Optical coherence tomography of the macular ganglion cell layer in children with neurofibromatosis type 1 is a useful tool in the assessment for optic pathway gliomas.

BACKGROUND: Optic pathway glioma (OPG) is a feared complication to neurofibromatosis type 1 (NF1) since it can cause visual impairment in young children. The main goal of screening is to detect symptomatic OPGs that require treatment. Optical coherence tomography (OCT) has been suggested as a tool for detection of neuro-retinal damage. AIMS: To investigate whether the ganglion cell layer assessed by OCT is a reliable measure to identify and detect relapses of symptomatic OPGs in children with NF1. METHODS: Children (3-6 years) with NF1, with and without known OPG and children with sporadic OPG (S-OPG) resident in the Stockholm area, were invited and followed in a prospective study during a three-year period. Brain magnetic resonance tomography (MRI) had been performed in children with symptoms of OPG. Outcome measures were VA in logMAR, visual field index (VFI), average thicknesses of the ganglion cell-inner plexiform layer (GC-IPL), and peripapillary retinal nerve fiber layer (pRNFL). RESULTS: There were 25 children with MRI-verified OPG and 52 with NF1 without symptomatic OPG. Eyes from NF1 patients without symptoms of OPG showed significantly better results in all four analyzed parameters compared to eyes with NF1-associated OPG. Mean GC-IPL measurements seemed stable and reliable, significantly correlated to pRNFL (correlation coefficient (r) = 0.662, confidence interval (CI) = .507 to .773 p<0.001), VA (r = -0.661, CI = -7.45 to -.551, p<0.001) and VFI (r = 0.644, CI = .452 to .774, p<0.001). GC-IPL measurements were easy to obtain and acquired at considerably younger age than pRNFL (5.6±1.5 vs 6.8±1.3; p<0.001). CONCLUSIONS: The mean GC-IPL thickness could distinguish well between eyes with OPG and eyes without symptomatic OPG in children with NF1. As thinning of GC-IPL assessed with OCT could indicate underlying OPG, it should be included in the screening protocol of children with questionable VA measurements and in particular in children with NF1.

Structural impact of arrested foveal development in children born extremely preterm without ROP at 6.5 years of age.

OBJECTIVES: To characterize changes of foveal topography and microstructure of persisting foveal immaturity at 6.5 years of age in children born extremely preterm without retinopathy of prematurity (EPT-NoROP). METHODS: Images from previous optical coherence tomography examinations of 37 EPT-NoROP and 92 control eyes were selected from a regional cohort of the EXPRESS (Extremely Preterm Infants in Sweden) study. Thickness of ganglion cell + inner plexiform layer (GCL+), outer nuclear layer (ONL), retinal thickness (RT) at the foveal centre (FC), foveal depth (FD) and RT at the foveal rim were evaluated. RESULTS: Layer thickness of GCL+, ONL and RT was increased at FC in the EPT-NoROP group. More than two-thirds had thickness values above the control limit (control mean +2 SD) at FC (GCL + 68%, ONL 76%, and RT 68%), and 50% had reduced FD compared to controls. All parameters showed a high correlation within the EPT-NoROP group, whereas no or weaker correlation was seen in control eyes. The EPT-NoROP sub-groups, divided based on the control limit, did not differ in terms of associated factors such as gestational age, birth weight, visual acuity, and refraction. CONCLUSIONS: Extreme prematurity without impact of ROP is associated with increased GCL + , ONL, and RT thickness at FC as well as reduced FD compared to full-term controls at age 6.5. This indicates that prematurity per se may have a profound effect on foveal anatomical maturation during the first months after birth. Our results suggest RT at FC to be a simple and useful measure of foveal anatomical immaturity.

Optical Coherence Tomography Identifies Visual Pathway Involvement Earlier than Visual Function Tests in Children with MRI-Verified Optic Pathway Gliomas.

