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Altered myelin maturation in four year old children born very preterm.

ABSTRACT: Children born very preterm (VPT; <32?weeks gestational age [GA]) are at greater risk for a range of cognitive deficits that typically manifest at school age. Here we examine the hypothesis that these children have altered myelin maturational that can be detected by myelin sensitive MRI measures prior to school age. We included 33 four-year old children born VPT (mean GA; 28.7?weeks) and 23 four-year old full term (FT) children and completed magnetization transfer (MT), T1-weighted (T1-w) and T2-weighted (T1-w) magnetic resonance imaging as well as developmental assessments. Both MT ratio (MTR) and T1-w/T2-w ratio images were calculated, and group differences were probed using tract-based spatial statistics (TBSS) in white matter, and region of interest (ROI) analysis in white, subcortical gray and cortical gray matter. The relations between MTR and T1-w/T2-w ratio, as well as with developmental assessments, were investigated in all three brain divisions. In children born VPT, TBSS and ROI analysis revealed that both MTR and T1-w/T2-w ratio were significantly reduced in white matter compared to children born FT. ROI analysis showed reductions in T1-w/T2-w ratio in VPT children compared to FT children in the thalamus, putamen and amygdala, as well as in the occipital and temporal lobes. Across the VPT and FT children, T1-w/T2-w ratio and MTR were highly correlated across white, subcortical gray and cortical gray matter. Both measures correlated positively with developmental assessments in individual white matter tracts and cortical and subcortical ROIs, suggesting that higher MTR and T1-w/T2-w ratio is related to better cognitive performance. Together these findings are consistent with delayed myelination in VPT born children.

SUBMITTER: Vandewouw MM

PROVIDER: S-EPMC6413416 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Altered myelin maturation in four year old children born very preterm.

Vandewouw Marlee M MM Young Julia M JM Shroff Manohar M MM Taylor Margot J MJ Sled John G JG

NeuroImage. Clinical 20181211

Children born very preterm (VPT; <32 weeks gestational age [GA]) are at greater risk for a range of cognitive deficits that typically manifest at school age. Here we examine the hypothesis that these children have altered myelin maturational that can be detected by myelin sensitive MRI measures prior to school age. We included 33 four-year old children born VPT (mean GA; 28.7 weeks) and 23 four-year old full term (FT) children and completed magnetization transfer (MT), T1-weighted (T1-w) and T2- ...[more]

PMID: 30573411

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Project description:Purpose Language difficulties are prevalent among children born preterm. Existing studies have largely used standardized language tests, providing limited scope for detailed descriptive examination of preterm language. This study aimed to examine differences in conversational language between children born < 30 weeks and at term as well as correlations between language sample analysis (LSA) and a standardized language tool. Method Two hundred four 3-year-olds (103 born < 30 weeks, 101 born at term) recruited at birth provided a 10-min language sample and completed the Preschool Language Scales-Fifth Edition (I. Zimmerman, Steiner, & Pond, 2011). LSA was conducted using the Systematic Analysis of Language Transcripts and Index of Productive Syntax. Group differences were analyzed using linear regression, and Pearson correlation coefficient (coef) was used to determine correlations between measures. Results Children born < 30 weeks scored lower than term-born peers on multiple metrics when controlled for confounding factors (sex, high social risk, multilingualism, and diagnosed neurodevelopmental disorders), including mean length of utterance in morphemes (coef = -0.28, 95% confidence interval [CI] [-0.56, 0.01]) and words (coef = -0.29, 95% CI [-0.53, -0.05]), number of different word roots (coef = -10.04, 95% CI [-17.93, -2.14]), and Index of Productive Syntax sentence structures (coef = -1.81, 95% CI [-3.10, -0.52]). Other variables (e.g., number of utterances, number of nouns and adjectives) were not significantly different between groups. LSA and the Preschool Language Scales-Fifth Edition were at most moderately correlated (≤ .45). Conclusions Three-year-old children born preterm demonstrated poorer conversational language than children born at term, with some specific areas of deficit emerging. Furthermore, formal assessment and LSA appear to provide relatively distinct and yet complementary data to guide diagnostic and intervention decisions. Supplemental Material https://doi.org/10.23641/asha.11368073.

Project description:IntroductionThe underlying microstructural properties of white matter differences in children born very preterm (<32 weeks gestational age) can be investigated in depth using multi-shell diffusion imaging. The present study compared white matter across the whole brain using diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) metrics in children born very preterm and full-term children at six years of age. We also investigated associations between white matter microstructure with early brain injury and developmental outcomes.MethodMulti-shell diffusion imaging, T1-weighted anatomical MR images and developmental assessments were acquired in 23 children born very preterm (16 males; mean scan age: 6.57 ± 0.34 years) and 24 full-term controls (10 males, mean scan age: 6.62 ± 0.37 years). DTI metrics were obtained and neurite orientation dispersion index (ODI) and density index (NDI) were estimated using the NODDI diffusion model. FSL's tract-based spatial statistics were performed on traditional DTI metrics and NODDI metrics. Voxel-wise comparisons were performed to test between-group differences and within-group associations with developmental outcomes (intelligence and visual motor abilities) as well as early white matter injury and germinal matrix/intraventricular haemorrhage (GMH/IVH).ResultsIn comparison to term-born children, the children born very preterm exhibited lower fractional anisotropy (FA) across many white matter regions as well as higher mean diffusivity (MD), radial diffusivity (RD), and ODI. Within-group analyses of the children born very preterm revealed associations between higher FA and NDI with higher IQ and VMI. Lower ODI was found within the corona radiata in those with a history of white matter injury. Within the full-term group, associations were found between higher NDI and ODI with lower IQ.ConclusionChildren born very preterm exhibit lower FA and higher ODI than full-term children. NODDI metrics provide more biologically specific information beyond DTI metrics as well as additional information of the impact of prematurity and white matter microstructure on cognitive outcomes at six years of age.

