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.

Reliability of the Dutch-language version of the Communication Function Classification System and its association with language comprehension and method of communication.

AIM: The aims of this study were to determine the intra- and interrater reliability of the Dutch-language version of the Communication Function Classification System (CFCS-NL) and to investigate the association between the CFCS level and (1) spoken language comprehension and (2) preferred method of communication in children with cerebral palsy (CP). METHOD: Participants were 93 children with CP (50 males, 43 females; mean age 7y, SD 2y 6mo, range 2y 9mo-12y 10mo; unilateral spastic [n=22], bilateral spastic [n=51], dyskinetic [n=15], ataxic [n=3], not specified [n=2]; Gross Motor Function Classification System level I [n=16], II [n=14], III, [n=7], IV [n=24], V [n=31], unknown [n=1]), recruited from rehabilitation centres throughout the Netherlands. Because some centres only contributed to part of the study, different numbers of participants are presented for different aspects of the study. Parents and speech and language therapists (SLTs) classified the communication level using the CFCS. Kappa was used to determine the intra- and interrater reliability. Spearman's correlation coefficient was used to determine the association between CFCS level and spoken language comprehension, and Fisher's exact test was used to examine the association between the CFCS level and method of communication. RESULTS: Interrater reliability of the CFCS-NL between parents and SLTs was fair (r=0.54), between SLTs good (r=0.78), and the intrarater (SLT) reliability very good (r=0.85). The association between the CFCS and spoken language comprehension was strong for SLTs (r=0.63) and moderate for parents (r=0.51). There was a statistically significant difference between the CFCS level and the preferred method of communication of the child (p<0.01). Also, CFCS level classification showed a statistically significant difference between parents and SLTs (p<0.01). INTERPRETATION: These data suggest that the CFCS-NL is a valid and reliable clinical tool to classify everyday communication in children with CP. Preferably, professionals should classify the child's CFCS level in collaboration with the parents to acquire the most comprehensive information about the everyday communication of the child in various situations both with familiar and with unfamiliar partners.

Comprehension of spoken language in non-speaking children with severe cerebral palsy: an explorative study on associations with motor type and disabilities.

AIM: To assess spoken language comprehension in non-speaking children with severe cerebral palsy (CP) and to explore possible associations with motor type and disability. METHOD: Eighty-seven non-speaking children (44 males, 43 females, mean age 6y 8mo, SD 2y 1mo) with spastic (54%) or dyskinetic (46%) CP (Gross Motor Function Classification System [GMFCS] levels IV [39%] and V [61%]) underwent spoken language comprehension assessment with the computer-based instrument for low motor language testing (C-BiLLT), a new and validated diagnostic instrument. A multiple linear regression model was used to investigate which variables explained the variation in C-BiLLT scores. Associations between spoken language comprehension abilities (expressed in z-score or age-equivalent score) and motor type of CP, GMFCS and Manual Ability Classification System (MACS) levels, gestational age, and epilepsy were analysed with Fisher's exact test. A p-value <0.05 was considered statistically significant. RESULTS: Chronological age, motor type, and GMFCS classification explained 33% (R=0.577, R(2) =0.33) of the variance in spoken language comprehension. Of the children aged younger than 6 years 6 months, 52.4% of the children with dyskinetic CP attained comprehension scores within the average range (z-score ≥-1.6) as opposed to none of the children with spastic CP. Of the children aged older than 6 years 6 months, 32% of the children with dyskinetic CP reached the highest achievable age-equivalent score compared to 4% of the children with spastic CP. No significant difference in disability was found between CP-related variables (MACS levels, gestational age, epilepsy), with the exception of GMFCS which showed a significant difference in children aged younger than 6 years 6 months (p=0.043). INTERPRETATION: Despite communication disabilities in children with severe CP, particularly in dyskinetic CP, spoken language comprehension may show no or only moderate delay. These findings emphasize the importance of introducing alternative and/or augmentative communication devices from early childhood.

Spoken language comprehension of phrases, simple and compound-active sentences in non-speaking children with severe cerebral palsy.

