scholarly journals A Systematic Review and Meta-Analysis of Immunoglobulin G Abnormalities and the Therapeutic Use of Intravenous Immunoglobulins (IVIG) in Autism Spectrum Disorder

2021 ◽  
Vol 11 (6) ◽  
pp. 488
Author(s):  
Daniel A Rossignol ◽  
Richard E Frye
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Immunoglobulin G ◽  
Meta Analysis ◽  
Intravenous Immunoglobulins ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Effect Sizes ◽  
Aberrant Behavior ◽  
Children With Asd

Autism spectrum disorder (ASD) is a neurodevelopmental disorder affecting approximately 2% of children in the United States. Growing evidence suggests that immune dysregulation is associated with ASD. One immunomodulatory treatment that has been studied in ASD is intravenous immunoglobulins (IVIG). This systematic review and meta-analysis examined the studies which assessed immunoglobulin G (IgG) concentrations and the therapeutic use of IVIG for individuals with ASD. Twelve studies that examined IgG levels suggested abnormalities in total IgG and IgG 4 subclass concentrations, with concentrations in these IgGs related to aberrant behavior and social impairments, respectively. Meta-analysis supported possible subsets of children with ASD with low total IgG and elevated IgG 4 subclass but also found significant variability among studies. A total of 27 publications reported treating individuals with ASD using IVIG, including four prospective, controlled studies (one was a double-blind, placebo-controlled study); six prospective, uncontrolled studies; 2 retrospective, controlled studies; and 15 retrospective, uncontrolled studies. In some studies, clinical improvements were observed in communication, irritability, hyperactivity, cognition, attention, social interaction, eye contact, echolalia, speech, response to commands, drowsiness, decreased activity and in some cases, the complete resolution of ASD symptoms. Several studies reported some loss of these improvements when IVIG was stopped. Meta-analysis combining the aberrant behavior checklist outcome from two studies demonstrated that IVIG treatment was significantly associated with improvements in total aberrant behavior and irritability (with large effect sizes), and hyperactivity and social withdrawal (with medium effect sizes). Several studies reported improvements in pro-inflammatory cytokines (including TNF-alpha). Six studies reported improvements in seizures with IVIG (including patients with refractory seizures), with one study reporting a worsening of seizures when IVIG was stopped. Other studies demonstrated improvements in recurrent infections, appetite, weight gain, neuropathy, dysautonomia, and gastrointestinal symptoms. Adverse events were generally limited but included headaches, vomiting, worsening behaviors, anxiety, fever, nausea, fatigue, and rash. Many studies were limited by the lack of standardized objective outcome measures. IVIG is a promising and potentially effective treatment for symptoms in individuals with ASD; further research is needed to provide solid evidence of efficacy and determine the subset of children with ASD who may best respond to this treatment as well as to investigate biomarkers which might help identify responsive candidates.

scholarly journals Network Meta-Analysis of Physical Activity Interventions On Cognitive Functions In Children With Autism Spectrum Disorder: A Protocol of Randomized Controlled Trials

2021 ◽  
Author(s):  
Longxi Li ◽  
Anni Wang ◽  
Qun Fang ◽  
Michelle E. Moosbrugger
Keyword(s):  
Physical Activity ◽  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Cognitive Functions ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Controlled Trials ◽  
Extant Literature ◽  
Children With Asd

Abstract Background: Autism spectrum disorder (ASD) symptoms are usually observed by the age of 2 years. However, the mechanism of ASD is still encompassed in a block box and no identified cure exists. Based on accumulating evidence, intensive early treatment such as physical activity or exercise can make a significant difference in the cognitive control and development in children with ASD. This study aims to update the knowledge on extant literature and explore the efficacy of physical activity intervention strategies (PAIS) on cognitive functions in children with ASD. Methods: A systematic review and network meta-analysis will be conducted following the preferred reporting items for systematic review and meta-analysis protocols for Network Meta-Analyses (PRISMA-NMA). Nine bibliographic databases (APA PsycInfo, Cochrane Central Register of Controlled Trials, Dimensions, ERIC, MEDLINE Complete, PubMed, Scopus, SPORTDiscus, Web of Science) will be systematically searched to screen eligible articles based on a series of inclusion and exclusion criteria. A study will be considered for inclusion if the study: (a) is not classified as a systematic review with or without meta-analysis; (b) is published from inception to date; (c) includes children aged 0-12 years with ASD; (d) quantitively measures cognitive outcomes; (e) treatment includes at least one PAIS. The internal validity and quality of evidence will be evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Statistical analyses will be produced in RStudio 3.6 with the BUGSnet package and Comprehensive Meta-Analysis 3.3. Discussion: This study will provide an updated review of the extant literature by using an appropriate network meta-analytic model and address the questions regarding efficacy of PAIS that significantly impact cognitive functions in children with ASD with implications for future decision making. Systematic review registration: PROSPERO CRD42021279054.

