Assessment of functioning in ADHD according to World Health Organization standards: First revision of the International Classification of Functioning, Disability and Health Core Sets.

AIM: To conduct the first revision of the World Health Organization International Classification of Functioning, Disability and Health (ICF) Core Sets for attention-deficit/hyperactivity disorder (ADHD). METHOD: A Delphi-like method was used, integrating evidence from stakeholder feedback and developing and piloting the ADHD ICF Core Set platform to inform revisions to the ADHD Core Sets. RESULTS: A total of 27 second-level ICF codes were added to the comprehensive ADHD Core Set: body functions of temperament and personality, and basic sensory functions; activities and participation in terms of learning to read and write, spoken communication, community life, religion and spirituality, education, economy, and human rights; environmental factors for domestic animals; and several societal services. The revised comprehensive Core Set contains 98 ICF codes: 18 body function codes; 47 activities and participation codes; and 33 environmental factor codes. Extensive changes were also made to the age-appropriate brief Core Sets to allow their independent use in research and clinical practice. INTERPRETATION: Although substantially expanded, the revised ICF Core Sets better reflect the lived experience of individuals with ADHD and clinical implementation preferences than the initial sets. We recommend further feasibility and validation studies of these Core Sets with the goal of optimizing their acceptance and practicability, and strengthening their evidence base.

Using machine learning to improve diagnostic assessment of ASD in the light of specific differential and co-occurring diagnoses.

BACKGROUND: Diagnostic assessment of ASD requires substantial clinical experience and is particularly difficult in the context of other disorders with behavioral symptoms in the domain of social interaction and communication. Observation measures such as the Autism Diagnostic Observation Schedule (ADOS) do not take into account such co-occurring disorders. METHOD: We used a well-characterized clinical sample of individuals (n = 1,251) that had received detailed outpatient evaluation for the presence of an ASD diagnosis (n = 481) and covered a range of additional overlapping diagnoses, including anxiety-related disorders (ANX, n = 122), ADHD (n = 439), and conduct disorder (CD, n = 194). We focused on ADOS module 3, covering the age range with particular high prevalence of such differential diagnoses. We used machine learning (ML) and trained random forest models on ADOS single item scores to predict a clinical best-estimate diagnosis of ASD in the context of these differential diagnoses (ASD vs. ANX, ASD vs. ADHD, ASD vs. CD), in the context of co-occurring ADHD, and an unspecific model using all available data. We employed nested cross-validation for an unbiased estimate of classification performance and made available a Webapp to showcase the results and feasibility for translation into clinical practice. RESULTS: We obtained very good overall sensitivity (0.89-0.94) and specificity (0.87-0.89). In particular for individuals with less severe symptoms, our models showed increases of up to 35% in sensitivity or specificity. Furthermore, we analyzed item importance profiles of the ANX, ADHD, and CD models in comparison with the unspecific model revealing distinct patterns of importance for specific ADOS items with respect to differential diagnoses. CONCLUSIONS: ML-based diagnostic classification may improve clinical decisions by utilizing the full range of information from detailed diagnostic observation instruments such as the ADOS. Importantly, this strategy might be of particular relevance for older children with less severe symptoms for whom the diagnostic decision is often particularly difficult.

Reconciling the seemingly irreconcilable: The WHO's ICF system integrates biological and psychosocial environmental determinants of autism and ADHD: The International Classification of Functioning (ICF) allows to model opposed biomedical and neurodiverse views of autism and ADHD within one framework.

