Onset In Early Childhood Research Articles

8585 Using Stimulants to Treat Childhood Obesity

Abstract Disclosure: C. Elatrash: None. S.R. Sisley: None. Background: Hyperphagia, characterized by excessive hunger, can significantly contribute to weight gain in early-onset childhood obesity and lacks an FDA-approved therapy. Stimulants commonly used in the treatment of attention deficit and hyperactivity disorder (ADHD) have a significant side effect of suppressing appetite. However, there is no data on the effectiveness of stimulants to reduce measures of obesity in children with severe obesity and hyperphagia. Methods: We retrospectively analyzed electronic medical records of children < 17 years old with severe, early-onset obesity (defined as a Body Mass Index (BMI) ≥ 120% of the 95th percentile (BMI%95th) prior to age 5 years) who were seen in the Genetic Disorders of Obesity Program (GDOP) at Texas Children’s Hospital (TCH). We included children who had a history of abnormal food behavior consistent with a clinical diagnosis of hyperphagia by having 2 of 9 symptoms of hyperphagia (consuming large portions, consistently feeling hungry, not feeling full with one serving, temper tantrums over food, asking for food frequently, sneaking food, getting up at night to eat, hiding food, constant asking for snacks) and were prescribed lisdexamfetamine treatment for hyperphagia for 6 months. We extracted BMI %95th for up to 12 months prior to treatment and 6 months after treatment. Paired t-tests were utilized to compare data from pre- vs. post-treatment. Results: Our cohort included 22 patients and was 68.2% female, 50% non-Hispanic White, 36.4% Hispanic white, and 13.6% black, with a mean age of 7.73 years±3.82 (range 3-17 years). There was a significant decrease in BMI%95th after treatment with lisdexamfetamine (167.3±38.8 vs. 158.0±40.2; p<0.001). We also observed a significant change in the rate of weight gain after lisdexamfetamine treatment; prior to treatment, patients gained 0.6 BMI%95th points/month compared to a loss of 1.9 points/month after treatment (p=0.002). 16 (72.72%) patients reported tolerable side effects, the rate of side effects was (33)33.33%. 19(57.57%) lasted from 1 week to 1 month and 6(18.18%) lasted more than 1 month. Side effects included adverse behavioral (9)27.27%, sleep disturbance (5)15.15%, and headache (4)12.12%. Conclusion: Children with severe obesity and clinical hyperphagia showed reductions in BMI%95th after six months of lisdexamfetamine treatment. Future research is needed to confirm the clinical efficacy of lisdexamfetamine in this high-risk population. Keywords: Childhood obesity, Stimulants, Hyperphagia, Pharmacologic Treatment Presentation: 6/3/2024

Heterozygous loss-of-function variants in SPTAN1 cause a novel early childhood onset distal myopathy with chronic neurogenic features.

Neurogenetic disorders caused by pathogenic variants in four genes encoding non-erythrocytic spectrins ( SPTAN1, SPTBN1, SPTBN2, SPTBN4) range from peripheral and central nervous system involvement to complex syndromic presentations. Heterozygous pathogenic variants in SPTAN1 are exemplary for this diversity with phenotypes spanning almost the entire spectrum. Through international collaboration we identified 14 families with genetically unsolved distal weakness and unreported heterozygous SPTAN1 loss-of-function variants including frameshift, nonsense and splice-acceptor variants. Clinical data, electrophysiology, muscle CT or MRI and muscle biopsy findings were collected and standardized. SPTAN1 protein, mRNA expression analysis and cDNA sequencing was performed on muscle tissue from two patients. All 20 patients presented with early childhood onset distal weakness. The severity varied both within families and between different families. Foot abnormalities ranged from hammer toes and pes cavus to distal arthrogryposis. Electrophysiology showed mixed myogenic and neurogenic features. Muscle MRI or CT in 10 patients showed fatty infiltration of the distal lower limb anterior compartment and/or selective involvement of the extensor hallucis longus muscle. Muscle biopsy revealed myopathic changes with mild dystrophic and chronic neurogenic changes in 7 patients. Finally, we provide proof for nonsense mediated decay in tissues derived from two patients. We provide evidence for the association of SPTAN1 loss-of-function variants with childhood onset distal myopathy in 14 families. This finding extends the phenotypic spectrum of SPTAN1 loss-of-function variants ranging from intellectual disability to distal weakness with a predominant myogenic cause. SPTAN1 loss-of-function variants, including frameshift, nonsense and splice site variants cause a novel childhood onset distal weakness syndrome with primarily skeletal muscle involvement. Hereditary motor neuropathies and distal myopathic disorders present a well-known diagnostic challenge as they demonstrate substantial clinical and genetic overlap. The emergence of SPTAN1 loss-of-function variants serves as a noteworthy example, highlighting a growing convergence in the spectrum of genotypes linked to both hereditary motor neuropathies and distal myopathies.

