Visual-motor functions are affected in young adults who were born premature and screened for retinopathy of prematurity.

AIM: To assess visual-motor integration in young adults previously included in a prospective study on the incidence of retinopathy of prematurity (ROP). METHODS: The study encompassed 59 preterm individuals, born 1988-1990, with a birth weight ≤1500 g, and 44 full-term controls, aged 25-29 years. Ophthalmological examination, including visual acuity and contrast sensitivity, and the Beery Visual-Motor Integration (VMI) with supplemental tests of visual perception and motor coordination, were performed. A short questionnaire was filled in. RESULTS: The preterm individuals had significantly lower scores than the controls in all VMI tests, median values and interquartile ranges: Beery VMI 87 (21) vs 103 (11), visual perception 97 (15) vs 101 (8) and motor coordination 97 (21) vs 102 (15), respectively. Within the preterm group, no correlations were found between the VMI tests and ROP, gestational age, birth weight or visual acuity. Contrast sensitivity was correlated to visual perception. Neurological complication at 2.5 years was a risk factor for lower scores on Beery VMI. The preterm subjects reported six times as many health problems as compared to the controls. CONCLUSION: Being born preterm seemed to have life-long effects. This study shows that visual-motor integration was affected in young adults born preterm.

Average 2.5-year neurodevelopmental test results in children born very preterm did not rule out cognitive deficits at 6.5 years of age.

AIM: The aim of the study was to investigate cognitive outcomes at 6.5 years in children born very preterm, in relation to neonatal characteristics and 2.5-year neurodevelopment. METHODS: A prospective cohort, with gestational age 22.3-31.9 weeks, born 2004-2007, were examined at 2.5 years with the Bayley Scales of Infant and Toddler Development (Bayley-III) (n = 100) and at 6.5 years with the Wechsler Intelligence Scales (n = 91). RESULTS: Neonatal factors independently related to 6.5-year outcome were gestational age, retinopathy of prematurity and treated persistent ductus arteriosus. The Bayley-III cognitive scores explained only 44% of the Full-Scale Intelligence Quotient result at 6.5 years, and 22% of the children had Wechsler index results below -1 SD, indicating cognitive impairment, after average test results at 2.5 years. The relative risk to score below -1 SD on the Full-Scale IQ was 2.83 (95% CI 1.45-5.53) in children with gestational age below 28 weeks and 2.22 (95% CI 1.18-4.17) at gestational age 28-31 weeks. CONCLUSION: Very preterm infants born in the 2000s had increased risks for impaired cognition at 6.5 years, but individual predictions based on neonatal risks and 2.5-year test results were not enough to identify all high-risk children.

Severity of retinopathy of prematurity was associated with a higher risk of cerebral dysfunction in young adults born extremely preterm.

AIM: This Swedish study evaluated whether the severity of retinopathy of prematurity (ROP) in extremely preterm infants was related to their overall outcome in young adulthood. METHODS: We followed 39 individuals born between 1988 and 1993 at less than 28 gestational weeks, included in the Stockholm Neonatal Project. A total of 19 were treated for severe ROP, and 20 had no or mild ROP. They were assessed for general cognitive abilities and mental health at 18 years of age and compared with 23 term-born controls. Visual acuity was examined at 21-25 years. They were asked about their education and everyday life. RESULTS: The 19 individuals with severe treated ROP had lower visual acuity and higher risk for intellectual deficits, cerebral palsy and neuropsychiatric diagnoses than those with no or mild ROP and the term controls. Three were visually impaired, none were blind. They were less physically active than the other groups and had more problems finding their way around. However, nine were at university. CONCLUSION: Young adults treated for severe ROP had more problems resulting from cerebral dysfunction than those with no or mild ROP and term-born controls. Retinal and brain pathologies in the extremely preterm infant constitute different expressions of neurovascular disease.

Cognitive Development Trajectories in Preterm Children With Very Low Birth Weight Longitudinally Followed Until 11 Years of Age.

