Brain volumes and cognitive function in very-low-birth-weight (VLBW) young adults

BackgroundPreterm born very-low-birth-weight (VLBW: birth weight ≤1500 g) survivors have increased risk of perinatal brain injury that may cause deviant brain development and later neuroimpairments, including reduced cognitive functioning.AimsIn this long-term follow up study of three year-cohorts (birth years 1986–88) of VLBW subjects and term born controls with normal birth weight, the aim was to examine differences in brain volumes at age 20 years. In addition, the relationships between brain volumes and cognitive abilities and perinatal variables were explored.MethodsForty-four VLBW subjects and 60 controls were assessed with cognitive testing (Wechsler Adult Intelligence Scale – WAIS-III) and structural MRI at 1.5 T, using the FreeSurfer 5.1 software for volumetric analysis. A subpopulation had MRI performed also at age 15, and for this group changes in brain volumes with age were examined.ResultsThe VLBW subjects had smaller brain volumes, especially of thalamus, globus pallidus and parts of the corpus callosum, and larger lateral ventricles than controls at age 20. However, no significant group differences in longitudinal change from age 15 to 20 were observed. The most immature and smallest VLBW subjects at birth, and those with the highest perinatal morbidity, showed most pronounced volume deviations. Positive associations between several brain volumes and full IQ, as well as three of four IQ indices in the VLBW group, were observed.ConclusionReduced volumes of grey and white matter and ventricular dilatation in VLBW young adults may indicate permanent effects on brain development from perinatal brain injury with influence on later cognitive function.     

Abnormal cerebral MRI findings and neuroimpairments in very low birth weight (VLBW) adolescents

BACKGROUND: High prevalence of abnormal cerebral MRI findings as well as major and minor motor, perceptual and cognitive impairments has been reported in very low birth weight (VLBW) children. AIM: To investigate whether cerebral MRI pathology relates to different types of neuroimpairments in adolescents with VLBW. METHODS: At age 15, 55 adolescents with birth weight < or = 1500 g (VLBW) were examined. Motor function was evaluated by Movement Assessment Battery for Children (ABC) and the Grooved Pegboard (GP) test, cognitive function by Wechsler Intelligence Scales, and visuo-motor and visual perceptual function by The Developmental Test of Visual-Motor Integration (VMI) with the supplementary tests of Visual Perception (VP), and Motor Coordination (MC). Executive functions were assessed by Wisconsin Card Sorting Test (WCST) and the Stroop test. Cerebral MRI was assessed semi-quantitatively for ventricular, white and grey matter pathology. RESULTS: There was a rather weak relationship between MRI pathology and neuroimpairments. Poor performance on the WCST was related with ventricular dilatation (VD), white matter reduction and corpus callosum thinning. There was a correlation between results on the VMI test and the Movement ABC test and MRI pathology, but the correlation became much weaker when children with cerebral palsy were excluded. There was no relationship between MRI findings and estimated intelligence quotient (IQ) scores. Normal MRI predicted normal or near normal neuropsychological functioning. CONCLUSION: Cerebral MRI pathology suggestive of perinatal white matter injury was related to disadvantages in performances on executive functions, to a lesser degree to motor and visual perceptual problems, but not to cognitive impairments in VLBW adolescents.     

Intraurethral knot in a very-low-birth-weight infant: radiological recognition, surgical management and prevention

We report a case where a knot developed in a urinary catheter and became lodged within the urethra of a very-low-birth-weight (VLBW) preterm infant. The catheter was removed with the assistance of a urologist. We recommend using caution when placing urinary catheters in VLBW infants and question the appropriateness of feeding tubes as catheters. Recognition on radiographs of malpositioned bladder catheters is vital to the care of these patients. All staff involved in the insertion, maintenance or removal of these catheters should be suitably trained to minimize the risk of knots and related complications.     

