Disorders In Children Research Articles

Exploring Maternal Diet-Epigenetic-Gut Microbiome Crosstalk as an Intervention Strategy to Counter Early Obesity Programming.

Alterations in a mother's metabolism and endocrine system, due to unbalanced nutrition, may increase the risk of both metabolic and non-metabolic disorders in the offspring's childhood and adulthood. The risk of obesity in the offspring can be determined by the interplay between maternal nutrition and lifestyle, intrauterine environment, epigenetic modifications, and early postnatal factors. Several studies have indicated that the fetal bowel begins to colonize before birth and that, during birth and nursing, the gut microbiota continues to change. The mother's gut microbiota is primarily transferred to the fetus through maternal nutrition and the environment. In this way, it is able to impact the establishment of the early fetal and neonatal microbiome, resulting in epigenetic signatures that can possibly predispose the offspring to the development of obesity in later life. However, antioxidants and exercise in the mother have been shown to improve the offspring's metabolism, with improvements in leptin, triglycerides, adiponectin, and insulin resistance, as well as in the fetal birth weight through epigenetic mechanisms. Therefore, in this extensive literature review, we aimed to investigate the relationship between maternal diet, epigenetics, and gut microbiota in order to expand on current knowledge and identify novel potential preventative strategies for lowering the risk of obesity in children and adults.

Plasma fatty acids and attention deficit hyperactivity disorder: a Mendelian randomization investigation.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder of childhood, and pathogenesis is not fully understood. Observational studies suggest an association between fatty acids abnormalities and ADHD, but there are contradictions and differences between these findings. To address this uncertainty, we employed a two-sample bidirectional Mendelian Randomization (MR) analysis to investigate the causal relationship between fatty acids and ADHD. We conducted a two-sample Mendelian Randomization (MR) study, selecting single nucleotide polymorphisms (SNPs) highly correlated with fatty acid levels from the CHARGE Consortium as our instruments. The outcome data were sourced from the Psychiatric Genomics Consortium (PGC) dataset on ADHD, comprising 225,534 individuals, with 162,384 cases and 65,693 controls. Inverse variance weighting, MR-Egger, and weighted median methods were employed to estimate the causal relationship between fatty acids and ADHD. Cochran's Q-test was used to quantify heterogeneity of instrumental variables. Sensitivity analyses included MR-Egger intercept tests, leave-one-out analyses, and funnel plots. The MR analysis revealed no significant associations between genetically predicted levels of various saturated, monounsaturated, and polyunsaturated fatty acids (including omega-3 and omega-6) and ADHD risk in the CHARGE and PGC cohorts. Notably, an initial association with Dihomo-gamma-linolenic acid (DGLA) (OR = 1.009, p = 0.032 by IVW) did not persist after correction for multiple testing (adjusted p-value = 0.286). Sensitivity analysis supported our findings, indicating robustness. Moreover, there was a lack of evidence supporting a causal link from ADHD to fatty acids. While our study on the basis of genetic data does not provide evidence to support the causal role of fatty acids in ADHD, it does not preclude their potential involvement in reducing the risk of ADHD. Further research is needed to explore this possibility.

Application of Dempster-Shafer Theory Method in Expert System for Diagnosis of Psychological Disorders in Children

Application of Dempster-Shafer Theory Method in Expert System for Diagnosis of Psychological Disorders in Children

Eating disorders in childhood and adolescence

Eating disorders in childhood and adolescence

122. BISS and YMRS as Measures to Assess Bipolar Disorder in Children and Adolescents

122. BISS and YMRS as Measures to Assess Bipolar Disorder in Children and Adolescents

Attention Deficit Hyperactivity Disorder in Children and Adolescents: Lessons from the COVID-19 Pandemic

Attention Deficit Hyperactivity Disorder in Children and Adolescents: Lessons from the COVID-19 Pandemic

Championing the Cause of Rare Blood Disorders in Children

Championing the Cause of Rare Blood Disorders in Children

Calcium-sensing receptor signaling is amplified in patients with a FAM111A gene mutation