Early Childhood Onset Vanishing White Matter Disease with Multiple Cranial Nerve Enhancement: A New Consensus Criteria?

Vanishing White Matter Disease (VWM), also known as Childhood Ataxia with Central Nervous System Hypomyelination (CACH), although a rare neurological condition, is a prevalent hereditary leukoencephalopathy with a characteristic phenotype of gradual neurologic deterioration with ataxia being a prominent feature. It is characterized by a wide range of onset, from antenatal and infantile periods to early childhood and later adulthood periods. The early childhood form is considered the prevailing form, characterized by a preceding phase of normal development until the second or 3rd year of life, followed by progressive neurologic deterioration, accentuated by certain stressors, such as infections or minor trauma. Diagnosis is achieved based on the clinical pretext combined with distinctive MRI brain features, confirmed by DNA analysis detection of elf2B mutation. Our case is a healthy 18-month-old male who after a preceding upper respiratory tract infection, developed an ataxic gait, encephalopathy, and recurrent generalized seizures. Physical assessment revealed signs of generalized spasticity and hyperreflexia. Neuroimaging revealed diffuse symmetric supratentorial and infratentorial diffuse white matter hypomyelination. Interestingly, there was notable enhancement of the 3rd and 5th cranial nerves. Differential diagnosis included acute demyelinating leukoencephalopathies; and neuromatobolic disorders with acute presentations (including leukodystrophies, hypomyelinating disorders, and mitochondrial encephalopathies). In the early course of his management, he received immunomodulatory therapy in the form of pulse steroids, intravenous immunoglobulins, and oral tapering course of steroids. He had limited response to these interventions. Whole exome sequencing yielded a homozygous mutation in EIF2B3, confirming the diagnosis of VWMD/CACH. The presence of enhancing cranial neuropathies represent an atypical phenotype reported in other case reports and should alert the physician to avoid unnecessary intervention with immunosuppressive therapies.

Clinical Spectrum of Atopic Dermatitis in Pediatric Age Group from a Tertiary Care Center in India: A Cross-sectional Study

Introduction: Atopic dermatitis (AD) is a chronic, inflammatory, relapsing skin disorder with early age of onset in infancy and early childhood. A gradual increase in the prevalence of AD has been observed recently, especially in low-income countries like ours. Objective: We aimed to study the epidemiology and clinical profile of AD among pediatric age group in a tertiary care hospital in North India. Materials and Methods: A hospital-based cross-sectional study was conducted over 1 year in the department of dermatology and sexually transmitted diseases in a tertiary care center in India. All children diagnosed with AD, aged 0–18 years, were recruited, and their clinical and demographic data were recorded. Results: In the 62 children having AD, the mean age was 7.7 ± 6.3 years. Majority of children belonged to the age group of 1–5 years. The mean age of onset of AD was 2.3 ± 2.2 years. A personal history of atopy was present in 53.2% of children, whereas 48.3% of children had a family history of atopy. Acute AD was the most common clinical type that was noted in 43.5%. Hyperlinearity of palms, keratosis pilaris, pityriasis alba, and periorbital darkening were found in 59.6%, 33.8%, 24.1%, and 29% of children, respectively. Conclusion: The prevalence of AD is low in developing countries like India, but it is slowly rising due to rapidly evolving urbanization and environmental changes. Disease manifestation is usually mild to moderate in Indian patients; hence, vigilant eyes and high clinical suspicion are required for accurate diagnosis and efficient management of AD in Indian settings.

Genetic Analysis of SCN11A, SCN10A, and SCN9A in Familial Episodic Pain Syndrome (FEPS) in Japan and Proposal of Clinical Diagnostic Criteria.

Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of SCN11A, SCN10A, and SCN9A, which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for SCN11A, SCN10A, and SCN9A. In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of SCN11A, SCN10A, and SCN9A, respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.

Review: Binocular double vision in the presence of visual field loss.

Binocular double vision in strabismus is marked by diplopia (seeing the same object in two different directions) and visual confusion (seeing two different objects in the same direction). In strabismus with full visual field, the diplopia coexists with visual confusion across most of the binocular field. With visual field loss, or with use of partial prism segments for field expansion, the two phenomena may be separable. This separability is the focus of this review and offers new insights into binocular function. We show that confusion is necessary but is not sufficient for field expansion. Diplopia plays no role in field expansion but is necessary for clinical testing of strabismus, making such testing difficult in field loss conditions with confusion without diplopia. The roles of the three-dimensional structure of the real world and the dynamic of eye movements within that structure are considered as well. Suppression of one eye's partial view under binocular vision that develops in early-onset (childhood) strabismus is assumed to be a sensory adaption to diplopia. This assumption can be tested using the separation of diplopia and confusion.

Interictal EEG features as computational biomarkers of West syndrome.

West syndrome (WS) is a devastating epileptic encephalopathy with onset in infancy and early childhood. It is characterized by clustered epileptic spasms, developmental arrest, and interictal hypsarrhythmia on electroencephalogram (EEG). Hypsarrhythmia is considered the hallmark of WS, but its visual assessment is challenging due to its wide variability and lack of a quantifiable definition. This study aims to analyze the EEG patterns in WS and identify computational diagnostic biomarkers of the disease. Linear and non-linear features derived from EEG recordings of 31 WS patients and 20 age-matched controls were compared. Subsequently, the correlation of the identified features with structural and genetic abnormalities was investigated. WS patients showed significantly elevated alpha-band activity (0.2516 vs. 0.1914, p < 0.001) and decreased delta-band activity (0.5117 vs. 0.5479, p < 0.001), particularly in the occipital region, as well as globally strengthened theta-band activity (0.2145 vs. 0.1655, p < 0.001) in power spectrum analysis. Moreover, wavelet-bicoherence analysis revealed significantly attenuated cross-frequency coupling in WS patients. Additionally, bi-channel coherence analysis indicated minor connectivity alterations in WS patients. Among the four non-linear characteristics of the EEG data (i.e., approximate entropy, sample entropy, permutation entropy, and wavelet entropy), permutation entropy showed the most prominent global reduction in the EEG of WS patients compared to controls (1.4411 vs. 1.5544, p < 0.001). Multivariate regression results suggested that genetic etiologies could influence the EEG profiles of WS, whereas structural factors could not. A combined global strengthening of theta activity and global reduction of permutation entropy can serve as computational EEG biomarkers for WS. Implementing these biomarkers in clinical practice may expedite diagnosis and treatment in WS, thereby improving long-term outcomes.

Phototherapeutic keratectomy for cornealepithelial-stromaldystrophies in pediatric patients.

Corneal dystrophies may develop gradually from early onset in childhood and persist for years to decades. Visual impairment or repeated ocular irritations caused by corneal dystrophies severely affect the quality of life. Although various surgical treatment options are indicated for adult patients, the treatment plan for pediatric patients remains unclear. Herein we describe clinical observations of phototherapeutic keratectomy for corneal epithelial-stromal dystrophies in three pediatric patients (five eyes). Corneal opacities were successfully removed, and visual acuity was greatly improved in all operated eyes. The procedure of phototherapeutic keratectomy seems to be feasible in the treatment of corneal epithelial-stromal dystrophies in c hildren, with advantages of minimal invasion and good visual outcomes.

Advances in Mendelian randomization studies on autism spectrum disorder

Autism spectrum disorder (ASD) is a pervasive neurodevelopmental disorder with onset in infancy or early childhood. Mendelian randomization (MR) is a statistical method used to infer causal relationships between exposures and outcomes. This article summarizes MR studies related to ASD. Existing research supports a causal relationship between maternal inflammatory bowel disease in children with ASD, parental education levels, screen time exposure, obesity, insomnia, serum transferrin, decreased blood selenium, abnormal signals in brain functional MRI, interleukin-6, phosphodiesterase 2A, mitogen-activated protein kinase kinase 3, mitochondrial ribosomal protein L33, serotonin, and ASD. However, it does not support a causal relationship between parental rheumatoid arthritis, systemic lupus erythematosus, neonatal jaundice in children with ASD, cytomegalovirus infection, asthma, oral ulcers, vitamin D levels, and ASD. This article reviews the etiological factors related to ASD and MR studies, aiming to explore and deepen the understanding of the pathophysiology of ASD. It provides strong statistical support for the prevention, diagnosis, and treatment of ASD, and offers new methods and strategies for the etiological analysis of complex traits.

