Gro Løhaugen

Young adults born preterm with very low birth weight demonstrate widespread white matter alterations on brain DTI

Preterm birth with very low birth weight (VLBW, ≤1500 g) is connected to reduced white matter (WM) integrity in childhood and adolescence. These changes in WM are correlated to motor, sensory and neuropsychological impairments. CNS myelination continues into the early twenties, but the consequences of this for WM integrity in VLBWs have not been explored. DTI and tract based spatial statistics (TBSS) was carried out to test for voxelwise differences in fractional anisotropy (FA), eigenvalues and mean diffusivity (MD) between a preterm VLBW group (n=49) and a control group born at term (n=59) at 18-22 years of age. TBSS was also used to explore the relationship between perinatal clinical data and general cognitive ability (total IQ), respectively, and the DTI metrics (FA and MD), with gender and age as a confounder. In the VLBW group several major WM tracts particularly in the posterior region had significantly reduced FA caused by an increase in the two lowest eigenvalues. MD was significantly increased in the VLBWs in 50% of the same regions as the FA changes, but encompassing also more peripheral WM. In the VLBW group, FA was found to correlate positively with birth weight and negatively with number of days in intensive care and on mechanical ventilator, particularly in the corpus callosum. FA was found to correlate positively with total IQ in the young preterm adults. In the controls there was no correlation between FA and total IQ. Our results indicate that the neurologic sequelae of preterm birth with VLBW are a lifelong condition inducing structural and functional impairments also in adulthood in VLBW survivors. The greatest risk of having reduced WM integrity in adulthood was found in the most immature VLBW neonates requiring mechanical ventilation and long-term intensive care.

Segmental brain volumes and cognitive and perceptual correlates in 15-year-old adolescents with low birth weight.

OBJECTIVE To determine whether preterm very low birth weight (VLBW) or term born small for gestational age (SGA) adolescents have reduced regional brain volumes. We also asked which perinatal factors are related to reduced brain volume in VLBW adolescents, which regional brain volumes are associated with cognitive and perceptual functioning, and if these differ between the groups. STUDY DESIGN Fifty adolescent preterm VLBW (< or =1500 g) births and 49 term SGA births (birth weight <10th percentile) were compared with 57 normal-weight term births. An automated MRI segmentation technique was used. Cognitive and perceptual functions were evaluated by WISC-III and Visual Motor Integration (VMI) tests. RESULTS The VLBW group had reduced volumes for thalamus and cerebellar white matter (P < .002). The SGA group had smaller total brains, and proportionally smaller regional brain volumes. Cerebellar white matter in the VLBW, hippocampus in the SGA, and cerebral cortical in the control group were volumes that significantly predicted cognitive and perceptual functions. CONCLUSIONS We speculate that white matter injury may explain the impaired cognitive and perceptual functioning in the prematurely born, whereas hippocampal injury may be related to cognitive dysfunction in term SGA adolescents.

Cognitive profile in young adults born preterm at very low birthweight

Aim  The aim of this study was to assess cognitive function at the age of 19 years in individuals of very low birthweight (VLBW; ≤1500g) and in term‐born comparison individuals.

Computerized Working Memory Training Improves Function in Adolescents Born at Extremely Low Birth Weight

OBJECTIVE To evaluate the effect of a computerized working memory training program on both trained and non-trained verbal aspects of working memory and executive and memory functions in extremely low birth weight (ELBW; <1000 g) infants. STUDY DESIGN Sixteen ELBW infants and 19 term-born control subjects aged 14 to 15 years participated in the training program, and 11 adolescents were included as a non-intervention group. Extensive neuropsychological assessment was performed before and immediately after training and at a 6-month follow-up examination. Both training groups used the CogMed RM program at home 5 days a week for 5 weeks. RESULTS Both groups improved significantly on trained and non-trained working memory tasks and on other memory tests indicating a generalizing effect. Working memory capacity was improved, and effects were maintained at the 6-month follow-up examination. There was no significant improvement in the non-intervention group at the 6-week follow-up examination. CONCLUSIONS The computerized training program Cogmed RM was an effective intervention tool for improving memory and reducing core learning deficits in adolescents born at ELBW.

White matter abnormalities and executive function in children with very low birth weight

The aim of this study was to investigate any structural–functional relationship between changes in white matter microstructure seen on diffusion tensor imaging and results of an executive function test in adolescents with very low birth weight (VLBW). Thirty-four VLBW adolescents were examined at 15 years of age. Executive function was assessed by the Wisconsin Card Sorting Test. Diffusion tensor imaging scans were performed at 1.5 T for calculation of individual fractional anisotropy maps. Through a voxel-wise regression analysis, correlations were found between the results on Wisconsin Card Sorting Test and fractional anisotropy values in the left cingulum and both inferior fronto-occipital fascicles. We speculate that impairments in executive function in VLBW children may be influenced by disturbed connectivity between posterior brain regions and the prefrontal cortex.