Introduction: A six-year-old female presented with seizures, low blood calcium (Ca2+), low parathyroid hormone (PTH) and increased urinary Ca2+ excretion. She was diagnosed with Autosomal Dominant Hypocalcemia (ADH), a childhood disorder characterized by low blood Ca2+ and inappropriately low PTH. She had no mutations in genes known to cause ADH (Ca2+-sensing receptor ( CASR) and G-protein subunit alpha 11 ( GNA11)). Consequently, we performed whole exome sequencing and a trio analysis that identified a novel FAM111A gene mutation (c.1454G>A, p.C485Y). Although FAM111A is a protease, the specific protein targets are unknown. In addition, FAM111A regulates DNA replication and thus gene expression. Interestingly, FAM111A gene mutations cause Kenny Caffey syndrome (KCS) and Osteocraniostenosis (OCS), conditions characterized by low blood Ca2+, low PTH, and bony abnormalities. The molecular mechanism mediating these phenotypes are unknown. We hypothesize that mutations in FAM111A cause increased CASR signaling, resulting in low blood Ca2+ and high urine Ca2+ levels. The CASR is a G-protein coupled receptor, which upon activation by extracellular Ca2+, initiates signaling cascades that increase intracellular Ca2+ levels and decrease cyclic adenosine monophosphate (cAMP). CASR activation also increases the expression of the tight-junction protein claudin-14 (CLDN14). In the kidney, CLDN14 blocks Ca2+ reabsorption leading to increased urine Ca2+ excretion and lower blood Ca2+. Our objective was to determine if FAM111A wild-type (WT) suppresses CASR signaling and if the mutants fail to do so. Methods: Human embryonic cells (HEK293) were transfected with empty vector (EV) as a control, CASR and EV, FAM111A WT with EV or CASR and FAM111A WT or mutants (C485Y, ADH; Y511H, KCS; R569H, KCS; T338A, OCS; P527R, OCS; D528G, OCS; S541A, inactivated protease). We performed Fura2AM imaging of intracellular Ca2+ in transfected cells in the presence of increasing extracellular Ca2+ (0.5-11.3 mM) levels. Also, as an indication of CASR activity, we measured CLDN14 expression and cAMP levels, in transfected cells incubated in 0.5 mM or 5 mM extracellular Ca2+, via a dual luciferase assay and cAMP assay kit, respectively. Results: The change in peak intracellular Ca2+ concentration was two times higher (p<0.05) in cells with CASR plus EV or FAM111A mutants, compared to EV or FAM111A WT plus CASR. Similarly, luciferase activity as an indication of CLDN14 levels, was significantly higher (p<0.05) in CASR plus EV compared to EV and FAM111A WT plus CASR. Some mutants (C485Y, T338A, P527T, D528G, S542A) had similar CLDN14 levels to CASR plus EV, while others (Y511H, R569H) showed similar levels to FAM111A plus CASR. The cAMP levels were not different in cells with CASR and FAM111A WT compared to CASR with FAM111A mutants. Conclusions: FAM111A WT attenuates CASR activity. All FAM111A mutations assessed, enhanced CASR activity when measured by an increase in intracellular Ca2+. Some mutants increase CLDN14 expression, while others may affect a different CASR signaling pathway. Elucidating the mechanism of how FAM111A affects CASR activity and Ca2+ homeostasis will provide a better understanding of our patient’s condition as well as those with KCS or OCS. Canadian Institute of Health Research; Stollery Children’s Hospital Foundation through the Women and Children's Health Research Institute (WCHRI); Alberta Innovates Graduate Student Scholarship; WCHRI Graduate Studentship Award. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Expanding the Phenotype of the CACNA1C-Associated Neurological Disorders in Children: Systematic Literature Review and Description of a Novel Mutation.