Neurodevelopmental disorders (NDDs), such as autism and ADHD, are behaviorally defined adaptive functioning difficulties arising from variations, alterations and atypical maturation of the brain. While it is widely agreed that NDDs are complex conditions with their presentation and functional impact underpinned by diverse genetic and environmental factors, contemporary and polarizing debate has focused on the appropriateness of the biomedical as opposed to the neurodiverse paradigm in framing conceptions of these conditions. Despite being largely overlooked by both research and practice, the International Classification of Functioning Disability and Health (ICF) endorsed by the World Health Organization in 2001 views functioning dynamically, offering a framework for investigating, assessing and treating NDDs holistically. Exemplified by autism and ADHD, we argue that the ICF provides not only a multitude of opportunities in accounting for the environmental determinants in researching and clinically managing NDDs, but opportunities for harmonizing the seemingly irreconcilable biomedical and neurodiverse paradigms. Also see the video abstract here: https://youtu.be/YwuWPDUOs5k.

Reliability of the Motor Optimality Score-Revised: A study of infants at elevated likelihood for adverse neurological outcomes.

AIM: To assess the inter-assessor reliability of the Motor Optimality Score-Revised (MOS-R) when used in infants at elevated likelihood for adverse neurological outcome. METHODS: MOS-R were assessed in three groups of infants by two assessors/cohort. Infants were recruited from longitudinal projects in Sweden (infants born extremely preterm), India (infants born in low-resource communities) and the USA (infants prenatally exposed to SARS-CoV-2). Intraclass correlation coefficients (ICC) and kappa (κw) were applied. ICC of MOS-R subcategories and total scores were presented for cohorts together and separately and for age-spans: 9-12, 13-16 and 17-25-weeks post-term age. RESULTS: 252 infants were included (born extremely preterm n = 97, born in low-resource communities n = 97, prenatally SARS-CoV-2 exposed n = 58). Reliability of the total MOS-R was almost perfect (ICC: 0.98-0.99) for all cohorts, together and separately. Similar result was found for age-spans (ICC: 0.98-0.99). Substantial to perfect reliability was shown for the MOS-R subcategories (κw: 0.67-1.00), with postural patterns showing the lowest value 0.67. CONCLUSION: The MOS-R can be used in high-risk populations with substantial to perfect reliability, both in regards of total/subcategory scores as well as in different age groups. However, the subcategory postural patterns as well as the clinical applicability of the MOS-R needs further study.

Updated systematic-narrative review on communication intervention in Rett Syndrome: 2010-2022.

Due to loss of spoken language and resulting complex communication needs, people with Rett syndrome are obvious candidates for communication intervention. To advance evidence-based practice and guide future research efforts, we identified and summarized 16 communication intervention studies published since a previous 2009 review on this topic. Studies were summarized in terms of (a) participants, (b) dependent variables related to communication, (c) intervention characteristics, (d) outcomes, and (e) certainty of evidence. Across the 16 studies, intervention was provided to a total of 100 participants from 3 to 47 years of age. Half of the studies used systematic instruction to teach aided AAC. Other interventions and associated technologies included music therapy, eye tracking technology, and transcranial stimulation. Positive outcomes (e.g., using AAC devices to make requests and/or initiate social-communication interactions) were reported in 13 of the studies. These 16 new studies provide additional guidance on how to enhance the communicative functioning of people with Rett syndrome. Future research directions are highlighted.

The development of visual attention in early infancy: Insights from a free-viewing paradigm.

Theories of visual attention suggest a cascading development of subfunctions such as alertness, spatial orientation, attention to object features, and endogenous control. Here, we aimed to track infants' visual developmental steps from a primarily exogenously to more endogenously controlled processing style during their first months of life. In this repeated measures study, 51 infants participated in seven fortnightly assessments at postterm ages of 4-16 weeks. Infants were presented with the same set of static and dynamic paired comparison stimuli in each assessment. Visual behavior was evaluated by a newly introduced scoring scheme. Our results confirmed the suggested visual developmental hierarchy and clearly demonstrated the suitability of our scoring scheme for documenting developmental changes in visual attention during early infancy. Besides the general ontogenetic course of development, we also discuss intra- and interindividual differences which may affect single assessments, and highlight the importance of repeated measurements for reliable evaluation of developmental changes.

[Physiotherapy in German Neonatal Intensive Care Units - Indication and Clinical Application of the General Movements Assessments]. / Physiotherapie in Deutschen Perinatalzentren.