This study investigates whether optical coherence tomography (OCT) could add useful information in the examination of children with optic pathway glioma (OPG) at high risk of developing vision loss. For this purpose, the relationship between ganglion cell-inner plexiform layer (GC-IPL) thickness and visual function, evaluated with tests of visual acuity (VA) and visual field (VF), as well as tumor site according to magnetic resonance imaging (MRI), were examined in a geographically defined group of children with OPG. METHODS: Children aged <18 years with OPG underwent ophthalmic examination including VA, VF (Zeiss HFA perimetry) and OCT imaging (Zeiss Cirrus HD-OCT). RESULTS: Out of 51 patients included, 45 provided 77 eyes with MRI-verified OPG, and 19 patients provided 25 eyes without OPG. Significant correlations were found between GC-IPL, VF and VA (p < 0.001). The GC-IPL pattern loss corresponded in 95% to VF defects and in 92% to MRI findings. CONCLUSIONS: Our study indicates that GC-IPL measures could serve as an early marker of vision-threatening changes related to OPG and as a valuable link between MRI and visual function tests. Thinning of GC-IPL and differences in topography between eyes are strong indicators of and predictive of vision loss related to OPG.

Developmental trajectories of global motion and global form perception from 4 years to adulthood.

Literature on the development of global motion and global form perception demonstrated their asynchronous developmental trajectories. However, former studies have failed to clearly establish the critical period of maturation for these specific abilities. This study aimed to analyze the developmental trajectories of global motion and global form discrimination abilities by controlling for basic visual functions and general cognitive ability and to present the global motion and global form normative scores. A sample of 456 children and adolescents (4-17 years of age) and 76 adults recruited from the Italian and Swedish general population participated in the study. Motion and form perception were evaluated by the motion coherence test and form coherence test, respectively. Raven's matrices were used to assess general cognitive ability, the Lea Hyvärinen chart test was used for full- and low-contrast visual acuity, and the TNO test was used for stereopsis. General cognitive ability and basic visual functions were strongly related to motion and form perception development. Global motion perception had an accelerated maturation compared with global form perception. For motion perception, an analysis of the oblique effect's development showed that it is present at 4 years of age. The standardized scores of global motion and form coherence tests can be used for clinical purposes.

Profile of macular ganglion cell-inner plexiform layer thickness in healthy 6.5 year- old Swedish children.

BACKGROUND: The purpose was to study the macular ganglion cell- inner plexiform layer (GC-IPL) thickness in healthy 6.5 year- old Swedish children using Optical Coherence Tomography (OCT) and to study topography symmetry within eyes and between eye pairs. METHODS: A total of 181 eyes of 92 healthy children (39 girls, 53 boys) aged 6.5 and serving as a term-born control group in the Extremely Preterm Infants in Sweden Study (EXPRESS), were examined with Cirrus HD-OCT. Main outcome measures were average and minimum values of GC-IPL thickness of the device's predefined macular sectors. Single sectors, combined sectors defined as superior and inferior hemispheres and temporal and nasal sectors were evaluated. Intra-individual GC-IPL thickness between eye pairs was analyzed. Visual acuity, refraction and general cognition were assessed and correlated to GC-IPL outcome. RESULTS: Eighty-five children completed the OCT examination and 155 out of 181 scans (86%) were analyzed. The mean average GC-IPL thickness was 85.9 µm (± 5.3; 5th and 95th percentiles were 76.0 and 94.6 µm). The mean minimum GC-IPL thickness was 83.6 µm (± 4.9; 5th and 95th percentiles were 75.4 and 92.3 µm). The difference in thickness between nasal and temporal sectors and between superior and inferior hemisphere sectors were less than 2 µm. The difference between average GC-IPL thickness and minimum GC-IPL thickness was 2.3 µm (± 1.9; 5th and 95th percentiles were 0.0 and 6.0 µm). The difference between the thickest and thinnest sector within eye was 6.4 µm (± 2.2; 5th and 95th percentiles were 3.0 and 10.0 µm). There was a moderate correlation in the difference between the nasal combined and the temporal combined sectors within eye pairs (p < 0.0001, Spearman's ρ 0.58). The average GC-IPL thickness was weakly positively correlated with SE (spherical equivalent; combined sphere and ½ cylinder) (p = 0.031, Spearman's ρ 0.23). CONCLUSIONS: This study provides normative GC-IPL thickness values for healthy 6.5 year- old Swedish children. The GC-IPL thickness variations within eyes and within eye pairs are generally small. It could therefore be assumed that larger variations are sensitive markers of focal GC-IPL thinning due to damage to the primary visual pathways in children.