Background: CACNA1C gene encodes the alpha 1 subunit of the CaV1.2 L-type Ca2+ channel. Pathogenic variants in this gene have been associated with cardiac rhythm disorders such as long QT syndrome, Brugada syndrome and Timothy syndrome. Recent evidence has suggested the possible association between CACNA1C mutations and neurologically-isolated (in absence of cardiac involvement) phenotypes in children, giving birth to a wider spectrum of CACNA1C-related clinical presentations. However, to date, little is known about the variety of both neurological and non-neurological signs/symptoms in the neurologically-predominant phenotypes. Methods and Results: We conducted a systematic review of neurologically-predominant presentations without cardiac conduction defects, associated with CACNA1C mutations. We also reported a novel de novo missense pathogenic variant in the CACNA1C gene of a children patient presenting with constructional, dressing and oro-buccal apraxia associated with behavioral abnormalities, mild intellectual disability, dental anomalies, gingival hyperplasia and mild musculoskeletal defects, without cardiac conduction defects. Conclusions: The present study highlights the importance of considering the investigation of the CACNA1C gene in children's neurological isolated syndromes, and expands the phenotype of the CACNA1C related conditions. In addition, the present study highlights that, even in absence of cardiac conduction defects, nuanced clinical manifestations of the Timothy syndrome (e.g., dental and gingival defects) could be found. These findings suggest the high variable expressivity of the CACNA1C gene and remark that the absence of cardiac involvement should not mislead the diagnosis of a CACNA1C related disorder.

컬러테라피를 활용한 심리치료 관련 국내 학술지 연구동향 분석

The purpose of this study is to analyze research trends in domestic academic journals related to psychotherapy using color therapy as an alternative approach following the government's recent announcement of a mental health policy innovation plan and to suggest directions for follow-up research. For this purpose, 29 papers published from 2009 to 2023 were analyzed. The research results are as follows. First, research was conducted steadily from 2009 to 2023, and was highest in 2022 (17.24%). Second, it was presented at 18 domestic academic conferences, and ‘art therapy research’ was the most common (20.69%). Third, the study subjects had the highest proportion of adults, followed by college students, others (mixed), adolescents, children, and the elderly. Fourth, the types of research methods were quantitative research, literature research, qualitative research, and mixed research. Fifth, the type of study content had a positive effect on psychotherapy in the general subareas(ego, emotions/psychology, stress, maladjustment & problem behavior, interpersonal relationships) and diagnostic subareas(emotional disorders, childhood disorders, brain injury disorders). Based on the research results, it is suggested that psychotherapy using color therapy can be usefully applied in the field.

Arthroscopic Management of Dysplasia Epiphysealis Hemimelica (Trevor Disease) of the Ankle

Dysplasia epiphysealis hemimelica (Trevor disease) is a rare skeletal development disorder of childhood, characterized by irregular ossification centers, which may develop together or individually, leading to asymmetric epiphyseal cartilage overgrowth, affecting 1 side of the epiphyses or the epiphyses equivalents (the medial side being affected twice as often as the lateral), until skeletal maturity is reached. Trevor disease around the ankle is locally aggressive with a poor outcome, especially in tumors involving the articular surface. The purpose of this Technical Note is to describe the details of arthroscopic management of dysplasia epiphysealis hemimelica (Trevor disease) of the ankle.

Seronegative Polyarticular Juvenile Idiopathic Arthritis: A Case Report.

Juvenile idiopathic arthritis (JIA) is a chronic rheumatologic childhood disorder of unknown etiology usually presenting with peripheral arthritis. Usually involving the small joints symmetrically, polyarticular JIA is characterized by involvement of 5 or more peripheral joints and is further categorized depending on RA Factor positivity. We aim to report a case of seronegative polyarticular JIA to increase awareness regarding this disease. A 15-year-old boy presented with 3-month history of bilateral symmetrical joint pains, swelling and morning stiffness lasting 3-4 hours. For his ankle and knee pain, he had consulted a local doctor who suspected Rheumatic Fever and started penicillin and analgesics resulting in minimal improvement. He was a student but was unable to attend school in last 2 months due to this illness and had become bed-bound for last 2 weeks. On examination, there was swelling and tenderness of ankles, knees, elbows, wrists, metacarpophalangeal and proximal interphalangeal joints bilaterally. On investigation, ESR, CRP and serum ferritin were raised with normal complete blood count, urinalysis, liver and renal function tests, ASO test, blood and urine cultures, TSH, serum CPK and serum aldolase. Echocardiography did not reveal any abnormalities. His ANA, RA factor and Anti-CCP antibodies were negative. He was diagnosed with Seronegative Polyarticular Juvenile Idiopathic Arthritis and started on oral prednisolone and methotrexate. Currently the patient is asymptomatic on methotrexate 20mg/week. Our patient with symmetrical polyarthritis had negative ANA, RA Factor and Anti-CCP antibodies leading to a diagnosis of seronegative polyarticular JIA. Early screening and prompt management of JIA is required to improve prognosis and reduce risk of disability. The differential diagnosis of childhood joint pains is wide and variable including diseases of autoimmune, cardiac and haematological systems. For diagnosis of JIA, arthritis persisting for more than 6 weeks with onset of symptoms prior to 16 years of age is required with exclusion of secondary causes of joint inflammation. Keywords: Juvenile Idiopathic Arthritis, ANA, RA Factor, Anti-CCP antibodies, Methotrexate.

