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EClinicalMedicine Jul 2023Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use...
Use of melatonin for children and adolescents with chronic insomnia attributable to disorders beyond indication: a systematic review, meta-analysis and clinical recommendation.
BACKGROUND
Melatonin has become a widely used sleeping aid for young individuals currently not included in existing guidelines. The aim was to develop a recommendation on the use of melatonin in children and adolescents aged 2-20 years, with chronic insomnia due to disorders beyond indication.
METHODS
We performed a systematic search for guidelines, systematic reviews, and randomised trials (RCTs) in Medline, Embase, Cochrane Library, PsycInfo, Cinahl, Guidelines International Network, Trip Database, Canadian Agency for Drugs and Technologies in Health, American Academy of Sleep Medicine, European Sleep Research Society and Scandinavian Health Authorities databases. A separate search for adverse events was also performed. The latest search for guidelines, systematic reviews, and adverse events was performed on March 17, 2023. The latest search for RCTs was performed on to February 6, 2023. The language was restricted to English, Danish, Norwegian, and Swedish. Eligible participants were children and adolescents (2-20 years of age) with chronic insomnia due to underlying disorders, in whom sleep hygiene practices have been inadequate and melatonin was tested. Studies exclusively on autism spectrum disorders or attention deficit hyperactive disorder were excluded. There were no restrictions on dosage, duration of treatment, time of consumption or release formula. Primary outcomes were quality of sleep, daytime functioning and serious adverse events, assessed at 2-4 weeks post-treatment. Secondary outcomes included total sleep time, sleep latency, awakenings, drowsiness, quality of life, non-serious adverse events, and all-cause dropouts (assessed at 2-4 weeks post-treatment), plus quality of sleep and daytime functioning (assessed at 3-6 months post-treatment). Pooled estimates were calculated using inverse variance random effects model. Statistical heterogeneity was calculated using I statistics. Risk of bias was assessed using Cochrane risk of bias tool. Publication bias was assessed using funnel plots. A multidisciplinary guideline panel constructed the recommendation using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). The certainty of evidence was considered either high, moderate, low or very low depending on the extent of risk of bias, inconsistency, imprecision, indirectness, or publication bias. The evidence-to-decision framework was used to discuss the feasibility and acceptance of the constructed recommendation and its impact on resources and equity. The protocol is registered with the Danish Health Authority.
FINDINGS
We identified 13 RCTs, including 403 patients with a wide range of conditions. Melatonin reduced sleep latency by 14.88 min (95% CI 23.42-6.34, 9 studies, I = 60%) and increased total sleep time by 18.97 min (95% CI 0.37-37.57, 10 studies, I = 57%). The funnel plot for total sleep time showed no apparent indication of publication bias. No other clinical benefits were found. The number of patients experiencing adverse events was not statistically increased however, safety data was scarce. Certainty of evidence was low.
INTERPRETATION
Low certainty evidence supports a moderate effect of melatonin in treating sleep continuity parameters in children and adolescents with chronic insomnia due to primarily medical disorders beyond indication. The off-label use of melatonin for these patients should never be the first choice of treatment, but may be considered by medical specialists with knowledge of the underlying disorder and if non-pharmacological interventions are inadequate. If treatment with melatonin is initiated, adequate follow-up to evaluate treatment effect and adverse events is essential.
FUNDING
The Danish Health Authority. The Parker Institute, Bispebjerg and Frederiksberg Hospital, supported by the Oak Foundation.
PubMed: 37457114
DOI: 10.1016/j.eclinm.2023.102049 -
Brain Sciences Apr 2024Autism spectrum disorder (ASD) and obsessive compulsive disorder (OCD) are two common and impairing neurodevelopmental conditions with partial symptomatic overlap. The... (Review)
Review
Prevalence and Correlates of the Concurrence of Autism Spectrum Disorder and Obsessive Compulsive Disorder in Children and Adolescents: A Systematic Review and Meta-Analysis.
BACKGROUND
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.
METHOD
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.
RESULTS
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.
CONCLUSIONS
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.
