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Frontiers in Psychiatry 2021Individuals with autism spectrum disorder often present somatic and/or psychiatric co-morbid disorders. The DSM-5 allows for consideration of additional diagnoses...
Individuals with autism spectrum disorder often present somatic and/or psychiatric co-morbid disorders. The DSM-5 allows for consideration of additional diagnoses besides ASD and may have impacted the prevalence of co-morbidities as well as being limited in capturing the true differences in prevalence observed between males and females. We describe the prevalence of ASD and frequently observed co-morbidities in children and adolescents (<18 years) in the United States and five European countries. Two systematic literature reviews were conducted in PubMed and Embase for the period 2014-2019 and focusing on the prevalence of ASD and nine co-morbidities of interest based on their frequency and/or severity: Attention Deficit Hyperactivity Disorder (ADHD), anxiety, depressive disorders, epilepsy, intellectual disability (ID), sleep disorders, sight/hearing impairment/loss, and gastro-intestinal syndromes (GI). Thirteen studies on prevalence of ASD and 33 on prevalence of co-morbidities were included. Prevalence of ASD was 1.70 and 1.85% in US children aged 4 and 8 years respectively, while prevalence in Europe ranged between 0.38 and 1.55%. Additionally, current evidence is supportive of a global increase in ASD prevalence over the past years. Substantial heterogeneity in prevalence of co-morbidities was observed: ADHD (0.00-86.00%), anxiety (0.00-82.20%), depressive disorders (0.00-74.80%), epilepsy (2.80-77.50%), ID (0.00-91.70%), sleep disorders (2.08-72.50%), sight/hearing impairment/loss (0.00-14.90%/0.00-4.90%), and GI syndromes (0.00-67.80%). Studies were heterogeneous in terms of design and method to estimate prevalence. Gender appears to represent a risk factor for co-morbid ADHD (higher in males) and epilepsy/seizure (higher in females) while age is also associated with ADHD and anxiety (increasing until adolescence). Our results provide a descriptive review of the prevalence of ASD and its co-morbidities in children and adolescents. These insights can be valuable for clinicians and parents/guardians of autistic children. Prevalence of ASD has increased over time while co-morbidities bring additional heterogeneity to the clinical presentation, which further advocates for personalized approaches to treatment and support. Having a clear understanding of the prevalence of ASD and its co-morbidities is important to raise awareness among stakeholders.
PubMed: 34777048
DOI: 10.3389/fpsyt.2021.744709 -
BMJ Open Jul 2017Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding. (Meta-Analysis)
Meta-Analysis Review
Comparative safety of antiepileptic drugs for neurological development in children exposed during pregnancy and breast feeding: a systematic review and network meta-analysis.
OBJECTIVES
Compare the safety of antiepileptic drugs (AEDs) on neurodevelopment of infants/children exposed in utero or during breast feeding.
DESIGN AND SETTING
Systematic review and Bayesian random-effects network meta-analysis (NMA). MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched until 27 April 2017. Screening, data abstraction and quality appraisal were completed in duplicate by independent reviewers.
PARTICIPANTS
29 cohort studies including 5100 infants/children.
INTERVENTIONS
Monotherapy and polytherapy AEDs including first-generation (carbamazepine, clobazam, clonazepam, ethosuximide, phenobarbital, phenytoin, primidone, valproate) and newer-generation (gabapentin, lamotrigine, levetiracetam, oxcarbazepine, topiramate, vigabatrin) AEDs. Epileptic women who did not receive AEDs during pregnancy or breast feeding served as the control group.
PRIMARY AND SECONDARY OUTCOME MEASURES
Cognitive developmental delay and autism/dyspraxia were primary outcomes. Attention-deficit hyperactivity disorder, language delay, neonatal seizures, psychomotor developmental delay and social impairment were secondary outcomes.
RESULTS
The NMA on cognitive developmental delay (11 cohort studies, 933 children, 18 treatments) suggested that among all AEDs only valproate was statistically significantly associated with more children experiencing cognitive developmental delay compared with control (OR=7.40, 95% credible interval (CrI) 3.00 to 18.46). The NMA on autism (5 cohort studies, 2551 children, 12 treatments) suggested that oxcarbazepine (OR 13.51, CrI 1.28 to 221.40), valproate (OR 17.29, 95% CrI 2.40 to 217.60), lamotrigine (OR 8.88, CrI 1.28 to 112.00) and lamotrigine+valproate (OR 132.70, CrI 7.41 to 3851.00) were associated with significantly greater odds of developing autism compared with control. The NMA on psychomotor developmental delay (11 cohort studies, 1145 children, 18 treatments) found that valproate (OR 4.16, CrI 2.04 to 8.75) and carbamazepine+phenobarbital+valproate (OR 19.12, CrI 1.49 to 337.50) were associated with significantly greater odds of psychomotor delay compared with control.
