Social cognition, emotion regulation and social competence in classical galactosemia patients without intellectual disability.

OBJECTIVE: Classical galactosemia (CG) is an inborn error of galactose metabolism. Many CG patients suffer from long-term complications including poor cognitive functioning. There are indications of social dysfunction but limited evidence in the literature. Therefore, this study aims to improve our understanding of social competence in CG by investigating social cognition, neurocognition and emotion regulation. METHODS: A comprehensive (neuro)psychological test battery, including self and proxy questionnaires, was administered to CG patients without intellectual disability. Social cognition was assessed by facial emotion recognition, Theory of Mind and self-reported empathy. Standardised results were compared to normative data of the general population. RESULTS: Data from 23 patients (aged 8-52) were included in the study. On a group level, CG patients reported satisfaction with social roles and no social dysfunction despite the self-report of lower social skills. They showed deficits in all aspects of social cognition on both performance tests (emotion recognition and Theory of Mind) and self-report questionnaires (empathy). Adults had a lower social participation than the general population. Parents reported lower social functioning, less adaptive emotion regulation and communication difficulties in their children. Individual differences in scores were present. CONCLUSION: This study shows that CG patients without intellectual disability are satisfied with their social competence, especially social functioning. Nevertheless, deficits in social cognition are present in a large proportion of CG patients. Due to the large variability in scores and discrepancies between self- and proxy-report, an individually tailored, comprehensive neuropsychological assessment including social cognition is advised in all CG patients. Treatment plans need to be customised to the individual patient.

Risk factors for neurocognitive impairment and the relation with structural brain abnormality in children and young adults with severe chronic kidney disease.

BACKGROUND: Severe chronic kidney disease (CKD) in children and young adults has shown to be associated with abnormal brain development, which may contribute to neurocognitive impairments. We aimed to investigate risk factors for neurocognitive impairment and investigate the relation with structural brain abnormalities in young severe CKD patients. METHODS: This cross-sectional study includes 28 patients with severe CKD (eGFR < 30), aged 8-30 years (median 18.5 years), on different treatment modalities (pre-dialysis [n = 8], dialysis [n = 8], transplanted [n = 12]). We assessed neurocognitive functioning using a comprehensive test battery and brain structure by magnetic resonance imaging metrics of brain volume and white matter integrity (fractional anisotropy [FA] and mean diffusivity [MD] measured with diffusion tensor imaging). Multivariate regression and mediation analyses were performed between clinical CKD parameters, brain structure, and neurocognitive outcome. RESULTS: A combination of risk factors (e.g., longer time since kidney transplantation, longer dialysis duration and late CKD onset) was significantly associated with lower intelligence and/or worse processing speed and working memory. Lower FA in a cluster of white matter tracts was associated with lower intelligence and mediated the relation between clinical risk factors and lower intelligence. CONCLUSIONS: Young severe CKD patients with a prolonged duration of kidney replacement therapy, either dialysis or transplantation are at particular risk for impairments in intelligence, processing speed, and working memory. Disrupted white matter integrity may importantly contribute to these neurocognitive impairments. Prospective, longitudinal studies are needed to elucidate the mechanisms involved in CKD and treatment that affect white matter integrity and neurocognitive outcome in young patients. A higher resolution version of the Graphical abstract is available as Supplementary information.

Neurocognitive, Psychosocial, and Quality of Life Outcomes After Multisystem Inflammatory Syndrome in Children Admitted to the PICU.

OBJECTIVES: To investigate neurocognitive, psychosocial, and quality of life (QoL) outcomes in children with Multisystem Inflammatory Syndrome in Children (MIS-C) seen 3-6 months after PICU admission. DESIGN: National prospective cohort study March 2020 to November 2021. SETTING: Seven PICUs in the Netherlands. PATIENTS: Children with MIS-C (0-17 yr) admitted to a PICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Children and/or parents were seen median (interquartile range [IQR] 4 mo [3-5 mo]) after PICU admission. Testing included assessment of neurocognitive, psychosocial, and QoL outcomes with reference to Dutch pre-COVID-19 general population norms. Effect sizes (Hedges' g ) were used to indicate the strengths and clinical relevance of differences: 0.2 small, 0.5 medium, and 0.8 and above large. Of 69 children with MIS-C, 49 (median age 11.6 yr [IQR 9.3-15.6 yr]) attended follow-up. General intelligence and verbal memory scores were normal compared with population norms. Twenty-nine of the 49 followed-up (59%) underwent extensive testing with worse function in domains such as visual memory, g = 1.0 (95% CI, 0.6-1.4), sustained attention, g = 2.0 (95% CI 1.4-2.4), and planning, g = 0.5 (95% CI, 0.1-0.9). The children also had more emotional and behavioral problems, g = 0.4 (95% CI 0.1-0.7), and had lower QoL scores in domains such as physical functioning g = 1.3 (95% CI 0.9-1.6), school functioning g = 1.1 (95% CI 0.7-1.4), and increased fatigue g = 0.5 (95% CI 0.1-0.9) compared with population norms. Elevated risk for posttraumatic stress disorder (PTSD) was seen in 10 of 30 children (33%) with MIS-C. Last, in the 32 parents, no elevated risk for PTSD was found. CONCLUSIONS: Children with MIS-C requiring PICU admission had normal overall intelligence 4 months after PICU discharge. Nevertheless, these children reported more emotional and behavioral problems, more PTSD, and worse QoL compared with general population norms. In a subset undergoing more extensive testing, we also identified irregularities in neurocognitive functions. Whether these impairments are caused by the viral or inflammatory response, the PICU admission, or COVID-19 restrictions remains to be investigated.