PubMed: 38672028
DOI: 10.3390/brainsci14040379 -
European Child & Adolescent Psychiatry Feb 2024A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of... (Review)
Review
A better understanding of the endocannabinoid system and a relaxation in regulatory control of cannabis globally has increased interest in the medicinal use of cannabinoid-based products (CBP). We provide a systematic review of the rationale and current clinical trial evidence for CBP in the treatment of neuropsychiatric and neurodevelopmental disorders in children and adolescents. A systematic search of MEDLINE, Embase, PsycINFO, and the Cochrane Central Register of Trials was performed to identify articles published after 1980 about CBP for medical purposes in individuals aged 18 years or younger with selected neuropsychiatric or neurodevelopmental conditions. Risk of bias and quality of evidence was assessed for each article. Of 4466 articles screened, 18 were eligible for inclusion, addressing eight conditions (anxiety disorders (n = 1); autism spectrum disorder (n = 5); foetal alcohol spectrum disorder (n = 1); fragile X syndrome (n = 2); intellectual disability (n = 1); mood disorders (n = 2); post-traumatic stress disorder (n = 3); and Tourette syndrome (n = 3)). Only one randomised controlled trial (RCT) was identified. The remaining seventeen articles included one open-label trial, three uncontrolled before-and-after trials, two case series and 11 case reports, thus the risk of bias was high. Despite growing community and scientific interest, our systematic review identified limited and generally poor-quality evidence for the efficacy of CBP in neuropsychiatric and neurodevelopmental disorders in children and adolescents. Large rigorous RCTs are required to inform clinical care. In the meantime, clinicians must balance patient expectations with the limited evidence available.
Topics: Child; Humans; Adolescent; Cannabinoids; Anxiety Disorders; Stress Disorders, Post-Traumatic; Tourette Syndrome
PubMed: 36864363
DOI: 10.1007/s00787-023-02169-w -
JAMA Network Open Nov 2023Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Exome sequencing (ES) has been established as the preferred first line of diagnostic testing for certain neurodevelopmental disorders, such as global developmental delay and autism spectrum disorder; however, current recommendations are not specific to or inclusive of congenital hydrocephalus (CH).
OBJECTIVE
To determine the diagnostic yield of ES in CH and whether ES should be considered as a first line diagnostic test for CH.
DATA SOURCES
PubMed, Cochrane Library, and Google Scholar were used to identify studies published in English between January 1, 2010, and April 10, 2023. The following search terms were used to identify studies: congenital hydrocephalus, ventriculomegaly, cerebral ventriculomegaly, primary ventriculomegaly, fetal ventriculomegaly, prenatal ventriculomegaly, molecular analysis, genetic cause, genetic etiology, genetic testing, exome sequencing, whole exome sequencing, genome sequencing, microarray, microarray analysis, and copy number variants.
STUDY SELECTION
Eligible studies included those with at least 10 probands with the defining feature of CH and/or severe cerebral ventriculomegaly that had undergone ES. Studies with fewer than 10 probands, studies of mild or moderate ventriculomegaly, and studies using genetic tests other than ES were excluded. A full-text review of 68 studies was conducted by 2 reviewers. Discrepancies were resolved by consensus.
DATA EXTRACTION AND SYNTHESIS
Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and Meta-Analysis of Observational Studies in Epidemiology guidelines were used by 2 reviewers to extract data. Data were synthesized using a random-effects model of single proportions. Data analysis occurred in April 2023.
MAIN OUTCOMES AND MEASURES
The primary outcome was pooled diagnostic yield. Additional diagnostic yields were estimated for specific subgroups on the basis of clinical features, syndromic presentation, and parental consanguinity. For each outcome, a 95% CI and estimate of interstudy heterogeneity (I2 statistic) was reported.
RESULTS
From 498 deduplicated and screened records, 9 studies with a total of 538 CH probands were selected for final inclusion. The overall diagnostic yield was 37.9% (95% CI, 20.0%-57.4%; I2 = 90.1). The yield was lower for isolated and/or nonsyndromic cases (21.3%; 95% CI, 12.8%-31.0%; I2 = 55.7). The yield was higher for probands with reported consanguinity (76.3%; 95% CI, 65.1%-86.1%; I2 = 0) than those without (16.2%; 95% CI, 12.2%-20.5%; I2 = 0).
CONCLUSIONS AND RELEVANCE
In this systematic review and meta-analysis of the diagnostic yield of ES in CH, the diagnostic yield was concordant with that of previous recommendations for other neurodevelopmental disorders, suggesting that ES should also be recommended as a routine diagnostic adjunct for patients with CH.
Topics: Female; Pregnancy; Humans; Autism Spectrum Disorder; Exome Sequencing; Pathology, Molecular; Patients; Hydrocephalus
PubMed: 37991765
DOI: 10.1001/jamanetworkopen.2023.43384 -
Frontiers in Human Neuroscience 2023Autism spectrum disorder (ASD) is an increasingly prevalent and heterogeneous neurodevelopmental condition, characterized by social communicative differences, and a...