BACKGROUND: Children with severe cerebral palsy (CP) (i.e. 'non-speaking children with severely limited mobility') are restricted in many domains that are important to the acquisition of language. AIMS: To investigate comprehension of spoken language on sentence type level in non-speaking children with severe CP. METHODS & PROCEDURES: From an original sample of 87 non-speaking children with severe CP, 68 passed the pre-test (i.e. they matched at least five spoken words to the corresponding objects) of a specifically developed computer-based instrument for low motor language testing (C-BiLLT), admitting them to the actual C-BiLLT computer test. As a result, the present study included 68 children with severe CP (35 boys, 33 girls; mean age 6;11 years, SD 3;0 years; age range 1;9-11;11 years) who were investigated with the C-BiLLT for comprehension of different sentence types: phrases, simple active sentences (with one or two arguments) and compound sentences. The C-BiLLT provides norm data of typically developing (TD) children (1;6-6;6 years). Binomial logistic regression analyses were used to compare the percentage correct of each sentence type in children with severe CP with that in TD children (subdivided into age groups) and to compare percentage correct within the CP subtypes. OUTCOMES & RESULTS: Sentence comprehension in non-speaking children with severe CP followed the developmental trajectory of TD children, but at a much slower rate; nevertheless, they were still developing up to at least age 12 years. Delays in sentence type comprehension increased with sentence complexity and showed a large variability between individual children and between subtypes of CP. Comprehension of simple and syntactically more complex sentences were significantly better in children with dyskinetic CP than in children with spastic CP. Of the children with dyskinetic CP, 10-13% showed comprehension of simple and compound sentences within the percentage correct of TD children, as opposed to none of the children with spastic CP. CONCLUSION & IMPLICATIONS: In non-speaking children with severe CP sentence comprehension is delayed rather than deviant. Results indicate the importance of following comprehension skills across all age groups, even beyond age 12 years. Moreover, the subtype of CP should be considered when establishing an educational programme for sentence comprehension, and augmentative and alternative communication support. In addition, educational programmes for children with severe CP should take into account the linguistic hierarchy of sentence comprehension when focusing on the input and understanding of spoken language comprehension.

Reliability and validity of the C-BiLLT: a new instrument to assess comprehension of spoken language in young children with cerebral palsy and complex communication needs.

In clinical practice, a variety of diagnostic tests are available to assess a child's comprehension of spoken language. However, none of these tests have been designed specifically for use with children who have severe motor impairments and who experience severe difficulty when using speech to communicate. This article describes the process of investigating the reliability and validity of the Computer-Based Instrument for Low Motor Language Testing (C-BiLLT), which was specifically developed to assess spoken Dutch language comprehension in children with cerebral palsy and complex communication needs. The study included 806 children with typical development, and 87 nonspeaking children with cerebral palsy and complex communication needs, and was designed to provide information on the psychometric qualities of the C-BiLLT. The potential utility of the C-BiLLT as a measure of spoken Dutch language comprehension abilities for children with cerebral palsy and complex communication needs is discussed.

Clinical-based phenotypes in children with pediatric post-COVID-19 condition.

BACKGROUND: Pediatric post coronavirus disease 2019 (COVID-19) condition (PPCC) is a heterogeneous syndrome, which can significantly affect the daily lives of children. This study aimed to identify clinically meaningful phenotypes in children with PPCC, to better characterize and treat this condition. METHODS: Participants were children with physician-diagnosed PPCC, referred to the academic hospital Amsterdam UMC in the Netherlands between November 2021 and March 2023. Demographic factors and information on post-COVID symptoms, comorbidities, and impact on daily life were collected. Clinical clusters were identified using an unsupervised and unbiased approach for mixed data types. RESULTS: Analysis of 111 patients (aged 3-18 years) revealed three distinct clusters within PPCC. Cluster 1 (n = 62, median age = 15 years) predominantly consisted of girls (74.2%). These patients suffered relatively more from exercise intolerance, dyspnea, and smell disorders. Cluster 2 (n = 33, median age = 13 years) contained patients with an even gender distribution (51.5% girls). They suffered from relatively more sleep problems, memory loss, gastrointestinal symptoms, and arthralgia. Cluster 3 (n = 16, median age = 11 years) had a higher proportion of boys (75.0%), suffered relatively more from fever, had significantly fewer symptoms (median of 5 symptoms compared to 8 and 10 for clusters 1 and 2 respectively), and experienced a lower impact on daily life. CONCLUSIONS: This study identified three distinct clinical PPCC phenotypes, with variations in sex, age, symptom patterns, and impact on daily life. These findings highlight the need for further research to understand the potentially diverse underlying mechanisms contributing to post-COVID symptoms in children.

Determinants of spoken language comprehension in children with cerebral palsy.

PURPOSE: To identify determinants of spoken language comprehension (SLC) in children with cerebral palsy (CP). MATERIALS AND METHODS: Cross-sectional data of 207 children with CP were included: 82 toddlers (18 months-3;11 years), 59 preschool children (4;0-5;11 years), and 66 schoolchildren (6;0-8;11 years), across all Gross Motor Function Classification System (GMFCS) levels. SLC was assessed using the Computer-Based instrument for Low motor Language Testing (C-BiLLT). Potential determinants were retrieved from medical files and through parental questionnaires. Per developmental stage, multivariable regression analyses were used to assess determinants of SLC. RESULTS: Fifty-nine percent of the children showed below average SLC. Significant determinants for SLC differed per developmental stage. In toddlers: age, motor type, functional communication and speech function (R2 = 0.637); in preschool children: functional communication, speech function and language activities (R2 = 0.820), and in schoolchildren: functional communication, intellectual functioning and arm-hand functioning (R2 = 0.807). For all developmental stages, functional mobility was not a significant determinant. CONCLUSIONS: A large proportion of children with CP across all GMFCS levels have SLC impairments. Findings indicate that SLC is strongly determined by functional communication classified with CFCS. We recommend standardized assessment and monitoring of SLC in all children with CP. IMPLICATIONS FOR REHABILITATIONChildren across all GMFCS levels can experience difficulties in spoken language comprehension.At all developmental stages, functional communication (classified with CFCS) is an important determinant of spoken language comprehension.Standardized assessment and monitoring of spoken language comprehension, language production, speech, and communication of all children with CP, is strongly recommended.When children show below average performances, especially in spoken language comprehension, intervening with speech and language therapy and guidance for parents, is advised.