BACKGROUND: Standardized recommendations for inpatient and outpatient physiotherapy for preterm infants are lacking in Germany. The aim of this study was to investigate the prescription practice in German neonatal intensive care units. Are standardized assessments used to determine indications? How important is the General Movements Assessment in postnatal diagnostics? METHODS: We conducted an online survey in German neonatal intensive care units asking 21 questions on indication and prescription practices for inpatient and outpatient physiotherapy in preterm infants' care as well as on General Movements Assessment and its clinical application via Lime Survey. RESULTS: 81% of the participating sites "always" or "often" recommend indication-based inpatient physiotherapy for preterm infants and 53% "always"/"often" recommend outpatient therapy. Indications are mainly based on these symptoms (N=344) or diagnoses (N=273) (multiple answers): hypotonia (94%), abnormal and imbalanced muscle tone (92%), neurological abnormalities (97%) and brain damage (94%). Standardized testing is used by 41% of the participants. The General Movements Assessment is known to 87% of the neonatal intensive care units, 11% use it several times a week, 17% several times a month for indication of physiotherapy. CONCLUSION: Physiotherapy is frequently prescribed for preterm infants. The majority of indications are based on symptoms or clinical pictures rather than on standardized tests. The General Movements Assessment is a widely known method but not systematically applied at the moment.

Fetal movements: the origin of human behaviour.

The study of the onset and ontogeny of human behaviour has made it clear that a multitude of fetal movement patterns are spontaneously generated, and that there is a close association between activity and the development of peripheral and central structures. The embryo starts moving by 7.5 week's gestation; 2 to 3 weeks later, a number of movement patterns including general movements, isolated limb and head movements, hiccup, and breathing movements, appear. Some movements (e.g. yawning, smiling, 'pointing'; we show these in eight videos in this review) precede life-long patterns; others have intrauterine functions, such as sucking/swallowing for amniotic fluid regulation, breathing movements for lung development, or eye movements for retinal cell diversity. In cases of developmental brain dysfunction, fetal general movements alter their sequence and gestalt, which suggests a dysfunction of the developing nervous system. The scarcity of longitudinal studies calls for further comprehensive research on the predictive value of prenatal functional deviations. What this paper adds Motor output can occur in the absence of sensory input. Structural development is activity-dependent. Fetal general movements are among the first movement patterns to occur. Pregnancy-related and maternal factors impact quantity and modulation of fetal general movements. Prenatal general movement assessment has not yet brought the expected breakthrough.

Prelexical phonetic and early lexical development in German-acquiring infants: canonical babbling and first spoken words.

Prelexical phonetic capacities have widely been described to be a precursor for later speech and language development. However, studies so far varied greatly in the measurements used for the detection of canonical babbling onset or the description of infants' phonetic capacities at one or more set time points. The comparability of results is, therefore, questionable. Thus, the aims of this study were to investigate the associations between (1) different measurements of CBO, (2) different aspects of phonetic capacity at the age of 9 months and (3) age of CBO and phonetic capacities at 9 months. A further aim (4) was to explore whether one of the measures would be suitable to predict the age of word onset (WO) in 20 healthy German-acquiring individuals. The data were derived from monthly recorded spontaneous speech samples between 0 and 18 months. It was found that the different applied prelexical measures equally well serve as valid estimators for the detection of CBO or of infants' phonetic capacities. Further, age of CBO and phonetic capacities at 9 months were significantly associated even though the age of CBO did not reliably predict phonetic capacities. Prelexical measures and WO were not related. Reasons for no indication of a significant association are discussed.

The contribution of environmental exposure to the etiology of autism spectrum disorder.

