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Reduced hippocampal subfield volumes and memory function in school-aged children born preterm with very low birthweight (VLBW).

ABSTRACT: BACKGROUND:The hippocampus, an essential structure for learning and memory, has a reduced volume in preterm born (gestational age < 37 weeks) individuals with very low birth weight (VLBW: birth weight < 1500 g), which may affect memory function. However, the hippocampus is a complex structure with distinct subfields related to specific memory functions. These subfields are differentially affected by a variety of neuropathological conditions, but it remains unclear how these subfields may be affected by medical complications following preterm birth which may cause aberrant brain development, and the consequences of this on learning and memory function in children with VLBW. METHODS:Children born preterm with VLBW (n = 34) and term-born controls from the Norwegian Mother and Child Cohort Study (MoBa) (n = 104) underwent structural MRI and a neuropsychological assessment of memory function at primary school age. FreeSurfer 6.0 was used to analyze the volumes of hippocampal subfields which were compared between groups, as was memory performance. Correlations between abnormal hippocampal subfields and memory performance were explored in the VLBW group. RESULTS:All absolute hippocampal subfield volumes were lower in the children with VLBW compared to MoBa term-born controls, and the volumes of the left and right dentate gyrus and the right subiculum remained significantly lower after correcting for total intracranial volume. The VLBW group had inferior working memory performance and the score on the subtest Spatial Span backwards was positively correlated to the volume of the right dentate gyrus. CONCLUSIONS:Hippocampal subfield volumes seem to be differently affected by early brain development related to preterm birth. The dentate gyrus appears particularly susceptible to adverse effects of preterm birth. Reduced working memory function among children with VLBW was associated with smaller volume of right dentate gyrus. This finding demonstrates alterations in hippocampal structure-function relationships associated with early brain development related to preterm birth.

SUBMITTER: Aanes S

PROVIDER: S-EPMC6536855 | biostudies-other | 2019 May

REPOSITORIES: biostudies-other

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Reduced hippocampal subfield volumes and memory function in school-aged children born preterm with very low birthweight (VLBW).

Aanes Synne S Bjuland Knut Jørgen KJ Sripada Kam K Sølsnes Anne Elisabeth AE Grunewaldt Kristine H KH Håberg Asta A Løhaugen Gro C GC Skranes Jon J

NeuroImage. Clinical 20190511

<h4>Background</h4>The hippocampus, an essential structure for learning and memory, has a reduced volume in preterm born (gestational age < 37 weeks) individuals with very low birth weight (VLBW: birth weight < 1500 g), which may affect memory function. However, the hippocampus is a complex structure with distinct subfields related to specific memory functions. These subfields are differentially affected by a variety of neuropathological conditions, but it remains unclear how these subfields may ...[more]

PMID: 31136968

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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 (<32 weeks gestation) have altered brain growth and white matter maturation relative to their full-term peers, and approximately 30% will experience neurodevelopmental impairment. We investigated the relationship between neurodevelopmental impairment and MRI measures of white matter microstructure and brain volume. Children born before 30 weeks' gestation or who had very low birthweight (< 1500 g) underwent neurodevelopmental assessment and MRI at age 7 years as part of the PIANO study, a New Zealand-based cohort study. Fractional anisotropy (FA) and diffusivity measures were derived from diffusion tensor imaging to index white matter microstructure. Volumes were derived from T1-weighted imaging. Neurodevelopmental impairment was defined as a score < 85 on the Wechsler Intelligence Scale for Children, <5th centile on the Movement Assessment Battery for Children or a diagnosis of cerebral palsy by a paediatrician. Relationships between MRI and neurodevelopmental impairment were assessed with general linear models adjusted for sex, gestational age at birth, birthweight z-score, age at assessment, New Zealand Deprivation index score and multiplicity. Children with neurodevelopmental impairment (n = 38) had smaller total brain, cortical grey matter and cerebral white matter volumes compared to children without neurodevelopmental impairment (n = 62) (p < 0.05, false discovery rate corrected), but the regional volume differences did not remain significant after adjustment for total brain volume. Lower FA and higher radial diffusivity were observed in the superior longitudinal fasciculi, uncinate fasciculi and right hemisphere corticospinal tract in children with neurodevelopmental impairment. This may reflect differences in cellular properties such as myelination or axonal packing. Neurodevelopmental impairment may reflect smaller overall brain volume and altered microstructure in white matter tracts that are important for language, cognitive and motor functioning.

Project description:ObjectiveThe control of gait requires executive and attentional functions. As preterm children show executive and attentional deficits compared to full-term children, performing concurrent tasks that impose additional cognitive load may lead to poorer walking performance in preterm compared to full-term children. Knowledge regarding gait in preterm children after early childhood is scarce. We examined straight walking and if it is more affected in very preterm than in full-term children in dual-task paradigms.Study designTwenty preterm children with very low birth-weight (≤ 1500 g), 24 preterm children with birth-weight > 1500 g, and 44 full-term children, born between 2001 and 2006, were investigated. Gait was assessed using an electronic walkway system (GAITRite) while walking without a concurrent task (single-task) and while performing one concurrent (dual-task) or two concurrent (triple-task) tasks. Spatio-temporal gait parameters (gait velocity, cadence, stride length, single support time, double support time), normalized gait parameters (normalized velocity, normalized cadence, normalized stride length) and gait variability parameters (stride velocity variability, stride length variability) were analyzed.ResultsIn dual- and triple-task conditions children showed decreased gait velocity, cadence, stride length, as well as increased single support time, double support time and gait variability compared to single-task walking. Further, results showed systematic decreases in stride velocity variability from preterm children with very low birth weight (≤ 1500 g) to preterm children with birth weight > 1500 g to full-term children. There were no significant interactions between walking conditions and prematurity status.ConclusionsDual and triple tasking affects gait of preterm and full-term children, confirming previous results that walking requires executive and attentional functions. Birth-weight dependent systematic changes in stride velocity variability indicate poorer walking performance in preterm children who were less mature at birth.