CONCLUSIONS
Valproate alone or combined with another AED is associated with the greatest odds of adverse neurodevelopmental outcomes compared with control. Oxcarbazepine and lamotrigine were associated with increased occurrence of autism. Counselling is advised for women considering pregnancy to tailor the safest regimen.
TRIAL REGISTRATION NUMBER
PROSPERO database (CRD42014008925).
Topics: Anticonvulsants; Autistic Disorder; Bayes Theorem; Breast Feeding; Carbamazepine; Child; Epilepsy; Female; Humans; Lamotrigine; Observational Studies as Topic; Oxcarbazepine; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Triazines; Valproic Acid
PubMed: 28729328
DOI: 10.1136/bmjopen-2017-017248 -
Psychological Medicine Feb 2015Autism spectrum disorders (ASDs) are persistent disabling neurodevelopmental disorders clinically evident from early childhood. For the first time, the burden of ASDs... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Autism spectrum disorders (ASDs) are persistent disabling neurodevelopmental disorders clinically evident from early childhood. For the first time, the burden of ASDs has been estimated for the Global Burden of Disease Study 2010 (GBD 2010). The aims of this study were to develop global and regional prevalence models and estimate the global burden of disease of ASDs.
METHOD
A systematic review was conducted for epidemiological data (prevalence, incidence, remission and mortality risk) of autistic disorder and other ASDs. Data were pooled using a Bayesian meta-regression approach while adjusting for between-study variance to derive prevalence models. Burden was calculated in terms of years lived with disability (YLDs) and disability-adjusted life-years (DALYs), which are reported here by world region for 1990 and 2010.
RESULTS
In 2010 there were an estimated 52 million cases of ASDs, equating to a prevalence of 7.6 per 1000 or one in 132 persons. After accounting for methodological variations, there was no clear evidence of a change in prevalence for autistic disorder or other ASDs between 1990 and 2010. Worldwide, there was little regional variation in the prevalence of ASDs. Globally, autistic disorders accounted for more than 58 DALYs per 100 000 population and other ASDs accounted for 53 DALYs per 100 000.
CONCLUSIONS
ASDs account for substantial health loss across the lifespan. Understanding the burden of ASDs is essential for effective policy making. An accurate epidemiological description of ASDs is needed to inform public health policy and to plan for education, housing and financial support services.
Topics: Age Factors; Autism Spectrum Disorder; Bayes Theorem; Cost of Illness; Global Health; Humans; Incidence; Quality-Adjusted Life Years; Sex Distribution
PubMed: 25108395
DOI: 10.1017/S003329171400172X -
Frontiers in Psychiatry 2023Autism spectrum disorder (ASD) is one the most disabling developmental disorders, imposing an extremely high economic burden. Obtaining as accurate prevalence estimates...
UNLABELLED
Autism spectrum disorder (ASD) is one the most disabling developmental disorders, imposing an extremely high economic burden. Obtaining as accurate prevalence estimates as possible is crucial to guide governments in planning policies for identification and intervention for individuals with ASD and their relatives. The precision of prevalence estimates can be heightened by summative analyses of the data collected around the world. To that end, we conducted a three-level mixed-effects meta-analysis. A systematic search of the Web of Science, PubMed, EMBASE, and PsycINFO databases from 2000 up to 13 July 2020 was performed, and reference lists of previous reviews and existing databases of prevalence studies were screened. Overall, 79 studies were included in the analysis of ASD and 59-in the analysis of previously existing relevant diagnoses: 30 for Autistic Disorder (AD), 15 for Asperger Syndrome (AS), and 14 for Atypical Autism (AA) and Pervasive Developmental Disorder - Not Otherwise Specified (PDD-NOS); these research reports covered the period from 1994 to 2019. Pooled prevalence estimates were 0.72% (95% CI = 0.61-0.85) for ASD, 0.25% (95% CI = 0.18-0.33) for AD, 0.13% (95% CI = 0.07-0.20) for AS, and 0.18% (95% CI = 0.10-0.28) for the combined group of AA and PDD-NOS. Estimates were higher (1) for the studies that used records-review surveillance rather than other designs; (2) in North America compared with other geographical regions; and (3) in high-income compared with lower-income countries. The highest prevalence estimates were registered in the USA. There was an increase in autism prevalence estimates over time. The prevalence was also significantly higher for children aged between 6 and 12 years compared to children under the age of 5 and over the age of 13 years.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42019131525, identifier CRD42019131525.