scholarly journals The Effectiveness of Cobalamin (B12) Treatment for Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 11 (8) ◽  
pp. 784
Author(s):  
Daniel A. Rossignol ◽  
Richard E. Frye
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Meta Analysis ◽  
Neurodevelopmental Disorder ◽  
The United States ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Effect Sizes ◽  
Controlled Study ◽  
Redox Ratio

Autism spectrum disorder (ASD) is a common neurodevelopmental disorder affecting 2% of children in the United States. Biochemical abnormalities associated with ASD include impaired methylation and sulphation capacities along with low glutathione (GSH) redox capacity. Potential treatments for these abnormalities include cobalamin (B12). This systematic review collates the studies using B12 as a treatment in ASD. A total of 17 studies were identified; 4 were double-blind, placebo-controlled studies (2 examined B12 injections alone and 2 used B12 in an oral multivitamin); 1 was a prospective controlled study; 6 were prospective, uncontrolled studies, and 6 were retrospective (case series and reports). Most studies (83%) used oral or injected methylcobalamin (mB12), while the remaining studies did not specify the type of B12 used. Studies using subcutaneous mB12 injections (including 2 placebo-controlled studies) used a 64.5–75 µg/kg/dose. One study reported anemia in 2 ASD children with injected cyanocobalamin that resolved with switching to injected mB12. Two studies reported improvements in markers of mitochondrial metabolism. A meta-analysis of methylation metabolites demonstrated decreased S-adenosylhomocysteine (SAH), and increased methionine, S-adenosylmethionine (SAM), SAM/SAH ratio, and homocysteine (with small effect sizes) with mB12. Meta-analysis of the transsulfuration and redox metabolism metabolites demonstrated significant improvements with mB12 in oxidized glutathione (GSSG), cysteine, total glutathione (GSH), and total GSH/GSSG redox ratio with medium to large effect sizes. Improvements in methylation capacity and GSH redox ratio were significantly associated with clinical improvements (with a mean moderate effect size of 0.59) in core and associated ASD symptoms, including expressive communication, personal and domestic daily living skills, and interpersonal, play-leisure, and coping social skills, suggesting these biomarkers may predict response to B12. Other clinical improvements observed with B12 included sleep, gastrointestinal symptoms, hyperactivity, tantrums, nonverbal intellectual quotient, vision, eye contact, echolalia, stereotypy, anemia, and nocturnal enuresis. Adverse events identified by meta-analysis included hyperactivity (11.9%), irritability (3.4%), trouble sleeping (7.6%), aggression (1.8%), and worsening behaviors (7.7%) but were generally few, mild, not serious, and not significantly different compared to placebo. In one study, 78% of parents desired to continue mB12 injections after the study conclusion. Preliminary clinical evidence suggests that B12, particularly subcutaneously injected mB12, improves metabolic abnormalities in ASD along with clinical symptoms. Further large multicenter placebo-controlled studies are needed to confirm these data. B12 is a promising treatment for ASD.

scholarly journals Treatment Effect of Bumetanide in Children With Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 12 ◽  
Author(s):  
Tiantian Wang ◽  
Ling Shan ◽  
Chunyue Miao ◽  
Zhida Xu ◽  
Feiyong Jia
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Therapeutic Effect ◽  
Rating Scale ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Children With Asd ◽  
Core Symptoms ◽  
Positive Effect