Background: There is a high prevalence of cognitive dysfunction in very low birthweight (500-1250 g) infants (VLBW). Understanding long-term risk factors associated with cognitive development in preterm children requires longitudinal characterization. Thus, follow-up evaluations, including identification of risks and resilience influences-are important to promote health and cognitive abilities of children born preterm. Aim: To examine changes in cognitive development from birth until 11 years of age in preterm children with very low birthweight. Methods: 24 VLBW infants, at the Karolinska University Hospital, Stockholm, were assessed with regards to cognitive functioning at three times during development at 18 months, 5 and 11 years of age using standardized tests. Longitudinal data were analyzed using Generalized Estimating Equation (GEE) univariate and multivariate models. Results: The follow-up rate was 100%. Level of cognitive functioning at 18 months and at 11 years was similar. Females had higher cognitive scores than males at all three timepoints. We found that intraventricular hemorrhage (IVH) and prolonged invasive ventilatory support (>7 days) had a negative effect on cognitive functioning. Higher levels of parental education had a favorable influence on cognitive functioning over time. Conclusion: Level of cognitive development at 18 months was highly predictive of level of cognitive function at 11 years of age and differences in assessment scores between male and female VLBW infants persisted. Additional longitudinal studies, performed before school entry and across childhood, are needed to further elucidate the cognitive trajectories of preterm children.

A longitudinal model of executive function development from birth through adolescence in children born very or extremely preterm.

Executive function deficits are often reported as a specific weakness in preterm children. Yet, executive function development is still not fully understood. In a prospective longitudinal study, 115 preterm born children, ≤31 weeks of gestation, were recruited at birth and subject to neuropsychological assessments at ages 5.5 and 18 years. By applying Miyake and colleagues' integrative framework of executive function to our data, two core components of executive function, working memory and cognitive flexibility, were identified through confirmatory factor analysis. Developmental stability was investigated in a serial multiple mediator structural equation model. Biological, medical, and social factors as well as mental development at 10 months were entered as predictors. Both components of executive function were highly stable from 5.5 to 18 years. Gestational age, intrauterine growth, lack of perinatal medical complications, and female sex were positively related to mental development at 10 months, which together with parental education influenced both core executive functions at 5.5 years. Working memory at 5.5 years mediated outcome in working memory at 18 years. In addition to the mediation of cognitive flexibility at 5.5 years, perinatal medical complications and restricted intrauterine growth had a continued direct negative impact on cognitive flexibility at 18 years. The application of a theoretical framework added to our understanding of executive function development in preterm born children. The study supports early identification of executive deficits among children born preterm, as deficits are unlikely to diminish with maturation.

Visual tracking in very preterm infants at 4 mo predicts neurodevelopment at 3 y of age.

BACKGROUND: Typically developing infants track moving objects with eye and head movements in a smooth and predictive way at 4 mo of age, but this ability is delayed in very preterm infants. We hypothesized that visual tracking ability in very preterm infants predicts later neurodevelopment. METHOD: In 67 very preterm infants (gestational age<32 wk), eye and head movements were assessed at 4 mo corrected age while the infant tracked a moving object. Gaze gain, smooth pursuit, head movements, and timing of gaze relative the object were analyzed off line. Results of the five subscales included in the Bayley Scales of Infant Development (BSID-III) at 3 y of age were evaluated in relation to the visual tracking data and to perinatal risk factors. RESULTS: Significant correlations were obtained between gaze gain and cognition, receptive and expressive language, and fine motor function, respectively, also after controlling for gestational age, severe brain damage, retinopathy of prematurity, and bronchopulmonary dysplasia. CONCLUSION: This is the first study demonstrating that the basic ability to visually track a moving object at 4 mo robustly predicts neurodevelopment at 3 y of age in children born very preterm.

Social variables predict gains in cognitive scores across the preschool years in children with birth weights 500 to 1250 grams.

