Birgitta Böhm

Preterm Children Have Disturbances of White Matter at 11 Years of Age as Shown by Diffusion Tensor Imaging

Preterm birth frequently involves white matter injury and affects long-term neurologic and cognitive outcomes. Diffusion tensor imaging has been used to show that the white matter microstructure of newborn, preterm children is compromised in a regionally specific manner. However, until now it was not clear whether these lesions would persist and be detectible on long-term follow-up. Hence, we collected diffusion tensor imaging data on a 1.5-T scanner, and computed fractional anisotropy and coherence measures to compare the white matter integrity of children born preterm to that of control subjects. The subjects for the preterm group (10.9 ± 0.29 y; n = 9; birth weight ≤ 1500 g; mean gestational age, 28.6 ± 1.05 wk) possessed attention deficits, a common problem in preterms. They were compared with age- and sex-matched control children (10.8 ± 0.33 y; n = 10; birth weight ≥ 2500; gestational age, ≥ 37 wk). We found that the preterm group had lower fractional anisotropy values in the posterior corpus callosum and bilaterally in the internal capsules. In the posterior corpus callosum this difference in fractional anisotropy values may partially be related to a difference in white matter volume between the groups. An analysis of the coherence measure failed to indicate a group difference in the axonal organization. These results are in agreement with previous diffusion tensor imaging findings in newborn preterm children, and indicate that ex-preterm children with attention deficits have white matter disturbances that are not compensated for or repaired before 11 y of age.

Developmental risks and protective factors for influencing cognitive outcome at 5½ years of age in very‐low‐birthweight children

In a population-based follow-up study (the Stockholm Neonatal Project), 182 children with a birthweight of 1500 g or less (very-low birthweight: VLBW) and a control group of 125 children born healthy at term were examined with the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R) and a neuropsychological test battery (Nepsy) at 5 1/2 years of age. The WPPSI-R results of the VLBW children fell well within the normal range: WPPSI-R full-scale IQ 95.7, verbal subscale IQ 99.9, and performance subscale IQ 91.6. Nevertheless, the control group had significantly better results than the VLBW group which could be attributed to the greater variability of the VLBW group, with a larger proportion falling in the lower area of the IQ distribution, especially on the performance subscale. Likewise, the control group displayed better executive function (Nepsy). Paternal education was equal in the two groups and was the single most important predictor of IQ, possibly acting as a protective factor. The need for glasses or lenses was inversely associated with all IQ measures and severe retinopathy of prematurity (ROP) had the most negative impact on full-scale and performance IQ. These two IQ measures were also negatively associated with intrauterine growth retardation late in pregnancy. We conclude that VLBW children, in the absence of these identified risk factors, have normal cognitive development.

Impulse control, working memory and other executive functions in preterm children when starting school

Aim: The aim of this study was to explore whether children born preterm have deficient executive functions (EF) in comparison with children born at full term, and, if so, whether this is dependent on inferior intelligence scores and can be correlated to specific neonatal risk factors and gender. Methods: In a population‐based study, the executive functions of 182 preterm children (birthweight less than 1500 g, VLBW) and 125 controls from the Stockholm Neonatal Project were assessed at 5± y with a neuropsychological test battery (Nepsy 1990). Results: The controls surpassed the VLBW children on tests of executive functions (EF), even after controlling for intelligence (IQ); a necessary correction since there were significant correlations between measures of EF and IQ. EF was associated with retinopathy of prematurity (ROP), and with visual impairment as a whole. In both groups, girls surpassed boys on tests of executive functions.

Structural Correlates of Preterm Birth in the Adolescent Brain

OBJECTIVE: The Stockholm Neonatal Project involves a prospective, cross-sectional, population-based, cohort monitored for 12 to 17 years after birth; it was started with the aim of investigating the long-term structural correlates of preterm birth and comparing findings with reports on similar cohorts. METHODS: High-resolution anatomic and diffusion tensor imaging data measuring diffusion in 30 directions were collected by using a 1.5-T MRI scanner. A total of 143 adolescents (12.18–17.7 years of age) participated in the study, including 74 formerly preterm infants with birth weights of ≤1500 g (range: 645–1486 g) and 69 term control subjects. The 2 groups were well matched with respect to demographic and socioeconomic data. The anatomic MRI data were used for calculation of total brain volumes and voxelwise comparison of gray matter (GM) volumes. The diffusion tensor imaging data were used for voxelwise comparison of white matter (WM) microstructural integrity. RESULTS: The formerly preterm individuals possessed 8.8% smaller GM volume and 9.4% smaller WM volume. The GM and WM volumes of individuals depended on gestational age and birth weight. The reduction in GM could be attributed bilaterally to the temporal lobes, central, prefrontal, orbitofrontal, and parietal cortices, caudate nuclei, hippocampi, and thalami. Lower fractional anisotropy was observed in the posterior corpus callosum, fornix, and external capsules. CONCLUSIONS: Although preterm birth was found to be a risk factor regarding long-term structural brain development, the outcome was milder than in previous reports. This may be attributable to differences in social structure and neonatal care practices.

Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants

OBJECTIVE To examine associations between brain white matter abnormalities, including diffuse excessive high signal intensities, detected on neonatal magnetic resonance imaging (MRI) with neurodevelopmental outcome at age 30 months. STUDY DESIGN This was a prospective, population-based study of infants born at <27 weeks gestation (n=117) undergoing conventional MRI at term equivalent age (n=107). At age 30 months corrected, 91 of the preterm infants (78%) and 85 term-born controls were assessed with the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). RESULTS Cerebral palsy (CP) was present in 7% of the preterm group. On the BSID-III, mean composite scores were 96±9.5 for the cognitive scale, 97±14 for language scales, and 103±15 for motor scales, all within the normal range for age. Compared with the term-born controls, however, the preterm infants did not perform as well on all 3 scales, also when MRI was normal. Significant associations were seen between moderate to severe white matter abnormalities and CP (P<.001). The presence of diffuse excessive high signal intensities was not associated with performance on the BSID-III or with CP. CONCLUSION This 3-year cohort of extremely preterm infants had low rates of major brain injury and impaired outcome. Neonatal MRI provides useful information, but this information needs to be treated with caution when predicting outcome.

Visual‐motor and executive functions in children born preterm: The Bender Visual Motor Gestalt Test revisited

Visual-motor development and executive functions were investigated with the Bender Test at age 5½ years in 175 children born preterm and 125 full-term controls, within the longitudinal Stockholm Neonatal Project. Assessment also included WPPSI-R and NEPSY neuropsychological battery for ages 4-7 (Korkman, 1990). Bender protocols were scored according to Brannigan & Decker (2003), Koppitz (1963) and a complementary neuropsychological scoring system (ABC), aimed at executive functions and developed for this study. Bender results by all three scoring systems were strongly related to overall cognitive level (Performance IQ), in both groups. The preterm group displayed inferior visual-motor skills compared to controls also when controlling for IQ. The largest group differences were found on the ABC scoring, which shared unique variance with NEPSY tests of executive function. Multiple regression analyses showed that hyperactive behavior and inattention increased the risk for visual-motor deficits in children born preterm, whereas no added risk was seen among hyperactive term children. Gender differences favoring girls were strongest within the preterm group, presumably reflecting the specific vulnerability of preterm boys. The results indicate that preterm children develop a different neurobehavioral organization from children born at term, and that the Bender test with a neuropsychological scoring is a useful tool in developmental screening around school start.

Cognitive development at 5.5 years of children with chronic lung disease of prematurity

Background: Preterm infants with chronic lung disease (CLD) had impaired cognitive development and poorer eye-hand coordination at 10 months of age. Aims: To study whether this effect of CLD persisted until school age and whether the severity of CLD affected outcome. Method: Cognition and visual-motor skills were examined (Wechsler preschool and primary scale of intelligence, and tests from the Nepsy scale) in 60 very preterm children, without intraventricular haemorrhage or periventricular leucomalacia, at 5.5 years of age. Thirty two children suffered from CLD and 28 were controls. Results: The groups did not differ significantly in cognitive outcome. Children with CLD and controls attained a full scale intelligence quotient (IQ) of 94.4 and 99.1, a verbal IQ of 99.6 and 101.5, and a performance IQ of 90.9 and 96.7 respectively. Similarly, no difference was found in tests of eye-hand control. However, the children with the most severe form of CLD had significantly lower performance (84.8) and full scale(87.6) IQs and worse visual-motor performance than the controls. CLD grade III, together with the need for glasses or lenses, had a significant impact on the explained variance. Conclusions: At school age, children born very preterm and who experienced severe CLD had deficits in cognition, visual-motor perception, and performance. The findings suggest a need to consider intervention programmes for such infants.

Cognitive outcome varies in adolescents born preterm, depending on gestational age, intrauterine growth and neonatal complications

The aim of this study was to investigate long‐term cognitive outcome in a cohort of 18‐year‐olds born preterm and previously assessed at the age of 5.5.

Individual cognitive patterns and developmental trajectories after preterm birth

Cognitive outcome after preterm birth is heterogeneous, and group level analyses may disguise individual variability in development. Using a person-oriented approach, this study investigated individual cognitive patterns and developmental trajectories from preschool age to late adolescence. As part of a prospective longitudinal study, 118 adolescents born preterm, with a birth weight < 1,500 g, participated in neuropsychological assessments at age 5½ years and at 18 years. At each age, four cognitive indices, two tapping general ability and two tapping executive functions, were formed to reflect each individual’s cognitive profile. Cluster analyses were performed at each age separately, and individual movements between clusters across time were investigated. At both 5½ and 18 years, six distinct, and similar, cognitive patterns were identified. Executive functions were a weakness for some but not all subgroups, and verbal ability was a strength primarily among those whose overall performance fell within the normal range. Overall, cognitive ability at 5½ years was highly predictive of ability at age 18. Those who performed at low levels at 5½ years did not catch up but rather deteriorated in relative performance. Over half of the individuals who performed above the norm at 5½ years improved their relative performance by age 18. Among those performing around the norm at 5½ years, half improved their relative performance over time, whereas the other half faced increased problems, indicating a need for further developmental monitoring. Perinatal factors were not conclusively related to outcome, stressing the need for cognitive follow-up assessment of the preterm-born child before school entry.

Growth hormone treatment improves vitality and behavioural issues in children with Prader-Willi syndrome.

Prader‐Willi syndrome is a neurogenetic disorder, with characteristics such as obesity, short stature, muscular weakness, intellectual deficiencies and deviant social behaviour. This study evaluated whether growth hormone treatment of children with Prader‐Willi syndrome resulted in possible and lasting effects on their cognition and behaviour.