Sensory Processing in Children and Adolescents with Neurofibromatosis Type 1.

Despite the evidence of elevated autistic behaviors and co-occurring neurodevelopmental difficulties in many children with neurofibromatosis type 1 (NF1), we have a limited understanding of the sensory processing challenges that may occur with the condition. This study examined the sensory profile of children and adolescents with NF1 and investigated the relationships between the sensory profiles and patient characteristics and neuropsychological functioning. The parent/caregivers of 152 children with NF1 and 96 typically developing children completed the Sensory Profile 2 (SP2), along with standardized questionnaires assessing autistic behaviors, ADHD symptoms, internalizing symptoms, adaptive functioning, and social skills. Intellectual functioning was also assessed. The SP2 data indicated elevated sensory processing problems in children with NF1 compared to typically developing children. Over 40% of children with NF1 displayed differences in sensory registration (missing sensory input) and were unusually sensitive to and unusually avoidant of sensory stimuli. Sixty percent of children with NF1 displayed difficulties in one or more sensory modalities. Elevated autistic behaviors and ADHD symptoms were associated with more severe sensory processing difficulties. This first detailed assessment of sensory processing, alongside other clinical features, in a relatively large cohort of children and adolescents with NF1 demonstrates the relationships between sensory processing differences and adaptive skills and behavior, as well as psychological well-being. Our characterization of the sensory profile within a genetic syndrome may help facilitate more targeted interventions to support overall functioning.

Cognitive and academic outcomes in children with chronic kidney disease.

BACKGROUND: Few data exist on the cognitive and academic functioning of children with chronic kidney disease (CKD) over the trajectory of their illness. We aimed to determine the association between CKD stages and cognitive and academic performance in children over time. METHODS: We included 53 participants (aged 6-18 years) with CKD stages 1-5 (n = 37), on dialysis (n = 3), or with functioning kidney transplant (n = 22) from three units in Australia from 2015 to 2019. Participants undertook a series of psychometric tests and were invited for repeated assessments annually. We used linear regression and linear mixed models to investigate the effect of CKD stage, adjusted for socioeconomic status. RESULTS: At baseline, full-scale intelligence quotient (FSIQ) (95%CI) of children on kidney replacement therapy (KRT) was in the low average range (87: 78, 96) and average (101: 95, 108) for children with CKD 1-5. Mean (95%CI) FSIQ, word reading, numerical operations, and spelling scores for children on KRT were 14.3 (- 25.3, - 3.3), 11 (- 18.5, - 3.6), 8.5 (- 17.6, 0.76), and 10 (- 18.6, - 1.3) points lower than children with CKD Stages 1-5. Spelling and numerical operations scores declined by 0.7 (- 1.4, - 0.1) and 1.0 (- 2.0, 0.2) units per year increase in age, regardless of CKD stage. CONCLUSIONS: Children treated with KRT have low average cognitive abilities and lower academic performance for numeracy and literacy compared to both children with CKD 1-5 and to the general population. However, the rate of decline in academic performance over time is similar for children across the full spectrum of CKD. A higher resolution version of the Graphical abstract is available as Supplementary information.

Association between socioeconomic status and academic performance in children and adolescents with chronic kidney disease.

BACKGROUND: Lower socioeconomic status (SES) is associated with lower academic achievement; however, this relationship is understudied in children with chronic kidney disease (CKD). This study examined the relationship between SES and academic performance in children and adolescents with CKD. METHODS: A total of 377 participants aged 6-18 years with CKD stages 1-5 (n = 199), on dialysis (n = 43) or with a kidney transplant (n = 135) were recruited. Five SES measures and a composite SES index were examined for associations with parent-rated average or above average academic performance in numeracy and literacy using multivariable logistic regression. RESULTS: Participants' median age was 12.6 years (IQR 8.9-15.5). Adjusted odds ratios (aOR) (95%CI) for better performance in numeracy and literacy, respectively, were 0.71 (0.44-1.15) and 0.75 (0.45-1.23) for children whose caregivers had lower educational attainment; 0.46 (0.26-0.80) and 0.53 (0.30-0.93) for lower household income; 0.52 (0.32-0.85) and 0.44 (0.26-0.73) for caregivers who were unemployed; 0.68 (0.41-1.12) and 0.59 (0.35-1.00) for caregivers with poor self-rated financial status; and 0.93 (0.53-1.64) and 1.00 (0.56-1.79) for caregivers who did not own their own home. Compared with the highest SES index quartile, the aORs for better performance by SES quartile in descending order were 1.24 (0.60-2.54), 0.76 (0.37-1.58), and 0.39 (0.18-0.86) for numeracy and 0.88 (0.41-1.85), 0.77 (0.35-1.66), and 0.32 (0.14-0.72) for literacy. No interactions were identified between SES and CKD stage, child age, or gender. CONCLUSIONS: Across all CKD stages, children from lower SES families are less likely to perform well in literacy and numeracy than those from higher SES households. A higher resolution version of the Graphical abstract is available as Supplementary information.