[Retinal hemorrhages in abusive head trauma]. / Ögonbottenblödningar vid våld mot huvudet på små barn.

Brain injuries due to abusive head trauma (AHT) in infants are not rare and they are probably under-diagnosed. Retinal hemorrhages (RH) constitute a cardinal symptom of AHT and AHT is the most common cause of RH in infants next to childbirth. Retinoschisis with or without retinal folds is highly suggestive of AHT and never seen secondary to childbirth. Bilateral extensive RH that are too numerous to count, multilayered and extending to the peripheral retina in infants < 3 years of age, in combination with brain injury and in absence of leukemia, ruptured brain aneurysm/AVM, fatal head crush or known severe accidental trauma must be considered to be caused by AHT in the absence of any other compelling factors. The ophthalmologist has an important role and a responsibility in describing the pattern of RH and in evaluating the likelihood of the diagnosis in the medical report and in communication with pediatricians and child protection team.

Cerebral visual impairment captured with a structured history inventory in extremely preterm born children aged 6.5 years.

PURPOSE: To investigate whether a questionnaire can identify cerebral visual impairment (CVI) in a group of 6.5-year-old children born extremely preterm (EPT) as accurately as direct assessments. METHODS: This prospective population-based study included 120 children born before 27 weeks' gestational age (66 males; mean, 25.4 ± 1.0 weeks) and 97 full-term controls (56 males; mean, 39.9 ± 1.1 weeks) at the age of 6.5 years, as part of the Extremely Preterm Infants in Sweden Study (EXPRESS). A questionnaire for detection of CVI was evaluated and compared with visual, perceptual, and cognitive assessments. RESULTS: Parents of children born EPT reported more CVI features than the parents of control children, with median sum scores of 25 (95% CI, 18.1-31.9) and 11 (95% CI, 8.8-13.2), respectively (P < 0.001), and a median difference of 14 (95% CI, 6.6-21.4). Low rates of reported CVI features were significantly associated with better results from direct assessments within the EPT group and with less pronounced differences compared to controls. CONCLUSIONS: The questionnaire discriminated well between children born EPT and controls, and the scores were congruent with other evidence of visual, perceptual, and cognitive deficits. The easily used questionnaire compared favorably with direct assessment in identifying CVI in children born EPT and also provides valuable information to clinicians, and parents about the daily life problems associated with CVI.

INCREASED FOVEAL GANGLION CELL AND INNER PLEXIFORM LAYER THICKNESS IN CHILDREN AGED 6.5 YEARS BORN EXTREMELY PRETERM.

PURPOSE: To analyze the ganglion cell layer and inner plexiform layer (GCL+) thickness in children born extremely preterm and control children. METHODS: A study of 6.5-year-old children born before the gestational age of 27 weeks and age-matched controls. The GCL+ thickness and foveal depth (FD) were analyzed in a single optical coherence tomography B-scan. Association with neonatal risk factors and sex was investigated. Extremely preterm was divided into no, mild, and severe retinopathy of prematurity, retinopathy of prematurity treatment, and no, mild, and severe intraventricular hemorrhage. RESULTS: Adequate measurements were obtained from 89 children born extremely preterm and 92 controls. Extremely preterm children had increased total (5 µm, P < 0.001) and central (21 µm, P < 0.001) GCL+ thickness and reduced FD (-53 µm, P < 0.001) compared with controls. Extremely preterm children receiving retinopathy of prematurity treatment had increased GCL+ thickness and reduced FD compared with other subgroups. Sex and gestational age were associated with increased central GCL+ thickness and reduced FD. Reduced total GCL+ thickness was associated with severe intraventricular hemorrhage. CONCLUSION: Extremely preterm birth can cause incomplete extrusion of the GCL+ and reduced FD. Retinopathy of prematurity treatment, gestational age, and male sex were associated to increased central GCL+ thickness and reduced FD, while severe intraventricular hemorrhage was associated with reduced total GCL+ thickness.

