Diagnosis Of Neurodevelopmental Disorders Research Articles

Optical genome mapping unveils hidden structural variants in neurodevelopmental disorders

While short-read sequencing currently dominates genetic research and diagnostics, it frequently falls short of capturing certain structural variants (SVs), which are often implicated in the etiology of neurodevelopmental disorders (NDDs). Optical genome mapping (OGM) is an innovative technique capable of capturing SVs that are undetectable or challenging-to-detect via short-read methods. This study aimed to investigate NDDs using OGM, specifically focusing on cases that remained unsolved after standard exome sequencing. OGM was performed in 47 families using ultra-high molecular weight DNA. Single-molecule maps were assembled de novo, followed by SV and copy number variant calling. We identified 7 variants of interest, of which 5 (10.6%) were classified as likely pathogenic or pathogenic, located in BCL11A, OPHN1, PHF8, SON, and NFIA. We also identified an inversion disrupting NAALADL2, a gene which previously was found to harbor complex rearrangements in two NDD cases. Variants in known NDD genes or candidate variants of interest missed by exome sequencing mainly consisted of larger insertions (> 1kbp), inversions, and deletions/duplications of a low number of exons (1–4 exons). In conclusion, in addition to improving molecular diagnosis in NDDs, this technique may also reveal novel NDD genes which may harbor complex SVs often missed by standard sequencing techniques.

Impact of maternal immune activation and sex on placental and fetal brain cytokine and gene expression profiles in a preclinical model of neurodevelopmental disorders

Maternal inflammation during gestation is associated with a later diagnosis of neurodevelopmental disorders including autism spectrum disorder (ASD). However, the specific impact of maternal immune activation (MIA) on placental and fetal brain development remains insufficiently understood. This study aimed to investigate the effects of MIA by analyzing placental and brain tissues obtained from the offspring of pregnant C57BL/6 dams exposed to polyinosinic: polycytidylic acid (poly I: C) on embryonic day 12.5. Cytokine and mRNA content in the placenta and brain tissues were assessed using multiplex cytokine assays and bulk-RNA sequencing on embryonic day 17.5. In the placenta, male MIA offspring exhibited higher levels of GM-CSF, IL-6, TNFα, and LT-α, but there were no differences in female MIA offspring. Furthermore, differentially expressed genes (DEG) in the placental tissues of MIA offspring were found to be enriched in processes related to synaptic vesicles and neuronal development. Placental mRNA from male and female MIA offspring were both enriched in synaptic and neuronal development terms, whereas females were also enriched for terms related to excitatory and inhibitory signaling. In the fetal brain of MIA offspring, increased levels of IL-28B and IL-25 were observed with male MIA offspring and increased levels of LT-α were observed in the female offspring. Notably, we identified few stable MIA fetal brain DEG, with no male specific difference whereas females had DEG related to immune cytokine signaling. Overall, these findings support the hypothesis that MIA contributes to the sex- specific abnormalities observed in ASD, possibly through altered neuron developed from exposure to inflammatory cytokines. Future research should aim to investigate how interactions between the placenta and fetal brain contribute to altered neuronal development in the context of MIA.

Unmasking the Struggle: A Scoping Review Exploring Post-Traumatic Stress Symptoms in Caregivers of Individuals with Neurodevelopmental, Psychiatric and Neurocognitive Disorders.

The impact of caregiving on caregivers' mental health is typically considered within the caregiver stress and burden literature; however, more recently, research has investigated the experience of post-traumatic stress symptoms (PTSS) in caregivers. As an emerging area of research, it is timely to conduct a scoping review to map the existing literature in relation to PTSS among adult caregivers of children and adults with neurodevelopmental disorders (NDD), neurocognitive disorders, and psychiatric disorders. The scoping review was conducted using Preferred Reporting Items of Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines and Arksey and O'Malley's five-stage methodology framework. Published and unpublished gray literature between 2005 and 2022 was included in the scoping review. Nine thousand one hundred and twenty-five studies were originally identified for screening and 22 studies were selected for inclusion in the final review. Trauma and PTSS experienced by NDD caregivers were related to news breaking, NDD diagnosis, and behavioral issues, whereas caregivers of individuals with psychosis reported aggression and violence as traumatic events. Studies showed that up to half of caregivers reported PTSS, although no conclusions could be drawn about prevalence rates. A wide variety of tools measuring PTSS were used across the 22 studies. Many symptoms of PTSS were reported by caregivers, and cognitive appraisals were associated with PTSS in caregivers. The findings highlight the importance of recognizing the impact of trauma in caregiver mental health and the potential value of using traumatic stress frameworks with these populations. Research should be expanded to establish prevalence rates and to examine the long-term impact of trauma on caregiving as caregivers and care recipients age.