Psychometric Properties and Factor Analysis of a Short Form of the Multidimensional Measure of Emotional Abuse.

The 28-item Multidimensional Measure of Emotional Abuse (MMEA) assesses four common forms of emotional abuse in intimate relationships and has been used extensively to study the development of intimate partner violence (IPV), the consequences of emotional abuse, and the outcomes of IPV interventions. The current study provides psychometric analyses of a shortened version of the MMEA using self-report data from a sample of men receiving treatment at a community-based relationship violence intervention program (RVIP; N = 467) and reports from their relationship partners (N = 252), and data from a sample of undergraduate students (N = 194) who reported on their own and their partners' abusive behavior. Theoretical and statistical considerations, including internal consistency after item deletion, were used to select items for the shortened version. In the clinic sample (for self- and partner reports) and in the undergraduate sample (for self-report only), the 16-item MMEA-Short Form (MMEA-SF) retains the 4-factor structure of the 28-item MMEA. In both samples and across reporting methods (self and partner), the 16-item MMEA-SF has good internal consistency, good concurrent validity with the Revised Conflict Tactics Scales (CTS2) psychological aggression subscale, and similar correlations with CTS2 physical assault subscale as the original 28-item MMEA version. The MMEA-SF can reduce assessment burden while maintaining good domain coverage and strong psychometric properties and will be an asset to researchers and practitioners who need a brief, multifaceted measure of emotional relationship abuse in both clinic and undergraduate samples.

Longer term outcomes following serogroup B invasive meningococcal disease.

AIM: To characterise the physical, psychological, and quality of life burden associated with serogroup B invasive meningococcal disease (IMD) in children. METHODS: Children aged up to 14 years at the time of serogroup B IMD, who were admitted to intensive care units of two tertiary paediatric hospitals in New South Wales, Australia between January 2009 and December 2013 were recruited. Children underwent clinical and neuropsychological assessments up to 6 years post-disease. RESULTS: Eleven children were assessed, with a median age of 16 months (range 4-46 months) at time of disease. The median follow-up time was 50 months (range 10-67 months). Seven (63.6%) cases had one or more long-term sequelae involving permanent and evolving physical disability. Three cases had ongoing medical conditions including two with seizures and one with ataxia and hypermetropia. Five required ongoing medical and allied health care. Other complications identified included anxiety, speech delay, low average full-scale IQ score (median 85, interquartile range 89-103) and borderline memory impairment. CONCLUSIONS: Serogroup B IMD is associated with significant long-term morbidity and burden on the child and family with substantial economic implications. The impact of this on the total cost of IMD needs to be further quantified, and better considered in vaccine cost-effectiveness analyses.

Social skills and autism spectrum disorder symptoms in children with neurofibromatosis type 1: evidence for clinical trial outcomes.

AIM: We examined key features of two outcome measures for social dysfunction and autism spectrum disorder traits, the Social Responsiveness Scale, Second Edition (SRS-2) and the Social Skills Improvement System - Rating Scales (SSIS-RS), in children with neurofibromatosis type 1 (NF1). The aim of the study was to provide objective evidence as to which behavioural endpoint should be used in clinical trials. METHOD: Cross-sectional behavioural and demographic data were pooled from four paediatric NF1 tertiary referral centres in Australia and the United States (N=122; 65 males, 57 females; mean age [SD] 9y 2mo [3y], range 3-15y). RESULTS: Distributions of SRS-2 and SSIS-RS scores were unimodal and both yielded deficits, with a higher proportion of severely impaired scores on the SRS-2 (16.4%) compared to the SSIS-RS (8.2%). Pearson's product-moment correlations revealed that both questionnaires were highly related to each other (r=-0.72, p<0.001) and to measures of adaptive social functioning (both p<0.001). Both questionnaires were significantly related to attention-deficit/hyperactivity disorder symptoms, but only very weakly associated with intelligence. INTERPRETATION: The SRS-2 and SSIS-RS capture social dysfunction associated with NF1, suggesting both may be suitable choices for assessing social outcomes in this population in a clinical trial. However, careful thought needs to be given to the nature of the intervention when selecting either as a primary endpoint. WHAT THIS PAPER ADDS: The Social Responsiveness Scale, Second Edition yielded a large deficit relative to population norms. The Social Skills Improvement System - Rating Scales yielded a moderate deficit relative to population norms. Both scales were highly correlated, suggesting that they are measuring a unitary construct.