Physical Fitness and Risk of Mental Disorders in Children and Adolescents

With the rising prevalence of mental disorders among children and adolescents, identifying modifiable associations is critical. To examine the association between physical fitness and mental disorder risks. This nationwide cohort study used data from the Taiwan National Student Fitness Tests and National Health Insurance Research Databases from January 1, 2009 to December 31, 2019. Participants were divided into 2 cohorts targeting anxiety and depression (1 996 633 participants) and attention-deficit/hyperactivity disorder (ADHD; 1 920 596 participants). Participants were aged 10 to 11 years at study entry and followed up for at least 3 years, had a nearly equal gender distribution, and an average follow-up of 6 years. Data were analyzed from October 2022 to February 2024. Assessments of physical fitness included cardiorespiratory fitness (CF), muscular endurance (ME), muscular power (MP), and flexibility, measured through an 800-m run time, bent-leg curl-ups, standing broad jump, and sit-and-reach test, respectively. Kaplan-Meier method calculated the cumulative incidence of anxiety, depression, and ADHD across fitness quartiles. Additionally, multivariable Cox proportional hazards models were used that included all 4 fitness components and explored sex and income as modifiers. The anxiety and depression cohort had 1 996 633 participants (1 035 411 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years), while the ADHD cohort had 1 920 596 (975 568 participants were male [51.9%], and the median [IQR] age was 10.6 [10.3-11.0] years). Cumulative incidence of mental disorders was lower among participants in better-performing fitness quartiles, suggesting a dose-dependent association. Gender-specific analyses, controlling for confounders, revealed that improved CF, indicated by a 30-second decrease in run times, was associated with reduced risks of anxiety, depression, and ADHD in female participants, and lower risks of anxiety and ADHD in male participants (adjusted hazard ratio [aHR] for ADHD risk for female participants, 0.92; 95% CI, 0.90-0.94; P < .001; for male participants, 0.93; 95% CI, 0.92-0.94; P < .001). Enhanced ME, marked by an increase of 5 curl-ups per minute, was associated with decreased risks of depression and ADHD in female participants, and lower anxiety and ADHD risks in male participants (aHR for ADHD risk for female participants, 0.94; 95% CI, 0.92-0.97; P < .001; for male participants, 0.96; 95% CI, 0.95-0.97; P < .001). Improved MP, reflected by a 20-cm increase in jump distance, was associated with reduced risks of anxiety and ADHD in female participants and reduced anxiety, depression, and ADHD in male participants (aHR for ADHD risk for female participants, 0.95; 95% CI, 0.91-1.00; P = .04; for male participants, 0.96; 95% CI, 0.94-0.99; P = .001). This study highlights the potential protective role of cardiorespiratory fitness, muscular endurance, and muscular power in preventing the onset of mental disorders. It warrants further investigation of the effectiveness of physical fitness programs as a preventive measure for mental disorders among children and adolescents.