Mental health, quality of life and social relations in young adults born with low birth weight

BackgroundBeing born with low birth weight may have an impact on different aspects of mental health, psychosocial functioning and well-being; however results from studies in young adulthood have so far yielded mixed findings. The aim of this study was to assess the long-term impact in young adulthood on self-reported mental health, health-related quality of life, self-esteem and social relations by investigating differences between two low birth weight groups and a control group.MethodsIn a follow-up at 20 years of age, 43 preterm VLBW (birth weight ≤ 1500 g), 55 term SGA (birth weight < 10th percentile) and 74 control subjects completed the Adult Self-Report (ASR) of the Achenbach System of Empirically Based Assessment, the Adult Autism Spectrum Quotient (AQ), the Short Form 36 Health Survey, the Self-Perception Profile for Adolescents-Revised, and the Wechsler Adult Intelligent Scale III assessment.ResultsThe VLBW and SGA groups reported significantly more mental health problems than controls. The VLBW group predominantly had internalizing problems, and the non-significant association with ASR Total score was reduced by the Intelligence Quotient (IQ). The SGA group had increased scores on both internalizing and externalizing problems, and the association with ASR Total score remained significant after adjusting for IQ in this group. Both low birth weight groups reported less interaction with friends and lower quality of life related to mental health domains than controls. Self-esteem scores were lower than in the control group for athletic competence (VLBW) and social acceptance (SGA).ConclusionOur findings suggest that self-reported mental health and well-being in young adulthood may be adversely affected by low birth weight, irrespective of whether this is the result of premature birth or being born SGA at term.

Cortical thickness and cognition in very-low-birth-weight late teenagers

BACKGROUND Preterm born children with very low birth weight (VLBW: bw ≤ 1500 g) have an increased risk of perinatal brain injury which may influence the subsequent maturation of grey and white matter. Aberrant cortical development may have implications for future cognitive functioning. AIMS The aim of this study was to measure deviations in cortical thickness and to investigate the relationship between cortical thickness, perinatal variables and IQ measurements in VLBW late teenagers compared with term-born controls. STUDY DESIGN Prospective follow-up study of three year cohorts of children from birth to early adulthood. SUBJECT Forty-seven VLBW and 61 term born controls were examined at ages 18-21. OUTCOME MEASURES Cognitive function was assessed with the WAIS-III, measuring full IQ and IQ indices. We applied an automated method to reconstruct the cortical surface based on T1-weighted MRI images using the FreeSurfer software. RESULTS We found widespread areas of thinner cerebral cortex in the left parietal and temporal lobes and thicker cortex in frontal areas bilaterally in the VLBW group compared to controls. There were positive correlations between IQ and cortical thickness in areas in ventro-lateral frontal, parietal and temporal lobes in the VLBW group. The most pronounced cortical changes were seen in the VLBW subjects with the lowest birth weight and gestational age, and in those with IQ below 89. CONCLUSION Persistent cortical deviations seen in VLBW late teenagers are associated with immaturity at birth and level of cognitive functioning.

Follow-up at age 10 years in ELBW children — Functional outcome, brain morphology and results from motor assessments in infancy ☆ ☆☆

BACKGROUND Extremely-low-birth-weight (ELBW) children without severe brain injury or CP are at high risk of developing deficits within cognition, attention, behavior and motor function. Assessing the quality of an infants spontaneous motor-repertoire included in Prechtls General-Movement-Assessment (GMA) has been shown to relate to later motor and cognitive functioning in preterm children without CP. AIMS To investigate functional outcome and cerebral MRI morphometry at 10 years in ELBW children without CP compared to healthy controls and to examine any relationship with the quality of infant-motor-repertoire included in the GMA. STUDY DESIGN A cohort-study-design. SUBJECTS 31 ELBW children (mean birth-weight: 773 g, SD 146, mean gestational age 26.1 weeks, SD 1.8) and 33 term-born, age-matched controls. OUTCOME MEASURES GMA was performed in ELBW children at 3 months corrected age. At 10 years the children underwent comprehensive motor, cognitive, behavioral assessments and cerebral MRI. RESULTS The non-CP ELBW children had similar full-IQ but poorer working memory, poorer motor skills, and more attentional and behavioral problems compared to controls. On cerebral MRI reduced volumes of globus pallidus, cerebellar white matter and posterior corpus callosum were found. Cortical surface-area was reduced in temporal, parietal and anterior-medial-frontal areas. Poorer test-results and reduced brain volumes were mainly found in ELBW children with fidgety movements combined with abnormal motor-repertoire in infancy. CONCLUSION Non-CP ELBW children have poorer functional outcomes, reduced brain volumes and cortical surface-area compared with term-born controls at 10 years. ELBW children with abnormal infant motor-repertoire seem to be at increased risk of later functional deficits and brain pathology.