Understanding autism spectrum disorder and social functioning in children with neurofibromatosis type 1: protocol for a cross-sectional multimodal study.

INTRODUCTION: Children with the single-gene disorder neurofibromatosis type 1 (NF1) appear to be at an increased risk for autism spectrum disorder (ASD) and exhibit a unique social-cognitive phenotype compared with children with idiopathic ASD. A complete framework is required to better understand autism in NF1, from neurobiological levels through to behavioural and functional outcomes. The primary aims of this study are to establish the frequency of ASD in children with NF1, examine the social cognitive phenotype, investigate the neuropsychological processes contributing to ASD symptoms and poor social functioning in children with NF1, and to investigate novel structural and functional neurobiological markers of ASD and social dysfunction in NF1. The secondary aim of this study is to compare the neuropsychological and neurobiological features of ASD in children with NF1 to a matched group of patients with idiopathic ASD. METHODS AND ANALYSIS: This is an international, multisite, prospective, cross-sectional cohort study of children with NF1, idiopathic ASD and typically developing (TD) controls. Participants will be 200 children with NF1 (3-15 years of age), 70 TD participants (3-15 years) and 35 children with idiopathic ASD (7-15 years). Idiopathic ASD and NF1 cases will be matched on age, sex and intelligence. All participants will complete cognitive testing and parents will rate their child's behaviour on standardised questionnaires. Neuroimaging will be completed by a subset of participants aged 7 years and older. Children with NF1 that screen at risk for ASD on the parent-rated Social Responsiveness Scale 2nd Edition will be invited back to complete the Autism Diagnostic Observation Scale 2nd Edition and Autism Diagnostic Interview-Revised to determine whether they fulfil ASD diagnostic criteria. ETHICS AND DISSEMINATION: This study has hospital ethics approval and the results will be disseminated through peer-reviewed publications and international conferences.

The association between socioeconomic disadvantage and parent-rated health in children and adolescents with chronic kidney disease-the Kids with CKD (KCAD) study.

OBJECTIVE: To determine the association of socioeconomic disadvantage and parent-rated health in children with chronic kidney disease (CKD). METHODS: A total of 377 children (aged 6-18 years) with CKD stages I-V (n = 199), on dialysis (n = 43), or with a kidney transplant (n = 135) were recruited from 2012 to 2016 in Australia and New Zealand. Associations of five socioeconomic status (SES) components and the global SES index with parent-rated health of the child were examined using adjusted logistic regression. RESULTS: The median age of participants was 12.6 years (interquartile range (IQR) 8.9-15.5). In the entire cohort, the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for poor parent-rated health were 1.85 (1.13-3.03) for lower household income, 1.78 (1.08-2.96) for families that did not own their own home, 2.50 (1.50-4.16) for caregivers who rated their financial status as poor, 0.84 (0.51-1.38) for lower educational attainment, and 1.68 (1.04-2.72) for children whose primary caregivers were unemployed. With reference to the highest global SES index quartile, adjusted ORs for poor parent-rated health in descending order were 1.49 (0.69-3.21), 2.11 (1.06-4.20), and 2.20 (1.09-4.46), respectively. The association between low SES and poor parent-rated health was modified by CKD stage, where lower global SES index was independently associated with poor parent-rated health in children with CKD stages I-V, but not children on dialysis or with kidney transplants (p = 0.04). CONCLUSIONS: Low SES is associated with poor parent-rated health in children with CKD stages I-V, but not children on dialysis and with kidney transplants.

More or less: Newlyweds' preferred and received social support, affect, and relationship satisfaction.