Early and late onset childhood eczema: Role of preconceptional, pre-natal and post-natal environmental exposures

BackgroundDespite mounting evidence linking indoor and outdoor environments to eczema, the role of indoor and outdoor environmental pollutant(s) exposure during critical time window(s) on eczema remains unknown. ObjectiveTo investigate the correlations between childhood eczema and itchy rashes and exposure to outdoor air pollution and the home environment. MethodsA combined cross-sectional and retrospective cohort study of 8689 kindergarten students was conducted. We collected information about each child's health outcomes and home environment, as well as calculated individual exposure to air pollutants. Multiple logistic regression models were used to investigate the links between indoor and outdoor environments and childhood eczema and itchy rashes. ResultsChildhood ever doctor-diagnosed eczema (DDE) was linked to NO2, CO, PM2.5, PM2.5-10 and PM10 exposure during the preconceptional, pregnant, and postnatal periods, with ORs (95 % CI) ranging from 1.06 (1.00–1.13) to 1.21 (1.08–1.37). Ever doctor-diagnosed itchy rash (DDIR) was associated with SO2, CO, PM2.5, PM2.5-10 and PM10 exposure during preconceptional and postnatal periods, with ORs (95 % CI) ranging from 1.11 (1.02–1.20) to 1.31 (1.13–1.52). Preconceptional outdoor air pollution was associated with a higher risk of ever, early, and late DDE and DDIR. Indoor smoke, renovation, and dampness were all associated with DDE and DDIR. Postnatal exposure to plants has been linked to both ever and early DDE. There was no link between indoor environments and late DDE. Furthermore, pregnancy has been identified as a critical indoor exposure time window for DDE and DDIR. ConclusionsEarly-life exposure to outdoor air pollutants and indoor environments, particularly before birth, played important roles in childhood eczema.

Epidemiologic and clinical differences between early-onset and later-onset childhood vitiligo: A retrospective cohort study

Epidemiologic and clinical differences between early-onset and later-onset childhood vitiligo: A retrospective cohort study

Next Generation Sequencing in presumptive diagnosis of syndromes in childhood retinal dystrophies - case series from India

PurposeChildhood onset retinal dystrophies are heterogeneous group of diseases that include Leber congenital amaurosis (LCA), juvenile retinitis pigmentosa, early onset retinitis pigmentosa (EORP) and Severe Early Childhood Onset Retinal Dystrophy (SECORD) and can present either as an isolated condition or with associated non-ocular features. Genetic testing aids in the differential diagnosis of these conditions, for monitoring and timely management of the systemic manifestations. In this study, we present a case series of childhood onset retinal dystrophies where genetic testing has aided in the diagnosis of syndromic form of inherited retinal degenerations (IRD). MethodsPatients (N = 10) underwent complete ophthalmic examination including slit lamp biomicroscopy and dilated indirect ophthalmoscopy. ERG, fundus photograph and Optical Coherence Tomography was done for all patients if the child cooperated for the same. This was followed by targeted re-sequencing of IRD gene panel, on the Illumina Hiseq 2500 platform. Clinical follow up for other associated systemic features was advised based on the genetic results, for patients who were asymptomatic at the time of genetic diagnosis. The patients were monitored for the same periodically. ResultsMutations were identified in IQCB1, ALMS1, SLC19A2, CNNM4, and VPS13B genes suggested associated syndromes. In all these cases, the ocular phenotype was the first presentation in early infancy and genetic testing for IRD genes suggested syndromic disease. The patients could hence be followed up appropriately for other manifestations. ConclusionsMolecular diagnosis has helped in identifying the associated syndrome in these patients with childhood retinal dystrophies who were asymptomatic for some of the non-ocular features at the time of genetic testing. The patients can be benefitted by frequent clinical surveillance with a scope for effective and timely management of the systemic features wherever applicable.