[Idiopathic intracranial hypertension - Swedish consensus guidelines]. / Idiopatisk intrakraniell hyper­tension ­ riktlinjer saknas ännu - Förslag till nationellt handläggningsstöd för utredning, behandling och uppföljning.

Idiopathic intracranial hypertension (IIH) is a disorder affecting both the pediatric and adult population. Investigations and treatments may differ considerably. There are no evidence-based guidelines for treatment. During a national multidisciplinary meeting in Stockholm January 2018 IIH experts from several Swedish regions met to discuss how to manage this patient group. These guidelines are based on this meeting and a review of current medical knowledge. To summarize: All patients should be investigated and treated for underlying factors that could be the cause of high intracranial pressure (ICP) (such as obesity, secondary causes such as intracranial tumors or other factors reported to affect ICP). When treating IIH the preservation of vision is crucial. Follow-up depends on visual status. In case of acute risk of visual impairment prompt surgical intervention must be considered. Symptomatic treatment of headache is recommended.

Head and Trunk Movements During Turning Gait in Children with Cerebral Palsy.

Thirty children with cerebral palsy (CP) and 22 typical developing (TD) were tested with 3D-gait analysis. At turning, trunk rotation was larger in CP2 (GMFCS II) than in TD and CP1 (GMFCS I), and head flexion was larger in CP3 (GMFCS III) than TD. Maximum head and trunk flexion values during the entire trial were larger in CP3 than in the other groups, and trunk flexion was larger in CP2 than in TD. Trial time increased with GMFCS-level. Less trunk rotation than TD and CP1 reflects spatial insecurity in CP2, which in CP3 is compensated by the walker. The flexed head and trunk in CP3 and trunk in CP2 may reflect deficits in proprioception and sensation requiring visual control of the lower limbs.

Visual-motor integration and fine motor skills at 6½ years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: a population-based cohort study.

OBJECTIVES: This exploratory study aimed to investigate associations between neonatal brain volumes and visual-motor integration (VMI) and fine motor skills in children born extremely preterm (EPT) when they reached 6½ years of age. SETTING: Prospective population-based cohort study in Stockholm, Sweden, during 3 years. PARTICIPANTS: All children born before gestational age, 27 weeks, during 2004-2007 in Stockholm, without major morbidities and impairments, and who underwent MRI at term-equivalent age. MAIN OUTCOME MEASURES: Brain volumes were calculated using morphometric analyses in regions known to be involved in VMI and fine motor functions. VMI was assessed with The Beery-Buktenica Developmental Test of Visual-Motor Integration-sixth edition and fine motor skills were assessed with the manual dexterity subtest from the Movement Assessment Battery for Children-second edition, at 6½ years. Associations between the brain volumes and VMI and fine motor skills were evaluated using partial correlation, adjusted for total cerebral parenchyma and sex. RESULTS: Out of 107 children born at gestational age <27 weeks, 83 were assessed at 6½ years and 66/83 were without major brain lesions or cerebral palsy and included in the analyses. A representative subsample underwent morphometric analyses: automatic segmentation (n=34) and atlas-based segmentation (n=26). The precentral gyrus was associated with both VMI (r=0.54, P=0.007) and fine motor skills (r=0.54, P=0.01). Associations were also seen between fine motor skills and the volume of the cerebellum (r=0.42, P=0.02), brainstem (r=0.47, P=0.008) and grey matter (r=-0.38, P=0.04). CONCLUSIONS: Neonatal brain volumes in areas known to be involved in VMI and fine motor skills were associated with scores for these two functions when children born EPT without major brain lesions or cerebral palsy were evaluated at 6½ years of age. Establishing clear associations between early brain volume alterations and later VMI and/or fine motor skills could make early interventions possible.

