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

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.

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

Journal of Personalized Medicine ◽

10.3390/jpm11060488 ◽

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.

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The Association between Autism Spectrum Disorder and Pre- and Postnatal Antibiotic Exposure in Childhood—A Systematic Review with Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph16204042 ◽

2019 ◽

Vol 16 (20) ◽

pp. 4042 ◽

Cited By ~ 2

Author(s):

Eunmi Lee ◽

Jeonghyun Cho ◽

Ka Young Kim

Keyword(s):

Autism Spectrum Disorder ◽

Developmental Disorder ◽

Web Of Science ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Cochrane Library ◽

Antibiotic Exposure ◽

Children With Asd ◽

Meta Analyses

Autism spectrum disorder (ASD) is a developmental disorder that begins in early childhood and has been associated with several environmental and genetic factors. We aimed to conduct two-side meta-analyses to determine the association between ASD and pre- and postnatal antibiotic exposure in childhood. We searched PubMed, Embase, Web of Science, and Cochrane Library for articles published up to February 2019. We evaluated observational studies that assessed the association between ASD and antibiotic exposure. Of 1459 articles, nine studies were used in the meta-analysis. We found that early antibiotic exposure, including pre- and postnatal, significantly increased the ASD risk in children. Furthermore, early antibiotic exposure, including pre- and postnatal, was significantly increased in children with ASD. Specifically, prenatal antibiotic exposure was significantly increased in children with ASD; however, postnatal antibiotic exposure was not. Our results indicate an association between ASD and early antibiotic exposure; specifically, that prenatal antibiotic exposure is an important risk factor of ASD in children.

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Oxidative stress marker aberrations in children with autism spectrum disorder: a systematic review and meta-analysis of 87 studies (N = 9109)

Translational Psychiatry ◽

10.1038/s41398-020-01135-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Lei Chen ◽

Xiao-Jie Shi ◽

Hua Liu ◽

Xiao Mao ◽

Lue-Ning Gui ◽

...

Keyword(s):

Oxidative Stress ◽

Autism Spectrum Disorder ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Oxidative Stress Marker ◽

Cochrane Library ◽

Stress Profile ◽

Stress Marker ◽

Children With Asd

AbstractThere is increasing awareness that oxidative stress may be implicated in the pathophysiology of autism spectrum disorder (ASD). Here we aimed to investigate blood oxidative stress marker profile in ASD children by a meta-analysis. Two independent investigators systematically searched Web of Science, PubMed, and Cochrane Library and extracted data from 87 studies with 4928 ASD children and 4181 healthy control (HC) children. The meta-analysis showed that blood concentrations of oxidative glutathione (GSSG), malondialdehyde, homocysteine, S-adenosylhomocysteine, nitric oxide, and copper were higher in children with ASD than that of HC children. In contrast, blood reduced glutathione (GSH), total glutathione (tGSH), GSH/GSSG, tGSH/GSSG, methionine, cysteine, vitamin B9, vitamin D, vitamin B12, vitamin E, S-adenosylmethionine/S-adenosylhomocysteine, and calcium concentrations were significantly reduced in children with ASD relative to HC children. However, there were no significance differences between ASD children and HC children for the other 17 potential markers. Heterogeneities among studies were found for most markers, and meta-regressions indicated that age and publication year may influence the meta-analysis results. These results therefore clarified blood oxidative stress profile in children with ASD, strengthening clinical evidence of increased oxidative stress implicating in pathogenesis of ASD. Additionally, given the consistent and large effective size, glutathione metabolism biomarkers have the potential to inform early diagnosis of ASD.

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

10.21203/rs.3.rs-1141593/v1 ◽

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.

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Randomised controlled trials of antidepressant and anti-anxiety medications for people with autism spectrum disorder: systematic review and meta-analysis

BJPsych Open ◽

10.1192/bjo.2021.1003 ◽

2021 ◽

Vol 7 (6) ◽

Author(s):

Shoumitro Deb ◽

Meera Roy ◽

Rachel Lee ◽

Madiha Majid ◽

Bharati Limbu ◽

...