Exacerbation of Mirror Movement Disorder: A Complex Case of Childhood-onset Mirror Movements Aggravated by Essential Tremors, and Parkinson's Disease

Background Mirror movement (MM), also known as bimanual synkinesis, is characterized by simultaneous involuntary movements of homologous muscles accompanying voluntary movements of contralateral body regions. MM can be observed in various neurological conditions, including cerebral palsy, corticobasal syndrome, Parkinson's disease, certain types of symptomatic epilepsies, Creutzfeldt-Jakob's disease, Huntington's disease, and others. Case Description A 52-year-old female with a history of epileptic seizures, essential tremors and mild MM was presented to a neurology clinic for seizure management. She had a long-standing history of seizures since childhood. Initial neurological examination revealed mild MM disorder. During the follow up visits, patient’s mirror movements were exacerbated months before she was diagnosed with Parkinson’s disease. Multiple antiepileptic drug regiments along with Carbidopa-levodopa were used and dose adjustments were done during follow up visits to help stabilize the patient’s symptoms. Conclusion In conclusion, this case highlights the progressive nature of mirror movement disorder (MMD) and its association with other neurological conditions, such as epilepsy, essential tremors, and Parkinson's disease. The primary aim of this study was to showcase that individuals with early childhood onset of MMD may experience a deterioration of their condition as they acquire additional neurological disorders, such as essential tremors or Parkinson's disease. Moreover, this study seeks to elucidate how the exacerbation of mirror movement symptoms in such cases can serve as an early indicator of the onset of Parkinson's disease. Medication adjustments played a crucial role in managing the patient's symptoms, emphasizing the importance of individualized treatment plans and close monitoring.

What OPA1 models teach us about potential therapy

Autosomal dominant optic atrophy (DOA) is the most common inherited optic neuropathy, affecting approximately 1 in 25 000 people. DOA has an insidious onset in early childhood. It presents typically with bilateral central painless vision loss, dyschromatopsia, and optic disc pallor due to gradual retinal ganglion cell (RGC) loss and optic nerve degeneration. 60%–70% of genetically confirmed DOA cases are associated with variants in OPA1. OPA1 is an ubiquitously expressed GTPase that regulates mitochondrial homeostasis through coordination of inner membrane fusion, maintenance of cristae structure, and maintenance of bioenergetic output. Over 250 known pathogenic variants in OPA1 have been reported, with missense variants within the GTPase domain associated with an increased susceptibility to developing DOA plus (DOA+), a multisystemic syndromic form of the disease with extraocular features, including sensorineural hearing loss and ataxia. Current therapeutic options to treat DOA are limited. Idebenone has been shown to protect against visual loss in Leber's hereditary optic neuropathy (LHON). In DOA off ‐label retrospective series show some promise in some patients.Animal models for OPA1 DOA, have been reported, including Drosophila, C elegans, Danio rerio and mouse models. They have cast light on some potential therapeutic modalities. Despite limitations, murine models of DOA are currently indispensable for understanding pathophysiology of disease, drug testing and development. They replicate many symptoms and signs of human disease. However, there are caveats. Chemically induced Complex I deficits are very toxic. Genetic models of mitochondrial mutation affect protein integrity and function and can cause severe pathologies. This is made more problematic if there is a need for aging the mouse to bring out the full phenotype. We shall review the mouse models and describe some features that aid or our understanding of pathophysiological mechanisms. Our research has characterized the earliest morphological changes as a progressive loss of synapses, dendrite retraction and RGC remodelling and loss of connectivity. In the DOA mouse Opa1+/− mouse (B6;C3‐Opa1Q285STOP), heterozygous Opa1+/− mice develop visual defects, on psychophysics (optokinetic response) and electrophysiology (VEP, PhNR), consistent with RGC dysfunction. There is depressed mitochondrial Complex I and IV activity. Visible structural changes and disrupted axon morphology in the optic nerve are seen. We have carried out a randomized, placebo‐controlled trial of the benzoquinone idebenone in our ADOA mouse, which revealed a limited therapeutic effect on RGC dendropathy and visual function.It is apparent that there are large differences between the rodent and primate visual system. The fovea of the retina, a critical component for central vision is one of the only primate‐specific components of the mammalian nervous system and is thus, not found in rodent. For these reasons, there is a strong case to use human cells. We shall review data on induced human pluripotent stem cell (hiPSC) with OPA1 mutation, with or without differentiation to RGCs, as models, and on CRISPRCas9 correction of patient‐derived OPA1 iPSC lines.

