Multi-domain cognitive impairments at school age in very preterm-born children compared to term-born peers.
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ABSTRACT: Background
Preterm infants are at risk for functional impairments in motor, cognitive, and behavioral development that may persist into childhood. The aim of this study was to determine the co-occurrence of cognitive impairments in multiple cognitive domains at school age in very preterm born children compared to term-born children.Methods
Comparative study including 60 very preterm-born children (gestational age ≤ 32 weeks) and 120 term-born controls. At school age, we assessed intelligence with the WISC-III, and visuomotor integration with the NEPSY-II, verbal memory with the AVLT, attention with the TEA-ch, and executive functioning with the BRIEF. We investigated co-occurrence of various abnormal (<5th percentile) and suspect-abnormal (<15th percentile, including both suspect and abnormal) cognitive functions.Results
At mean age 8.8 years, 15% of preterm children had abnormal outcomes in multiple cognitive functions (≥2), versus 3% of the controls (odds ratio, OR 4.65, 95%-confidence interval, CI 1.33-16.35). For multiple suspect-abnormal cognitive outcomes, rates were 55% versus 25% (OR 3.02, 95%-CI 1.49-6.12). We found no pattern of co-occurrence of cognitive impairments among preterm children that deviated from term-born controls. However, low performance IQ was more frequently accompanied by additional cognitive impairments in preterms than in controls (OR 5.43, 95%-CI 1.75-16.81).Conclusions
A majority of preterm children showed co-occurrence of impairments in multiple cognitive domains, but with no specific pattern of impairments. The occurrence of multi-domain cognitive impairments is higher in preterms but this seems to reflect a general increase, not one with a pattern specific for preterm-born children.
SUBMITTER: Roze E
PROVIDER: S-EPMC8042721 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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.
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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.
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Project description:ObjectiveVery preterm (<32 weeks gestation; VP) and/or very low birth weight (<1500g; VLBW) children often have cognitive and mathematic difficulties. It is unknown whether VP/VLBW children's frequent mathematic problems significantly add to the burden of negative life-course consequences over and above effects of more general cognitive deficits. Our aim was to determine whether negative consequences of VP/VLBW versus healthy term birth on adult wealth are mediated by mathematic abilities in childhood, or rather explained by more general cognitive abilities.Methods193 VP/VLBW and 217 healthy term comparison participants were studied prospectively from birth to adulthood as part of a geographically defined study in Bavaria (South Germany). Mathematic and general cognitive abilities were assessed at 8 years with standardized tests; wealth information was assessed at 26 years with a structured interview and summarized into a comprehensive index score. All scores were z-standardized.ResultsAt 8 years, VP/VLBW (n = 193, 52.3% male) had lower mathematic and general cognitive abilities than healthy term comparison children (n = 217, 47.0% male). At 26 years, VP/VLBW had accumulated significantly lower overall wealth than term born comparison adults (-0.57 (1.08) versus -0.01 (1.00), mean difference 0.56 [0.36-0.77], p < .001). Structural equation modeling confirmed that VP/VLBW birth (β = -.13, p = .022) and childhood IQ (β = .24, p < .001) both directly predicted adult wealth, but math did not (β = .05, p = .413). Analyses were controlled for small-for-gestational-age (SGA) birth, child sex, and family socioeconomic status.ConclusionThis longitudinal study from birth to adulthood shows that VP/VLBW survivors' general cognitive rather than specific mathematic problems explain their diminished life-course success. These findings are important in order to design effective interventions at school age that reduce the burden of prematurity for those individuals who were born at highest neonatal risk.
| S-EPMC6415831 | biostudies-literature
Project description:IntroductionCompared to full-term (FT) born peers, children who were born very preterm (VPT; <32 weeks' gestation) are likely to display more cognitive and behavioral difficulties, including inattention, anxiety and socio-communication problems. In the published literature, such difficulties tend to be studied independently, thus failing to account for how different aspects of child development interact. The current study aimed to investigate children's cognitive and behavioral outcomes as interconnected, dynamically related facets of development that influence one another.MethodsParticipants were 93 VPT and 55 FT children (median age 8.79 years). IQ was evaluated with the Wechsler Intelligence Scale for Children-4th edition (WISC-IV), autism spectrum condition (ASC) traits with the social responsiveness scale-2nd edition (SRS-2), behavioral and emotional problems with the strengths and difficulties questionnaire (SDQ), temperament with the temperament in middle childhood questionnaire (TMCQ) and executive function with the behavior rating inventory of executive functioning (BRIEF-2). Outcome measures were studied in VPT and FT children using Network Analysis, a method that graphically represents partial correlations between variables and yields information on each variable's propensity to form a bridge between other variables.ResultsVPT and FT children exhibited marked topological differences. Bridges (i.e., the variables most connected to others) in the VPT group network were: conduct problems and difficulties with organizing and ordering their environment. In the FT group network, the most important bridges were: difficulties with initiating a task or activity and prosocial behaviors, and greater emotional problems, such as lower mood.DiscussionThese findings highlight the importance of targeting different aspects of development to support VPT and FT children in person-based interventions.