National population-based cohort study found that visual-motor integration was commonly affected in extremely preterm born children at six-and-a-half years.

AIM: This study aimed to explain the relationship between visual-motor integration (VMI) abilities and extremely preterm (EPT) birth, by exploring the influence of perinatal variables, cognition, manual dexterity and ophthalmological outcomes. METHODS: This was part of the population-based national Extremely Preterm Infant Study in Sweden (EXPRESS) study. We studied 355 children, born at a gestational age of <27 weeks from April 2004 to March 2007, and 364 term-born controls. At six-and-a-half years of age, we assessed VMI, cognitive function, motor skills and vision. VMI impairment was classified as <-1 standard deviation (SD). RESULTS: The mean (SD) VMI score was 87 (±12) in preterm children compared to 98 (±11) in controls (p < 0.001). VMI impairment was present in 55% of preterm infants and in 78% of children born at 22-23 weeks. Male sex and postnatal steroids showed a weak association with poorer visual-motor performance, whereas low manual dexterity and cognitive function showed a stronger association. CONCLUSION: Poor VMI performance was common in this EXPRESS cohort of children born EPT. Its strong association to cognition and manual dexterity confirms that all of these factors need to be taken into account when evaluating risks in preterm born children.

Motion Perception and Form Discrimination in Extremely Preterm School-Aged Children.

This population-based study evaluated motion and form perception in 71 children born extreme premature (EPT; < 27 gestational weeks), aged 6.5 years, as compared to a matched group of 79 control children born at term. Motion and form perception were evaluated by motion coherence and form coherence tests. The EPT group showed a poorer performance on both tasks as compared to the control group. However, after controlling for IQ and visual acuity, the EPT group showed only a significant deficit in motion perception. No association was found between motion perception accuracy and gestational age, previous retinopathy of prematurity, or previous intraventricular hemorrhage in the EPT group. The results highlight the long-term motion perception deficits in children born EPT.

Extreme prematurity, treated retinopathy, bronchopulmonary dysplasia and cerebral palsy are significant risk factors for ophthalmological abnormalities at 6.5 years of age.

AIM: This study evaluated the contributions of various prenatal and postnatal predictive factors to a documented high prevalence of ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm. METHODS: We carried out a prospective population-based study of all children born in Sweden at a gestational age of 22 + 0 to 26 + 6 weeks based on the Extremely Preterm Infants in Sweden Study. The main outcome measures were a combined score of visual impairment, refractive errors and strabismus at 6.5 years of age. Models of univariate and multivariable regression were used to analyse potential prenatal and postnatal predictive factors at different clinically relevant time-points from one minute after birth to 30 months. RESULTS: We focused on 399 known extremely preterm survivors and compared them to 300 full-term controls. Significant antecedents for ophthalmological abnormalities included prematurity per se, retinopathy of prematurity that required treatment, severe bronchopulmonary dysplasia and cerebral palsy. Severe intraventricular haemorrhage was no longer a significant risk factor when we adjusted it for the 30-month cognitive and neuromotor development outcomes. CONCLUSION: This time-course risk analysis model showed a changing panorama of significant risk factors for ophthalmological abnormalities in children aged 6.5 years who were born extremely preterm.

Deficits in Approximate Number System Acuity and Mathematical Abilities in 6.5-Year-Old Children Born Extremely Preterm.

Preterm children are at increased risk for poor academic achievement, especially in math. In the present study, we examined whether preterm children differ from term-born children in their intuitive sense of number that relies on an unlearned, approximate number system (ANS) and whether there is a link between preterm children's ANS acuity and their math abilities. To this end, 6.5-year-old extremely preterm (i.e., <27 weeks gestation, n = 82) and term-born children (n = 89) completed a non-symbolic number comparison (ANS acuity) task and a standardized math test. We found that extremely preterm children had significantly lower ANS acuity than term-born children and that these differences could not be fully explained by differences in verbal IQ, perceptual reasoning skills, working memory, or attention. Differences in ANS acuity persisted even when demands on visuo-spatial skills and attention were reduced in the ANS task. Finally, we found that ANS acuity and math ability are linked in extremely preterm children, similar to previous results from term-born children. These results suggest that deficits in the ANS may be at least partly responsible for the deficits in math abilities often observed in extremely preterm children.

