Jon Skranes

Changes in white matter diffusion anisotropy in adolescents born prematurely

Being born with very low birth weight (VLBW, birth weight<or=1500 g) or small for gestational age (SGA) carries an increased risk of cerebral white matter damage. The reduced cognitive and motor skills these two groups exhibit suggest that the early injuries to white matter persist into adolescence. White matter integrity was assessed using voxel-wise statistical analysis of fractional anisotropy (FA) maps between three groups of adolescents at age 15; the VLBW group (n=34), the SGA group (n=42) and a control group with normal birth weight (n=47). The FA maps were normalized to a study specific template and group differences were assessed using an analysis of covariance with gender as a confounder (FDR-corrected P<0.05). The main finding is that the VLBW group has significantly reduced FA values in several white matter regions, including the corpus callosum, internal capsule and superior fasciculus compared to the control group. Some of the observed reduction in anisotropy, particularly that observed in the corpus callosum, may have been caused by inaccurate spatial normalization, but this can only explain 30% of the area with reduced anisotropy. Analysis of the eigenvalues of the diffusion tensor show that the reduced FA values in the VLBW group is primarily due to an increase in the two lowest eigenvalues of the diffusion tensor. We speculate that this may be caused by reduced myelination. For the SGA group, we find no statistically significant differences in anisotropy compared to the control group.

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.

Perinatal risk and psychiatric outcome in adolescents born preterm with very low birth weight or term small for gestational age.

Objective: To study perinatal risk factors for psychiatric symptoms in adolescents born preterm with very low birth weight or at term, but small for gestational age (GA). Method: Mental health was assessed in 65 adolescents born with very low birth weight (VLBW) (birth weight ≤1500 g), 59 born term small for GA (birth weight <10th centile) and 81 control adolescents using Schedule for Affective Disorders and Schizophrenia for School-Age Children, Childrens Global Assessment Scale, Autism Spectrum Screening Questionnaire, Attention-Deficit Hyperactivity Disorder-Rating Scale IV and Achenbach System of Empirically Based Assessment. Perinatal data included birth weight, GA, head circumference, Apgar scores, intraventricular hemorrhage, days in neonatal intensive care unit, and days on mechanical ventilation. Results: In the very low birth weight group, lower birth weight was associated with inattention (p < .01), psychiatric diagnoses, and reduced psychosocial function (p ≤ .05). Intraventricular hemorrhage increased the risk for a high inattention score (odds ratio = 7.5; 95% confidence intervals: 1.2–46.8). Lower Apgar score at 1 min was associated with a high Autism Spectrum Screening Questionnaire score and lower Apgar score at 5 min with a high internalizing score (p ≤ .05). In the subgroup born appropriate for GA, internalizing symptoms were also associated with lower GA. In the term small for GA group, perinatal events were not associated with psychiatric problems. In contrast, low socioeconomic status was associated with externalizing symptoms. Conclusion: Lower birth weight, shorter gestation, and intraventricular hemorrhage were risk factors for psychiatric problems in the very low birth weight group. Lower Apgar score increased the risk for autism spectrum symptoms and internalizing symptoms. Among adolescents born term small for GA, the main risk factor for psychiatric symptoms was low socioeconomic status.

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.

Feeding problems, growth and nutritional status in children with cerebral palsy.

Aim:  The aim was to estimate the prevalence of feeding and nutritional problems in children with cerebral palsy (CP) in Norway.

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.

Working Memory Training Improves Cognitive Function in VLBW Preschoolers

BACKGROUND AND OBJECTIVE: Preterm born children perform poorer than term peers on tests of attention and executive functions including working memory tests. Our aim was to evaluate if preterm born preschoolers with very low birth weight (VLBW) would benefit from a computerized working memory training program and if the training would have a generalizing effect on memory, learning, attention, behavior, and anxiety. METHODS: A prospective intervention study with a stepped wedge design where 20 VLBW preschoolers aged 5 to 6 years participated. The children trained with the Cogmed JM program for 10 to 15 minutes a day, 5 days a week over a 5-week period. Extensive neuropsychological assessment and parental questionnaires regarding behavior and anxiety were performed before and 4 weeks after intervention. RESULTS: The children improved significantly on trained (mean Start Index 42.1 [SD 6.3]), mean Max Index 60.6 [SD 5.7]), and nontrained working memory tasks (Spatial Span backward; 2.3 [before] to 3.6 [after training] [confidence interval {CI} −2.2 to −0.4] and Spatial Span total score; 6.4–8.3 [CI −3.7 to −0.1]). A generalization effect was found on auditory attention (49.6–58.2 [CI −15.5 to −1.6]), phonological awareness (9.3–12.6 [CI −5.2 to −1.4]), visual (memory for faces 20.0–24.9 [CI −7.4 to −2.5]), as well as verbal memory (narrative memory; 12.9–17.5 [CI −7.1 to −2.0], and sentence repetition 15.7–17.7 [CI −3.3 to −0.7]). CONCLUSION: This study shows that VLBW preschoolers benefit from a computerized working memory training program. We speculate that such training before starting school may prevent or reduce cognitive problems that impact educational achievement.

Predictive value of early motor evaluation in preterm very low birth weight and term small for gestational age children

BACKGROUND Motor problems are common in children born preterm or small for gestational age. AIM To study the predictive value of early motor assessments for later motor skills. SUBJECTS Twenty-eight children born preterm with very low birth weight (VLBW: birth weight <or=1500 g), 57 children born small for gestational age (SGA: birth weight <10th centile) at term and 77 term-born controls with normal birth weight. METHODS The psychomotor development index (PDI) of the Bayley Scales of Infant Development was used as a measure of motor skills at age one, the Peabody Developmental Motor Scales (PDMS) at age five and the Movement Assessment Battery for Children (Movement ABC) at age 14. Low/borderline low scores were defined as <-2SD/-1SD (PDI) or <5th/15th centile (PDMS; Movement ABC). RESULTS In the VLBW group, motor problems in adolescence were identified both by low PDI (sensitivity: 0.80; 95%CI:0.38-0.96) and PDMS scores (sensitivity: 0.83; 95%CI:0.44-0.97). In the SGA and the control group sensitivity was poor for low PDI and moderate for low PDMS scores. However, in the SGA group, sensitivity increased when borderline low PDMS scores were used as cut-off (sensitivity: 0.75; 95%CI:0.41-0.93). Specificity of PDI and PDMS was high in all three groups. CONCLUSIONS Both PDI and PDMS may be valuable tools for early identification of motor problems in VLBW children, whereas PDMS best predicted motor problems in the two other groups. In all three groups, a normal motor examination at 1 and 5 years was highly predictive of normal motor skills at age 14.