Internalizing problems before and during the COVID-19 pandemic in independent samples of Dutch children and adolescents with and without pre-existing mental health problems.

The aim of the study was to assess internalizing problems before and during the pandemic with data from Dutch consortium Child and adolescent mental health and wellbeing in times of the COVID-19 pandemic, consisting of two Dutch general population samples (GS) and two clinical samples (CS) referred to youth/psychiatric care. Measures of internalizing problems were obtained from ongoing data collections pre-pandemic (NGS = 35,357; NCS = 4487) and twice during the pandemic, in Apr-May 2020 (NGS = 3938; clinical: NCS = 1008) and in Nov-Dec 2020 (NGS = 1489; NCS = 1536), in children and adolescents (8-18 years) with parent (Brief Problem Monitor) and/or child reports (Patient-Reported Outcomes Measurement Information System®). Results show that, in the general population, internalizing problems were higher during the first peak of the pandemic compared to pre-pandemic based on both child and parent reports. Yet, over the course of the pandemic, on both child and parent reports, similar or lower levels of internalizing problems were observed. Children in the clinical population reported more internalizing symptoms over the course of the pandemic while parents did not report differences in internalizing symptoms from pre-pandemic to the first peak of the pandemic nor over the course of the pandemic. Overall, the findings indicate that children and adolescents of both the general and clinical population were affected negatively by the pandemic in terms of their internalizing problems. Attention is therefore warranted to investigate long-term effects and to monitor if internalizing problems return to pre-pandemic levels or if they remain elevated post-pandemic.

Structural brain abnormalities in children and young adults with severe chronic kidney disease.

BACKGROUND: The pathophysiology of neurological dysfunction in severe chronic kidney disease (CKD) in children and young adults is largely unknown. We aimed to investigate brain volumes and white matter integrity in this population and explore brain structure under different treatment modalities. METHODS: This cross-sectional study includes 24 patients with severe CKD (eGFR < 30) aged 8-30 years (median = 18.5, range = 9.1-30.5) on different therapy modalities (pre-dialysis, n = 7; dialysis, n = 7; transplanted, n = 10) and 21 healthy controls matched for age, sex, and parental educational level. Neuroimaging targeted brain volume using volumetric analysis on T1 scans and white matter integrity with tract-based spatial statistics and voxel-wise regression on diffusion tensor imaging (DTI) data. RESULTS: CKD patients had lower white matter integrity in a widespread cluster of primarily distal white matter tracts compared to healthy controls. Furthermore, CKD patients had smaller volume of the nucleus accumbens relative to healthy controls, while no evidence was found for abnormal volumes of gray and white matter or other subcortical structures. Longer time since successful transplantation was related to lower white matter integrity. Exploratory analyses comparing treatment subgroups suggest lower white matter integrity and smaller volume of the nucleus accumbens in dialysis and transplanted patients relative to healthy controls. CONCLUSIONS: Young CKD patients seem at risk for widespread disruption of white matter integrity and to some extent smaller subcortical volume (i.e., nucleus accumbens). Especially patients on dialysis therapy and patients who received a kidney transplant may be at risk for disruption of white matter integrity and smaller volume of the nucleus accumbens.

Convergent validity of functional communication tools and spoken language comprehension assessment in children with cerebral palsy.

