White Matter Injury and General Movements in High-Risk Preterm Infants.

BACKGROUND AND PURPOSE: Very preterm infants (birth weight, <1500 g) are at increased risk of cognitive and motor impairment, including cerebral palsy. These adverse neurodevelopmental outcomes are associated with white matter abnormalities on MR imaging at term-equivalent age. Cerebral palsy has been predicted by analysis of spontaneous movements in the infant termed "General Movement Assessment." The goal of this study was to determine the utility of General Movement Assessment in predicting adverse cognitive, language, and motor outcomes in very preterm infants and to identify brain imaging markers associated with both adverse outcomes and aberrant general movements. MATERIALS AND METHODS: In this prospective study of 47 preterm infants of 24-30 weeks' gestation, brain MR imaging was performed at term-equivalent age. Infants underwent T1- and T2-weighted imaging for volumetric analysis and DTI. General movements were assessed at 10-15 weeks' postterm age, and neurodevelopmental outcomes were evaluated at 2 years by using the Bayley Scales of Infant and Toddler Development III. RESULTS: Nine infants had aberrant general movements and were more likely to have adverse neurodevelopmental outcomes, compared with infants with normal movements. In infants with aberrant movements, Tract-Based Spatial Statistics analysis identified significantly lower fractional anisotropy in widespread white matter tracts, including the corpus callosum, inferior longitudinal and fronto-occipital fasciculi, internal capsule, and optic radiation. The subset of infants having both aberrant movements and abnormal neurodevelopmental outcomes in cognitive, language, and motor skills had significantly lower fractional anisotropy in specific brain regions. CONCLUSIONS: Aberrant general movements at 10-15 weeks' postterm are associated with adverse neurodevelopmental outcomes and specific white matter microstructure abnormalities for cognitive, language, and motor delays.

Patients with KCNJ11-related diabetes frequently have neuropsychological impairments compared with sibling controls.

AIMS: KCNJ11-related diabetes is the most common form of permanent neonatal diabetes and has been associated with a spectrum of neurodevelopmental problems. We compared neurodevelopmental outcomes in patients with KCNJ11 mutations and their sibling controls. METHODS: Through our Monogenic Diabetes Registry (http://monogenicdiabetes.uchicago.edu/), we evaluated 23 patients with KCNJ11 mutations with (n = 9) and without (n = 14) global developmental delay successfully treated with sulfonylurea and 20 healthy sibling controls, using a battery of targeted neuropsychological and behavioural assessments with scaled scores that are comparable across a wide range of ages. RESULTS: Patients with KCNJ11-related diabetes without global developmental delay had significant differences compared with sibling controls on a range of assessments including IQ, measures of academic achievement and executive function. KCNJ11 patients with global delay exhibited significant differences in behavioural symptoms with a tendency to avoid social contact and displayed a reduced ability to adapt to new circumstances. Parents reported more immature behaviour, gross mood swings, bizarre thoughts, other unusual and severe behaviours, and there were also significant deficits in all subdomains of daily living skills. CONCLUSIONS: This series represents the largest and most comprehensive study of neuropsychological and behavioural dysfunction of individuals with KCNJ11 diabetes and is the first to compare outcome with sibling controls. Our data demonstrate the variety of neurodevelopmental problems seen in those with KCNJ11 mutations, even in those without recognized global developmental delays. These data can be used to counsel families and guide structured neurodevelopmental assessments and treatments based on the initial genetic diagnosis in patients with neonatal diabetes.

Victimization and depression among youth with disabilities in the US child welfare system.

AIM: This study aimed to examine the prevalence of victimization among a United States-wide cohort of youth with disabilities (YWD) investigated for maltreatment in the child welfare system (CWS) and their correlation with mental health. METHODS: Data were drawn from baseline interviews in the second National Survey of Child and Adolescent Well-Being, a national representative survey of youth involved in the CWS. Interviews took place between 2008 and 2009 and included 675 youth, 11-17 years old and residing with biological families across 83 counties nationwide. The sample consisted of 405 females (60.1%) and 270 males (39.9%), mean age = 13.5 years. We identified YWD if they reported one or more physical or neurodevelopmental health condition (n = 247). Reported victimization experiences and Children's Depression Inventory (CDI) scores were analysed using weighted regression analyses. RESULTS: One-quarter of YWD in the CWS reported three or more victimizations during the prior year compared with 19% of youth without disabilities. The odds of YWD reporting a one-unit increase in level of victimization was 75% higher (P < 0.05) than youth without disabilities. Prevalence of clinical depression was significantly higher among YWD (14 vs. 5.5%; P < 0.05). Unlike youth without disabilities, the odds of clinical depression were 92% higher for every one-unit increase in victimization among YWD, controlling for covariates (P < 0.05). Of CWS-involved youth who reported three or more victimizations, 24.4% of YWD and 2.2% of non-disabled youth had CDI scores in the clinical range. CONCLUSION: YWDs in the US CWS are at high risk of experiencing victimization and clinical depression. Our findings suggest that health professionals need to screen CWS-involved YWD for multiple forms of victimization, and develop and implement trauma-informed services that target the mental health sequelae that may jeopardize their independence in adulthood.