A Novel Variant in TPM3 Causing Muscle Weakness and Concomitant Hypercontractile Phenotype.

A novel variant of unknown significance c.8A > G (p.Glu3Gly) in TPM3 was detected in two unrelated families. TPM3 encodes the transcript variant Tpm3.12 (NM_152263.4), the tropomyosin isoform specifically expressed in slow skeletal muscle fibers. The patients presented with slowly progressive muscle weakness associated with Achilles tendon contractures of early childhood onset. Histopathology revealed features consistent with a nemaline rod myopathy. Biochemical in vitro assays performed with reconstituted thin filaments revealed defects in the assembly of the thin filament and regulation of actin-myosin interactions. The substitution p.Glu3Gly increased polymerization of Tpm3.12, but did not significantly change its affinity to actin alone. Affinity of Tpm3.12 to actin in the presence of troponin ± Ca2+ was decreased by the mutation, which was due to reduced interactions with troponin. Altered molecular interactions affected Ca2+-dependent regulation of the thin filament interactions with myosin, resulting in increased Ca2+ sensitivity and decreased relaxation of the actin-activated myosin ATPase activity. The hypercontractile molecular phenotype probably explains the distal joint contractions observed in the patients, but additional research is needed to explain the relatively mild severity of the contractures. The slowly progressive muscle weakness is most likely caused by the lack of relaxation and prolonged contractions which cause muscle wasting. This work provides evidence for the pathogenicity of the TPM3 c.8A > G variant, which allows for its classification as (likely) pathogenic.

Periconceptional maternal diet quality and offspring wheeze trajectories: Japan Environment and Children's Study.

The role of prenatal diet on childhood wheezing and subsequent risk of asthma is inconclusive, which may be partly due to the heterogeneity in wheezing phenotypes. We aimed to identify wheeze trajectories in early childhood and to examine their associations with periconceptional maternal diet quality. Data from 70,530 mother-child pairs of liveborn singletons from the Japan Environment and Children's Study were analysed. Wheezing was reported by caregivers using a modified International Study of Asthma and Allergies in Childhood questionnaire yearly from 1 to 4 years of age, from which trajectories were derived using group-based trajectory modelling. Maternal diet in the year preceding the first trimester of pregnancy was assessed using a validated food frequency questionnaire; overall diet quality was determined using the balanced diet score based on the Japanese Food Guide Spinning Top. Bayesian inference of multinomial logistic regression models was performed to examine the association between maternal diet quality and wheeze trajectory in early childhood. We identified four wheeze trajectories: 'never/infrequent' (69.1%; reference group), 'early-childhood onset' (6.2%), 'transient early' (16.5%) and 'persistent' (8.2%). After adjustment for confounders, a higher quartile of maternal balanced diet score was associated with a lower risk of belonging to the 'transient early' and 'persistent' wheeze trajectories compared with the 'never/infrequent' wheeze trajectory by 10% of both. Maternal balanced diet score was not associated with belonging to the 'early-childhood onset' wheeze trajectory. Improving maternal diet quality prior to conception may reduce certain wheeze phenotypes in early childhood.

Exploring the Association Between Trauma, Instability, and Youth Cardiometabolic Health Outcomes Over Three Years

PurposeChildhood adversity plays a fundamental role in predicting youth cardiometabolic health. Our understanding of how adverse experiences in childhood should best be conceptualized remains elusive, based on one-dimensional measures of adversity. The present study fills a major gap in existing research by examining two distinct forms of threat and instability-related exposures that may impact cardiometabolic risk (CMR) in adolescence. MethodsWe explore two specific subtypes of adversity: trauma (e.g., badly hurt, victim of crime, loss of close person) and instability (e.g., moving, change of schools, change in household structure) as differential influences that can accumulate to impact early childhood onset of CMR (body mass index, high-density lipoprotein (HDL), low-density lipoprotein, diastolic and systolic blood pressure, triglycerides, C-reactive protein, insulin sensitivity). Secondary data were drawn from a randomized control behavioral trial of youth recruited during sixth grade from urban Cleveland (Ohio) schools beginning in 2012–2014 (n = 360) and followed for 3 years. Participants reported on 12 adverse experiences, six trauma- and six instability-specific. Multiple regression assessed effects of prospective and accumulative indices of trauma and instability with 3-year trajectories of eight objective CMR markers. ResultsInstability was associated with increased body mass index, decreased high-density lipoprotein, and increased C-reactive protein slopes. Trauma was associated with trends in triglyceride levels but not with any other CMR outcomes. DiscussionExperiences with instability distinctly impacted adolescent CMR. Future research is needed to examine factors that can enhance stability for families in marginalized communities.