Ambulatory pediatricians: how to bridge the gaps in diagnosis and care coordination for neurodevelopmental disorders in France.

The organization of healthcare pathways for neurodevelopmental disorders (NDD) relies on different levels of expertise depending on the complexity of these disorders. NDDs affect between 8% and 15% of children. Historically, national recommendations and healthcare planning measures were initially devoted to autism spectrum disorders and were gradually extended to Attention deficit hyperactivity disorder (ADHD) and specific learning and development disorders. Private doctors play an increasing role in these pathways at different levels of care due to difficulties in organization, particularly in the health and social sector. The aim of this work was to evaluate the contribution of second-line private doctors in the diagnosis and care of children affected by NDD. A first series of surveys in 2016 evaluated the level of commitment of primary care pediatricians; this online national survey was repeated in 2023 among 1,430 members of the French Association of Ambulatory Pediatrics (Association Française de Pédiatrie Ambulatoire: AFPA) to assess their training, current and future involvement, and activity in NDD care. Analysis was performed by the main author using Epi-Info software. The study identified in 2023 214 second-line private doctors (14% of all pediatricians in activity), of which 185 agreed to appear in a directory published the same year by the AFPA to facilitate referrals from other professionals. Sex ratio of responders is usual for paediatricians: 79.5%/20.5% (F/M), with a distribution among ages showing a slight increase of the age range between age 51-60 (30.5%). Our data indicate that in France in 2022, second-line private doctors made 48%-53% of NDD diagnoses, 24%-26.4% of follow-up consultations and declare to be accountable for 21% of initial prescriptions for Methylphenidate. Among these second-line doctors, 40% had completed a post-university degree on NDD, 74.3% had completed professional development training (PDT) and 85.2% had completed either or both types of training. Most doctors participating in the survey wanted to improve their level of practice, suggesting that in five years, the number of second-line private doctors will increase by 20% to 244 despite 24 planned retirements within the same period. This data probably underestimates the role of private doctors in NDD diagnosis, follow-up, and initial Methylphenidate prescriptions given the unfavourable working conditions (no financial compensation for long appointments, difficulty accessing paramedical and psychological assessments). Our data confirms that diagnosis and care coordination in the various presentations of NDD may rely on different types of practices and specializations: medical and social professionals, mental health professionals, but also a growing body of medical doctors involved in developmental and behavioural pediatrics. This data and reflection will be helpful for organizing healthcare in France or in other countries. Main study limitation relies in the self-declaration of MD's involvement in NDD and could not evaluate the activity of employed MD's from the social and medico social sector, nor be based on the national databases for prescription. It remains however the first attempt of characterization of medical activity at the national level in France for NDD.

OTs Should Be Using Video Modeling to Teach Self-Care to Children with NDDs

ABSTRACT An evidence-based project aimed at finding whether utilizing video modeling as an occupational therapy (OT) intervention increased basic self-care skills in school-aged children with neurodevelopmental disorders (NDDs). A total of 11 pediatric outpatient OT clients, 6–12 years old, with one or more NDDs, participated in this project. Pre- and post-intervention surveys completed by their parents garnered information regarding parental views on their children’s self-care skills, parental stress, and quality of life. Real-time data gathered during the intervention revealed the efficacy of video modeling, showing an overall increase in the completion of basic self-care skills from 16.1% at baseline to 96.4%. Meaningful gains were achieved in all eight self-care skills addressed and with all participants, elucidating a combined mean percentage of 79.3% improvement using video modeling. Post-intervention, qualitative data showed resultant perspectives of less parental stress, improved quality of life for the children and their parents, and improved independence with basic self-care skills. Considering the increasing diagnosis of NDDs, the call for evidence-based interventions from both payers and NDD-related organizations, and the future socioeconomic ramifications of not addressing basic self-care skills, this project reveals the efficacy of video modeling as a viable, accessible, cost-effective intervention which can be utilized across environments to address these concerns.

