Efficacy of Interventions Based on Applied Behavior Analysis for Autism Spectrum Disorder: A Meta-Analysis

Objective To systematically evaluate evidence for the use of interventions based on appied behavior analysis (ABA) to manage various symptoms of children with autism spectrum disorder (ASD).Methods Sensitivity analyses were conducted by removing any outlying studies and subgroup analyses were performed to compare the effectiveness of ABA and early start denver model (ESDM), picture exchange communication systems (PECS) and discrete trial training (DTT).Results 14 randomized control trials of 555 participants were included in this meta-analysis. The overall standardized mean difference was d=-0.36 (95% CI -1.31, 0.58; Z=0.75, p=0.45) for autism general symptoms, d=0.11 (95% CI -0.31, 0.54; Z=0.52, p=0.60) for socialization, d=0.30 (95% CI -0.02, 0.61; Z=1.84, p=0.07) for communication and d=-3.52 (95% CI -6.31, -0.72; Z=2.47, p=0.01) for expressive language, d=-0.04 (95% CI -0.44, 0.36; Z=0.20, p=0.84) for receptive language. Those results suggested outcomes of socialization, communication and expressive language may be promising targets for ABA-based interventions involving children with ASD. However, significant effects for the outcomes of autism general symptoms, receptive language, adaptive behavior, daily living skills, IQ, verbal IQ, nenverbal IQ, restricted and repetitive behavior, motor and cognition were not observed.Conclusion The small number of studies included in the present study limited the ability to make inferences when comparing ABA, ESDM, PECS and DTT interventions for children with ASD.

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Efficiency of expressive and receptive language teaching in children with autism spectrum disorder

Research Society and Development ◽

10.33448/rsd-v9i8.5268 ◽

2020 ◽

Vol 9 (8) ◽

pp. e104985268

Author(s):

Daniel Carvalho de Matos ◽

Neylla Cristina Pereira Cordeiro ◽

Bruna Pereira Mendes ◽

Ana Vitória Salomão de Carvalho ◽

Flor de Maria Araújo Mendonça Silva ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Expressive Language ◽

Receptive Language ◽

Autism Spectrum ◽

Previous Literature ◽

Spectrum Disorder ◽

Children With Asd ◽

Intraverbal Training ◽

The Difference ◽

Tact Training

Research in Applied Behavior Analysis (ABA) investigated the efficiency of receptive and expressive language interventions in learners with Autism Spectrum Disorder (ASD). Listener responding by function, feature and class (LRFFC) and intraverbal (FFC) are some types of receptive and expressive language, respectively, which were targets in investigations. The previous literature demonstrated experimentally that teaching intraverbal first is more efficient, in the sense that it produced a better emergence effect of related untaught LRFFC in children with ASD, contrary to the recommendation by a traditional literature, which suggests that receptive skills, such as the LRFFC, should be taught first. The current research had the goal to compare the efficiency of intraverbal and LRFFC training as well, considering the effects on the possible emergence of related untaught repertoire in two children with ASD. The difference from the previous literature was that, during the teaching of LRFFC responses, the tact (labeling) of pictures involved was also taught, considering that this was a recommendation of previous research. The purpose was to assess if tact training would increase the efficiency of LRFFC training. The results showed that both instructional sequences (training LRFFC - probing intraverbal; training intraverbal - probing LRFFC) successfully established emergent responding, regarding the untaught related repertoire for both participants. However, intraverbal training produced emergence of LRFFC to a lesser extent for both. Data were discussed in the sense that tact training during LRFFC training probably increased its efficiency and that preexisting skills, regarding each participant, also influenced the efficiency of teaching.

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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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Voxel-based meta-analysis of regional white-matter volume differences in autism spectrum disorder versus healthy controls

Psychological Medicine ◽

10.1017/s0033291710002187 ◽

2010 ◽

Vol 41 (7) ◽

pp. 1539-1550 ◽

Cited By ~ 92

Author(s):

J. Radua ◽

E. Via ◽

M. Catani ◽

D. Mataix-Cols

Keyword(s):

Autism Spectrum Disorder ◽

White Matter ◽

Diffusion Tensor ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Sensitivity Analyses ◽

