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Congenital heart disease (CHD) patients are at risk for alterations in the cerebral white matter microstructure (WMM) throughout development. It is unclear whether the extent of WMM alterations changes with age, especially during adolescence when the WMM undergoes rapid maturation. We investigated differences in WMM between patients with CHD and healthy controls from childhood until early adulthood in a pooled sample of children, adolescents, and young adults. The association between WMM and EF was assessed. Patients with CHD (N=78) and controls (N=137) between 9 and 32 years of age underwent diffusion tensor imaging and an executive function test-battery. Mean fractional anisotropy (FA) was calculated for each white matter tract. Linear regression tested age and group effects (CHD vs control) and their interaction on FA. Relative Variable Importance (RI) estimated the independent contribution of tract FA, presence of CHD, CHD complexity, and parental education to the variability in EF. Mean FA was lower in patients compared to controls in almost all tracts (p between 0.057 and <0.001). WMM alterations in patients were not different depending on age (all interaction effects p>0.074). Predictors of EF were CHD group (RI=43%), parental education (RI=23%), CHD complexity (RI=10%), FA of the hippocampal cingulum (RI=6%) and FA of the corticospinal tract (RI=6%). The lack of group-FA-interactions indicates that the extent of altered FA remains similar across age. Altered FA is associated with EF impairments. CHD is a chronic disease with cerebral and neurocognitive impairments persisting into adulthood and, thus, long-term follow-up programs may improve overall outcome for this population. [ABSTRACT FROM AUTHOR]

Introduction Premature infants are particularly vulnerable to brain injuries with associated cognitive and behavioural deficits. The worldwide first randomised interventional multicentre trial investigating the neuroprotective effects of erythropoietin (entitled 'Does erythropoietin improve outcome in very preterm infants?' (NCT00413946)) included 450 very preterm infants in Switzerland. MRI at term equivalent age showed less white matter (WM) injury in the erythropoietin group compared with the placebo group. Despite these promising imaging findings, neurodevelopmental outcome at 2 years showed no beneficial effect of early erythropoietin. One explanation could be that the assessment of more complex cognitive functions such as executive functions (EFs) is only possible at a later age. We hypothesise that due to improved WM development and fewer WM injuries, children born preterm treated with early erythropoietin will have better EF abilities at 7-12 years than those treated with placebo. Methods and analysis 365 children who were included into the primary analysis of the original trial (NCT00413946) will be eligible in this prospective follow-up study at the age of 7-12 years. 185 children born at term will be control children. Primary outcome measures are EF abilities and processing speed, while secondary outcomes are academic performance, IQ, fine motor abilities and global brain connectivity. A comprehensive test battery will be applied to assess EFs. MRI will be performed to assess global brain connectivity. Cognitive scores and MRI measures will be compared between both groups using the Wilcoxon test. Propensity score matching will be used to balance gender, age, socioeconomic status and other potentially unbalanced variables between the children born preterm and the healthy control children. Ethics and dissemination The cantonal ethical committee granted ethical approval for this study (KEK 2017-00521). Written consent will be obtained from the parents. Findings from this study will be disseminated via international and national conference presentations and publications in peer-reviewed journals. [ABSTRACT FROM AUTHOR]

Introduction: Premature infants are particularly vulnerable to brain injuries with associated cognitive and behavioural deficits. The worldwide first randomised interventional multicentre trial investigating the neuroprotective effects of erythropoietin (entitled 'Does erythropoietin improve outcome in very preterm infants?' (NCT00413946)) included 450 very preterm infants in Switzerland. MRI at term equivalent age showed less white matter (WM) injury in the erythropoietin group compared with the placebo group. Despite these promising imaging findings, neurodevelopmental outcome at 2 years showed no beneficial effect of early erythropoietin. One explanation could be that the assessment of more complex cognitive functions such as executive functions (EFs) is only possible at a later age. We hypothesise that due to improved WM development and fewer WM injuries, children born preterm treated with early erythropoietin will have better EF abilities at 7-12 years than those treated with placebo., Methods and Analysis: 365 children who were included into the primary analysis of the original trial (NCT00413946) will be eligible in this prospective follow-up study at the age of 7-12 years. 185 children born at term will be control children. Primary outcome measures are EF abilities and processing speed, while secondary outcomes are academic performance, IQ, fine motor abilities and global brain connectivity. A comprehensive test battery will be applied to assess EFs. MRI will be performed to assess global brain connectivity. Cognitive scores and MRI measures will be compared between both groups using the Wilcoxon test. Propensity score matching will be used to balance gender, age, socioeconomic status and other potentially unbalanced variables between the children born preterm and the healthy control children., Ethics and Dissemination: The cantonal ethical committee granted ethical approval for this study (KEK 2017-00521). Written consent will be obtained from the parents. Findings from this study will be disseminated via international and national conference presentations and publications in peer-reviewed journals., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)