The Effect of Neurodevelopmental Disorders on the Prognosis of Children Undergoing Heart Transplantation: A Retrospective Analysis of the National Inpatient Sample 2011–2019

Background: Many international governing bodies recommend against heart transplantation in patients with severe cognitive-behavioral disabilities, however no clear criteria are offered to define severity. Patients with neurodevelopmental disorders may face systematic discrimination when being evaluated for transplant. We set out to investigate whether children with neurodevelopmental disorders that undergo heart transplantation have poorer in-hospital outcomes compared to neurotypical children. Methods: A retrospective analysis of the National Inpatient Sample database was conducted to identify pediatric patients with neurodevelopmental disorders who underwent heart transplantation from 2011–2019. Baseline characteristics and in-hospital outcomes between patients were compared. Binary logistic regression was used to investigate the association between the documented presence of a neurodevelopmental disorder and in-hospital outcomes in children undergoing heart transplantation. Results: We identified a weighted sample of 3770 pediatric cardiac transplant patients, of whom 245 (6.5%) had a documented diagnosis of neurodevelopmental disorder. There was no significant difference in the odds of major adverse cardiovascular events (all-cause mortality, stroke complications or myocardial infarction), surgical complications, infection, venous thromboembolic events, delirium/restraint use, or cardiac dysrhythmia. Patients with neurodevelopmental disorders had lower overall length of stay (44.0 days interquartile range (IQR): 16.0–90.0 vs. 57.08 days IQR: 22.0–112.0, p < 0.050), and cost of stay ($956,031 IQR: 548,559.0–1,801,412.0 vs. $1,074,793 IQR: 599,089.8–2,129,086.0, p < 0.050). Patients with neurodevelopmental disorders had significantly lower odds of acute transplant complications (adjusted odds ratio (aOR): 0.39, 95% confidence interval (CI): 0.21–0.74, p < 0.050) vascular complications (aOR: 0.36, 95% CI: 0.19–0.66, p < 0.050) and acute kidney injury (AKI) (aOR: 0.52, 95% CI: 0.33–0.83, p < 0.050). Conclusions: These data suggest that patients with neurodevelopmental disorders have overall similar if not potentially improved post-transplant outcomes in the acute setting compared to neurotypical patients, possibly secondary to selection bias in the patient selection process.

Prevalence and factors of sleep problems among Japanese children: a population-based study.

High prevalence of sleep problems in not only children with neurodevelopmental disorders (NDS) but also non NDS has been established. However, there are few studies that have looked into population-based and age-specific prevalence of sleep problems of children. Moreover, there are even fewer studies that have investigated the correlation of demographic and lifestyle-related factors affecting sleep problems in children. Considering these, the purpose of this study is to assess the correlation of the prevalence of sleep problems and selected socio-demographic and lifestyle-related factors in 5-year-old Japanese children in population-based study. Study children (SC) were recruited from two cohorts of the Hirosaki City 5-Year-Old Child Developmental Health Checkup Study. The first cohort consisted of 281 (162 males, 119 females) children recruited from 2014 to 2015, and the second cohort consisted of 2055 (1,068 males, 987 females) children from 2018 to 2019. In total there were 2,336 SC participants (1,230 males and 1,106 females). To determine the prevalence of sleep problems the Japanese Sleep Questionnaire for Preschoolers (JSQ-P) was utilized, and sleep problems are defined by a total score of ≥86. To determine socio-demographic and lifestyle-related factors affecting sleep, 10 factors (NDS diagnosis, birth month, childcare place, income, number of siblings, bedtime, waking time, sleeping hours, sleep onset delay, and screen time) were selected. Finally, to determine the correlation between prevalence of sleep problems and the selected demographic and lifestyle-related factors, data was analyzed using chi-square test. The prevalence rate of sleep problems in 5-year-olds was 18% (369/2,055). Further, the prevalence of sleep problems was high in participants with ASD (50.4%), ADHD (39.8%), <2 million yen of income (30.5%), no siblings (24.2%), >22:00 of bedtime (30.7%), >7:30 of waking time (30.7%), <9 h of sleeping hours (25.3%), >30 min of sleep onset delay (35.3%), and ≥2 h of screen time (21.1%). The findings report 18% prevalence rate of sleep problems in 5-year-old children. Further, the findings establish a significant correlation of sleep problems and NDS, specific socio-demographic, and lifestyle-related factors. In considering the identified modifiable lifestyle-related factors contributing to sleep problems among the participants (i.e., bed/waking times and screen times), sleep programs to address these concerns are suggested.