Optimizing neurodevelopmental outcomes after prematurity: lessons in neuroprotection and early intervention.

In recent decades, advances in maternal-fetal, obstetrics, and neonatal medicine have led to the increased survival of preterm infants. Very preterm infants (<32 weeks gestation), who comprise a small fraction (1.4%) of all neonates, have had dramatic increases in their survival. In addition, late preterm infants (33-36 weeks gestation) are a growing population of all preterm births and may include over 10% of all births. Both populations experience ongoing and significant challenges once they are discharged from the neonatal intensive care unit (NICU), including medical, nutritional, and developmental issues. Similarly, preterm infants may experience ongoing challenges once they enter school. As a result, clinicians should be aware of the unique neurodevelopmental issues that affect this population of children, including what they experience at different developmental stages. This review will describe how selected neonatal interventions impact on very preterm and late preterm infants. In addition, we will discuss the developmental and functional components of school readiness in very preterm and late preterm infants, using the International Classification of Functioning, Disability, and Health (ICF) as a framework for health, enablement, disability, and participation. This framework allows us to describe children's strengths and challenges across body structure and body function, activities, and social roles in the context of child and family supports. We will explicitly describe the role of physicians and health professional teams in providing ongoing support and coordination of care throughout childhood for preterm infants who have experienced neonatal intensive care.

Concurrent validity of the parent-completed Ages and Stages Questionnaires, 2nd Ed. with the Bayley Scales of Infant Development II in a low-risk sample.

Abstract Background This study assessed the concurrent validity of the Ages and Stages Questionnaire (ASQ) compared with Bayley Scales of Infant Development II (BSID II) amongst children aged 24 months. Methods Data were collected from 53 infants and mothers who participated in the New York State Angler Cohort Child Development Study. Parents completed the 24-month ASQ to assess communication, personal-social, problem-solving ability, and fine and gross motor control. The BSID II was administered by a clinical psychologist at the 24-month home visit for cognitive and psychomotor assessment. The ASQ was scored using age-specific norms of <2 SDs below any domain mean to define failure. A BSID II score of <85 indicated mild or severe delay, while a score of <70 suggested a severe delay. Results Scores on the ASQ communication and personal-social domains were moderately correlated with the BSID II Mental Scale (R= 0.52, P < 0.001; R= 0.45, P < 0.01) and ASQ gross motor with the BSID II Motor Scale (R= 0.46, P < 0.01), whereas ASQ problem-solving and fine motor domains were not significantly correlated with BSID II scores. The ASQ had a sensitivity of 100% and specificity of 87% at 24 months (n= 40) for severely delayed status. Conclusions Results suggest the ASQs provide a simple, valid, and cost-effective method for clinicians and field-based researchers to reduce the number of standardized assessments required to identify developmentally delayed infants at age 24 months. Future studies should further assess the validity of the ASQs in larger, more diverse populations of infants.

Neuroimaging and cerebral palsy in children.

Cerebral palsy (CP) is a description of a spectrum of central nervous system (CNS) impairments that affect mobility, communication, intellectual ability, and neurobehavior as a result of developmental brain dysfunction. CP is the most common contributor to motor disability in children with prevalence of about 2-3/1000 live births globally. Presently, no curative therapies or successful methods of prevention on a population level are available for children with one of the cerebral palsy syndromes. Despite these challenges, orthopedic, rehabilitation, neuropharmacological, and other management interventions can help maintain mobility, prevent deformity, and promote quality of life for children with CP. Typically, the diagnosis of CP is based on clinical observations and parent concerns regarding delays in attaining motor milestones (e.g., rolling, sitting, crawling, walking), not on laboratory testing or neuroimaging. However, since 2004 the American Academy of Neurology (AAN) has recommended that neuroimaging of the CNS be part of diagnostic process for cerebral palsy. Although the guideline was initially met with controversy and criticism, neuroimaging has allowed a broader appreciation of timing of lesions, extent of white matter involvement, and the complexity of the motor spectrum of disability. In this article we shall describe the major types of neuroimaging techniques and review their roles in identification and evaluation of children with one of the cerebral palsy syndromes. The authors will focus on the emerging knowledge of how brain structure can inform us about children's functioning, especially among children with prematurity, recognizing that we are only beginning to understand brain plasticity and developmental resiliency.