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Project description:ImportanceCognitive delay is the most common form of impairment among children born very preterm (VPT) at 32 weeks or less or with very low birth weight (VLBW) of 1250 g or less. It is important to identify factors that are robust predictors of long-term outcome because the ability to predict future prognosis will assist in health care and educational service planning and provision.ObjectiveTo identify prognostic factors for poor cognitive development in children born VPT or with VLBW.Evidence reviewA systematic review was conducted using MEDLINE, EMBASE, and PyscINFO databases to identify studies published between January 1, 1990, and June 1, 2014, reporting multivariable prediction models for neurodevelopment in VPT or VLBW children. Thirty-one studies comprising 98 risk factor models for cognitive outcome were identified. Two independent reviewers extracted key information on study design, outcome definition, risk factor selection, model development, and reporting and conducted a risk-of-bias assessment.FindingsThere was evidence that male sex, nonwhite race/ethnicity, lower level of parental education, and lower birth weight were predictive of global cognitive impairment in children younger than 5 years. In older children, only the influence of parental education was sustained. Male sex was also predictive of language impairment in early infancy, but not in middle childhood. Gestational age was a poor predictor of cognitive outcome, probably because of a reduced discriminatory power in cohorts restricted to a narrow gestational age range. The prognostic value of neonatal brain injury was unclear; however, studies adopted mixed strategies for managing children with physical or neurosensory disability.Conclusions and relevanceThe influence of perinatal risk factors on cognitive development of VPT or VLBW children appears to diminish over time as environmental factors become more important. It is difficult to isolate cognitive outcomes from motor and neurosensory impairment, and the strategy for dealing with untestable children has implications for risk prediction.
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Project description:ObjectiveTo determine whether the relationship of gestational age (GA) with brain volumes and cognitive functions is linear or whether it follows a threshold model in preterm and term born children during school-age.Study designWe studied 106 children (M = 10 years 1 month, SD = 16 months; 40 females) enrolled in primary school: 57 were healthy very preterm children (10 children born 24-27 completed weeks' gestation (extremely preterm), 14 children born 28-29 completed weeks' gestation, 19 children born 30-31 completed weeks' gestation (very preterm), and 14 born 32 completed weeks' gestation (moderately preterm)) all born appropriate for GA (AGA) and 49 term-born children. Neuroimaging involved voxel-based morphometry with the statistical parametric mapping software. Cognitive functions were assessed with the WISC-IV. General Linear Models and multiple regressions were conducted controlling age, sex, and maternal education.ResultsCompared to groups of children born 30 completed weeks' gestation and later, children born <28 completed weeks' gestation had less gray matter volume (GMV) and white matter volume (WMV) and poorer cognitive functions including decreased full scale IQ, and processing speed. Differences in GMV partially mediated the relationship between GA and full scale IQ in preterm born children.ConclusionsIn preterm children who are born AGA and without major complications GA is associated with brain volume and cognitive functions. In particular, decreased brain volume becomes evident in the extremely preterm group (born <28 completed weeks' gestation). In preterm children born 30 completed weeks' gestation and later the relationship of GA with brain volume and cognitive functions may be less strong as previously thought.
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Project description:AimThis study determined whether cognitive outcomes differed between very preterm (VPT) and extremely preterm (EPT) children who were monolingual or multilingual when they reached the corrected ages of two and five years.MethodsThe data were collected at the Emma Children's Hospital, Amsterdam, The Netherlands, as part of our national neonatal follow-up programme and comprised 325 VPT/EPT children born between January 1, 2007 and January 1, 2012. The study used the Third Editions of the Bayley Scales of Infant and Toddler Development and the Wechsler Preschool and Primary Scale of Intelligence.ResultsWe compared 234 monolingual children, 65 multilingual children who spoke Dutch and at least one foreign language at home and 26 multilingual children who didn't speak Dutch at home. The best performers on the cognitive scale at two years of age and the verbal subscales at five years of age were the monolingual children, followed by the children who spoke Dutch and at least one foreign language at home, then the children who only spoke foreign languages at home.ConclusionIn our study cohort from The Netherlands, multilingualism lowered the cognitive and verbal outcomes of VPT/EPT children at the corrected ages of two and five years.
| S-EPMC6585714 | biostudies-literature
Project description:BackgroundThe 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.MethodsChildren 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.ResultsAll 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.ConclusionsHippocampal 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.
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Project description:Language deficits are reported in preterm born children across development. Recent neuroimaging studies have found functional alterations in large-scale brain networks underlying these language deficits, but the early childhood development of the language network has not been investigated. Here, we compared intrinsic language network connectivity in 4-year-old children born VPT and term-born controls, using defined language regions (Broca's area, Wernicke's areas, and their homologues in the right hemisphere). Resting-state functional magnetic resonance imaging (fMRI) was obtained, and the group differences in whole-brain connectivity were examined from each seed as well as correlations with language outcomes. We found significantly decreased functional connectivity in almost all language regions in children born VPT compared to their term controls. Notably, Broca's area homologue in the right hemisphere emerged as a functional hub of decreased connectivity in VPT group, specifically to bilateral inferior frontal and supramarginal gyri; connectivity strength between Broca's area homologue with the right supramarginal and the left inferior frontal gyri was associated with better language outcomes at 4 years of age. Wernicke's area and its homologue also showed decreased inter-hemispheric connections to bilateral supramarginal gyri in the VPT group. Decreased intra- and inter-hemispheric connectivity among primary language regions suggests immature and altered function in the language network in children born VPT.
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