Matching theories of social support suggest that receiving the amount and type of support one prefers from one's romantic partner promotes more favorable affect and higher relationship satisfaction. Individuals who feel they are provided with less support from their partner than they desire (underprovision) generally experience less positive affect, more negative affect, and tend to be less satisfied in their relationships. However, research findings are mixed with regard to whether receiving more of a particular type of support from one's partner than one desires (overprovision) is associated with more favorable affect and higher relationship satisfaction. The purpose of the present study was to examine whether underprovision and overprovision of two theoretically important types of social support from spouses-emotional or informational support-were associated with more favorable affect and higher relationship satisfaction in a sample of newlywed couples. Participants were 114 newlywed couples. Data were analyzed using Actor-Partner Interdependence Moderation Models. Results suggested that receiving more emotional support was associated with more favorable affect and higher relationship satisfaction regardless of support preferences. Also, wives who received more informational support from their husbands had higher relationship satisfaction regardless of support preferences. In contrast to findings for relationship satisfaction, the association between informational support and affect were consistent with matching hypotheses. Husbands who experienced underprovision of informational support from their wives, experienced less favorable affect. In contrast, wives who experienced overprovision of informational support from their husbands experienced higher depressive symptoms. Implications for research, theory, and practice are discussed. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Preliteracy impairments in children with neurofibromatosis type 1.

AIM: This cross-sectional study aimed to examine the preliteracy abilities of young children with neurofibromatosis type 1 (NF1) and to identify which of these abilities best predicted conventional literacy (spelling). METHOD: Forty-two children with NF1 (23 males, 19 females; mean age [SD] 5y 6mo [6mo]) were compared with 32 unaffected children (15 males, 17 females; mean age [SD] 5y 4mo [6mo]). All children completed a comprehensive cognitive assessment including measures of phonological processing (phonological awareness, phonological memory, rapid automatic naming) and letter-sound knowledge. RESULTS: Children with NF1 performed significantly poorer than the comparison group across all cognitive and preliteracy domains, with specific weaknesses evident in phonological awareness (F1,68 =14.13, p<0.001, partial η2 =0.17), phonological memory (F1,68 =13.87, p<0.001, partial η2 =0.17), and letter-sound knowledge (F1,71 =5.65, p=0.020, partial η2 =0.07). Within the group with NF1 group, over a third of children demonstrated impairment in at least one phonological processing domain and the risk of phonological impairment was 5.60 times that of unaffected children. Children's letter-sound knowledge was the strongest predictor of conventional literacy (spelling). INTERPRETATION: This study establishes that preliteracy deficits are present and detectable in young children with NF1. As a result of the high incidence of preliteracy impairment, we recommend screening phonological awareness and letter-sound knowledge to identify risk of future learning disorders. WHAT THIS PAPER ADDS: Young children with neurofibromatosis type 1 are at elevated risk of preliteracy deficits. The most affected domains are phonological awareness and phonological memory. Letter-sound knowledge is the strongest predictor of conventional literacy (spelling).

Neurocognitive and Educational Outcomes in Children and Adolescents with CKD: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: Poor cognition can affect educational attainment, but the extent of neurocognitive impairment in children with CKD is not well understood. This systematic review assessed global and domain-specific cognition and academic skills in children with CKD and whether these outcomes varied with CKD stage. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Electronic databases were searched for observational studies of children with CKD ages 21 years old or younger that assessed neurocognitive or educational outcomes. Risk of bias was assessed using a modified Newcastle-Ottawa scale. We used random effects models and expressed the estimates as mean differences with 95% confidence intervals stratified by CKD stage. RESULTS: Thirty-four studies (25 cross-sectional, n=2095; nine cohort, n=991) were included. The overall risk of bias was high because of selection and measurement biases. The global cognition (full-scale intelligence quotient) of children with CKD was classified as low average. Compared with the general population, the mean differences (95% confidence intervals) in full-scale intelligence quotient were -10.5 (95% confidence interval, -13.2 to -7.72; all CKD stages, n=758), -9.39 (95% confidence interval, -12.6 to -6.18; mild to moderate stage CKD, n=582), -16.2 (95% confidence interval, -33.2 to 0.86; dialysis, n=23), and -11.2 (95% confidence interval, -17.8 to -4.50; transplant, n=153). Direct comparisons showed that children with mild to moderate stage CKD and kidney transplants scored 11.2 (95% confidence interval, 2.98 to 19.4) and 10.1 (95% confidence interval, -1.81 to 22.0) full-scale intelligence quotient points higher than children on dialysis. Children with CKD also had lower scores than the general population in executive function and memory (verbal and visual) domains. Compared with children without CKD, the mean differences in academic skills (n=518) ranged from -15.7 to -1.22 for mathematics, from -9.04 to -0.17 for reading, and from -14.2 to 2.53 for spelling. CONCLUSIONS: Children with CKD may have low-average cognition compared with the general population, with mild deficits observed across academic skills, executive function, and visual and verbal memory. Limited evidence suggests that children on dialysis may be at greatest risk compared with children with mild to moderate stage CKD and transplant recipients.