Surfactant administration acutely affects cerebral and systemic hemodynamics and gas exchange in very-low-birth-weight infants

OBJECTIVES: To determine whether surfactant administration affects cerebral and systemic hemodynamics and gas exchange in very low birth weight infants and to determine the predominant factor influencing changes in mean cerebral blood flow velocity (mCBFv) after surfactant instillation. STUDY DESIGN: Fourteen very low birth weight infants with respiratory distress syndrome had continuous monitoring of mCBFv, Paco(2), mean arterial blood pressure (MABP), and Pao(2) before, during, and after the second dose of surfactant. Peak values and relative changes of the 4 variables for 45 minutes after surfactant were calculated. Logistic regression was used to determine the predominant factor influencing changes in mCBFv after surfactant. RESULTS: Birth weight was 832 +/- 162 grams and gestational age was 25.7 +/- 1.5 weeks. The time from birth to monitoring was 6.9 +/- 1.0 hours. Mean CBFv increased 75.7% +/- 51.6% after surfactant and peaked at 14.4 +/- 5.9 minutes. Paco(2) was highly associated (OR=107.3, P <.0001) with mCBFv; as Paco(2) increased, mCBFv increased. In contrast, MABP (OR=6.7, P=.047) had less impact on mCBFv. Pao(2) was not associated with mCBFv. CONCLUSIONS: The increases in mCBFv after surfactant administration were predominantly due to increases in Paco(2) and not changes in MABP.     

Fractional anisotropy in white matter tracts of very-low-birth-weight infants

Background Advances in neonatal intensive care have not yet reduced the high incidence of neurodevelopmental disability among very-low-birth-weight (VLBW) infants. As neurological deficits are related to white-matter injury, early detection is important. Diffusion tensor imaging (DTI) could be an excellent tool for assessment of white-matter injury. Objective To provide DTI fractional anisotropy (FA) reference values for white-matter tracts of VLBW infants for clinical use. Materials and methods We retrospectively analysed DTI images of 28 VLBW infants (26–32 weeks gestational age) without evidence of white-matter abnormalities on conventional MRI sequences, and normal developmental outcome (assessed at age 1–3 years). For DTI an echoplanar sequence with diffusion gradient (b = 1,000 s/mm²) applied in 25 non-collinear directions was used. We measured FA and apparent diffusion coefficient (ADC) of different white-matter tracts in the first 4 days of life. Results A statistically significant correlation was found between gestational age and FA of the posterior limb of the internal capsule in VLBW infants (r = 0.495, P<0.01). Conclusion Values of FA and ADC were measured in white-matter tracts of VLBW infants. FA of the pyramidal tracts measured in the first few days after birth is related to gestational age.     

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.     

Ursodeoxycholic acid (UDCA) therapy in very-low-birth-weight infants with parenteral nutrition-associated cholestasis

OBJECTIVE: To determine the effect of ursodeoxycholic acid (UDCA) in very-low-birth-weight (VLBW) infants with parenteral nutrition-associated cholestasis (PNAC).STUDY DESIGN: A retrospective study of all VLBW infants with PNAC who were admitted to a tertiary referral center was conducted. Patients were classified as treatment group (receiving UDCA within 14 days after onset of cholestasis) or control group (no medical treatment). Patients who received abdominal surgery were excluded. RESULTS: A total of 30 patients were recruited, including 12 in the treatment group and 18 in the control group. The demographic data, total fasting duration, onset of cholestasis, age to tolerance of full feeds, and the duration of parenteral nutrition (PN) before the onset of cholestasis were comparable between the two groups. There was a trend in the control group to later onset of cholestasis. The patients who received UDCA therapy with doses of 10 to 30 mg/kg/day had a shorter duration of cholestasis than the control group (62.8 vs 92.4 days, P=.006). Furthermore, the peak serum levels of direct bilirubin also was significantly lower in the treatment group. CONCLUSION: UDCA can improve the course of PNAC in VLBW infants.     

Evaluation of cortical thickness and bone density by roentgen microdensitometry in growing males and females

The bone mineral content (BMC) and the cortical thickness at the distal radius and at the II metacarpal were assessed in growing individuals (167 females and 158 males) by radiometric and quantitative roentgen microdensitometric methods. BMC adjusted for age and pubertal status was significantly higher in males than in females. However, the BMC corrected for bone volume (volumetric bone density, g/cm³) and the metacarpal cortical index (cortical area/total area) were identical in males and females. BMC rose progressively with age, approaching a plateau by the end of puberty. Lower but still significant increases with age were also observed for volumetric bone density of the metacarpus and the metacarpal index. These increases were also most marked by the end of pubertal maturation and might be related to diminution of bone turnover.Conclusion This study provides the normative data of bone mass in growing individuals by making use of a reasonably accurate and easily available technique. The results obtained indicate that most of the differences between males and females and the changes with age are related to changes in skeletal dimension rather than density.     