BACKGROUND: The majority of children with cerebral palsy (CP) experience challenges in functional communication from a young age. A pivotal aspect of functional communication is language comprehension. A variety of classification systems and questionnaires are available to classify and describe functional communication skills in children with CP. A better understanding of the convergent validity of (subsections of) these tools, as well as their relationship with spoken language comprehension, will be valuable in both clinical practice and research. AIMS: To investigate the convergent validity of (subsections of) functional communication tools and the relationship with spoken language comprehension in children with CP. METHODS & PROCEDURES: Cross-sectional data on 138 children were subdivided into three developmental stages based on (Dutch) educational phases: ages 18 months-3;11y (n = 59), 4;0-5;11 years (n = 37) and 6;0-8;11 years (n = 42). The following functional communication tools were used to classify and describe functional communication: Communication Function Classification System (CFCS), subscales of the Caregivers Priorities and Child Health Index of Life with Disabilities-Dutch Version (CPCHILD-DV) and the Focus on Communication Under Six-34 (FOCUS-34) questionnaire. Spoken language comprehension was assessed with the Computer-Based instrument for Low motor Language Testing (C-BiLLT). Correlations between the functional communication tools, and with the C-BiLLT, were calculated using Pearson's and Spearman's correlation coefficients. It was hypothesized a priori that correlations of at least 0.60 suggest good convergent validity. OUTCOMES & RESULTS: At all developmental stages, a significant ordered decreasing tendency of communication outcomes was found across CFCS levels; lower CFCS levels were associated with lower scores on the CPCHILD-DV and FOCUS-34, and with a lower level of spoken language comprehension (C-BiLLT). Correlation coefficients of the functional communication tools exceeded 0.60 at all developmental stages. Correlations between C-BiLLT raw scores and the functional communication tools varied between 0.351 and 0.591 at developmental stage 18 months-3;11 years, between 0.781 and 0.897 at developmental stage 4;0-5;11 years, and between 0.635 and 0.659 at developmental stage 6;0-8;11 years. CONCLUSIONS & IMPLICATIONS: The functional communication tools assessed in this study showed convergent validity at all developmental stages. The CFCS, currently most widely used in paediatric rehabilitation, is adequate in the classification of functional communication. However, for more detailed clinical goal setting and evaluation of change in functional communication, the additional use of FOCUS-34 or CPCHILD-DV is recommended. WHAT THIS PAPER ADDS: What is already known on the subject A range of functional communication tools are available that help describe and classify functional communication in children with CP. These include the CFCS, subsections of CPCHILD-DV and FOCUS-34. The CFCS classifies functional communication in daily life with familiar and unfamiliar partners. Specific subsections of the CPCHILD-DV and FOCUS-34 include items that pertain to communicative participation. The innovative C-BiLLT provides a standardized method to assess spoken language comprehension in children with CP and significant motor impairments. What this paper adds to existing knowledge In the present study, convergent validity was confirmed between CFCS and specific subsections of the CPCHILD-DV and FOCUS-34. Correlations between these functional communication tools and the C-BiLLT were moderate to strong. What are the potential or actual clinical implications of this work? For clinical and research purposes (for instance, accurate prescription of augmentative and alternative communication-AAC), healthcare and educational professionals together with parents need to know how functional communication tools converge and how functional communication levels relate to the comprehension of spoken language. The CFCS provides a valid classification of functional communication abilities in children with CP. However, to measure change in functional communication and to evaluate treatment outcomes, use of additional functional communication tools such as the CPCHILD-DV and FOCUS-34 is recommended. When discrepancies are found between communicative abilities and spoken language comprehension, it is strongly recommended that valid tools are used in a more detailed examination of the child's spoken language comprehension skills and functional communication.

The impact of lockdown during the COVID-19 pandemic on mental and social health of children and adolescents.

PURPOSE: During the COVID-19 pandemic in the Netherlands, governmental regulations resulted in a lockdown for adults as well as children/adolescents. Schools were closed and contact with other people was limited. In this cross-sectional, population-based study, we aimed to investigate the mental/social health of children/adolescents during COVID-19 lockdown. METHODS: Two representative samples of Dutch children/adolescents (8-18 years) before COVID-19 (2018, N = 2401) and during lockdown (April 2020, N = 844) were compared on the Patient-Reported Outcomes Measurement Information System (PROMIS) domains: global health, peer relationships, anxiety, depressive symptoms, anger, sleep-related impairment by linear mixed models and calculating relative risks (RR (95% CI)) for the proportion of severe scores. Variables associated with worse mental/social health during COVID-19 were explored through multivariable regression models. The impact of COVID-19 regulations on the daily life of children was qualitatively analyzed. RESULTS: Participants reported worse PROMIS T-scores on all domains during COVID-19 lockdown compared to before (absolute mean difference range 2.1-7.1 (95% CI 1.3-7.9). During lockdown, more children reported severe Anxiety (RR = 1.95 (1.55-2.46) and Sleep-Related Impairment (RR = 1.89 (1.29-2.78) and fewer children reported poor Global Health (RR = 0.36 (0.20-0.65)). Associated factors with worse mental/social health were single-parent family, ≥ three children in the family, negative change in work situation of parents due to COVID-19 regulations, and a relative/friend infected with COVID-19. A large majority (> 90%) reported a negative impact of the COVID-19 regulations on daily life. CONCLUSION: This study showed that governmental regulations regarding lockdown pose a serious mental/social health threat on children/adolescents that should be brought to the forefront of political decision-making and mental healthcare policy, intervention, and prevention.