Gross motor profile in rett syndrome as determined by video analysis.

Movement impairment is a fundamental but variable component of the Rett syndrome phenotype. This study used video supplemented by parent report data to describe the gross motor profile in females with Rett syndrome (n=99) and to investigate the impact of age, genotype, scoliosis and hand stereotypies. Factor analysis enabled the calculation of general and complex gross motor skills scores. Most subjects were able to sit, slightly less than half were able to walk and a minority were able to transfer without assistance. General gross motor skills declined with age and were poorer in those who had surgically treated scoliosis but not conservatively managed scoliosis. Complex gross motor skills did not decline with age and were better in those without scoliosis. Those with a p.R133C, p.R294X, or a p.R255X mutation appear to have better motor skills overall than those with a p.R270X or large deletion mutation. Motor scores were not related to the frequency of hand stereotypies. This information is useful for the clinician and family when planning support strategies and interventions.

Development of a video-based evaluation tool in Rett syndrome.

This paper describes the development of a video-based evaluation tool for use in Rett syndrome (RTT). Components include a parent-report checklist, and video filming and coding protocols that contain items on eating, drinking, communication, hand function and movements, personal care and mobility. Ninety-seven of the 169 families who initially agreed to participate returned a videotape within 8 months of the first request. Subjects whose videos were returned had a similar age profile to those who did not provide a video but were more likely to have classical than atypical RTT. Evidence of the content and social validity and inter-rater reliability on 11 videos is provided. Video may provide detailed, objective assessment of function and behaviour in RTT.

Describing the phenotype in Rett syndrome using a population database.

BACKGROUND: Mutations in the MECP2 gene have been recently identified as the cause of Rett syndrome, prompting research into genotype-phenotype relations. However, despite these genetic advances there has been little descriptive epidemiology of the full range of phenotypes. AIMS: To describe the variation in phenotype in Rett syndrome using four different scales, by means of a population database. METHODS: Using multiple sources of ascertainment including the Australian Paediatric Surveillance Unit, the development of an Australian cohort of Rett syndrome cases born since 1976 has provided the first genetically characterised population based study of Rett syndrome. Follow up questionnaires were administered in 2000 to families and used to provide responses for items in four different severity scales. RESULTS: A total of 199 verified cases of Rett syndrome were reported between January 1993 and July 2000; 152 families provided information for the follow up study. The mean score using the Kerr scale was 22.9 (SD 4.8) and ranged from 20.5 in those under 7 years to 24.2 in those over 17 years. The mean Percy score was 24.9 (SD 6.6) and also increased with age group from 23.0 to 26.9. The mean Pineda score was 16.3 (SD 4.5) and did not differ by age group. The mean WeeFIM was 29.0 (SD 11.9), indicating extreme dependence, and ranged from 18 to 75. CONCLUSION: We have expanded on the descriptive epidemiology of Rett syndrome and shown different patterns according to the severity scale selected. Although all affected children are severely functionally dependent, it is still possible to identify some variation in ability, even in children with identified MECP2 mutations.

Functional status of school-aged children with Down syndrome.

OBJECTIVE: To field test, in questionnaire format, the Functional Independence Measure for Children (WeeFIM, a schedule usually administered by interview) on parents of a cohort of school-aged children with Down syndrome. METHODS: The parents of 211 Western Australian children with Down syndrome participated in the present study, representing 79.9% of all children with Down syndrome in the State. Subjects were identified using two sources: (i) the Birth Defects Registry; and (ii) the Disability Services Commission. RESULTS: The total WeeFIM score was 106.2 +/- 17.0 (mean +/- SD) out of a possible 126. Girls scored higher than boys (108.6 vs 103.6; P = 0.05). Scores increased across all age groups (P < 0.0001), even relative to normative data. Performance was strongest in the transfer and locomotion domains and weakest in social cognition. CONCLUSION: We found that severe functional limitations are rare in school-aged children with Down syndrome. Some support and supervision are required for complex self-care, communication and social skill tasks. This study demonstrates the feasibility of using the WeeFIM for collecting population survey data in children with developmental disability. This may be useful for the longitudinal tracking of such populations, as well as the monitoring of response to interventions.

Newborn screening compared to clinical identification of biochemical genetic disorders.