Project description:Preterm birth (gestational age?<?37 weeks) with very low birth weight (VLBW, birth weight???1500?g) is associated with lifelong cognitive deficits, including in executive function, and persistent alterations in cortical and subcortical structures. However, it remains unclear whether "catch-up" growth is possible in the preterm/VLBW brain. Longitudinal structural MRI was conducted with children born preterm with VLBW (n?=?41) and term-born peers participating in the Norwegian Mother and Child Cohort Study (MoBa) (n?=?128) at two timepoints in early school age (mean ages 8.0 and 9.3 years). Images were analyzed with the FreeSurfer 5.3.0 longitudinal stream to assess differences in development of cortical thickness, surface area, and brain structure volumes, as well as associations with executive function development (NEPSY Statue and WMS-III Spatial Span scores) and perinatal health markers. No longitudinal group?×?time effects in cortical thickness, surface area, or subcortical volumes were seen, indicating similar brain growth trajectories in the groups over an approximately 16-month period in middle childhood. Higher IQ scores within the VLBW group were associated with greater surface area in left parieto-occipital and inferior temporal regions. Among VLBW preterm-born children, cortical surface area was smaller across the cortical mantle, and cortical thickness was thicker occipitally and frontally and thinner in lateral parietal and posterior temporal areas. Smaller volumes of corpus callosum, right globus pallidus, and right thalamus persisted in the VLBW group from timepoint 1 to 2. VLBW children had on average IQ 1?SD below term-born MoBa peers and significantly worse scores on WMS-III Spatial Span. Executive function scores did not show differential associations with morphometry between groups cross-sectionally or longitudinally. This study investigated divergent or "catch-up" growth in terms of cortical thickness, surface area, and volumes of subcortical gray matter structures and corpus callosum in children born preterm/VLBW and did not find group?×?time interactions. Greater surface area at mean age 9.3 in left parieto-occipital and inferior temporal cortex was associated with higher IQ in the VLBW group. These results suggest that preterm VLBW children may have altered cognitive networks, yet have structural growth trajectories that appear generally similar to their term-born peers in this early school age window.

Project description:Importance:Children born preterm are at an elevated risk of academic underachievement. However, the extent to which performance across domain-specific subskills in reading and mathematics is associated with preterm birth remains unclear. Objective:To conduct a systematic review and meta-analysis of academic outcomes of school-aged children born preterm, compared with children born at term, appraising evidence for higher- and lower-order subskills in reading and mathematics. Data Sources:PubMed/MEDLINE, PsycINFO, and the Cumulative Index of Nursing and Allied Health Literature electronic databases from January 1, 1980, to July 30, 2018, were searched for population, exposure, and outcome terms such as child (population), preterm birth (exposure), and education* (outcome). Study Selection:Peer-reviewed English-language publications that included preterm-born children and a comparison group of term-born children aged 5 to 18 years and born during or after 1980 and that reported outcomes on standardized assessments from cohort or cross-sectional studies were screened. Of the 9833 articles screened, 33 unique studies met the inclusion criteria. Data Extraction and Synthesis:Data were analyzed from August 1 to September 29, 2018. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed. Two reviewers independently screened the databases and extracted sample characteristics and outcomes scores. Pooled mean differences (MDs) were analyzed using random-effects models. Main Outcomes and Measures:Performance on standardized assessment of higher-order subskills of reading comprehension and applied mathematics problems; lower-order reading subskills of decoding, pseudoword decoding, and word identification; and lower-order mathematics subskills of knowledge, calculation, and fluency. Results:Outcomes data were extracted for 4006 preterm and 3317 term-born children, totaling 7323 participants from 33 unique studies. Relative to children born at term, children born preterm scored significantly lower in reading comprehension (mean difference [MD], -7.96; 95% CI, -12.15 to -3.76; I2?=?81%) and applied mathematical problems (MD, -11.41; 95% CI, -17.57 to -5.26; I2?=?91%) assessments. Across the assessments of lower-order skills, children born preterm scored significantly lower than their term-born peers in calculation (MD, -10.57; 95% CI, -15.62 to -5.52; I2?=?92%), decoding (MD, -10.18; 95% CI, -16.83 to -3.53; I2?=?71%), mathematical knowledge (MD, -9.88; 95% CI, -11.68 to -8.08; I2?=?62%), word identification (MD, -7.44; 95% CI, -9.08 to -5.80; I2?=?69%), and mathematical fluency (MD, -6.89; 95% CI, -13.54 to -0.23; I2?=?72%). The associations remained unchanged after sensitivity analyses for reducing heterogeneity. Conclusions and Relevance:These findings provide evidence that preterm birth is associated with academic underperformance in aggregate measures of reading and mathematics, as well as a variety of related subskills.

Dataset Information

Reduced hippocampal subfield volumes and memory function in school-aged children born preterm with very low birthweight (VLBW).

Publications

Reduced hippocampal subfield volumes and memory function in school-aged children born preterm with very low birthweight (VLBW).

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