Juvenile Idiopathic Arthritis.

Juvenile idiopathic arthritis (JIA) comprises a group of heterogenous disorders characterized by childhood-onset chronic joint inflammation. It is the most common rheumatologic disease in the pediatric population and an important cause of chronic illness in children. Early recognition and treatment are vital to prevent sequelae of uncontrolled inflammation on the developing skeleton. JIA can have significant complications that general pediatricians should be aware of, especially uveitis, which can be insidious and asymptomatic in very young children, and macrophage activation syndrome, which can be life-threatening if not recognized and appropriately treated. Although advances have been made in the past few decades, the etiology of JIA remains incompletely understood. Efforts are underway to refine the classification of JIA. The currently accepted classification scheme identifies subsets of JIA that are important clinically in terms of prognosis and tailoring treatment approaches. However, it is limited in identifying homogenous groups of children with early childhood onset and antinuclear antibody positivity, which may have different pathogenic mechanisms that could be important in developing more targeted and effective treatment approaches in the future. Treatment strategies for JIA have changed significantly in recent years with the availability of multiple newer targeted therapies, often modeled after medications used in adult-onset forms of arthritis. These treatments, and likely many others to come, have markedly improved symptom control and reduced complications in patients with JIA.

Energy expenditure deficits drive obesity in a mouse model of Alström syndrome.

Alström syndrome (AS) is a rare multisystem disorder of which early onset childhood obesity is a cardinal feature. Like humans with AS, animal models with Alms1 loss-of-function mutations develop obesity, supporting the notion that ALMS1 is required for the regulatory control of energy balance across species. This study aimed to determine which component(s) of energy balance are reliant on ALMS1. Comprehensive energy balance phenotyping was performed on Alms1tvrm102 mice at both 8 and 18 weeks of age. It was found that adiposity gains occurred early and rapidly in Alms1tvrm102 male mice but much later in females. Rapid increases in body fat in males were due to a marked reduction in energy expenditure (EE) during early life and not due to any genotype-specific increases in energy intake under chow conditions. Energy intake did increase in a genotype-specific manner when mice were provided a high-fat diet, exacerbating the effects of reduced EE on obesity progression. The EE deficit observed in male Alms1tvrm102 mice did not persist as mice aged. Either loss of ALMS1 causes a developmental delay in the mechanisms controlling early life EE or activation of compensatory mechanisms occurs after obesity is established in AS. Future studies will determine how ALMS1 modulates EE and how sex moderates this process.

Current Approaches in the Multimodal Management of Asthma in Adolescents-From Pharmacology to Personalized Therapy.

Asthma and adolescence are two sensitive points and are difficult to manage when they coexist. The first is a chronic respiratory condition, with frequent onset in early childhood (between 3 and 5 years), which can improve or worsen with age. Adolescence is the period between childhood and adulthood (12-19 years), marked by various internal and external conflicts and a limited capacity to understand and accept any aspect that is delimited by the pattern of the social circle (of the entourage) frequented by the individual. Therefore, the clinician is faced with multiple attempts regarding the management of asthma encountered during the adolescent period, starting from the individualization of the therapy to the control of compliance (which depends equally on the adverse reactions, quality of life offered and support of the close circle) and the social integration of the subject, communication probably having a more important role in the monitoring and evolution of the condition than the preference for a certain therapeutic scheme. Current statistics draw attention to the increase in morbidity and mortality among children with bronchial asthma, an aspect demonstrated by the numerous hospitalizations recorded, due either to an escalation in the severity of this pathology or to faulty management. The purpose of this article is to review the delicate aspects in terms of controlling symptoms and maintaining a high quality of life among teenagers.