Differential Diagnosis of Inflammatory Bowel Disease and Functional Bowel Disorder in Children Based on Ultrasonography

Objective: To study the diagnostic efficiency (DE) of sonographic signs in differentiation of inflammatory bowel disease (IBD) and functional bowel disorder (FBD) in children and to develop an optimal mathematical model for differential diagnosis of IBD and FBD using comprehensive assessment of sonographic signs.Material and methods: We examined 79 children with and without clinical signs of large-bowel disease. All the children underwent bowel ultrasonography with strain elastography. We also determined the level of fecal calprotectin (FC). The FC level &gt; 120 μg/g was a cutoff value to differentiate IBD from FBD.Results: We determined the DE of sonographic signs in verification of IBD and FBD: large-bowel wall thickening (DE, 87%; P &lt; .0001), large-bowel wall stratification (DE, 93.1%; P &lt; .0001), enlarged mesenteric lymph nodes (DE, 53.4%; P=.591), interloop ascites (DE, 98.3%; P &lt; .0001), Color Doppler findings in the large-bowel wall (DE, 98.3%; P &lt; .0001), strain elastography findings in the large-bowel wall (DE, 96.5%; P &lt; .0001). We developed an optimal model for differentiation of FBD and IBD using the analysis of sonographic signs (DE, 98.7%).Conclusions: The sonographic signs (large-bowel wall thickening, large-bowel wall stratification, interloop ascites, color Doppler findings in the large-bowel wall, stiffness found on strain elastography) can be effectively used for differential diagnosis of FBD and IBD in children. The developed mathematical model enables to reliably differentiate children with FBD and IBD.

The Role of Sleep Disturbances in the Onset and Maintenance of Psychiatric Disorders in Childhood and Adolescence: A Review of Subjective and Polysomnographic Findings

The Role of Sleep Disturbances in the Onset and Maintenance of Psychiatric Disorders in Childhood and Adolescence: A Review of Subjective and Polysomnographic Findings

Correlation between auto-immune diseases and type 1 diabetes mellitus in the pediatric age group in Erbil city

Background and objective: Type-1 diabetes mellitus is the most common chronic endocrine disorder of childhood and adolescence and is characterized by immune-mediated destruction of pancreatic cells, which has been proven to be correlated with and increase the risk of developing autoimmune thyroid disease, celiac disease, Addison’s disease, and further autoimmune diseases. The aim of this study is to evaluate the prevalence of autoimmune disease-related markers in type 1 diabetes mellitus in children and adolescents in Erbil city. Methods: One hundred children and adolescents with type 1 diabetes mellitus were enrolled in this cross-sectional study. Patients &lt;1 year old were excluded from the study. Autoimmune thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) along with tissue transglutaminase (IgA and IgG) antibodies were measured with further evaluation by thyroid function test and endoscopy with biopsy (for positive serological autoantibodies level). Results: Elevated anti-thyroglobulin, anti-thyroid peroxidase, and tissue transglutaminase IgA and IgG antibodies were determined in 24.0%, 26%, 10%, and 8%, respectively. 50.0% of cases with positive anti-thyroid peroxidase antibodies had overt hypothyroidism; on the flip side, 3.8% had subclinical hypothyroidism. As well, the high level of thyroid autoantibodies was significantly correlated to the prevalence of overt hypothyroidism (P &lt;0.001). Nine of the patients with positive tissue transglutaminase antibodies were verified to have biopsy-proven celiac disease. Conclusion: Children and adolescents with type 1 diabetes mellitus are at risk of developing positive antithyroid and celiac-related autoantibodies, so they are at risk of progressing to autoimmune thyroid and celiac diseases.

1136 Sleep Disorders in Children and Adolescents with Long COVID

1136 Sleep Disorders in Children and Adolescents with Long COVID

The relative usefulness of the identification and analysis of biomarkers for the diagnosis of autism spectrum disorders in early childhood and the implementation of personalized precision medicine

Despite progress towards understanding the etiological mechanisms of autism spectrum disorder (ASD), efficient treatment strategy for the primary clinically presented autistic features remain elusive. Up to the heterogeneity and complex nature of ASD, clinical presentation differ in severity and usually accompanied with multiple comorbidities, including gastrointestinal (GI) problems, sleep disturbances, epilepsy, and attention deficit hyperactivity disorder (ADHD). Discovery of biomarkers of ASD is essential not only for clarifying the clinical features of this disorder but also as an primary diagnostic implement that could help to tailor early interventions. Therefore, this review describes the core areas of ASD biomarker research, including GABAergic/glutamatergic imbalance, mitochondrial dysfunction, hyperserotonemia, and impaired gut microbiota, all of which have demonstrated success in diagnosing ASD and could serve as targets for implementing personalized precision medicine. Additionally, this review includes accomplishment that focus on the importance of precision medicine and the current trials that make use of ASD biomarkers detection.

