Marit Martinussen

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.

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.

Mesenteric blood flow velocity and its relation to transitional circulatory adaptation in appropriate for gestational age preterm infants

We investigated the early postnatal changes of the mesenteric circulation and its relation to the systemic circulation in 15 preterm infants. The infants were studied before the first feeding on d 1 and pre- and postprandially on d 3, 4, 5, and 7. Blood flow velocity was measured by ultrasound Doppler in the superior mesenteric artery, middle cerebral artery, and the aortic orifice for cardiac output calculations. Blood pressure and heart rate were monitored. From d 1 to d 3, the preprandial stroke volume decreased [1.5 ± 0.3 to 1.3 ± 0.2 mL/kg (mean ± SD),p < 0.05], whereas blood pressure (36 ± 3 to 50 ± 7 mm Hg, p < 0.001), superior mesenteric artery mean velocity(Vmean) (0.17 ± 0.08 to 0.30 ± 0.11 m/s,p < 0.05), and middle cerebral artery Vmean increased (0.15 ± 0.05 to 0.22 ± 0.03 m/s, p < 0.001). From d 3 through d 7, the preterm infants demonstrated higher preprandial end diastolic flow velocity in the superior mesenteric artery than we previously reported in term infants (0.15 ± 0.05 versus 0.12 ± 0.04, p < 0.05). Like the term infants, preterm infants increased their superior mesenteric artery Vmean by 83% postprandially and maintained a stable cerebral circulation with feeding. Unlike the term infants, feeding in the preterm infants induced a blood pressure decrease (51 ± 6 to 48 ± 6 mm Hg, p < 0.01) and a cardiac output increase (176 ± 30 to 188 ± 32 mL/kg/min, p < 0.001). These findings suggest that, in contrast to term infants, healthy preterm infants require compensatory systemic hemodynamic changes in response to feeding.

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.

Mesenteric blood flow velocity and its relation to circulatory adaptation during the first week of life in healthy term infants.

ABSTRACT: We investigated early postnatal changes of the mesenteric circulation and its relationship to the systemic circulation in two groups of newborn infants. Group I (n = 10) was studied before the first feeding at 1 h and preprandially at 6 and 24 h. Group II (n = 10) was studied before the first feeding at 2 h of age and preprandially and postprandially at d 3, 4, and 5. Blood flow velocity was measured with ultrasound Doppler in the superior mesenteric artery (SMA), middle cerebral artery, subclavian artery, and aortic orifice for cardiac out-put (CO) calculations. Blood pressure and heart rate were monitored. SMA mean velocity (Vmean) decreased from 1 [0.33 ± 0.07 m/s (mean ± SD)] to 6 h (0.23 ± 0.08 m/s,p < 0.005) in group I, probably due to ductal steal, returning to the 1-h value at 24 h. In contrast, middle cerebral artery Vmean remained unchanged in the first 24 h. From d 3, SMA Vmean increased 92% postprandially, with no relation to increasing amounts of food. The postprandial increase in SMA Vmean was not associated with changes in CO and blood pressure; however, a fall in relative mesenteric vascu-lar resistance suggested regional redistribution of CO. Middle cerebral artery Vmean increased from h 2 to d 3 with a further increase on d 4 (p < 0.01). This increase was associated with an increase in blood pressure. The relative fraction of CO to middle cerebral artery increased during the first days of life, suggesting a redistribution of blood flow to the metabolically active organs in the neonatal period.

Phototherapy-associated changes in mesenteric blood flow response to feeding in term neonates

Doppler blood flow velocity of the superior mesenteric artery was measured preprandially and postprandially in 12 term neonates during phototherapy and 4 hours after discontinuation of this therapy. The postprandial increase in blood flow velocity was significantly less during than after phototherapy. We suggest that the phototherapy-induced peripheral vasodilation may be responsible for diverting blood from the intestines and limiting the normal neonatal postprandial response.

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.

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.

Relationship between intrauterine growth retardation and early postnatal superior mesenteric artery blood flow velocity.

During the first week of life, we examined the changes in the systemic, intestinal and cerebral circulation, and the circulatory responses to feeding in 10 small for gestational age (SGA) infants using the ultrasound Doppler technique. From day 1 to day 3, preprandial cardiac output decreased (p < 0.01), whereas mean blood pressure (p < 0.01), superior mesenteric artery mean flow velocity (Vmean; p < 0.01) and middle cerebral artery Vmean (p < 0.01) increased. On day 1, cardiac output was higher in the SGA than in those of term and preterm appropriate for gestational age infants reported from our laboratory. Preprandial superior mesenteric artery Vmean was inversely related to the degree of growth retardation (r = 0.63, p < 0.05). However, growth retardation did not influence the postprandial increase in superior mesenteric artery Vmean and end-diastolic flow velocity, or the cerebral circulation.