Healthy Controls ◽

White Matter Volume ◽

Matter Volume

BackgroundWe conducted a meta-analysis of voxel-based morphometry (VBM) studies in autism spectrum disorder (ASD) to clarify the changes in regional white-matter volume underpinning this condition, and generated an online database to facilitate replication and further analyses by other researchers.MethodPubMed, ScienceDirect, Web of Knowledge and Scopus databases were searched between 2002 (the date of the first white-matter VBM study in ASD) and 2010. Manual searches were also conducted. Authors were contacted to obtain additional data. Coordinates were extracted from clusters of significant white-matter difference between patients and controls. A new template for white matter was created for the signed differential mapping (SDM) meta-analytic method. A diffusion tensor imaging (DTI)-derived atlas was used to optimally localize the changes in white-matter volume.ResultsThirteen datasets comprising 246 patients with ASD and 237 healthy controls met inclusion criteria. No between-group differences were found in global white-matter volumes. ASD patients showed increases of white-matter volume in the right arcuate fasciculus and also in the left inferior fronto-occipital and uncinate fasciculi. These findings remained unchanged in quartile and jackknife sensitivity analyses and also in subgroup analyses (pediatric versus adult samples).ConclusionsPatients with ASD display increases of white-matter volume in tracts known to be important for language and social cognition. Whether the results apply to individuals with lower IQ or younger age and whether there are meaningful neurobiological differences between the subtypes of ASD remain to be investigated.

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Association of Peripheral Blood Levels of Cytokines With Autism Spectrum Disorder: A Meta-Analysis

Frontiers in Psychiatry ◽

10.3389/fpsyt.2021.670200 ◽

2021 ◽

Vol 12 ◽

Author(s):

Huaying Zhao ◽

Hongqi Zhang ◽

Shijie Liu ◽

Wulin Luo ◽

Yongfeng Jiang ◽

...

Keyword(s):

Autism Spectrum Disorder ◽

Peripheral Blood ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder ◽

The Other ◽

Sensitivity Analyses ◽

Systemic Review ◽

Blood Levels ◽

Random Effects Models

Background: Although increasing evidence suggests an association between alterations in peripheral cytokines and autism spectrum disorder (ASD), a consensus is lacking. To determine whether abnormal cytokine profiles in peripheral blood were associated with ASD, we performed this systemic review and meta-analysis.Methods: A systematic literature search was conducted through the Embase, PubMed, Web of Knowledge, PsycINFO, and Cochrane databases up to 4 June 2020. Clinical studies exploring the aberration of peripheral cytokines of autistic patients and controls were included in our meta-analysis. We pooled extracted data using fixed- or random-effects models based on heterogeneity tests with Comprehensive Meta-analysis software. We converted standardized mean differences to Hedges' g statistic to obtain the effect sizes adjusted for sample size. Subgroup analyses, sensitivity analyses, meta-regression, and publication bias tests were also carried out.Results: Sixty-one articles (326 studies) were included to assess the association between 76 cytokines and ASD. We conducted our meta-analysis based on 37 cytokines with 289 studies. Since there were fewer than three studies on any of the other 39 cytokines, we only provided basic information for them. The levels of peripheral IL-6, IL-1β, IL-12p70, macrophage migration inhibitory factor (MIF), eotaxin-1, monocyte chemotactic protein-1 (MCP-1), IL-8, IL-7, IL-2, IL-12, tumor necrosis factor-α (TNF-α), IL-17, and IL-4 were defined as abnormal cytokines in the peripheral blood of ASD patients compared with controls. The other 24 cytokines did not obviously change in ASD patients compared with the controls.Conclusions: The findings of our meta-analysis strengthen the evidence for an abnormal cytokine profile in ASD. These abnormal cytokines may be potential biomarkers for the diagnosis and treatment of ASD in the future.

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Play and Communication in Children With Autism Spectrum Disorder

Journal of Early Intervention ◽

10.1177/1053815112453766 ◽

2012 ◽

Vol 34 (2) ◽

pp. 82-103 ◽

Cited By ~ 15

Author(s):

Rebecca G. Lieberman ◽

Paul Yoder

Keyword(s):

Autism Spectrum Disorder ◽

Young Children ◽

Controlled Trial ◽

Meta Analysis ◽

Children With Autism ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Intentional Communication ◽

Object Play ◽

Children With Asd

The association between object play and intentional communication was examined in children with autism spectrum disorder (ASD). Meta-analysis of concurrent and longitudinal correlational studies revealed significant associations between object play and intentional communication in young children with ASD. One well-conducted and internally valid, randomized, controlled trial suggests a bidirectional causal relationship between object play and intentional communication. Further experiments are needed to replicate these findings and test a play-as-stronger-cause hypothesis. Findings of the review have implications for development and implementation of effective interventions for young children with ASD when communication is the target and play serves as the context for intervention strategies. One model for conceptualization of treatment is proposed.