Two-year Prevalence of Central Auditory Processing Disorders in Children.

Central auditory processing disorder (CAPD) refers to difficulties in processing audible signals not attributable to impaired hearing sensitivity or mental impairment. The demographic characteristics of pediatric CAPD and its prevalence are still debatable. Due to varied definitions and differences in the diagnostic criteria for CAPD, the approximate prevalence measure varies from 0.5 to 7% of the population. Thus, a retrospective study on prevalence in individuals with CAPD was conducted. A total of 3537 cases with ear-related problems were reported to Audiology OPD at All India Institute of Speech and Hearing from June 2017 to July 2019 between the age range of 6-18 years. Of these, 32 cases were diagnosed with CAPD, and this data was available for review. The prevalence of individuals with CAPD reported in this duration was 0.7%. The results also revealed that the prevalence was higher among males and individuals of lower socio-economic status. Their significant symptoms were poor academic performance and difficulty following commands or instructions. The data also revealed that speech perception in noise was the most affected process, followed by binaural integration in these individuals. The study provides insight into the vulnerable population who can get CAPD (e.g., children and males or people from lower socio-economic backgrounds).

Prevalence and Correlates of the Concurrence of Autism Spectrum Disorder and Obsessive Compulsive Disorder in Children and Adolescents: A Systematic Review and Meta-Analysis.

Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are two common and impairing neurodevelopmental conditions with partial symptomatic overlap. The aim of this study is to systematically and meta-analytically examine the following: (i) the prevalence of an OCD diagnosis among young people with ASD, (ii) the prevalence of an ASD diagnosis among young people with OCD, and (iii) the clinical and therapeutic implications of such comorbidity. A multistep literature search was performed from database inception until 17 November 2023. This PRISMA/MOOSE-compliant systematic review, registered in PROSPERO (CRD42023480543), identified studies reporting on the prevalence, sociodemographic, psychopathologic, prognostic, and therapeutic correlates of OCD and ASD concurrence in children and adolescents. A quantitative meta-analysis with random effects was conducted to analyse the pooled prevalence of OCD among samples with a mean age of < 18 years old with ASD and the prevalence of ASD among individuals under 18 with OCD. Sensitivity analyses were performed to investigate the effect of diagnostic criteria and different continents. Meta-regression analyses were conducted to examine the effect of gender, age, IQ, and OCD severity scores. A narrative review of the clinical and therapeutical implications of the comorbidity was provided. 42 studies were selected for the systematic review (SR), and 31 of them were also included in one of the meta-analyses. The pooled prevalence of OCD among ASD youth samples (n = 8916, mean age = 10.6 ± 1.6; 16.4% female) was 11.6% (95% confidence intervals [CI] = 6.9%; 18.8%), and the pooled prevalence of ASD among OCD children and adolescent samples (n = 6209, mean age = 14.1 ± 1.4; 45.7% female) was 9.5% (95% CI = 6.0%; 14.7%). Meta-regressions found a statistically higher prevalence of ASD among samples with a lower prevalence of females (β = -4.7; 95%CI = -8.6; -0.8). Children with both OCD and ASD present higher rates of functional impairment, psychopathology, and other comorbidities, compared to youth with either of the disorders alone. OCD and ASD are highly concurrent conditions in youth, with symptomatic, prognostic, severity, and therapeutic implications. Future research should focus on conducting longitudinal cohort studies prospectively to determine development trajectories, along with randomized controlled trials to assess the efficacy of specific therapeutic interventions.