PubMed: 36846240
DOI: 10.3389/fpsyt.2023.1071181 -
PloS One 2019Although caring for a child with intellectual and developmental disabilities (IDD) can have positive outcomes, parents may be at a greater risk of depression and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although caring for a child with intellectual and developmental disabilities (IDD) can have positive outcomes, parents may be at a greater risk of depression and anxiety, due to a number of associated stressors, such as increased caregiver demands and financial strain. This systematic review updates previous data, exploring the relationship between parenting a child with IDD and parental depression and anxiety.
METHODS
Five electronic databases were searched for eligible English-language articles, published between January 2004 and July 2018. All epidemiological study designs were eligible, provided the level of depression and/or anxiety was compared between parents of children (aged <18) with and without IDD. No limit was placed on geographic location. The proportion of positive associations between parenting a child with IDD and depression/anxiety were disaggregated by disability type, geographic region, and sample size. The percentage of parents at risk of moderate depression or anxiety were calculated using recognised clinical cut-off scores for each screening tool. Meta-analyses, in which pooled effect sizes of elevated depression and anxiety symptoms were calculated, were conducted across two IDD conditions, autism and cerebral palsy.
RESULTS
Of the 5,839 unique records screened, 19 studies fulfilled the inclusion criteria. The majority of studies were conducted in high-income (n = 8, 42%) or upper-middle income countries (n = 10, 53%). Of the 19 studies, 69% focused on parents of children with cerebral palsy (n = 7, 37%) or autism (n = 6, 32%). Nearly all studies found a positive association between parenting a child with IDD and depression (n = 18, 95%) and anxiety (n = 9, 90%) symptoms. Factors associated with higher levels of depression symptoms amongst parents of children with IDD included disability severity (n = 8, 78%) and lower household income (n = 4, 80%). Approximately one third (31%) of parents of children with IDD reach the clinical cut-off score for moderate depression, compared with 7% of parents of children without IDD. 31% of parents of children with IDD reach the cut-off score for moderate anxiety, compared with 14% of parents of children without IDD. The meta-analyses demonstrated moderate effect sizes for elevated depression amongst parents of children with autism and cerebral palsy.
CONCLUSIONS
Results indicate elevated levels of depressive symptoms amongst parents of children with IDD. Quality concerns amongst the existing literature support the need for further research, especially in low- and middle-income countries.
Topics: Adult; Anxiety; Autistic Disorder; Caregivers; Cerebral Palsy; Child; Developmental Disabilities; Female; Humans; Intellectual Disability; Male; Parents; Sample Size
PubMed: 31361768
DOI: 10.1371/journal.pone.0219888 -
Stem Cell Reviews and Reports Jan 2022Assess the safety and efficacy of upcoming stem cell treatments and analyze their effects on the cognitive and behavioral impairments in patients diagnosed with autism. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
Assess the safety and efficacy of upcoming stem cell treatments and analyze their effects on the cognitive and behavioral impairments in patients diagnosed with autism.
METHODS
We included controlled and noncontrolled, randomized and non-randomized trials evaluating stem cell therapy as a treatment in patients with autism spectrum disorder compared to placebo or without comparator.
DATA SOURCES
Scopus, Web of Science, MEDLINE and EMBASE. Risk of bias was assessed using Cochrane's Risk of Bias tool and the NIH's Quality Assessment Tool for Studies With No Control Group.
RESULTS
Eleven trials including 461 patients proved eligible. ABC scale meta-analysis showed a mean raw of -11.97 in the intervention groups (95 % CI -91.45 to 67.52, p < 0.01). CARS scale reported a mean raw of -9.08 (95 % CI -15.43 to -2.73, p < 0.01). VABS scale was reported by their domains: communication domain reported a mean raw of 2.69 (95 % CI 1.30 to 4.08, p = 0.92); daily living domain, 1.99 (95 % CI 0.83 to 3.15, p = 0.51); motor domain, 1.06 (95 % CI -0.37 to 2.48, p = 0.20); socialization domain, 3.09 (95 % CI 1.71 to 4.48, p = 0.61); adaptive behavior domain, 2.10 (95 % CI 1.04 to 3.16, p = 0.36). Furthermore, the most common side effects reported included fever, hyperactivity, vomit, headache, and aggressiveness; no serious adverse events were reported.