OBJECTIVE: To determine the extent that social variables influence cognitive development of very low birth weight (VLBW) infants across the preschool years. STUDY DESIGN: Participants were VLBW (500-1250 g) children enrolled in the Caffeine for Apnea of Prematurity randomized trial between 1999 and 2004. We investigated the relationships between 4 potential social advantages: higher maternal education, higher paternal education, caregiver employment, and 2 biologic parents in the same home--and gain in cognitive scores. Cognitive assessments were performed at the corrected ages of 18 months (Mental Development Index score on the Bayley Scales of Infant Development II) and 5 years (Full Scale IQ on the Wechsler Preschool and Primary Scale of Intelligence III). Cognitive gain was computed by subtracting each individual 18-month Mental Development Index score from the corresponding Full Scale IQ at 5 years. RESULTS: Data were available for 1347 children. Mean (SD) cognitive scores were 90.8 (15.7) at 18 months and 98.9 (14.5) at 5 years. Multivariable regression showed that higher maternal education, higher paternal education, and caregiver employment had independent and additive effects of similar size on cognitive gain (P < .001); the mean cognitive gain between 18 months and 5 years increased by 3.6 points in the presence of each of these advantages. When all 3 were present, cognitive scores improved on average by 10.9 points compared with children without any of these advantages. CONCLUSION: In VLBW children, a count of 3 social advantages strongly predicts gains in cognitive scores across the preschool years.

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.

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

AIM: 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. METHODS: We tested 134 adolescents born preterm with a very low birthweight of <1500 g and 94 term-born controls with a comprehensive cognitive battery at 18 years of age. The cohort was subdivided into 73 extremely preterm, 42 very preterm and 19 moderately preterm infants with gestational ages of 23-27, 28-31 and 32-36 weeks, respectively. The moderately preterm group was dominated by adolescents born small for gestational age. RESULTS: Very preterm adolescents performed on a par with term-born controls. In contrast, extremely preterm adolescents displayed inferior results on all cognitive tests, more so if they had suffered neonatal complications. Moderately preterm adolescents scored lower than very preterm and full-term born adolescents, particularly on complex cognitive tasks. CONCLUSION: Adolescents born at 28 weeks of gestation or later, with appropriate birthweight and no perinatal complications, functioned like term-born peers at 18 years of age. Extremely preterm birth per se posed a risk for long-term cognitive deficits, particularly executive deficits. Adolescents born moderately preterm but small for gestational age were at risk of general cognitive deficits.

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

AIM: 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. METHODS: We randomised six girls and 13 boys to either a treatment group or a control group. The treatment group received growth hormone (Genotropin(®) 0.033 mg/kg/day) for 2 years, while the control group did not receive treatment in the first year and then received a double dose in the second year. Treatment was then stopped in both groups for 6 months. RESULTS: Both groups showed the same intellectual disabilities at the start of the study, and no difference was found after the first and second years. The parents reported that the children showed increased vitality during treatment. When treatment was stopped, the children showed a marked exacerbation of behavioural problems, a significant increase in body fat and a decrease in insulin-like growth factor 1 levels. CONCLUSION: We believe this is the first study to show that abrupt-ceasing growth hormone treatment led to a successive deterioration in behavioural problems in children with Prader-Willi syndrome.

Individual neuropsychological profiles at age 5½ years in children born preterm in relation to medical risk factors.

Follow-up studies of preterm children have reported a range of cognitive deficits, particularly in executive functions, visuospatial abilities, and learning. However, few researchers have adopted a person-oriented approach, exploring individual neuropsychological profiles. The aim of this study was to identify typical neuropsychological profiles among preterm children and control children, respectively. A second aim was to investigate if neuropsychological profiles at age 5½ might be associated with perinatal medical risk factors. As part of the longitudinal Stockholm Neonatal Project, NEPSY for 4- to 7-year-old children ( Korkman, 1990 ), WPPSI-R, and Movement ABC were administered at age 5½ years to 145 preterm (mean gestational age 28 weeks) and 117 control children born at term. For the present study, the NEPSY results of each child were transformed into summary z scores for each of 5 neuropsychological domains: attention, memory, sensory-motor, verbal, and visuospatial functions. Subsequently, Ward's cluster analysis was performed for the preterm and control groups separately, identifying 5 neuropsychological profiles in both groups explaining around 56% and 57% of the variance, respectively. Overall, preterm children had lower neuropsychological results but also more diverging profiles compared to controls. The variability in outcome could not be sufficiently explained by birth weight, gestational age, or medical risks. The results suggest that prematurity interacts dynamically with genetic, medical, and environmental factors in neuropsychological development.

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.

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

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 or= 2500; gestational age, >or= 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 5 1/2 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.