CENTRAL MACULAR THICKNESS IN 6.5-YEAR-OLD CHILDREN BORN EXTREMELY PRETERM IS STRONGLY ASSOCIATED WITH GESTATIONAL AGE EVEN WHEN ADJUSTED FOR RISK FACTORS.

PURPOSE: To assess the macular thickness in 6.5-year-old children born extremely preterm (EPT) in comparison with children born at term and to investigate risk factors associated with the macular thickness in the preterm group. METHODS: A population-based study of 6.5-year-old children born before the gestational age of 27 weeks and age-matched control subjects. Macular assessments with optical coherence tomography were performed, and the results were compared with neonatal risk factors and sex. RESULTS: Adequate optical coherence tomography measurements were obtained from 134 children born EPT (mean gestational age of 25 weeks [range 23-26]) and 145 control subjects. The mean (range) of central macula thickness was significantly increased (P < 0.001) in the EPT group (right eyes: 282 µm [238-356], left eyes: 283 µm [229-351]), compared with the control group (right eyes: 249 µm [208-293], left eyes: 248 µm [207-290]). A multiple linear mixed model analysis of the EPT group revealed gestational age, retinopathy of prematurity, and male gender as important risk factors for an increased macular thickness. The macular thickness decreased by 3.9 µm per gestational week, when adjusted for retinopathy of prematurity and sex. CONCLUSION: Extremely preterm birth constitutes a substantial risk factor for a thick central macula, even when adjusted for retinopathy of prematurity and male gender.

Ophthalmological findings in children with encephalitis.

PURPOSE: To evaluate ophthalmological abnormalities in children with acute encephalitis. METHODS: Thirty-six children included in a hospital-based prospectively and consecutively collected cohort of children with acute encephalitis were investigated for ophthalmological abnormalities. The investigation included clinical ophthalmological examination, fundus photography, neuro-ophthalmological examinations as well as visual and stereo acuity. Results on laboratory examinations, clinical findings, neuroimaging and electroencephalography registrations were recorded for all children. RESULTS: The median age was 4.0 years (Interquartile Range 1.9-9.8). The aetiology was identified in 74% of cases. Three of 36 patients were found to have abnormal ophthalmological findings related to the encephalitis. Transient sixth nerve palsy was seen in a 15-year-old child and transient visual impairment was seen in a 3.5-year-old child. Bilateral miosis and ptosis, i.e. autonomic nerve system symptoms, were seen in an 11-month-old child, with herpes simplex 1 and N-methyl-d-aspartate receptor antibody encephalitis. All three children recovered and improved their ophthalmological function with time. CONCLUSION: Only 3 of 36 children were found to have ophthalmological abnormalities due to encephalitis and they all improved with time. Thus, ophthalmological consultation does not seem to fit in a screening programme for childhood encephalitis but should be considered in selected cases.

The role of visual stimuli on standing posture in children with bilateral cerebral palsy.