CONCLUSIONS
The body of evidence suggests that stem cell therapy significantly improves scales in patients with autism spectrum disorder, hence, future studies should help us have more confidence in the results. We found no serious adverse events related to the stem cell therapy.
Topics: Autism Spectrum Disorder; Cell- and Tissue-Based Therapy; Humans
PubMed: 34515938
DOI: 10.1007/s12015-021-10257-0 -
JAMA Pediatrics Apr 2023The Modified Checklist for Autism in Toddlers (M-CHAT) and the M-CHAT, Revised With Follow-up (M-CHAT-R/F)-henceforth referred to as M-CHAT(-R/F)-are the most commonly... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The Modified Checklist for Autism in Toddlers (M-CHAT) and the M-CHAT, Revised With Follow-up (M-CHAT-R/F)-henceforth referred to as M-CHAT(-R/F)-are the most commonly used toddler screeners for autism spectrum disorder (ASD). Their use often differs from that in the original validation studies, resulting in a range of estimates of sensitivity and specificity. Also, given the variability in reports of the clinical utility of the M-CHAT(-R/F), researchers and practitioners lack guidance to inform autism screening protocols.
OBJECTIVE
To synthesize variability in sensitivity and specificity of M-CHAT(-R/F) across multiple factors, including procedures for identifying missed cases, likelihood level, screening age, and single compared with repeated screenings.
DATA SOURCES
A literature search was conducted with PubMed, Web of Science, and Scopus to identify studies published between January 1, 2001, and August 31, 2022.
STUDY SELECTION
Articles were included if the studies used the M-CHAT(-R/F) (ie, original or revised version) to identify new ASD cases, were published in English-language peer-reviewed journals, included at least 10 ASD cases, reported procedures for false-negative case identification, screened children by 48 months, and included information (or had information provided by authors when contacted) needed to conduct the meta-analysis.
DATA EXTRACTION AND SYNTHESIS
The systematic review and meta-analysis was conducted within the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline. The Quality Assessment of Diagnostic Accuracy Studies-2 tool evaluated bias in sample selection. Data extraction and quality assessment were performed by 2 authors independently. The overall diagnostic accuracy of the M-CHAT(-R/F) was assessed with the hierarchic summary receiver operating characteristic (HSROC) model.
MAIN OUTCOMES AND MEASURES
Sensitivity, specificity, diagnostic odds ratios, and HSROC curves of M-CHAT(-R/F).
RESULTS
The review included 50 studies with 51 samples. The pooled sensitivity of M-CHAT(-R/F) was 0.83 (95% CI, 0.77-0.88), and the pooled specificity was 0.94 (95% CI, 0.89-0.97). Heterogeneity analyses revealed greater diagnostic accuracy for low- vs high-likelihood samples, a concurrent vs prospective case confirmation strategy, a large vs small sample size, use of M-CHAT(-R/F) Follow-up, and non-English vs English only.
CONCLUSIONS AND RELEVANCE
Overall, results of this study suggest the utility of the M-CHAT(-R/F) as an ASD screener. The wide variability in psychometric properties of M-CHAT(-R/F) highlights differences in screener use that should be considered in research and practice.
Topics: Humans; Child, Preschool; Autistic Disorder; Autism Spectrum Disorder; Checklist; Sensitivity and Specificity; ROC Curve
PubMed: 36804771
DOI: 10.1001/jamapediatrics.2022.5975 -
The Australian and New Zealand Journal... Feb 2021Currently, pharmaceutical treatment options for autism spectrum disorder are limited. Brain glutaminergic dysregulation is observed in autism spectrum disorder.... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Currently, pharmaceutical treatment options for autism spectrum disorder are limited. Brain glutaminergic dysregulation is observed in autism spectrum disorder. -acetylcysteine, which can be converted to glutathione and subsequently release glutamate into the extracellular space, and thus reduce glutamatergic neurotransmission at synapses, is considered a potential drug for autism spectrum disorder treatment. Here, we analyzed the treatment effects of -acetylcysteine on autism spectrum disorder in randomized controlled trials.
STUDY DESIGN
Updated systematic review and meta-analysis.
DATA SOURCES
By systematically searching the PubMed, Embase and Cochrane Library, we obtained five randomized controlled trials.
