Very low birth weight (VLBW) children are at high risk of perinatal white matter injury, which, when subtle, may not be seen using conventional magnetic resonance imaging. The relationship between clinical findings and fractional anisotropy (FA) measurements in white matter of adolescents born prematurely with VLBW was studied in 34 subjects (age = 15 years, birth weight =1500 g) and 47 age-matched controls born at term, who were examined both clinically and with diffusion tensor imaging (DTI). Perceptual and cognitive functions were evaluated by visual motor integration (VMI) with supplementary tests and sub-tests from WISC-III, motor function by movement ABC and Grooved Pegboard test and psychiatric symptoms by the schedule for affective disorders and schizophrenia for school-age children semistructured interview, the Autism Spectrum Screening Questionnaire and attention deficit hyperactivity disorder (ADHD) rating scale IV. Overall functioning was scored on the children's global assessment scale. DTI scans were performed for calculation of FA maps and areas of significant differences in mean FA values between subjects and controls were compared with their clinical data. The VLBW children had reduced FA values in the internal and external capsule, corpus callosum and superior, middle superior and inferior fasciculus. Within this group of children, visual motor and visual perceptual deficits were associated with low FA values in the external capsule, posterior part of the internal capsule and in the inferior fasciculus. Children with low IQ had low FA values in the external capsule and inferior and middle superior fasciculus. Fine motor impairment was related to low FA values in the internal and external capsule and superior fasciculus. Eight VLBW children with inattention symptoms or a diagnosis of ADHD had significantly lower FA values in several areas. Mild social deficits correlated with reduced FA values in the external capsule and superior fasciculus. We conclude that DTI was able to detect differences in FA between VLBW adolescents and controls in several white matter areas at risk of periventricular leucomalacia in VLBW newborns. Our results show that low FA values in these areas were associated with perceptual, cognitive, motor and mental health impairments. These conclusions indicate that perinatal injury of white matter tracts persist with clinical significance in adolescence.
Infants with low birth weight are at increased risk of perinatal brain injury. Disruption of normal cortical development may have consequences for later motor, behavioural and cognitive development. The aim of this study was to measure cerebral cortical thickness, area and volume with an automated MRI technique in 15-year-old adolescents who had low birth weight. Cerebral MRI for morphometric analysis was performed on 50 very low birth weight (VLBW, birth weight =1500 g), 49 term small for gestational age births (SGA, birth weight <10th percentile at term) and 58 control adolescents. A novel method of cortical surface models yielded measurements of cortical thickness and area for each subject's entire brain and computed cross-subject statistics based on cortical anatomy. The cortical surface models demonstrated regional thinning of the parietal, temporal and occipital lobes in the VLBW group, whereas regional thickening was demonstrated in the frontal and occipital lobes. The areas of change were greatest in those with the shortest gestational age at birth and lowest birth weight. Cortical surface area and cortical volume were lower in the VLBW than in the Control group. Within the VLBW group, there was an association between surface area and estimation of the intelligence quotient IQ (IQ(est)) and between cortical volume and IQ(est). Furthermore, cortical grey matter as a proportion of brain volume was significantly lower in the VLBW, but not in the SGA group compared with Controls. This observed reorganization of the developing brain offers a unique opportunity to investigate any relationship between changes in cortical anatomy and cognitive and social impairments, and the increase in psychiatric disorders that have been found in VLBW children and adolescents.
Vitamin B12 (hereafter referred to as B12) deficiency in pregnancy is prevalent and has been associated with both lower birth weight (birth weight <2,500 g) and preterm birth (length of gestation <37 weeks). Nevertheless, current evidence is contradictory. We performed a systematic review and a meta-analysis of individual participant data to evaluate the associations of maternal serum or plasma B12 concentrations in pregnancy with offspring birth weight and length of gestation. Twenty-two eligible studies were identified (11,993 observations). Eighteen studies were included in the meta-analysis (11,216 observations). No linear association was observed between maternal B12 levels in pregnancy and birth weight, but B12 deficiency (<148 pmol/L) was associated with a higher risk of low birth weight in newborns (adjusted risk ratio = 1.15, 95% confidence interval (CI): 1.01, 1.31). There was a linear association between maternal levels of B12 and preterm birth (per each 1-standard-deviation increase in B12, adjusted risk ratio = 0.89, 95% CI: 0.82, 0.97). Accordingly, B12 deficiency was associated with a higher risk of preterm birth (adjusted risk ratio = 1.21, 95% CI: 0.99, 1.49). This finding supports the need for randomized controlled trials of vitamin B12 supplementation in pregnancy.
Objective The aim of this study was to examine whether preterm very low birth weight (VLBW) or term born small for gestational age (SGA) adolescents have a reduced regional brain volume. Furthermore, we examined what perinatal factors are related to reduced brain volume in VLBW adolescents, and which regional brain volumes are associated with cognitive and perceptual functioning, and if these differ between the groups. Study design Fifty adolescent preterm VLBW (≤1500g) 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 a reduced volume of thalamus and cerebellar white matter (P<0.002). The SGA group had a smaller total brain, and proportionally smaller regional brain volume. Cerebellar white matter in the VLBW, hippocampus in the SGA, and cerebral cortical in the control group were volumes which 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.
Objective To assess whether folic acid intake during the first trimester of pregnancy is related to asthma in the offspring by the age of 6 years. Study design Prospective cohort study of 1,499 women who were followed from first trimester of pregnancy. Their children were followed until they were 6 years old. Results 51% of the women used folic acid in the month before conception and 88% in the third month of pregnancy. The adjusted OR per 100 microgram increase in average daily intake of folic acid was 0.98 (95% CI:0.93-1.04). For categories of daily folate intake, there was no evidence of associations with childhood asthma nor evidence of any dose response relation for any time period (all ptrend>0.05) Conclusion Our results do not support any association of folic acid supplementation in pregnancy and asthma risk in offspring by age 6 years.
RESULTS Over half (53%) of the VLBW participants achieved a low IQ score (defined as >1SD below the mean in the comparison group; odds ratio 6.4 vs comparison individuals; 95% confidence interval 2.8-14.4; p<0.001). None of the VLBW group, compared with 22% of the comparison individuals, achieved a high IQ score (>1SD above the comparison mean). VLBW participants scored lower than comparison individuals on full, verbal, and performance IQ, as well as on all four indices (p£0.001). The subtest profile indicated problems on all subtests, but especially on those related to arithmetic and visual-perceptual tasks.INTERPRETATIONS Few studies have undertaken a comprehensive assessment of general cognitive outcome (IQ) among young adults of VLBW. Our results indicate that VLBW seems to have a global and lasting impact on cognitive ability. Full-scale IQ assessment may reveal important learning problems in young adults of VLBW, and should be performed to inform appropriate assistance to enhance academic achievement and the chances of permanent employment as adults.
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