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Composition of Gut Microbiota in Children with Autism Spectrum Disorder: A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu12030792 ◽

2020 ◽

Vol 12 (3) ◽

pp. 792 ◽

Cited By ~ 18

Author(s):

Lucía Iglesias-Vázquez ◽

Georgette Van Ginkel Riba ◽

Victoria Arija ◽

Josefa Canals

Keyword(s):

Autism Spectrum Disorder ◽

Gut Microbiota ◽

Psychiatric Symptoms ◽

Meta Analysis ◽

Public Health Problem ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Lower Percentage ◽

Children With Asd ◽

Meta Analyses

Background: Autism spectrum disorder (ASD) is a public health problem and has a prevalence of 0.6%–1.7% in children. As well as psychiatric symptoms, dysbiosis and gastrointestinal comorbidities are also frequently reported. The gut–brain microbiota axis suggests that there is a form of communication between microbiota and the brain underlying some neurological disabilities. The aim of this study is to describe and compare the composition of gut microbiota in children with and without ASD. Methods: Electronic databases were searched as far as February 2020. Meta-analyses were performed using RevMan5.3 to estimate the overall relative abundance of gut bacteria belonging to 8 phyla and 17 genera in children with ASD and controls. Results: We included 18 studies assessing a total of 493 ASD children and 404 controls. The microbiota was mainly composed of the phyla Bacteroidetes, Firmicutes, and Actinobacteria, all of which were more abundant in the ASD children than in the controls. Children with ASD showed a significantly higher abundance of the genera Bacteroides, Parabacteroides, Clostridium, Faecalibacterium, and Phascolarctobacterium and a lower percentage of Coprococcus and Bifidobacterium. Discussion: This meta-analysis suggests that there is a dysbiosis in ASD children which may influence the development and severity of ASD symptomatology. Further studies are required in order to obtain stronger evidence of the effectiveness of pre- or probiotics in reducing autistic behaviors.

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Meta-analysis of receptive and expressive language skills in autism spectrum disorder

Research in Autism Spectrum Disorders ◽

10.1016/j.rasd.2014.10.008 ◽

2015 ◽

Vol 9 ◽

pp. 202-222 ◽

Cited By ~ 54

Author(s):

Elaine Y.L. Kwok ◽

Heather M. Brown ◽

Rachael E. Smyth ◽

Janis Oram Cardy

Keyword(s):

Autism Spectrum Disorder ◽

Language Skills ◽

Expressive Language ◽

Meta Analysis ◽

Autism Spectrum ◽

Spectrum Disorder

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Sign Language Echolalia in Deaf Children With Autism Spectrum Disorder

Journal of Speech Language and Hearing Research ◽

10.1044/2016_jslhr-l-16-0292 ◽

2017 ◽

Vol 60 (6) ◽

pp. 1622-1634 ◽

Cited By ~ 6

Author(s):

Aaron Shield ◽

Frances Cooley ◽

Richard P. Meier

Keyword(s):

Autism Spectrum Disorder ◽

Sign Language ◽

Children With Autism ◽

Receptive Language ◽

Autism Spectrum ◽

Spectrum Disorder ◽

Deaf Children ◽

Children With Asd ◽

Language Modality ◽

Hearing Children

Purpose We present the first study of echolalia in deaf, signing children with autism spectrum disorder (ASD). We investigate the nature and prevalence of sign echolalia in native-signing children with ASD, the relationship between sign echolalia and receptive language, and potential modality differences between sign and speech. Method Seventeen deaf children with ASD and 18 typically developing (TD) deaf children were video-recorded in a series of tasks. Data were coded for type of signs produced (spontaneous, elicited, echo, or nonecho repetition). Echoes were coded as pure or partial, and timing and reduplication of echoes were coded. Results Seven of the 17 deaf children with ASD produced signed echoes, but none of the TD deaf children did. The echoic children had significantly lower receptive language scores than did both the nonechoic children with ASD and the TD children. Modality differences also were found in terms of the directionality, timing, and reduplication of echoes. Conclusions Deaf children with ASD sometimes echo signs, just as hearing children with ASD sometimes echo words, and TD deaf children and those with ASD do so at similar stages of linguistic development, when comprehension is relatively low. The sign language modality might provide a powerful new framework for analyzing the purpose and function of echolalia in deaf children with ASD.

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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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