Background: The therapeutic effect of bumetanide on autism spectrum disorder (ASD) seems to be controversial. To obtain better evidence on the efficacy of bumetanide, a systematic review and meta-analysis were performed.Methods: Randomized, placebo-controlled trials (RCTs) of bumetanide treatment in children with ASD were identified through systematic review from database inception to January 17, 2021. Subsequently, a meta-analysis was carried out to examine the effect of bumetanide on the severity of symptoms of ASD as assessed by the Childhood Autism Rating Scale (CARS) and Social Responsive Scale (SRS); core symptoms according to criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 of the American Psychiatric Association [social affect (SA), restricted, repetitive patterns of behavior, interests, or activities (RRB) and sensory symptoms]; and the therapeutic effect as assessed by Clinical Global Impressions-Efficacy (CGI-E).Results: In total, six RCTs involving 496 participants with ASD were identified in our study. The results showed that bumetanide could significantly improve the severity of the ASD symptoms measured by CARS and SRS. There was also evidence that bumetanide had positive effect on the core symptoms of ASD such as the SA and RRB, but there was no statistically significant effect on sensory symptoms. A significant positive effect on CGI-E scores in ASD patients was also observed.Conclusion: Our meta-analysis provided some support that bumetanide could improve the symptoms of children with ASD. However, additional large-scale longitudinal studies that provide clearer information and better control for confounding factors are needed to confirm our findings.

scholarly journals A systematic review and meta-analysis of the benefits of a gluten-free diet and/or casein-free diet for children with autism spectrum disorder

2021 ◽  
Author(s):  
Liuliu Quan ◽  
Xinjie Xu ◽  
Yonghong Cui ◽  
Heze Han ◽  
Robert L Hendren ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Data Extraction ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Cochrane Library ◽  
Gluten Free ◽  
Children With Asd ◽  
Standard Mean Difference

Abstract Context It has been suggested that a gluten-free and casein-free (GFCF) diet may alleviate the symptoms of autism spectrum disorder (ASD) and facilitate neurodevelopment of children with ASD. Studies to date have been inconclusive. Objective This study aimed to evaluate (through quantitative meta-analysis) the efficacy and safety of a GFCF diet for children with ASD. To our knowledge, this is the first time such an analysis has been carried out. Data Sources Eight electronic databases were searched, from the establishment of each database up to March 27, 2020: PubMed, Web of Science, Embase (Ovid), PsycINFO (Ovid), Cochrane Library, CNKI, Wanfang, and VIP databases. Data Extraction Two authors independently performed the data extraction and risk-of-bias assessment. Data Analysis A quantitative meta-analysis was performed with standard procedures by using Stata SE 15 software. Within the total of 8 studies, with 297 participants, 5 studies reported significant reductions in stereotypical behaviors [standard mean difference (SMD) = –0.41, 95% confidence interval (CI): –0.68 to –0.15], and 3 studies reported improvements in cognition (SMD = –0.46, 95% CI: –0.91 to –0.01) following GFCF dietary intervention. No statistically significant changes were observed in other symptomatic categories (all P > 0.05). Conclusion The current meta-analysis showed that a GFCF diet can reduce stereotypical behaviors and improve the cognition of children with ASD. Though most of the included studies were single-blind, the benefits of a GFCF diet that have been indicated are promising. Additional studies on a larger scale are warranted. Systematic Review Registration PROSPERO registration no. CRD42020177619.

Diagnostic test accuracy for use of machine learning in diagnosis of autism spectrum disorder: A Systematic Review and Meta-Analysis (Preprint)

2019 ◽  
Author(s):  
Sun Jae Moon ◽  
Jin Seub Hwang ◽  
Rajesh Kana ◽  
John Torous ◽  
Jung Won Kim
Keyword(s):  
Machine Learning ◽  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Meta Analysis ◽  
Learning Algorithms ◽  
Structural Mri ◽  
Autism Spectrum ◽  
Machine Learning Algorithms ◽  
Spectrum Disorder ◽  
Test Accuracy

