Ann-Mari Brubakk

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.

Psychiatric symptoms in low birth weight adolescents, assessed by screening questionnaires

ObjectiveThe aim of this study was to explore psychiatric symptoms in low birth weight adolescents, and the usefulness of questionnaires compared with psychiatric interview.Design/study groupsA population-based follow-up study of 56 very low birth weight (VLBW), 60 term small for gestational age (SGA) and 83 control adolescents at 14 years of age was made.Outcome measuresThe Achenbach System of Empirically Based Assessment (ASEBA) and the Strengths and Difficulties Questionnaire (SDQ) were rated by adolescents, parents and teachers. The results were compared with diagnostic assessment based on the semi-structured interview, Schedule for Affective Disorders and Schizophrenia for School Aged Children (K-SADS).ResultsVLBW adolescents had more psychiatric symptoms than controls, especially attention deficit, emotional, behavioural, social and also academic problems. Although less consistent, the SGA group had more emotional, conduct and attention deficit symptoms than controls. Results remained essentially the same when adolescents with low estimated IQ were excluded, and persisted after controlling for possible confounders. The sensitivity and specificity of ASEBA and SDQ differed between informants and groups.ConclusionVLBW adolescents are at risk of developing psychiatric symptoms, and reduced social and academic skills by the age of 14. Term SGA adolescents may have discrete emotional, behavioural and attention deficit symptoms. ASEBA and SDQ provide a useful supplement to psychiatric interview.

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.

Effects of preterm birth and fetal growth retardation on cardiovascular risk factors in young adulthood

BACKGROUND The association between low birth weight (LBW) and increased risk of obesity, hypertension and cardiovascular disease later in life is well documented in epidemiological studies. However, clinical follow-up studies of LBW populations have only partly supported this. AIMS Evaluate associations between LBW and body fat, blood pressure (BP), lung and endothelial function, and maximal oxygen uptake (VO(2max)) in 18 year old young adults. SUBJECTS Thirty-seven subjects born prematurely with birth weight <1501 g (VLBW group), 47 born at term with low weight (<10th centile) for gestational age (SGA group) and 63 controls with normal birth weight participated in the study. OUTCOME MEASURES Anthropometric measurements, BP, endothelial function, lung function and VO(2max) were recorded. RESULTS Both LBW groups were shorter, lighter, had smaller head circumference and higher subscapular-to-triceps skinfold-ratio than controls. Systolic and mean arterial BP was higher in the VLBW compared with the control group, whereas there were no differences between the groups in endothelial function. The VLBW group had reduced dynamic lung volumes lower carbon monoxide transfer factor and lower VO(2max) compared with controls. In particular young adults born VLBW who were also growth retarded in utero had higher indices of central body fat, higher BP and lower VO(2max). CONCLUSION We found that very preterm birth, but not growth retardation at term, was associated with higher BP and a less favourable fat distribution. In particular, the young adults born VLBW who were also growth retarded in utero had less favourable outcomes.

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.

Prenatal smoking exposure and psychiatric symptoms in adolescence

Aim: Explore associations between smoking in pregnancy and psychiatric symptoms in the adolescent offspring.

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.

The effects of variations in PaCO2 on brain blood flow and cardiac output in the newborn piglet.

ABSTRACT. The acute effects of normoxemic hypocarbia and hypercarbia were examined in six newborn piglets. Brain blood flow was maintained during hypocarbia until extremely low Paco2 (<15 mm Hg) levels were achieved at which time total brain and cerebral blood flow decreased significantly from baseline values. Blood flow to the thalamus, cerebellum and brain stem was unchanged from baseline conditions during hypocarbia. This suggests that the newborn brain is relatively insensitive to moderate degrees of hypocarbia. Extreme hypocarbia (Paco2 <15 mm Hg) was associated with a significant increase in heart rate, accompanied by a significant decrease in mean arterial blood pressure; however, cardiac output was not significantly different from baseline determinations. Hypercarbia with normoxemia was associated with significant increases in total brain blood flow, with greater blood flow to the brain stem, cerebellum, and thalamus than to the cerebrum. The percentage of cardiac output received by the brain was also significantly increased, although total cardiac output was unchanged. This demonstrates that the newborn cerebral vasculature is sensitive to hypercarbia and that regional differences in sensitivity may account for the greater increments in blood flow to the caudal portions of the brain than that to the cerebrum.