The High Rates of Comorbidity among Neurodevelopmental Disorders: Reconsidering the Clinical Utility of Distinct Diagnostic Categories.

The boundaries between neurodevelopmental disorders are often indistinct, even among specialists. But do these boundaries exist, or do experts struggle to distinguish and categorize symptoms in order to arrive at a dominant diagnosis while comorbidity continually leaves questions about where each disorder ends and begins? What should be reconsidered? The introduction of the term 'spectrum of neurodevelopmental disorders' could pave the way for a re-appraisal of the clinical continuum of neurodevelopmental disorders. This study aims to highlight the problems that emerge in the field of the differential diagnosis of neurodevelopmental disorders and propose a renegotiation of the distinctiveness criteria.

Neurodevelopmental Disorders Including Autism Spectrum Disorder and Intellectual Disability as a Risk Factor for Delayed Diagnosis of Catatonia.

Catatonia is a distinct and severe medical syndrome comprising motor, somatic, and psychiatric symptoms that is reported in upwards of 17% of young patients with autism spectrum disorders. Clinical experience indicates catatonia is often under-recognized in this clinical population. Here we characterize the clinical presentation of catatonia in patients with and without neurodevelopmental disorders (NDDs) including autism, including the time from symptom onset to diagnosis of catatonia. Retrospective chart review of electronic medical records at a large, academic pediatric medical center identified 113 pediatric and young adult patients with a charted history of catatonia, as identified by an encounter diagnosis or problem list entry between September 2017 and September 2021. Workup, treatments, and diagnoses (psychiatric, neurodevelopmental, and genetic) were identified. We observed a clear and substantial delay in identification of catatonia in those with NDDs (diagnosis after 330 days for those without psychosis) compared with neurotypical patients (∼16 days). Psychiatry involvement was associated with shorter delays. Intellectual disability and autism are risk factors for significantly delayed diagnosis of catatonia. It is unknown whether delayed diagnosis contributes to the difficulty in treating catatonia in this patient population or whether the treatment difficulties relate instead to differential and ongoing biological mechanisms and underlying encephalopathy. Overall, these findings highlight the importance of increased recognition of catatonia symptoms in patients with NDDs and suggest early referral to psychiatric specialists may shorten the delay to diagnosis.

Prevalence of Comprehensive Eye Examination in Preschool Children With Eye Conditions

IntroductionThe study's purpose is to assess the prevalence of comprehensive eye examinations (CEE) in multi-ethnic preschool children, including children with visually significant eye conditions, and identify factors associated with CEE. MethodsA sample of 9,197 African American (AA), Hispanic (HS), Asian American (AS), and non-Hispanic White (NHW) 6- to 72-month-old children was recruited for the Multi-Ethnic Pediatric Eye Disease Study from 2003-2011. Logistic regression performed in 2022 identified independent factors associated with parent-reported history of CEE. The proportion of children with previous CEE and the proportion with undetected amblyopia or strabismus were measured. ResultsCEE prevalence was 6.3% overall, and 38.3%, 24.8%, 19.1%, 15.1%, and 9.8% among children with strabismus, amblyopia, significant anisometropia, hyperopia, and astigmatism, respectively. Children without prior CEE were more likely to have undetected amblyopia or strabismus than those with CEE history (Ps<0.001). CEE prevalence was higher among older children. Prevalence varied by race/ethnicity, with 8.1%, 7.9%, 6.3%, and 4.9% of NHW, AS, AA, and HS children having had prior CEE, respectively; however, the differences did not remain after adjusting for other associated factors. Older age, a primary caregiver with a college/university degree or higher, having vision insurance, gestational age <33 weeks, neurodevelopmental disorder diagnosis, strabismus, and ocular disease history were all associated with a relatively higher CEE prevalence in multivariable analyses (P≤0.003 for all). ConclusionsCEE was uncommon among preschool children, including those with treatable vision disorders. Interventions, like parent education and vision insurance, are needed to improve CEE access and utilization for at-risk preschool children.