Autism spectrum disorder (ASD) is an increasingly prevalent and heterogeneous neurodevelopmental condition, characterized by social communicative differences, and a combination of repetitive behaviors, focused interests, and sensory sensitivities. Early speech and language delays are characteristic of young autistic children and are one of the first concerns reported by parents; often before their child's second birthday. Elucidating the neural mechanisms underlying these delays has the potential to improve early detection and intervention efforts. To fill this gap, this systematic review aimed to synthesize evidence on early neurobiological correlates and predictors of speech and language development across different neuroimaging modalities in infants with and without a family history of autism [at an elevated (EL infants) and low likelihood (LL infants) for developing autism, respectively]. A comprehensive, systematic review identified 24 peer-reviewed articles published between 2012 and 2023, utilizing structural magnetic resonance imaging (MRI; = 2), functional MRI (fMRI; = 4), functional near-infrared spectroscopy (fNIRS; = 4), and electroencephalography (EEG; = 14). Three main themes in results emerged: compared to LL infants, EL infants exhibited (1) atypical language-related neural lateralization; (2) alterations in structural and functional connectivity; and (3) mixed profiles of neural sensitivity to speech and non-speech stimuli, with some differences detected as early as 6 weeks of age. These findings suggest that neuroimaging techniques may be sensitive to early indicators of speech and language delays well before overt behavioral delays emerge. Future research should aim to harmonize experimental paradigms both within and across neuroimaging modalities and additionally address the feasibility, acceptability, and scalability of implementing such methodologies in non-academic, community-based settings.
PubMed: 37662636
DOI: 10.3389/fnhum.2023.1211676 -
Children (Basel, Switzerland) Jun 2024Traditional pharmacological treatments, although effective, often carry potential side effects, which positions art therapy and music therapy as promising... (Review)
Review
Interventions through Art Therapy and Music Therapy in Autism Spectrum Disorder, ADHD, Language Disorders, and Learning Disabilities in Pediatric-Aged Children: A Systematic Review.
Traditional pharmacological treatments, although effective, often carry potential side effects, which positions art therapy and music therapy as promising non-pharmacological alternatives to alleviate symptoms and improve social, cognitive, and emotional skills without the associated risks. Through a review in the SCOPUS and WOS databases following the PRISMA protocol, a total of 80 articles were analyzed through a series of determined categories and subcategories of analysis. The aim of this study is to evaluate and synthesize the existing evidence on the efficacy and applicability of art therapy and music therapy in the treatment of children with autism spectrum disorder (ASD), hyperactivity disorder (HSDD), developmental language disorders, and language learning difficulties, identifying best practices and key areas for future research. Among the main findings is that art therapy and music therapy have a significant impact on symptomatology, behavior, and communication as well as social, cognitive, and emotional skills in the pediatric populations studied. These therapies are highly valued by the participants with a large majority recognizing their adaptability to different educational and clinical contexts. It is concluded that these therapies have a high potential as viable alternatives or complements to traditional pharmacological treatments, justifying their application and further study in broader therapeutic contexts.
PubMed: 38929285
DOI: 10.3390/children11060706 -
Neurologia 2024Communication and language skills are among the most severely affected domains in individuals with autistic spectrum disorder (ASD). When a child diagnosed with ASD... (Review)
Review
INTRODUCTION
Communication and language skills are among the most severely affected domains in individuals with autistic spectrum disorder (ASD). When a child diagnosed with ASD lives in a bilingual environment, the parents often express concerns about whether their child should learn both languages simultaneously, turning to specialists for advice. Despite the lack of evidence of any negative effect, some professionals disagree on this subject. In this systematic review we study whether bilingualism affects language development in children with ASD.
METHODS
We reviewed the literature published in 4 different databases. After applying a series of selection criteria, we selected 12 scientific articles, including a total of 328 children diagnosed with ASD (169 bilingual and 159 monolingual), with ages ranging from 3 to 12 years. These patients were evaluated with different receptive and expressive language assessment instruments covering several areas. The assessments were performed directly on the children, although indirect assessment of parents was also performed in some studies.
CONCLUSIONS
There seems to be consensus regarding the assertion that bilingualism does not entail any additional difficulty for language development in children with ASD from the age of 3.
Topics: Child; Humans; Multilingualism; Language; Autism Spectrum Disorder; Language Development; Parents
PubMed: 38065434
DOI: 10.1016/j.nrleng.2023.12.007 -
Frontiers in Nutrition 2023Central nervous system (CNS) disorders present a growing and costly global health challenge, accounting for over 11% of the diseases burden in high-income countries.... (Review)
Review
Central nervous system (CNS) disorders present a growing and costly global health challenge, accounting for over 11% of the diseases burden in high-income countries. Despite current treatments, patients often experience persistent symptoms that significantly affect their quality of life. Dietary polysaccharides have garnered attention for their potential as interventions for CNS disorders due to their diverse mechanisms of action, including antioxidant, anti-inflammatory, and neuroprotective effects. Through an analysis of research articles published between January 5, 2013 and August 30, 2023, encompassing the intervention effects of dietary polysaccharides on Alzheimer's disease, Parkinson's disease, depression, anxiety disorders, autism spectrum disorder, epilepsy, and stroke, we have conducted a comprehensive review with the aim of elucidating the role and mechanisms of dietary polysaccharides in various CNS diseases, spanning neurodegenerative, psychiatric, neurodevelopmental disorders, and neurological dysfunctions. At least four categories of mechanistic bases are included in the dietary polysaccharides' intervention against CNS disease, which involves oxidative stress reduction, neuronal production, metabolic regulation, and gut barrier integrity. Notably, the ability of dietary polysaccharides to resist oxidation and modulate gut microbiota not only helps to curb the development of these diseases at an early stage, but also holds promise for the development of novel therapeutic agents for CNS diseases. In conclusion, this comprehensive review strives to advance therapeutic strategies for CNS disorders by elucidating the potential of dietary polysaccharides and advocating interdisciplinary collaboration to propel further research in this realm.