Autism spectrum disorder (ASD) is a neurodevelopmental condition of heterogeneous etiology. While it is widely recognized that genetic and environmental factors and their interactions contribute to autism phenotypes, their precise causal mechanisms remain poorly understood. This article reviews our current understanding of environmental risk factors of ASD and their presumed adverse physiological mechanisms. It comprehensively maps the significance of parental age, teratogenic compounds, perinatal risks, medication, smoking and alcohol use, nutrition, vaccination, toxic exposures, as well as the role of extreme psychosocial factors. Further, we consider the role of potential protective factors such as folate and fatty acid intake. Evidence indicates an increased offspring vulnerability to ASD through advanced maternal and paternal age, valproate intake, toxic chemical exposure, maternal diabetes, enhanced steroidogenic activity, immune activation, and possibly altered zinc-copper cycles and treatment with selective serotonin reuptake inhibitors. Epidemiological studies demonstrate no evidence for vaccination posing an autism risk. It is concluded that future research needs to consider categorical autism, broader autism phenotypes, as well as autistic traits, and examine more homogenous autism variants by subgroup stratification. Our understanding of autism etiology could be advanced by research aimed at disentangling the causal and non-causal environmental effects, both founding and moderating, and gene-environment interplay using twin studies, longitudinal and experimental designs. The specificity of many environmental risks for ASD remains unknown and control of multiple confounders has been limited. Further understanding of the critical windows of neurodevelopmental vulnerability and investigating the fit of multiple hit and cumulative risk models are likely promising approaches in enhancing the understanding of role of environmental factors in the etiology of ASD.

Psychometric Properties of the General Movement Optimality Score using Rasch Measurement.

AIM: To explore the psychometric properties of the general movements optimality score (GMOS) by examining its dimensionality, rating scale functioning, and item hierarchies using Rasch measurement. METHODS: Secondary data analysis of the GMOS data for video-recording of 383 infants with uni-, multidimensional, and mixed Rasch partial credit models. Videos were scored based on the global General Movement Assessment categories, and on the amplitude, speed, spatial range, proximal and distal rotations, onset and offset, tremulous and cramped components of the upper and lower extremities (21 items), resulting in the GMOS. RESULTS: The GMOS data fits best to a unidimensional mixed Rasch model with three different classes of infants, with all but two items contributing to the infants' separation. Rating scales functioned well for 19 items. Item difficulty hierarchies varied depending on infants' class. No floor effect and no substantive gaps between item difficulty estimates were found. CONCLUSION: The GMOS has strong psychometric properties to distinguish infants with different functional motor performance and provides a quantitative measure of quality of movement. INTERPRETATION: The GMOS can be confidently used to assist with early diagnosis, grade motor performance, and provide a solid base to study individual general movement developmental trajectories.

Zika Virus Infection in Pregnant Women in Rio de Janeiro.

BACKGROUND: Zika virus (ZIKV) has been linked to central nervous system malformations in fetuses. To characterize the spectrum of ZIKV disease in pregnant women and infants, we followed patients in Rio de Janeiro to describe clinical manifestations in mothers and repercussions of acute ZIKV infection in infants. METHODS: We enrolled pregnant women in whom a rash had developed within the previous 5 days and tested blood and urine specimens for ZIKV by reverse-transcriptase-polymerase-chain-reaction assays. We followed women prospectively to obtain data on pregnancy and infant outcomes. RESULTS: A total of 345 women were enrolled from September 2015 through May 2016; of these, 182 women (53%) tested positive for ZIKV in blood, urine, or both. The timing of acute ZIKV infection ranged from 6 to 39 weeks of gestation. Predominant maternal clinical features included a pruritic descending macular or maculopapular rash, arthralgias, conjunctival injection, and headache; 27% had fever (short-term and low-grade). By July 2016, a total of 134 ZIKV-affected pregnancies and 73 ZIKV-unaffected pregnancies had reached completion, with outcomes known for 125 ZIKV-affected and 61 ZIKV-unaffected pregnancies. Infection with chikungunya virus was identified in 42% of women without ZIKV infection versus 3% of women with ZIKV infection (P<0.001). Rates of fetal death were 7% in both groups; overall adverse outcomes were 46% among offspring of ZIKV-positive women versus 11.5% among offspring of ZIKV-negative women (P<0.001). Among 117 live infants born to 116 ZIKV-positive women, 42% were found to have grossly abnormal clinical or brain imaging findings or both, including 4 infants with microcephaly. Adverse outcomes were noted regardless of the trimester during which the women were infected with ZIKV (55% of pregnancies had adverse outcomes after maternal infection in the first trimester, 52% after infection in the second trimester, and 29% after infection in the third trimester). CONCLUSIONS: Despite mild clinical symptoms in the mother, ZIKV infection during pregnancy is deleterious to the fetus and is associated with fetal death, fetal growth restriction, and a spectrum of central nervous system abnormalities. (Funded by Ministério da Saúde do Brasil and others.).