Cortical surface area and thickness in adult survivors of pediatric acute lymphoblastic leukemia

Background

Advances in the treatment of acute lymphoblastic leukemia (ALL) have led to great improvements in survival rates and outcomes, but there is concern about cognitive late effects. We aimed to determine whether ALL survivors have smaller cortical surface area and/or thickness, and test whether this is related to disease and treatment variables and self‐reported executive functioning in everyday life.

Procedure

Magnetic resonance imaging (MRI) scans from 130 adult long‐term survivors of childhood ALL (age: 18–46 years; age at diagnosis: 0–16 years; years since diagnosis: 7–40) and 130 healthy controls were assessed to estimate and compare regional cortical surface area and thickness. Information on disease and treatment factors were obtained from patients’ records, and executive functioning in survivors was measured using a validated questionnaire (BRIEF‐A).

Results

Smaller cortical surface area was observed in several regions in both cerebral hemispheres in ALL survivors. In these regions, mean surface area was 4.1–5.5% smaller in ALL survivors compared to healthy controls. In contrast, only one region showed lower cortical thickness in ALL survivors. There were no significant associations between cortical surface area/thickness in these regions and disease or treatment variables. In ALL survivors, smaller surface area in prefrontal regions, encompassing parts of the superior frontal gyri and the left anterior cingulate cortex, was associated with problems in executive functioning, specifically with emotional control and self‐monitoring.

Conclusions

ALL survivors had smaller surface area in several cortical regions and smaller surface area in prefrontal regions was associated with reported problems in executive functioning. Pediatr Blood Cancer 2015;62:1027–1034. © 2015 The Authors. Pediatric Blood & Cancer published by Wiley Periodicals, Inc.     

The Incidence of Sleeping Problems in Preterm and Fullterm Infants Discharged from Neonatal Special Care Units: An Epidemiological Longitudinal Study

Abstract— Anecdotal reports have suggested that sleeping problems are a frequent complaint from parents of preterm infants. This prospective epidemiological study examined the incidence and stability of sleeping problems of very preterm (<32 weeks gestation at birth), preterm (32–36 weeks gestation) and fullterm infants, all admitted to special care baby units (SCBU) after birth, in comparison to healthy term infants over the first 5 years of life. Preterm infants were found to have fewer and shorter night-wakings at 5 months. No differences in sleeping behaviour compared with healthy term children were found at 20 and 56 months of age. Similar significant, and moderate, stability of nightwaking from one age to the next were found for exSCBU-graduates and healthy fullterm infants. Parental interventions such as staying the child until asleep and taking the infant into bed at night were related to nightwaking problems and increased parental distress. It is concluded that prematurity, and thus neurological immaturity and special care experience are less important than caretaking bf behaviour in the development of sleeping problems in both preterm and fullterm infants.     

Sex differences in cerebral volumes of 8-year-olds born preterm

We investigate sex-associated effects of preterm birth on cerebral gray matter (GM) and white matter (WM) volumes. Preterm children (n=65) and 31 healthy, term control children had usable magnetic resonance imaging (MRI) data acquired at 8 years of age. Both GM and WM volumes were significantly reduced in the preterm group compared with controls. However, only males with preterm birth had significantly reduced WM compared with term males (P=.021), whereas WM volumes were equivalent in the female groups. Lower birth weight was associated with reduced WM in both boys and girls with preterm birth, whereas intraventricular hemorrhage (IVH) was associated with reduced GM in girls only. Positive correlations between GM and cognitive outcome were observed in girls with preterm birth but not boys. We conclude that preterm birth has a significant impact on brain development with increased risk for smaller GM and WM cerebral volumes. Males appear particularly vulnerable to adverse effects of preterm birth on WM development. However, girls with preterm birth show stronger correlations between neuro-anatomical variables and both neonatal risk factors and cognitive outcome, compared with boys. These findings indicate that the sex of the very preterm newborn influences the mechanisms by which the developing brain is affected.     