Quality of melatonin use in children and adolescents: findings from a UK clinical audit

BackgroundMelatonin is commonly used to treat sleep disturbance in children and adolescents, although uncertainties about its optimal use remain.ObjectiveTo determine to what extent prescribing of melatonin complies with evidence-based clinical...

A-GCL: Adversarial graph contrastive learning for fMRI analysis to diagnose neurodevelopmental disorders.

Accurate diagnosis of neurodevelopmental disorders is a challenging task due to the time-consuming cognitive tests and potential human bias in clinics. To address this challenge, we propose a novel adversarial self-supervised graph neural network (GNN) based on graph contrastive learning, named A-GCL, for diagnosing neurodevelopmental disorders using functional magnetic resonance imaging (fMRI) data. Taking advantage of the success of GNNs in psychiatric disease diagnosis using fMRI, our proposed A-GCL model is expected to improve the performance of diagnosis and provide more robust results. A-GCL takes graphs constructed from the fMRI images as input and uses contrastive learning to extract features for classification. The graphs are constructed with 3 bands of the amplitude of low-frequency fluctuation (ALFF) as node features and Pearson's correlation coefficients (PCC) of the average fMRI time series in different brain regions as edge weights. The contrastive learning creates an edge-dropped graph from a trainable Bernoulli mask to extract features that are invariant to small variations of the graph. Experiment results on three datasets - Autism Brain Imaging Data Exchange (ABIDE) I, ABIDE II, and attention deficit hyperactivity disorder (ADHD) - with 3 atlases - AAL1, AAL3, Shen268 - demonstrate the superiority and generalizability of A-GCL compared to the other GNN-based models. Extensive ablation studies verify the robustness of the proposed approach to atlas selection and model variation. Explanatory results reveal key functional connections and brain regions associated with neurodevelopmental disorders.

Dynamics of changes as a determinant of diagnosis in neurodevelopmental disorders

Dynamics of changes as a determinant of diagnosis in neurodevelopmental disorders

14 Changes in Service Delivery Models for Children with Neurodevelopmental Disorders During the Covid-19 Pandemic

Objective:With the onset of the COVID-19 pandemic, many families face barriers in accessing critical services for their children. However, there is a disproportionate impact on families of children with Neurodevelopmental Disorders (NDDs), particularly those who are dependant on receiving regular services. The current study investigated how service delivery has changed for children and families with NDDs during the COVID-19 pandemic, to identify which groups are most at risk for service disruption and negative outcomes, and to provide actionable recommendations for community agencies that provide early interventions for future pandemics.Participants and Methods:Data was collected in the fall and winter of 2020/2021 during the Covid-19 pandemic. Families were recruited from a local service provider in British Columbia whose Early Years Support services delivery model was changed to online delivery during the pandemic. Children had a diagnosis of NDD or were on the waitlist for an assessment. Overall, 26 families participated in a semi-structured interview that asked about their experiences of receiving services for their children during the pandemic. Of these families, 20 subsequently completed online questionnaires that asked about their parenting stress levels and their children’s behaviour throughout the pandemic. Families of a range of compositions were drawn from different ethnicities (30% white, 25% South Asian, 20% Filipino, and the remaining 5% identified as Indigenous, African or East Asian). The mean age of children was 3.80 years (SD =0.72).Results:From the survey, we found that 58% of parents reported higher than average levels of mental health and behavioural challenges in their children during the Covid-19 pandemic. In addition, 45% of parents reported higher than average parenting stress levels. Qualitative interview data indicated that most parents reported positive experiences with receiving services during the Covid-19 pandemic and reported feeling supported even with social distancing measures. However, families also reported increased stress levels and isolation, particularly those who have children with Autism Spectrum Disorder, who rely on early funding (06 years) and early services. One of the themes that emerged from parents who were on the waitlist to receive an assessment was that wait times around assessments were very long, which contributed to parent stress levels. Parents also reported concerns around wait times to access services and difficulty of accessing online services due to internet and connection issues.Conclusions:The current study identified central themes of stressors and barriers experienced by families and children with NDDs in service delivery. Overall, parents reported satisfaction in changes in service delivery in most ways; however, they also reported stresses and barriers that included wait times, increased isolation, and accessing online services. Actionable steps to reduce family stress include better communication between service providers and families for wait times, and more variability in appointment times. Specific recommendations for current and future pandemics will be expanded on in the poster.