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Randomised Controlled Trials ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Current Evidence ◽

Cochrane Library ◽

Controlled Trials ◽

Randomised Controlled

Background Although widely used, the current evidence for the efficacy of antidepressant and anti-anxiety medications for people with autism spectrum disorder (ASD) is limited and conflicting. Aims We carried out a systematic review and meta-analysis of randomised controlled trials that assessed the effectiveness of these medications in people with ASD. Method We searched the following databases: Cochrane Library, Medline, EMBASE, CINAHL, PsycINFO, ERIC, DARE and ClinicalTrials.gov. Additionally, we hand-searched 11 relevant journals. We used the Cochrane risk-of-bias tool and Jadad score to assess the quality of each included study. We carried out a meta-analysis using a random effects model. Results We included 15 randomised controlled trials (13 on antidepressants and two on anti-anxiety medications) for a total of 958 people with ASD. Data showed contradictory findings among the studies, with larger studies mostly showing a non-significant difference in outcomes between the treatment and the placebo groups. Meta-analysis of pooled Yale-Brown Obsessive Compulsive Scale and Clinical Global Impression Scale data from nine studies (60%) did not show any statistically significant inter-group difference on either of the outcome measures. The adverse effects reported were mild and, in most studies, their rates did not show any significant inter-group difference. Conclusions Given the methodological flaws in the most included studies and contradictory findings, it is difficult to draw any definitive conclusion about the effectiveness of either antidepressant or anti-anxiety medications to treat either ASD core symptoms or associated behaviours. Robust, large-scale, randomised controlled trials are needed to address this issue.

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Effects of Non-Invasive Neurostimulation on Autism Spectrum Disorder: A Protocol for a Systematic Review

10.21203/rs.3.rs-1103851/v1 ◽

2021 ◽

Author(s):

Jiawei Zhang ◽

Hao Zhang

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Meta Analysis ◽

Neurodevelopmental Disorder ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Cochrane Library ◽

Clinical Effects ◽

Non Invasive ◽

Invasive Neurostimulation

Abstract Background Autism Spectrum Disorder (ASD) is a neurodevelopmental disorder marked by characteristic impairments in social communication and interaction, as well as restricted and repetitive behavior. There is a continued need for exploring effective interventions and evaluating treatment options for ASD. Transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are non-invasive neurostimulation techniques which have shown clinical benefits in adult psychiatric conditions. While in ASD patients, no guideline has so-far recommended on the application of NIBS due to a lack of high-quality synthetic evidence. Therefore, objective of this study will be to systematically evaluate the evidence on clinical effects of non-invasive neurostimulation in patients with ASD. Methods We designed and registered a study protocol for a systematic review. A comprehensive search from database inception onwards will be conducted in PubMed, EMBASE and Cochrane library. Randomized and non-randomized sham-controlled studies assessing the effects of noninvasive neurostimulation in patients with ASD will be identified. Eligibility of citations retrieved will be independently screened by two reviewers. The risk of bias and quality of included studies will be appraised using appropriate tools. A narrative synthesis around the features of the evidences will provided. There may be a chance for meta-analysis to pool the estimates of studies included if three studies or more meet the requirements for meta-analysis. If so, a random-effects model maybe applied. And we will evaluate heterogeneity between studies using the I² statistic. Discussion This systematic review will provide a broad and comprehensive evaluation of the evidence on clinical effects of TMS and tDCS in patients with ASD. Our findings will be reported according to the PRISMA guidelines and may add more confidence when healthcare professionals are making informed decisions about the choice of this therapy. Results will be published in a peer-reviewed journal. Systematic review registration: Submitted to PROSPERO, 20/11/2021

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

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.751575 ◽

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.