Behavior and well-being of extremely low birth weight teenagers in Iceland

Background

Preterm children are at risk for behavioral and emotional problems.

Aims

To evaluate behavior and emotional well-being of extremely low birth weight (ELBW) teenagers born in Iceland in 1991–1995.

Methods

Participants, 30 of 35 ELBW survivors (25 girls, 5 boys, mean age 16.8 years), were interviewed, underwent medical examination and answered the Youth Self-Report for ages 11–18 (YSR) of the Achenbach System of Empirically Based Assessment (ASEBA). The ELBW parents answered the ASEBA Child Behavior Checklist for ages 6–18 and the Autism Spectrum Screening Questionnaire (ASSQ). A comparison group of 30 teenagers (23 girls, 7 boys, mean age 16.5 years) answered the YSR questionnaire and their parents answered the CBCL and ASSQ questionnaires.

Results

ELBW teenagers and parents report more behavior problems than the full term comparison teenagers and parents. They score significantly higher on the YSR and CBCL syndrome scales except for YSR and CBCL rule-breaking behavior and CBCL thought problems. The ELBW teenagers self-report on total competence, activities, social participation and academic performance was not significantly lower than the comparison teenagers. Parents of ELBW teenagers rated total competence, social participation and school performance of their children significantly lower than parents of comparison teenagers. The YSR Positive Qualities Scale was not significantly different between the two teenage groups. Two ELBW teenagers scored above cut-off points on the ASSQ questionnaire and none of the comparison teenagers. Bullying was reported by 20% of ELBW parents compared to none of the comparison group.

Conclusion

ELBW teenagers experience emotional, behavior and social challenges. The teenagers value their positive qualities, activities and academic performance similar to peers.     

Aortic intima-media thickness and lipid profile in macrosomic newborns

Macrosomia is associated with alterations in lipoprotein composition and concentration at birth. Exposure to diabetes in utero has been established as a significant risk factor for some of the components of metabolic syndrome. The aim of this study was to investigate the effect of macrosomia on lipid metabolism, aortic intima-media thickness (aIMT) and subsequent atherogenic risk in newborn infants. Aortic intima-media thickness was measured in 40 macrosomic neonates of diabetic mothers (group A), 30 macrosomic neonates of healthy mothers (group B) and 30 healthy neonates (group C). Lipid profile was determined in all infants and their mothers. Mean aIMT was significantly higher in macrosomic neonates of diabetic and healthy mothers (0.56±0.06 and 0.49±0.03 mm respectively) than in controls (0.39±0.03 mm). Weight-adjusted aIMT in macrosomic neonates of diabetic mothers (0.129±0.013 mm/kg) was significantly higher than in groups B and C (0.114±0.008 and 0.113±0.011 mm/kg respectively). There were significant alterations of total serum, high-density lipoprotein (HDL), very low-density lipoprotein (VLDL) cholesterols and triglyceride levels in the macrosomic neonates of diabetic mothers compared with controls. Macrosomia was associated with increased lipid concentrations. Macrosomic neonates of diabetic mothers have significantly higher aIMT with lipid alterations. This may play a role in the pathogenesis of atherosclerosis in adult life.     

Increased cerebral microbleeds and cortical superficial siderosis in pediatric patients with Down syndrome

Background

Patients with Down syndrome carry a third copy of the amyloid precursor protein gene, which is localized on chromosome 21. Consequently, these patients are prone to develop early-onset Alzheimer disease and cerebral amyloid angiopathy. Post-mortem studies suggest increased amyloid deposition to be already detectable in children with Down syndrome. The aim of our study was to evaluate if amyloid-related changes in pediatric Down syndrome patients can be detected in vivo using MRI biomarkers of cerebral microbleeds and cortical superficial siderosis.