Comprehensive evaluation of the implementation of episignatures for diagnosis of neurodevelopmental disorders (NDDs)

Episignatures are popular tools for the diagnosis of rare neurodevelopmental disorders. They are commonly based on a set of differentially methylated CpGs used in combination with a support vector machine model. DNA methylation (DNAm) data often include missing values due to changes in data generation technology and batch effects. While many normalization methods exist for DNAm data, their impact on episignature performance have never been assessed. In addition, technologies to quantify DNAm evolve quickly and this may lead to poor transposition of existing episignatures generated on deprecated array versions to new ones. Indeed, probe removal between array versions, technologies or during preprocessing leads to missing values. Thus, the effect of missing data on episignature performance must also be carefully evaluated and addressed through imputation or an innovative approach to episignatures design. In this paper, we used data from patients suffering from Kabuki and Sotos syndrome to evaluate the influence of normalization methods, classification models and missing data on the prediction performances of two existing episignatures. We compare how six popular normalization methods for methylarray data affect episignature classification performances in Kabuki and Sotos syndromes and provide best practice suggestions when building new episignatures. In this setting, we show that Illumina, Noob or Funnorm normalization methods achieved higher classification performances on the testing sets compared to Quantile, Raw and Swan normalization methods. We further show that penalized logistic regression and support vector machines perform best in the classification of Kabuki and Sotos syndrome patients. Then, we describe a new paradigm to build episignatures based on the detection of differentially methylated regions (DMRs) and evaluate their performance compared to classical differentially methylated cytosines (DMCs)-based episignatures in the presence of missing data. We show that the performance of classical DMC-based episignatures suffers from the presence of missing data more than the DMR-based approach. We present a comprehensive evaluation of how the normalization of DNA methylation data affects episignature performance, using three popular classification models. We further evaluate how missing data affect those models’ predictions. Finally, we propose a novel methodology to develop episignatures based on differentially methylated regions identification and show how this method slightly outperforms classical episignatures in the presence of missing data.

Contributor biographies

Contributor biographies

B - 10 The Effect of Gestational Age on Development of Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder.

Studies show individuals with comorbid neurodevelopmental disorders of autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) have poorer emotional, behavioral, and cognitive outcomes. While preterm birth (< 37weeks) is an identified risk factor for ASD and ADHD, it is important to consider gestational age (ga) as it relates to the development of comorbid ASD/ADHD (ASD/ADHD). The current study aims to understand the relationship between level of prematurity (LoP) and neurodevelopmental disorders. Participants included 10,711 children/adolescents (52.5% male) from the Environmental Influences on Child Health Outcomes (ECHO) Program. LoP was categorized as Extremely Preterm (36weeks). Chi-square analysis was conducted to examine the relationship between LoP and neurodevelopmental disorder diagnoses as indicated in medical records. Logistic regression was also conducted to analyze the relationship between ga (weeks) and neurodevelopmental disorder diagnosis. 1521 individuals were diagnosed with ASD (n = 537), ADHD (n = 778), or ASD/ADHD (n = 206); ga ranged from 22 to 43weeks. Results indicated the relationship between LoP and diagnoses was significant, ꭓ2(9, 10,771) = 148.31, p < 0.001. Extremely Preterm individuals were more likely than Full-term individuals to have ASD, ADHD, or ASD/ADHD. It was found that the odds of having a neurodevelopmental disorder decreased by 5.8% per 1-week ga increase (95% CI[-0.069, -0.048]). Results indicate gestational age is associated with greater risk of neurodevelopmental disorders, including comorbid ASD/ADHD. Improved understanding of the association between level of prematurity and comorbid ASD/ADHD diagnoses may help inform early intervention services enhancing children's outcomes throughout the lifespan.