School-age outcomes of late-talking toddlers: Long-term effects of an early lexical deficit.

BACKGROUND: Early intervention for children identified as late talkers (LTs) at the age of 24 months is still a controversial issue in research and clinical routine. Previous studies have shown inconsistent results regarding predictors of early lexical deficits on school-age outcomes of late-talking toddlers. METHODS: In a five-wave follow-up study, we investigated various aspects of language and literacy abilities in 39 German-speaking third-graders who had been identified as LTs at the age of 24 months, compared to 39 typically developing children (TDC) also attending the third grade. The duration of auditory sensory memory was examined at the age of 4 years using mismatch negativity (MMN) of tones - an event-related potential not confounded by any language skill. In addition, the predictive value of memory performance was examined in a longitudinal perspective. RESULTS: Overall, LTs scored within normal range in language and literacy assessments. However, LTs differed from TDC in vocabulary size, verbalization of semantic relations, non-word repetition, and spelling. The findings can be explained by phonological working memory. The duration of auditory sensory memory and spatial working memory did not account for any variance. CONCLUSIONS: LTs sustain persistent phonological processing limitations even though their native language and literacy performance lay within the normal range at school age. Further research on second language acquisition, academic achievements, and the efficacy of early intervention in late-talking toddlers is recommended.

Annual Research Review: Quality of life and childhood mental and behavioural disorders - a critical review of the research.

BACKGROUND: An individual's subjective perception of well-being is increasingly recognized as an essential complement to clinical symptomatology and functional impairment in children's mental health. Measurement of quality of life (QoL) has the potential to give due weight to the child's perspective. SCOPE AND METHODOLOGY: Our aim was to critically review the current evidence on how childhood mental disorders affect QoL. First, the major challenges in this research field are outlined. Then we present a systematic review of QoL in children and adolescents aged 0-18 years formally diagnosed with a mental and behavioural disorder, as compared to healthy or typically developing children or children with other health conditions. Finally, we discuss limitations of the current evidence base and future directions based on the results of the systematic review and other relevant literature. FINDINGS AND CONCLUSIONS: The systematic review identified 41 eligible studies. All were published after the year 2000 and 21 originated in Europe. The majority examined QoL in neurodevelopmental disorders, including attention-deficit hyperactivity disorder (k = 17), autism spectrum disorder (k = 6), motor disorders (k = 5) and intellectual disability (k = 4). Despite substantial heterogeneity, studies demonstrate that self-reported global QoL is significantly reduced compared to typical/healthy controls across several disorders and QoL dimensions. Parents' ratings were on average substantially lower, casting doubt on the validity of proxy-report. Studies for large diagnostic groups such as depressive disorders, anxiety disorders, (early onset) schizophrenia and eating disorders are largely lacking. We conclude that representative, well-characterized normative and clinical samples as well as longitudinal and qualitative designs are needed to further clarify the construct of QoL, to derive measures of high ecological validity, and to examine how QoL fluctuates over time and is attributable to specific conditions or contextual factors.

A Novel Way to Measure and Predict Development: A Heuristic Approach to Facilitate the Early Detection of Neurodevelopmental Disorders.