A group of 28 patients with inherited metabolic disease (homocystinuria galactosaemia, maple syrup urine disease and biotinidase deficiency) diagnosed by screening were compared with a group of 17 similar patients identified clinically. The rate of hospitalization was similar for the two groups. The patients diagnosed clinically showed a higher incidence of mental retardation and their parents experienced greater stress and found greater difficulty in meeting their child's needs.

Functional status, medical impairments, and rehabilitation resources in 84 females with Rett syndrome: a snapshot across the world from the parental perspective.

PURPOSE: Rett syndrome is a neurological disorder almost exclusively affecting females. Information on its genetic basis has recently become available. However there is little information on the burden and impact of this disorder on the family despite the apparent variability in phenotype. The purpose of this study was to obtain information on the burden and impact of Rett syndrome by examining the functional abilities, medical needs and use of medical, therapy and accommodation services in the sample. METHOD: We used the internet to access an opportunistic sample of parents of 86 females with Rett syndrome. Data on functional status (using the Wee FIM in questionnaire format) morbidity patterns and use of services were collected. RESULTS: The response indicated that the instrument used would be appropriate for tracking these parameters in a population-based cohort. Subjects with Rett syndrome in this pilot sample were completely or partially dependent in all functional domains and significantly more so than children with Down syndrome. CONCLUSION: The complexity of dependency with need for quality medical surveillance throughout adolescence and adulthood requires accessible centres of excellence linking families and skilled professionals. We plan to use this instrument to obtain a more comprehensive profile of the health, functioning and service use of a total population of children with Rett syndrome.

Extreme prematurity and school outcomes.

The purpose of this study was to assess the impact of extreme prematurity on three global measures of school outcomes. Using a matched cohort design, exposed infants comprised all surviving singleton infants < or = 28 weeks gestation born at one regional neonatal intensive care hospital between 1983 and 1986 (n = 132). Unexposed infants comprised randomly selected full-term infants (> or = 37 weeks gestation) frequency matched on date of birth, zip code and health insurance. All children were selected from a regional tertiary children's centre serving western New York population. Standardised telephone interviews elicited information on grade repetition, special education placement and use of school-based services. Unconditional logistic regression was used to estimate odds ratios (OR) and corresponding 95% confidence intervals (CI) adjusted for potential confounders for children without major handicaps. Extreme prematurity was associated with a significant increase in risk of grade repetition (OR = 3.22; 95% CI = 1.63, 6.34), special education placement (OR = 3.16; 95% CI = 1.14, 8.76) and use of school-based services (OR = 4.56; 95% CI = 1.82, 11.42) in comparison with children born at term, even after controlling for age, race, maternal education, foster care placement and the matching factors. These findings suggest that survivors of extreme prematurity remain at risk of educational underachievement.

Severity of neonatal retinopathy of prematurity is predictive of neurodevelopmental functional outcome at age 5.5 years. Behalf of the Cryotherapy for Retinopathy of Prematurity Cooperative Group.

OBJECTIVE: The purpose of this study was to assess the relation between neonatal retinopathy of prematurity (ROP) in very low birth weight infants and neurodevelopmental function at age 5.5 years. METHODS: Longitudinal follow-up of children occurred in 2 cohorts of the Multicenter Cryotherapy for Retinopathy of Prematurity Study. The extended natural history cohort followed 1199 survivors of <1251 g birth weight from 5 centers. The threshold randomized cohort (ThRz) followed 255 infants <1251 g from 23 centers who developed threshold ROP and who consented to cryotherapy to not more than 1 eye. At 5.5 years both cohorts had ophthalmic and acuity testing and neurodevelopmental functional status determined with the Functional Independence Measure for Children (WeeFIM). RESULTS: Evaluations were completed on 88.7% of the extended natural history cohort; 87% had globally normal functional skills (WeeFIM: >95). As ROP severity increased, rates of severe disability increased from 3.7% among those with no ROP, to 19.7% of those with threshold ROP. Multiple logistic regression analysis demonstrated that better functional status was associated with favorable visual acuity, favorable 2-year neurological score, absence of threshold ROP, having private health insurance, and black race. Evaluations were completed on 87.4% of the ThRz children. In each functional domain, the 134 children with favorable acuity in their better eye had fewer disabilities than did the 82 children with unfavorable acuity: self-care disability 25.4% versus 76.8%, continency disability 4.5% versus 50.0%, motor disability 5.2% versus 42.7%, and communicative-social cognitive disability 22.4% versus 65.9%, respectively. CONCLUSION: Severity of neonatal ROP seems to be a marker for functional disability at age 5. 5 years among very low birth weight survivors. High rates of functional limitations in multiple domains occur in children who had threshold ROP, particularly if they have unfavorable visual acuity.