Developmental trajectories of young children with neurofibromatosis type 1: a longitudinal study from 21 to 40 months of age.

OBJECTIVE: To establish the developmental trajectory of young children with neurofibromatosis type 1 (NF1) during the first 4 years of life. STUDY DESIGN: In this longitudinal study, 39 children with NF1 and 39 controls were assessed with the Bayley Scales of Infant Development, Second Edition at 21 (time point 1, or T1) and 30 months (T2) of age, and the Wechsler Preschool and Primary Scale of Intelligence, Third Edition at 40 months (T3). Language was also assessed at T2 and T3. Parents rated their child's productive vocabulary at T1 and T2, and behavior at each time point. Linear mixed models were performed to examine cognitive development and behavior over time. Linear regressions were conducted to determine whether mental development and productive vocabulary at T1 or T2 predicted intellectual and language outcomes at T3. RESULTS: Over time, the NF1 group had significantly lower cognitive scores than controls. Parent ratings indicated no group differences in behavior at each time point. Earlier mental function significantly predicted later general intelligence. Earlier productive vocabulary was a significant predictor of later language skills. CONCLUSIONS: There are consistent differences over time in cognitive performance between children with NF1 and unaffected peers during the early childhood period. Earlier mental function and productive vocabulary are significant predictors of subsequent general intelligence and performance on language measures in NF1. This provides an opportunity for early identification and treatment for young children with NF1 who may show signs of impairments in these developmental domains.

Cognitive features that distinguish preschool-age children with neurofibromatosis type 1 from their peers: a matched case-control study.

OBJECTIVE: To examine the cognitive functioning of 40-month-old children with neurofibromatosis type 1 (NF1). STUDY DESIGN: In this case-control study, 43 children with NF1 and 43 comparison children (matched by age, sex, and maternal years of education) were assessed using the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Language, visual perception, preliteracy, and executive functioning were also examined. Parents completed questionnaires about their child's behavior. Group differences were examined using the paired-samples t test or the related Wilcoxon signed rank test. Conditional logistic regression was conducted to identify which cognitive variables predicted group membership (ie, NF1 or control). RESULTS: The NF1 group had significantly poorer general intelligence than matched comparisons. Preschool-age children with NF1 had significantly poorer language, visual perception, response inhibition, and preliteracy skills than comparison children. The Wechsler Preschool and Primary Scale of Intelligence, Third Edition, Object Assembly and Information subtests were significant predictors of group membership. Parent ratings indicated no group differences in behavior. CONCLUSIONS: After accounting for potentially confounding variables of age, sex, and maternal years of education, young children with NF1 have significantly poorer intellectual functioning, expressive language, and visual perception. These cognitive features that distinguish young children with NF1 from healthy peers can be detected in the preschool age group and are likely to impact on learning and performance during early school years. These areas should be targeted for intervention to maximize the developmental outcomes of young children with NF1.

Mental, motor, and language development of toddlers with neurofibromatosis type 1.

OBJECTIVE: To examine the mental, motor, and language development of toddlers with neurofibromatosis type 1 (NF1). STUDY DESIGN: In this cross-sectional study, 39 toddlers with NF1 (aged 21-30 months) and 42 age-matched control children were assessed using the Bayley Scales of Infant Development, Second Edition. Basic vocabulary was assessed with the language subtests from the Wechsler Preschool and Primary Scale of Intelligence, Third Edition. Parents completed questionnaires evaluating the children's expressive language, behavior, and executive functioning. The χ(2) test, independent t test, Mann-Whitney U test, and analysis of covariance were used to examine differences between the two groups. RESULTS: The toddlers with NF1 had significantly poorer mental and motor development than the control participants. Parental responses indicated that most of the children with NF1 had delayed language skills. No differences in behavior and executive functioning were noted between the two groups of children. CONCLUSIONS: Children with NF1 as young as age 30 months demonstrate early signs of mental, motor, and language difficulties. Age 2 years may be the appropriate time to perform an initial developmental assessment to identify mental, motor, and language impairments in children with NF1.