PURPOSE OF REVIEW: Substantial research exists focusing on the various aspects and domains of early human development. However, there is a clear blind spot in early postnatal development when dealing with neurodevelopmental disorders, especially those that manifest themselves clinically only in late infancy or even in childhood. RECENT FINDINGS: This early developmental period may represent an important timeframe to study these disorders but has historically received far less research attention. We believe that only a comprehensive interdisciplinary approach will enable us to detect and delineate specific parameters for specific neurodevelopmental disorders at a very early age to improve early detection/diagnosis, enable prospective studies and eventually facilitate randomised trials of early intervention. In this article, we propose a dynamic framework for characterising neurofunctional biomarkers associated with specific disorders in the development of infants and children. We have named this automated detection 'Fingerprint Model', suggesting one possible approach to accurately and early identify neurodevelopmental disorders.

"What" matters more than "Why" - Neonatal behaviors initiate social responses.

Newborns are born into a social environment that dynamically responds to them. Newborn behaviors may not have explicit social intentions but will nonetheless affect the environment. Parents contingently respond to their child, enabling newborns to learn about the consequences of their behaviors and encouraging the behavior itself. Consequently, newborn behaviors may serve both biological and social-cognitive purposes during development.

Same or different: Common pathways of behavioral biomarkers in infants and children with neurodevelopmental disorders?

The extent to which early motor patterns represent antecedents to later communicative functions, and the emergence of gesture and/or sign as potential communicative acts in neurodevelopmental disorders (NDDs), are research questions that have received recent attention. It is important to keep in mind that different NDDs have different neurological underpinnings, with correspondingly different implications for their conceptualization, detection, and treatment.

Parents' initial concerns about the development of their children later diagnosed with fragile X syndrome.

BACKGROUND: Retrospective parental reports have often been used to identify the early characteristics of children later diagnosed with a developmental disorder. METHOD: We applied this methodology to document 13 parents' initial concerns about the development of their 17 children later diagnosed with fragile X syndrome (FXS). Parents were additionally asked about when they noticed the emergence of behavioural signs related to FXS. RESULTS: More than half of the parents reported initial concerns prior to the child's first birthday and in most cases it was deviant motor behaviours that caused the first concerns. Behavioural signs related to the FXS phenotype were also reported to be perceptible in the first year of the child's life. CONCLUSIONS: Due to limitations of retrospective parental questionnaires, we suggest that other methodologies, such as home video analysis, are needed to complement our understanding of the pathways of developmental disorders with late clinical onsets.

The general movement optimality score: a detailed assessment of general movements during preterm and term age.

AIM: To explore the appropriateness of applying a detailed assessment of general movements and characterize the relationship between global and detailed assessment. METHOD: The analysis was based on 783 video recordings of 233 infants (154 males, 79 females) who had been videoed from 27 to 45 weeks postmenstrual age. Apart from assessing the global general movement categories (normal, poor repertoire, cramped-synchronized, or chaotic general movements), we scored the amplitude, speed, spatial range, proximal and distal rotations, onset and offset, tremulous and cramped components of the upper and lower extremities. Applying the optimality concept, the maximum general movement optimality score of 42 indicates the optimal performance. RESULTS: General movement optimality scores (GMOS) differentiated between normal general movements (median 39 [25-75th centile 37-41]), poor repertoire general movements (median 25 [22-29]), and cramped-synchronized general movements (median 12 [10-14]; p<0.01). The optimality score for chaotic general movements (mainly occurring at late preterm age) was similar to those for cramped-synchronized general movements (median 14 [12-17]). Short-lasting tremulous movements occurred from very preterm age (<32wks) to post-term age across all general movement categories, including normal general movements. The detailed score at post-term age was slightly lower compared to the scores at preterm and term age for both normal (p=0.02) and poor repertoire general movements (p<0.01). INTERPRETATION: Further research might demonstrate that the GMOS provides a solid base for the prediction of improvement versus deterioration within an individual general movement trajectory.