Neurocognitive Development in Perinatally Human Immunodeficiency Virus-infected Adolescents on Long-term Treatment, Compared to Healthy Matched Controls: A Longitudinal Study.

BACKGROUND: A cross-sectional analysis of the Neurological, cOgnitive and VIsual performance in hiv-infected Children cohort showed significant cognitive impairment in combination antiretroviral therapy (cART)-treated, perinatally human immunodeficiency virus (HIV)-infected adolescents (PHIV+) compared to age-, sex-, ethnicity- and socioeconomic status (SES)-matched HIV-negative controls (HIV-). In this longitudinal study, we compared cognitive development in the same adolescents over time. METHODS: We repeated the standardized cognitive test battery after a mean of 4.6 years (standard deviation 0.3). In participants who completed both assessments, we compared cognitive trajectories between groups in the domains of intelligence quotient (IQ), processing speed, working memory, executive functioning, learning ability, and visual-motor function, using linear mixed models. We explored associations with disease- and treatment-related factors and used multivariate normative comparison (MNC) to determine the prevalence of cognitive impairment. RESULTS: There were 21 PHIV+ and 23 HIV- participants that completed 2 assessments and were similar concerning age, sex, ethnicity, and SES. Compared to HIV- participants, in PHIV+ participants the IQ score increased significantly more over time (group*time 6.01, 95% confidence interval [CI] 1.5-10.50; P = .012), whereas executive functioning decreased significantly more (group*time -1.43 z score, 95% CI -2.12 to -0.75; P < .001), resulting in the disappearance and appearance of significant differences. Processing speed, working memory, learning ability, and visual-motor function trajectories were not statistically different between groups. Univariately, those who had started cART at an older age deviated more in executive functioning (-0.13 z score, 95% CI -0.24 to -0.02; P = .043). The prevalence of cognitive impairments by MNC was similar in both groups, at both time points. CONCLUSIONS: The cART-treated PHIV+ adolescents appeared to have similar global cognitive development, compared to their healthy peers. Executive functioning trajectory appears to deviate, potentially explained by earlier brain damage.

Factors associated with spoken language comprehension in children with cerebral palsy: a systematic review.

AIM: To identify factors that are relevant for spoken language comprehension in children with cerebral palsy (CP), following the International Classification of Functioning, Disability and Health - Children and Youth (ICF-CY) framework. METHOD: A systematic literature search was conducted using the electronic literature databases PubMed, Embase, PsycInfo, and Cochrane Library, from January 1967 to December 2019. Included studies involved children with CP, results regarding spoken language comprehension, and analysis of at least one associated factor. Factors were classified within ICF-CY domains. RESULTS: Twenty-one studies met inclusion criteria. Factors in the ICF-CY domains of body functions and structure were most frequently reported. White brain matter abnormalities, motor type, functional mobility, and intellectual functioning appear to be relevant factors in spoken language comprehension in CP. Factors in the domain of activities and participation, as well as contextual factors, have rarely been studied in the context of spoken language comprehension in CP. INTERPRETATION: Most factors known to be important for spoken language comprehension in typically developing children and/or known to be susceptible to change by interventions are understudied in CP.

Pediatric Perceived Cognitive Functioning: Psychometric Properties and Normative Data of the Dutch Item Bank and Short Form.

OBJECTIVE: With increasing numbers of children growing up with conditions that are associated with acquired brain injury, efficient neuropsychological screening for cognitive deficits is pivotal. Brief self-report measures concerning daily complaints can play an important role in such screening. We translated and adapted the pediatric perceived cognitive functioning (PedsPCF) self- and parent-report item bank to Dutch. This study presents (1) psychometric properties, (2) a new short form, and (3) normative data for the short form. METHODS: A general population sample of children and parents was recruited. Dimensionality of the PedsPCF was assessed using confirmatory factor analyses and exploratory bifactor analyses. Item response theory (IRT) modeling was used to evaluate model fit of the PedsPCF, to identify differential item functioning (DIF), and to select items for the short form. To select short-form items, we also considered the neuropsychological content of items. RESULTS: In 1441 families, a parent and/or child participated (response rate 66% at family level). Assessed psychometric properties were satisfactory and the predominantly unidimensional factor structure of the PedsPCF allowed for IRT modeling using the graded response model. One item showed meaningful DIF. For the short form, 10 items were selected. CONCLUSIONS: In this first study of the PedsPCF outside the United States, studied psychometric properties of the translated PedsPCF were satisfactory, and allowed for IRT modeling. Based on the IRT analyses and the content of items, we proposed a new 10-item short form. Further research should determine the relation of PedsPCF outcomes with neurocognitive measures and its ability to facilitate neuropsychological screening in clinical practice.