Impact of overweight and obesity in carotid intima-media thickness of portuguese adolescents

Aim: To measure carotid intima‐media thickness (cIMT) in obese, overweight and normal‐weight Portuguese adolescents, to evaluate the association between body weight early signs of atherosclerosis. Methods: Cross‐sectional study, enrolling 150 adolescents (50 normal weight, 50 overweight and 50 obese) with mean age of 12.9 years. All underwent clinical, analytical and carotid common artery ultrasonographic evaluation. Results: After adjusting for systolic blood pressure and plasma High‐density lipoprotein, Low‐density lipoprotein and Triglycerides levels, higher mean cIMT values were observed in both overweight and obese patients, when compared to normal‐weight group. Moreover, adolescents with metabolic syndrome (MS) had greater cIMT [normal‐weight: cIMT mean 0.418 mm (95% confidence intervals (95% CI) 0.399–0.437); overweight: 0.461 mm (95% CI: 0.444–0.477); obese: 0.472 mm (95% CI: 0.455–0.488); MS: 0.482 mm (95% CI: 0.444–0.520) p = 0.001]. When normal‐weight and overweight adolescents were exclusively compared, differences in cIMT remained significant (p < 0.001). cIMT was positively correlated with body mass index (BMI) (r = 0.439, p < 0.001), waist circumference (r = 0.301, p = 0.018) and diastolic blood pressure (r = 0.266, p = 0.001). Conclusions: We have shown that cIMT is positively associated with BMI increase in adolescents, even in moderate overweight ranges, independent of age, gender, systolic blood pressure and plasma lipid concentrations.     

Physical growth and cognitive abilities in concordant versus discordant birth weight twins at three years old

Background

Discordant birth weight twins have been shown to have high rates of adverse perinatal outcomes, but little is known about their growth and development.

Aim

To determine whether smaller and larger birth weight premature twins in concordant and discordant birth weight groups differ on measures of physical growth and intelligence at 3 years.

Study design

Prospective cohort study. Eight-four children, 52 concordant and 32 discordant birth weight twin pairs, were measured for height, weight, and head circumference and on intelligence at 3 years. Perinatal and demographic variables, including birth weight, head circumference, small for gestational age, zygosity, in vitro fertilization, gender and social class were recorded.

Results

Smaller and larger birth weight twins did not differ significantly from each other on any growth parameters in either concordant or discordant birth weight groups at 3 years of age. Smaller birth weight twins in the discordant birth weight group performed significantly less well on Verbal, Performance, and Full Scale IQ scores (Verbal IQ for smaller twins was 8.6 points lower, p < 0.005; Performance IQ, 11.9 points lower, p < 0.03; Full Scale IQ, 12.4 points lower, p < 0.004), but there were no significant intra-twin differences between larger and smaller birth weight concordant twins.

Conclusions

Smaller discordant birth weight twins performed significantly less well on intelligence, although they did not differ significantly from their larger twins on growth parameters at 3 years old. We conclude that smaller discordant birth weight twins had less optimal intra-uterine environments than their larger birth weight twin, which affected both their birth weights and brain development.     

亚低温对HIBD新生鼠大脑皮质神经元NSE表达及血糖水平影响的研究

目的：通过亚低温对新生鼠缺氧缺血脑损伤(HIBD)大脑皮质神经元特异性烯醇化酶(NSE)及血糖水平影响的研究,探讨亚低温对HIBD的保护作用机制。方法：建立新生鼠HIBD标准化动物模型,将其随机分为对照组、31℃亚低温和34℃亚低温干预组及假手术组,应用免疫组化染色观察大脑皮质区NSE阳性神经元数目,并利用微量血糖监测仪测定血糖。结果：缺血缺氧后12 h,24 h亚低温干预组大脑皮质NSE阳性神经元数目均显著低于对照组［31℃亚低温组：(54.3±6.5) vs (82.3±6.0),(34.6±5.6) vs (53.3±5.6),P<0.05 或 0.01;34℃亚低温组：(56.8±7.1) vs (82.3±6.0),(32.9±4.9) vs (53.3±5.6),P<0.05］。缺氧缺血后12 h,24 h 血糖水平［31℃亚低温组：(5.74±1.52),(5.89±1.62) mmol/L;34℃亚低温组：(5.69±1.48),(5.91±1.53) mmol/L］亦显著高于对照组［(3.64±1.22),(4.16±1.54) mmol/L］(P<0.01)。31℃亚低温和34℃亚低温干预两组间各个时期大脑皮质区NSE阳性神经元数目及血糖水平差异无显著性(P>0.05)。结论：亚低温可通过抑制神经元内NSE活性及升高血糖水平,对HIBD新生鼠大脑皮质神经细胞起到保护作用。