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Prevalence of Autism Spectrum Disorder (ASD) in all Individuals Diagnosed with Down Syndrome (DS): A Systematic Review and Meta-analysis Protocol

10.21203/rs.3.rs-1171029/v1 ◽

2021 ◽

Author(s):

Judy Seesahai ◽

Paige Church ◽

Lina Patel ◽

Thomas Rotter ◽

Elizabeth Asztalos ◽

...

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Down Syndrome ◽

Prevalence Rate ◽

Data Extraction ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Diagnostic Tools ◽

Future Research

Abstract BACKGROUNDTraditionally, autism spectrum disorder in people with Down syndrome was believed to be uncommon. This misconception is rooted in the challenges that a dual diagnosis poses. In fact, evidence indicates that children with Down syndrome are at risk for autism spectrum disorder with a potentially higher prevalence than the typically developing population. The purpose of this review is to determine the reported prevalence rate of autism spectrum disorder in all individuals with Down syndrome in comparison to the prevalence rate of autism spectrum disorder in the typical population when specific diagnostic tools are used. METHODSWe will conduct a systematic review of the prevalence and incidence data and perform a meta-analysis on these results. This study will consider all studies that reported on children and adults with an existing diagnosis of Down syndrome and diagnosed by the standardized assessments for autism spectrum disorder. We will also consider the diagnoses made by team assessment (psychologist, psychiatrist & developmental pediatrician), according to DSM-III, DSM-IV or DSM-V criteria for diagnosing autism spectrum disorder or if they use autism spectrum disorder screeners. Studies will be considered from all countries that have data reporting prevalence on this topic. We will not apply language restrictions, attempting to translate studies that are not in English. We will search five databases (MEDLINE, Embase, PsychINFO, Scopus, and CINAHL). Two reviewers will conduct all screening and data extraction independently. The articles will be categorized according to key findings and a critical appraisal performed.DISCUSSIONThe results of this review will bring increased awareness of the presence of autism spectrum disorder in individuals with Down syndrome. In doing so, this may facilitate a recommendation for screening and diagnosis for autism spectrum disorder in all individuals with Down syndrome. Based on the research demonstrating the benefits of early identification and intervention on the outcomes of children with autism, we anticipate similar benefits in this population. This will guide the allocation of resources and direct future research.SYSTEMATIC REVIEW REGISTRATIONWe registerd the review title prospectively on PROSPERO on November 8, 2021. Registration number: CRD42020213282

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The Effectiveness of Parent Training Interventions in Autism Spectrum Disorder: A Systematic Review

10.21203/rs.3.rs-77034/v1 ◽

2020 ◽

Author(s):

Seyed Hasan Tabatabaei ◽

Hassan Shahrokhi ◽

Kamal Gholipour ◽

Shabnam Izadi ◽

Ramin Rezapour ◽

...

Keyword(s):

Systematic Review ◽

Autism Spectrum Disorder ◽

Autism Spectrum ◽

Library Science ◽

Spectrum Disorder ◽

Cochrane Library ◽

Reference List ◽

Training Interventions ◽

Children With Asd ◽

Taking Care

Abstract Background: The role of parents in taking care of children with Autism Spectrum Disorder (ASD) is critical. This systematic review study aimed to investigate the effect of parents-based training interventions on taking care of children with ASD.Method: All relevant studies were searched through some electronic databases such as PubMed, Scopus, Google Scholar, Cochrane Library, Science Direct, Web of knowledge, and also via hand searching in relevant journals, checking the reference list of articles, expert contact, and grey literature from 1 January 2000 to 30 February 2020. Result: Eventually, 53 articles were considered. In total, 1758 parents of children with ASD participated in these studies that 49 studies were conducted in high-income countries, 19 studies in the home, 25 studies in the training centers.14 studies carried out only in training way, 39 studies in training along with practices and assignments, 30 individual interventions, 21 interventions in the group. Most studies had a range of 10 to 30 sessions in a 60 to 120-minute period. Also, the effectiveness of interventions was studied in both parents and children groups. Conclusion: According to the included studies, parents-based training interventions have significant impacts on parents and their children's behavior.

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

10.2196/preprints.14108 ◽

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.

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