to the control infants with an adjusted mean difference of 5.0 cm3 and a 95% confidence interval of -8.4 to -1.5 (p = 0.004). At 10 years of age the extremely preterm children had significantly smaller white matter volume compared to the control children with an adjusted mean difference of 6.0 cm3 and a 95% confidence interval of -10.9 to -1.0 (p = 0.010). CONCLUSION: Extremely preterm birth was associated with reduced grey matter volume at term age and reduced white matter volume at 10 years of age compared to term born controls.