The WeeFIM instrument: its utility in detecting change in children with developmental disabilities.

OBJECTIVE: To examine the utility of the WeeFIM instrument ("WeeFIM") in detecting changes in the functional status of children with disability. DESIGN: Prospective longitudinal design with correlation and responsiveness analysis. SETTING: Three facilities providing services to children with developmental disabilities in western New York State. PARTICIPANTS: Two hundred five children (72 girls, 133 boys) with identified medical disabilities receiving special services were administered the WeeFIM. Subjects ranged in age from 11 to 87 months and came from diverse socioeconomic and ethnic backgrounds. Scores for 174 children were available for 3 administrations performed over a 1-year period. MAIN OUTCOME MEASURES: The responsiveness of the WeeFIM instrument was examined using 5 statistical procedures: Reliability Change Index, Proportional Change Index, effect size, standardized response means, and paired t tests. RESULTS: All 5 indexes of responsiveness indicated statistically significant (p < .05) or reliable changes over time. The transfer subscale of the WeeFIM showed a skewed distribution that affected the results for some responsiveness indexes. The advantage, limitations, and assumptions of the responsiveness indexes are described and graphic examples of change over time are presented to validate the responsiveness of the WeeFIM instrument. CONCLUSION: The WeeFIM instrument showed the ability to document change in functional abilities over a 1-year period in children with chronic disabilities.

Functional limitations and key indicators of well-being in children with disability.

OBJECTIVES: To compare measures of well-being in children with and without different types and severity of limitations. DESIGN: Nationally representative data for American children aged 5 to 17 years were drawn from the 1994 and 1995 National Health Interview Surveys on Disability (NHIS-D) (N = 41,300) and the Year 2000 Health Supplement to the 1994 NHIS-D (N = 9530). Family resources, safety, health status, and health access were measures of environment. The presence and severity of limitations were measured in the domains of mobility, self-care, communication, and learning. RESULTS: Children with functional limitations were more likely to live in families with limited resources and have greater exposure to secondhand smoke, less access to health care, and lower health status. Children with a limitation were not less likely to have a regular source of medical care, but they more often were delayed or prevented from getting necessary health care due to cost or insurance. CONCLUSIONS: Standard measures of child well-being were appropriate for children with functional limitations and showed their unfavorable situations. Children with functional limitations more often have unfavorable family resources, less healthy home environments, poorer health status, and less health service access than other children, making them more susceptible to developmental difficulties beyond those difficulties associated with the challenges of their specific functional limitations.

Images of the phonon propagation across twist-bonded crystals.

We investigate identical but twist-bonded crystals using phonon imaging techniques. As in homogeneous crystals, very anisotropic flux patterns are observed. However, the shape of the pattern depends dramatically on the respective twist angle. The observed phonon images in wafer bonded GaAs/GaAs and Si/Si samples are essentially consistent with the predictions of the acoustic mismatch model for defect-free interfaces, with the exception of GaAs wafers twist bonded at a 45 degrees angle where modes with large shear stress are missing, which indicates strong dislocation scattering.

Functional outcomes in self-care, mobility, communication, and learning in extremely low-birth weight infants.

Gaps have existed in specifying degrees of severity of cerebral palsy assessment of self-care and communicative competencies, and specifying age-appropriate preschool educational and behavioral competencies. Imbedded in the concept of measuring functional status is the interaction between health and neurologic impairments, developmental challenges and competencies, family resources and disadvantages, and the child's current status. In reviewing historic outcomes of severe ROP over the past 40 years, it was noted that severe ROP caused blindness in 2% to 11% of survivors. There was a constant observation that approximately 50% of severe ROP survivors with blindness had multiple functional and developmental challenges beyond blindness alone. Similarly, in reviewing outcomes of cerebral palsy, it is imperative to describe the severity of cerebral palsy and functional consequences in motor, selfcare, communication, and learning. The reason to measure the functional status of children with neurodevelopmental impairments before first grade is that the degrees of severity of these disorders can be specified before attending school with peers. Subtler aspects of neurodevelopmental impairments need to assess impact on literacy, information learning, written language, social competencies with peers, and recreational and community participation. In this way, we can understand the vulnerabilities and resiliences of children and families of VLBW and ELBW status. This is a critical step in understanding long-term quality of life and independent living issues. In addition, our efforts can address those factors and pathways whereby multiple disabilities and multiple functional limitations cluster. Our biomedical intervention can prioritize strategies that lessen severe multiple disabilities and simultaneously support families, when despite our best efforts functional challenges are life long.