BACKGROUND Over the recent years, machine learning algorithms have been more widely and increasingly applied in biomedical fields. In particular, its application has been drawing more attention in the field of psychiatry, for instance, as diagnostic tests/tools for autism spectrum disorder. However, given its complexity and potential clinical implications, there is ongoing need for further research on its accuracy. OBJECTIVE The current study aims to summarize the evidence for the accuracy of use of machine learning algorithms in diagnosing autism spectrum disorder (ASD) through systematic review and meta-analysis. METHODS MEDLINE, Embase, CINAHL Complete (with OpenDissertations), PsyINFO and IEEE Xplore Digital Library databases were searched on November 28th, 2018. Studies, which used a machine learning algorithm partially or fully in classifying ASD from controls and provided accuracy measures, were included in our analysis. Bivariate random effects model was applied to the pooled data in meta-analysis. Subgroup analysis was used to investigate and resolve the source of heterogeneity between studies. True-positive, false-positive, false negative and true-negative values from individual studies were used to calculate the pooled sensitivity and specificity values, draw SROC curves, and obtain area under the curve (AUC) and partial AUC. RESULTS A total of 43 studies were included for the final analysis, of which meta-analysis was performed on 40 studies (53 samples with 12,128 participants). A structural MRI subgroup meta-analysis (12 samples with 1,776 participants) showed the sensitivity at 0.83 (95% CI-0.76 to 0.89), specificity at 0.84 (95% CI -0.74 to 0.91), and AUC/pAUC at 0.90/0.83. An fMRI/deep neural network (DNN) subgroup meta-analysis (five samples with 1,345 participants) showed the sensitivity at 0.69 (95% CI- 0.62 to 0.75), the specificity at 0.66 (95% CI -0.61 to 0.70), and AUC/pAUC at 0.71/0.67. CONCLUSIONS Machine learning algorithms that used structural MRI features in diagnosis of ASD were shown to have accuracy that is similar to currently used diagnostic tools.

Autism spectrum disorder and air pollution: a systematic review and meta-analysis

2021 ◽  
pp. 116856
Author(s):  
Frédéric Dutheil ◽  
Aurélie Comptour ◽  
Roxane Morlon ◽  
Martial Mermillod ◽  
Bruno Pereira ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Air Pollution ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder

scholarly journals Review of Cognitive Characteristics of Autism Spectrum Disorder Using Performance on Six Subtests on Four Versions of the Wechsler Intelligence Scale for Children

2021 ◽  
Author(s):  
Mizuho Takayanagi ◽  
Yoko Kawasaki ◽  
Mieko Shinomiya ◽  
Hoshino Hiroshi ◽  
Satoshi Okada ◽  
...  
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Block Design ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Intelligence Scale ◽  
Cognitive Characteristics ◽  
Children With Asd ◽  
The Right ◽  
The Impact

AbstractThis study was a systematic review of research using the Wechsler Intelligence Scale for Children (WISC) with Autism Spectrum Disorder (ASD) to examine cognitive characteristics of children with ASD beyond the impact of revisions based on WISC and diagnostic criteria changes. The classic “islets of ability” was found in individuals with full-scale IQs < 100. The “right-descending profiles” were observed among high IQ score individuals. High levels on the Block Design and low Coding levels were consistently found regardless of the variation in intellectual functioning or diagnosis. This review identified patterns of cognitive characteristics in ASD individuals using empirical data that researchers may have previously been aware of, based on their experiences, owing to the increased prevalence of ASD.

scholarly journals A systematic review and meta-analysis of studies on metaphor comprehension in individuals with autism spectrum disorder: Do task properties matter?

2019 ◽  
Vol 40 (6) ◽  
pp. 1421-1454 ◽  
Author(s):  
Tamar Kalandadze ◽  
Valentina Bambini ◽  
Kari-Anne B. Næss
Keyword(s):  
Systematic Review ◽  
Autism Spectrum Disorder ◽  
Syntactic Structure ◽  
Meta Analysis ◽  
Autism Spectrum ◽  
Spectrum Disorder ◽  
Response Format ◽  
Metaphor Comprehension ◽  
The Relationship

AbstractIndividuals with autism spectrum disorder (ASD) often experience difficulty in comprehending metaphors compared to individuals with typical development (TD). However, there is a large variation in the results across studies, possibly related to the properties of the metaphor tasks. This preregistered systematic review and meta-analysis (a) explored the properties of the metaphor tasks used in ASD research, and (b) investigated the group difference between individuals with ASD and TD on metaphor comprehension, as well as the relationship between the task properties and any between-study variation. A systematic search was undertaken in seven relevant databases. Fourteen studies fulfilled our predetermined inclusion criteria. Across tasks, we detected four types of response format and a great variety of metaphors in terms of familiarity, syntactic structure, and linguistic context. Individuals with TD outperformed individuals with ASD on metaphor comprehension (Hedges’ g = −0.63). Verbal explanation response format was utilized in the study showing the largest effect size in the group comparison. However, due to the sparse experimental manipulations, the role of task properties could not be established. Future studies should consider and report task properties to determine their role in metaphor comprehension, and to inform experimental paradigms as well as educational assessment.

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