The effects of COVID-19 on child mental health: Biannual assessments up to April 2022 in a clinical and two general population samples.

Background: The COVID-19 pandemic has had an acute impact on child mental and social health, but long-term effects are still unclear. We examined how child mental health has developed since the start of the COVID-19 pandemic up to 2 years into the pandemic (April 2022). Methods: We included children (age 8-18) from two general population samples (N = 222-1333 per measurement and N = 2401-13,362 for pre-covid data) and one clinical sample receiving psychiatric care (N = 334-748). Behavioral questionnaire data were assessed five times from April 2020 till April 2022 and pre-pandemic data were available for both general population samples. We collected parent-reported data on internalizing and externalizing problems with the Brief Problem Monitor and self-reported data on Anxiety, Depressive symptoms, Sleep-related impairments, Anger, Global health, and Peer relations with the Patient-Reported Outcomes Measurement Information System (PROMIS®). Results: In all samples, parents reported overall increased internalizing problems, but no increases in externalizing problems, in their children. Children from the general population self-reported increased mental health problems from before to during the pandemic on all six PROMIS domains, with generally worst scores in April 2021, and scores improving toward April 2022 but not to pre-pandemic norms. Children from the clinical sample reported increased mental health problems throughout the pandemic, with generally worst scores in April 2021 or April 2022 and no improvement. We found evidence of minor age effects and no sex effects. Conclusions: Child mental health in the general population has deteriorated during the first phase of the COVID-19 pandemic, has improved since April 2021, but has not yet returned to pre-pandemic levels. Children in psychiatric care show worsening of mental health problems during the pandemic, which has not improved since. Changes in child mental health should be monitored comprehensively to inform health care and policy.

Resting-state networks in awake five- to eight-year old children.

During the first 6-7 years of life children undergo a period of major neurocognitive development. Higher-order cognitive functions such as executive control of attention, encoding and retrieving of stored information and goal-directed behavior are present but less developed compared to older individuals. There is only very limited information from functional magnetic resonance imaging (fMRI) studies about the level of organization of functional networks in children in the early school period. In this study we perform continuous resting-state functional connectivity MRI in 5- to 8-year-old children in an awake state to identify and characterize resting-state networks (RSNs). Temporal concatenation independent component analysis (ICA) approach was applied to analyze the data. We identified 14 components consisting of regions known to be involved in visual and auditory processing, motor function, attention control, memory, and the default mode network (DMN). Most networks, in particular those supporting basic motor function and sensory related processing, had a robust functional organization similar to mature adult patterns. In contrast, the DMN and other RSNs involved in higher-order cognitive functions had immature characteristics, revealing incomplete and fragmented patterns indicating less developed functional connectivity. We therefore conclude that the DMN and other RSNs involved in higher order cognitive functioning are detectable, yet in an immature state, at an age when these cognitive abilities are mastered.

The sensory-reactivity PROM set: identification of a parent reported outcome measure set for autism spectrum disorder.

BACKGROUND: Most children with autism spectrum disorder (ASD) suffer from aberrant responses to sensory stimuli that significantly impact the quality of life. To develop sensory interventions, individually tailored outcome measures are crucially needed for the domain of sensory reactivity problems. Here, we describe the identification of relevant sensory themes according to caregivers of children with ASD according to the guidelines for developing a (parent proxy) patient-reported outcome measure set. Subsequently, we identify parallels between these themes and a well-validated and supported PROMIS® portal to facilitate implementation. Interviews with clinicians and focus groups and interviews with parents of children with ASD were used in the initial phase for concept elicitation. Codes and themes were generated by qualitative thematic data analysis on the transcripts and cognitive interviews with different parents were used for revisions. The resulting themes were compared to existing generic PROMIS-item banks and other existing questionnaires. RESULTS: A total of 11 parent-reported outcomes were identified that could be either classified as directly or indirectly related to sensory reactivity. Directly related themes comprised of: (1) sensory stimulation tolerance and (2) sensitivity to sensory stimuli. Indirectly related themes were: (3) irritable behavior (4) anxiety problems (5) mood problems (6) sleep problems (7) fatigue (8) physical complaints (9) daily functioning and participation (10) routines, structure and dealing with change and (11) problems in social interaction and communication. Seven out of 11 themes could be measured with generic PROMIS item banks. The four remaining outcomes (sensory stimulation tolerance; irritable behaviour; routines, structure and dealing with change; and sensitivity to sensory stimuli) were found suitable to be inventoried by existing PROMs. CONCLUSION: The majority of parent-reported problems seemed related to indirect consequences of sensory reactivity, which are suitable to be measured with generic item banks. In sum, we identified a sensory-reactivity PROM (parent-proxy) set consisting of PROMIS® item banks and additional domains that together form a comprehensive and readily available outcome set for sensory reactivity problems in children with ASD.