PubMed: 38075226
DOI: 10.3389/fnut.2023.1299117 -
Frontiers in Pediatrics 2023Studies have found that toxic heavy metals exposure could induce the generation of reactive oxygen species (ROS), and is of epigenetic effect, which might be associated...
BACKGROUND
Studies have found that toxic heavy metals exposure could induce the generation of reactive oxygen species (ROS), and is of epigenetic effect, which might be associated with the occurrence of Autistic Disorder (ASD). This systematic review and meta-analysis aims to elucidate the association between exposure to 4 heavy metals, cadmium (Cd), lead (Pb), arsenic(As), and mercury (Hg), and the occurrence of ASD in children.
METHODS
We searched PubMed, Web of Science, Embase, and Cochrane Library, from their inception to October 2022, for epidemiological investigations that explore the association between exposure to Cd, Pb, As, or Hg and the occurrence of child ASD.
RESULTS
A total of 53 studies were included, involving 5,054 individuals aged less than 18 (2,533 ASD patients and 2,521 healthy controls). Compared with the healthy controls, in hair and blood tests, concentrations of the 4 heavy metals were significantly higher in the ASD group than in the healthy control group, and the differences in Pb, arsenic and Hg were statistically significant ( < 0.05). In the urine test, concentrations of arsenic and Hg were significantly higher in the ASD group than in the healthy control group ( < 0.05), while the results of Cd and Pb were opposite to those of arsenic and Hg ( > 0.05). Subgroup analysis for geographic regions showed that ASD patients in Asia and Europe had higher concentrations of the 4 heavy metals, compared with the healthy controls, in which the differences in Pb, arsenic, and Hg were statistically significant ( < 0.05), while in North America, the healthy controls had higher Cd, arsenic, and Hg concentrations ( > 0.05).
CONCLUSION
Compared with the healthy control group, the ASD group had higher concentrations of Cd, Pb, arsenic, and Hg. These 4 heavy metals play different roles in the occurrence and progression of ASD. Moreover, there is significant heterogeneity among the included studies due to controversies about the study results among different countries and regions and different sources of detection materials. The results of this study firmly support the policies to limit heavy metals exposure, especially among pregnant women and young children, so as to help reduce the incidence of ASD.
PubMed: 37469682
DOI: 10.3389/fped.2023.1169733 -
Clinical Psychology Review Aug 2023Autistic children and adults are at increased risk of showing behaviours that may be described as challenging, however, little is known about whether or how these... (Meta-Analysis)
Meta-Analysis Review
Autistic children and adults are at increased risk of showing behaviours that may be described as challenging, however, little is known about whether or how these behaviours may change over time. Given the profound impact that challenging behaviour can have on both the autistic individual and their support network, it is critical that the trajectory of challenging behaviours be better understood. This systematic review and meta-analysis identified and synthesised observational longitudinal studies of challenging behaviour in autistic individuals. Fifty-six studies were included in the systematic review, and the effect sizes of 37 independent samples arising from 34 of these reports were examined through meta-analysis. Crucially, across the 37 samples, scores on the measures of challenging behaviour reduced by a small, yet significant, extent over time. Although age of the sample at baseline assessment did not moderate the effect, the time between the baseline assessment and final follow-up and age at final follow-up both moderated the magnitude of the effect, with challenging behaviour scores reducing to a larger extent in (a) studies with longer intervals between baseline and final follow-up and (b) studies with older samples at follow-up. The results from the current systematic review and meta-analysis have both theoretical and practical implications for understanding challenging behaviour over time in autistic individuals. Avenues for future research are also highlighted that may allow better understanding, and therefore support of, challenging behaviour in autistic individuals.
Topics: Humans; Child; Adult; Autistic Disorder; Longitudinal Studies; Social Behavior; Observational Studies as Topic
PubMed: 37515997
DOI: 10.1016/j.cpr.2023.102320