Entorhinal cortical thinning affects perceptual and cognitive functions in adolescents born preterm with very low birth weight (VLBW)

BACKGROUND The entorhinal cortex serves as an important gateway between the cerebral cortex and the hippocampus by receiving afferent information from limbic, modality sensory-specific, and multimodal association fibers from all the brain lobes. AIM To investigate whether thinning of entorhinal cortex is associated with reduced perceptual, cognitive and executive skills in very low birth weight (VLBW) adolescents. STUDY DESIGN Prospective, geographically based follow-up study of three year cohorts of preterm born VLBW children. SUBJECTS Forty-nine VLBW (birth weight ≤ 1500 g) and 58 term-born control adolescents were examined at the age of 14-15 years. OUTCOME MEASURES Perceptual and cognitive functions were assessed with Visual motor integration test, Grooved Pegboard test, Wechsler Intelligence Scale for Children-III and different executive function tests (Wisconsin card sorting test, Trail Making test, Knox cube test). An automated MRI technique at 1.5 T for morphometric analyses of cortical thickness was performed. Areas with cortical thinning in left and right entorhinal cortex in the VLBW group were chosen as regions of interest to look for associations between cortical thickness and clinical findings. RESULTS Thinning of the entorhinal cortex was correlated with low performance on perceptual and cognitive scores in the VLBW adolescents, but not in controls. In addition, thinning of the entorhinal cortices correlated with reduced performance on several executive tests, including perceptual speed and aspects of working memory. CONCLUSIONS Entorhinal cortical thinning is related with low IQ and reduced perceptual and executive functions in VLBW adolescents.

Visual–motor deficits relate to altered gray and white matter in young adults born preterm with very low birth weight

Individuals born preterm and at very low birth weight (birth weight ≤ 1500 g) are at an increased risk of perinatal brain injury and neurodevelopmental deficits over the long term. This study examined whether this clinical group has more problems with visual-motor integration, motor coordination, and visual perception compared to term-born controls, and related these findings to cortical surface area and thickness and white matter fractional anisotropy. Forty-seven preterm-born very low birth weight individuals and 56 term-born controls were examined at 18-22 years of age with a combined cognitive, morphometric MRI, and diffusion tensor imaging evaluation in Trondheim, Norway. Visual-motor skills were evaluated with the Beery-Buktenica Developmental Test of Visual-Motor Integration-V (VMI) copying test and its supplemental tests of motor coordination and visual perception. 3D T1-weighted MPRAGE images and diffusion tensor imaging were done at 1.5 T. Cortical reconstruction generated in FreeSurfer and voxelwise maps of fractional anisotropy calculated with Tract-Based Spatial Statistics were used to explore the relationship between MRI findings and cognitive results. Very low birth weight individuals had significantly lower scores on the copying and motor coordination tests compared with controls. In the very low birth weight group, VMI scores showed significant positive relationships with cortical surface area in widespread regions, with reductions of the superior temporal gyrus, insula, and medial occipital lobe in conjunction with the posterior ventral temporal lobe. Visual perception scores also showed positive relationships with cortical thickness in the very low birth weight group, primarily in the lateral occipito-temporo-parietal junction, the superior temporal gyrus, insula, and superior parietal regions. In the very low birth weight group, visual-motor performance correlated positively with fractional anisotropy especially in the corpus callosum, inferior fronto-occipital fasciculus bilaterally, and anterior thalamic radiation bilaterally, driven primarily by an increase in radial diffusivity. VMI scores did not demonstrate a significant relationship to cortical surface area, cortical thickness, or diffusion measures in the control group. Our results indicate that visual-motor integration problems persist into adulthood for very low birth weight individuals, which may be due to structural alterations in several specific gray-white matter networks. Visual-motor deficits appear related to reduced surface area of motor and visual cortices and disturbed connectivity in long association tracts containing visual and motor information. We conjecture that these outcomes may be due to perinatal brain injury or aberrant cortical development secondary to injury or due to very preterm birth.