Computer aided diagnosis of neurodevelopmental disorders and genetic syndromes based on facial images – A systematic literature review

Neurodevelopment disorders can result in facial dysmorphisms. Therefore, the analysis of facial images using image processing and machine learning techniques can help construct systems for diagnosing genetic syndromes and neurodevelopmental disorders. The systems offer faster and cost-effective alternatives for genotyping tests, particularly when dealing with large-scale applications. However, there are still challenges to overcome to ensure the accuracy and reliability of computer-aided diagnosis systems. This article presents a systematic review of such initiatives, including 55 articles. The main aspects used to develop these diagnostic systems were discussed, namely datasets - availability, type of image, size, ethnicities and syndromes - types of facial features, techniques used for normalization, dimensionality reduction and classification, deep learning, as well as a discussion related to the main gaps, challenges and opportunities.

A dataset of multicenter database on Perinatal Factors in Child Brain-Mind Development (PeriCBD)

Neurodevelopmental disorders (NDDs) refer to a series of mental disorders that plague the motor and behavioral development of children in the K12 basic education stage. The etiology and pathogenesis of these disorders remain unclear. Multicenter Children's Brain Development Database under Perinatal Factors (PeriCBD) is established by the State Key Laboratory of Cognitive Neuroscience and Learning, Beijing Normal University, relying on county/prefecture/district central hospitals to collect data on the brain development of children in high-incidence age groups of NDDs. The primary purpose is to construct a data information platform related to brain development patterns and individual differences in children aged 3-10 under perinatal factors. Meanwhile, the platform is expected to provide critical basic data for the national brain development research, predictive diagnosis, and treatment of NDDs in children. This paper takes the data collection work completed in Anyang Maternal and Child Health Hospital of Henan Province and the People's Hospital of Liangping District of Chongqing City as examples to introduce the organizational framework of PeriCBD, and clarify the unified collection, cleaning, and analysis process of subject behavior data and magnetic resonance imaging data. In addition, following the standardization in processes, such as data extraction, conversion, loading of database links, etc., the dataset aims to establish a paradigm for subsequent PeriCBD data collection and database were shown.

Deep-learning for automated markerless tracking of infants general movements

The presence of abnormal infant General Movements (GMs) is a strong predictor of progressive neurodevelopmental disorders, including cerebral palsy (CP). Automation of the assessment will overcome scalability barriers that limit its delivery to at-risk individuals. Here, we report a robust markerless pose-estimation scheme, based on advanced deep-learning technology, to track infant movements in consumer mobile device video recordings. Two deep neural network models, namely Efficientnet-b6 and resnet-152, were trained on manually annotated data across twelve anatomical locations (3 per limb) in 12 videos from 6 full-term infants (mean age = 17.33 (SD 2.9) wks, 4 male, 2 female), using the DeepLabCut™ framework. K-fold cross-validation indicates the generalization capability of the deep-nets for GM tracking on out-of-domain data with an overall performance of 95.52% (SD 2.43) from the best performing model (Efficientnet-b6) across all infants (performance range: 84.32–99.24% across all anatomical locations). The paper further introduces an automatic, unsupervised strategy for performance evaluation on extensive out-of-domain recordings through a fusion of likelihoods from a Kalman filter and the deep-net. Findings indicate the possibility of establishing an automated GM tracking platform, as a suitable alternative to, or support for, the current observational protocols for early diagnosis of neurodevelopmental disorders in early infancy.