Project description:BackgroundPrevious studies of preterm-born children (<37 weeks' gestation) have demonstrated decrements in lung function, exercise capacity, and increased respiratory symptoms compared to their term-born peers. However, it is unclear if these children have decreased levels of physical activity (PA) and increased sedentary behavior as a consequence of this increased respiratory morbidity. We therefore compared objectively measured PA in 7-year old preterm-born children with those born at term.MethodsChildren in the Millennium Cohort Study underwent assessment of PA at 7 years of age using accelerometry. 6422/12781 (50%) provided valid accelerometry and had gestational age data. A series of general linear models adjusted for confounders investigated the association between gestational age and levels of Total PA (average accelerometer counts per minute over the period of the recording), Moderate-to-Vigorous PA (MVPA) and sedentary behavior. Mediation analysis was performed to specifically investigate whether the observed association of gestational age on PA was mediated by respiratory symptoms.ResultsPA data were available for 79, 119, 275 and 5949 children born at 25-32, 33-34, 35-36 and 37-43 weeks' gestation respectively. Boys born at ≤32 weeks' gestation had modest but statistically significant reductions in MVPA when compared to term controls. This equated to a reduction of 9 minutes per day. No differences were found for Total PA or sedentary behavior. The association between gestational age and MVPA was not mediated by respiratory symptoms. In females, there was no association between gestational age and any measure of PA or sedentary behavior.ConclusionsBoys born at ≤32 weeks' gestation took part in less MVPA than their term-born peers at 7 years of age. The differences were modest, but equated to a reduction of over 1 hour per week. Since PA levels have been shown to decline during childhood and adolescence, this vulnerable group deserves further surveillance.

Project description:BackgroundExecutive function deficits in children born very preterm (VPT) have been linked to anatomical abnormalities in white matter and subcortical brain structures. This study aimed to investigate how altered brain metabolism contributes to these deficits in VPT children at school-age.MethodsFifty-four VPT participants aged 8-13 years and 62 term-born peers were assessed with an executive function test battery. Brain metabolites were obtained in the frontal white matter and the basal ganglia/thalami, using proton magnetic resonance spectroscopy (MRS). N-acetylaspartate (NAA)/creatine (Cr), choline (Cho)/Cr, glutamate + glutamine (Glx)/Cr, and myo-Inositol (mI)/Cr were compared between groups and associations with executive functions were explored using linear regression.ResultsIn the frontal white matter, VPT showed lower Glx/Cr (mean difference: -5.91%, 95% CI [-10.50, -1.32]), higher Cho/Cr (7.39%, 95%-CI [2.68, 12.10]), and higher mI/Cr (5.41%, 95%-CI [0.18, 10.64]) while there were no differences in the basal ganglia/thalami. Lower executive functions were associated with lower frontal Glx/Cr ratios in both groups (β = 0.16, p = 0.05) and higher mI/Cr ratios in the VPT group only (interaction: β = -0.17, p = 0.02).ConclusionLong-term brain metabolite alterations in the frontal white matter may be related to executive function deficits in VPT children at school-age.ImpactVery preterm birth is associated with long-term brain metabolite alterations in the frontal white matter. Such alterations may contribute to deficits in executive function abilities. Injury processes in the brain can persist for years after the initial insult. Our findings provide new insights beyond structural and functional imaging, which help to elucidate the processes involved in abnormal brain development following preterm birth. Ultimately, this may lead to earlier identification of children at risk for developing deficits and more effective interventions.

Project description:Individuals born very preterm (VPT; <32?weeks' gestational age) are at increased risk of impaired mathematics and word reading performance, as well as widespread white matter microstructural alterations compared with individuals born full term (FT; ?37?weeks' gestational age). To date, the link between academic performance and white matter microstructure is not well understood. This study aimed to investigate the associations between mathematics and reading performance with white matter microstructure in 114 VPT and 36 FT 13-year-old children. Additionally, we aimed to investigate whether the association of mathematics and reading performance with white matter microstructure in VPT children varied as a function of impairment. To do this, we used diffusion tensor imaging and advanced diffusion modelling techniques (Neurite Orientation Dispersion and Density Imaging and the Spherical Mean Technique), combined with a whole-brain analysis approach (Tract-Based Spatial Statistics). Mathematics performance across VPT and FT groups was positively associated with white matter microstructural measurements of fractional anisotropy and neurite density, and negatively associated with radial and mean diffusivities in widespread, bilateral regions. Furthermore, VPT children with a mathematics impairment (>1 standard deviation below FT mean) had significantly reduced neurite density compared with VPT children without an impairment. Reading performance was not significantly associated with any of the white matter microstructure parameters. Additionally, the associations between white matter microstructure and mathematics and reading performance did not differ significantly between VPT and FT groups. Our findings suggest that alterations in white matter microstructure, and more specifically lower neurite density, are associated with poorer mathematics performance in 13-year-old VPT and FT children. More research is required to understand the association between reading performance and white matter microstructure in 13-year-old children.

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Altered myelin maturation in four year old children born very preterm.

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Altered myelin maturation in four year old children born very preterm.

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