BACKGROUND: In children with bilateral cerebral palsy (CP) maintaining a standing position can be difficult. The fundamental motor task of standing independently is achieved by an interaction between the visual, somatosensory, and vestibular systems. In CP, the motor disorders are commonly accompanied by sensory and perceptual disturbances. Our aims were to examine the influence of visual stimuli on standing posture in relation to standing ability. METHODS: Three dimensional motion analysis with surface electromyography was recorded to describe body position, body movement, and muscle activity during three standing tasks: in a self-selected position, while blindfolded, and during an attention-demanding task. Participants were twenty-seven typically-developing (TD) children and 36 children with bilateral CP, of which 17 required support for standing (CP-SwS) and 19 stood without support (CP-SwoS). RESULTS: All children with CP stood with a more flexed body position than the TD children, even more pronounced in the children in CP-SwS. While blindfolded, the CP-SwS group further flexed their hips and knees, and increased muscle activity in knee extensors. In contrast, the children in CP-SwoS maintained the same body position but increased calf muscle activity. During the attention-demanding task, the children in CP-SwoS stood with more still head and knee positions and with less muscle activity. CONCLUSIONS: Visual input was important for children with CP to maintain a standing position. Without visual input the children who required support dropped into a further crouched position. The somatosensory and vestibular systems alone could not provide enough information about the body position in space without visual cues as a reference frame. In the children who stood without support, an intensified visual stimulus enhanced the ability to maintain a quiet standing position. It may be that impairments in the sensory systems are major contributors to the difficulties to stand erect in children with CP.

Neurodevelopmental Outcomes Among Extremely Preterm Infants 6.5 Years After Active Perinatal Care in Sweden.

IMPORTANCE: Active perinatal care increases the rate of survival of extremely preterm infants, but there are concerns that improved survival might increase the rate of disabled survivors. OBJECTIVE: To determine the neurodevelopmental outcomes of a national cohort of children 6.5 years of age who had been born extremely preterm (<27 weeks' gestational age) in Sweden. DESIGN, SETTING, AND PARTICIPANTS: Population-based prospective cohort study of consecutively born extremely preterm infants. All of these infants were born in Sweden during the period from April 1, 2004, to March 31, 2007. Of 707 live-born extremely preterm infants, 486 (68.7%) survived to 6.5 years of age. These children were assessed and compared with matched controls who had been born at term. Comparison estimates were adjusted for demographic differences. Assessments ended in February 2014, and analysis started thereafter. MAIN OUTCOMES AND MEASURES: Cognitive ability was measured with the fourth edition of the Wechsler Intelligence Scale for Children (WISC-IV), and the mean (SD) scores of the children who had been born extremely preterm were compared with those of the controls. Clinical examinations and parental questionnaires were used for diagnosis of cerebral palsy, hearing and vision impairments, and cognition for the children who were not assessed with the WISC-IV. RESULTS: Of 486 eligible infants who were born extremely preterm, 441 (90.7%) were assessed at 6.5 years of age (59 by medical record review only) alongside 371 controls. The adjusted mean (SD) full-scale WISC-IV score was 14.2 (95% CI, 12.1-16.3) points lower for children who had been born extremely preterm than for controls. Cognitive disability was moderate for 18.8% of extremely preterm children and 2.2% of controls (P < .001), and it was severe for 11.1% of extremely preterm children and 0.3% of controls (P < .001). Cerebral palsy was observed in 9.5% of extremely preterm children and 0.0% of controls (P < .001), blindness was observed in 2.0% of extremely preterm children and 0.0% of controls (P < .001), and hearing impairment was observed in 2.1% of extremely preterm children and 0.5% of controls (P = .07). Overall, 36.1% (95% CI, 31.7%-40.6%) of extremely preterm children had no disability, 30.4% (95% CI 26.3%-34.8%) had mild disability, 20.2% (95% CI, 16.6%-24.2%) had moderate disability, and 13.4% (95% CI, 10.5%-16.9%) had severe disability. For extremely preterm children, moderate or severe overall disability decreased with gestational age at birth (adjusted odds ratio per week, 0.65 [95% CI, 0.54-0.79]; P < .001) and increased from 26.6% to 33.5% (P = .01) for children assessed both at 2.5 and 6.5 years. CONCLUSIONS AND RELEVANCE: Of the 441 extremely preterm infants who had received active perinatal care, 293 (66.4%) had no or mild disability at 6.5 years; of the 371 controls, 11 (3.0%) had moderate or severe disability. Disability rates at 6.5 years increased relative to the rates at 2.5 years. Results are relevant for health care professionals and planners, and for clinicians counseling families facing extremely preterm births.