STUDY SELECTION
Meta-analyses were performed to examine the improvement in autistic behaviors as measured by the Aberrant Behavior Checklist, Social Responsiveness Scale and Repetitive Behavior Scale-Revised, using mean difference with a 95% confidence interval and a random-effects model.
DATA SYNTHESIS
After 8-12 weeks of -acetylcysteine supplementation, the pooled result of four trials revealed an improvement in Aberrant Behavior Checklist total score (mean difference = 1.31, 95% confidence interval = [0.42, 2.20]). When one trial was excluded, the sensitivity test result was stronger (mean difference = 1.88, 95% confidence interval = [0.92, 2.83]). The pooled results of three trials revealed significant improvements in hyperactivity (mean difference = 4.80, 95% confidence interval = [1.20, 8.40]) and irritability (mean difference = 4.07, 95% confidence interval = [1.13, 7.04]). Regarding Social Responsiveness Scale, the pooled result of two trials showed significant improvement in social awareness after 8-12 weeks of -acetylcysteine supplementation (mean difference = 1.34, 95% confidence interval = [0.09, 2.59]). No differences were observed in the pooled results of two trials using Repetitive Behavior Scale, either in the total or the subscales.
CONCLUSION
We concluded that -acetylcysteine is safe and tolerable, reduces hyperactivity and irritability and enhances social awareness in children with autism spectrum disorder. However, further evidence should be sought before a general recommendation.
Topics: Acetylcysteine; Autism Spectrum Disorder; Child; Humans; Irritable Mood; Randomized Controlled Trials as Topic
PubMed: 32900213
DOI: 10.1177/0004867420952540 -
BMJ (Clinical Research Ed.) Nov 2023To summarize the breadth and quality of evidence supporting commonly recommended early childhood autism interventions and their estimated effects on developmental... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To summarize the breadth and quality of evidence supporting commonly recommended early childhood autism interventions and their estimated effects on developmental outcomes.
DESIGN
Updated systematic review and meta-analysis (autism intervention meta-analysis; Project AIM).
DATA SOURCES
A search was conducted in November 2021 (updating a search done in November 2017) of the following databases and registers: Academic Search Complete, CINAHL Plus with full text, Education Source, Educational Administration Abstracts, ERIC, Medline, ProQuest Dissertations and Theses, PsycINFO, Psychology and Behavioral Sciences Collection, and SocINDEX with full text, , and ClinicalTrials.gov.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Any controlled group study testing the effects of any non-pharmacological intervention on any outcome in young autistic children younger than 8 years.
REVIEW METHODS
Newly identified studies were integrated into the previous dataset and were coded for participant, intervention, and outcome characteristics. Interventions were categorized by type of approach (such as behavioral, developmental, naturalistic developmental behavioral intervention, and technology based), and outcomes were categorized by domain (such as social communication, adaptive behavior, play, and language). Risks of bias were evaluated following guidance from Cochrane. Effects were estimated for all intervention and outcome types with sufficient contributing data, stratified by risk of bias, using robust variance estimation to account for intercorrelation of effects within studies and subgroups.
RESULTS
The search yielded 289 reports of 252 studies, representing 13 304 participants and effects for 3291 outcomes. When contributing effects were restricted to those from randomized controlled trials, significant summary effects were estimated for behavioral interventions on social emotional or challenging behavior outcomes (Hedges' g=0.58, 95% confidence interval 0.11 to 1.06; P=0.02), developmental interventions on social communication (0.28, 0.12 to 0.44; P=0.003); naturalistic developmental behavioral interventions on adaptive behavior (0.23, 0.02 to 0.43; P=0.03), language (0.16, 0.01 to 0.31; P=0.04), play (0.19, 0.02 to 0.36; P=0.03), social communication (0.35, 0.23 to 0.47; P<0.001), and measures of diagnostic characteristics of autism (0.38, 0.17 to 0.59; P=0.002); and technology based interventions on social communication (0.33, 0.02 to 0.64; P=0.04) and social emotional or challenging behavior outcomes (0.57, 0.04 to 1.09; P=0.04). When effects were further restricted to exclude caregiver or teacher report outcomes, significant effects were estimated only for developmental interventions on social communication (0.31, 0.13 to 0.49; P=0.003) and naturalistic developmental behavioral interventions on social communication (0.36, 0.23 to 0.49; P<0.001) and measures of diagnostic characteristics of autism (0.44, 0.20 to 0.68; P=0.002). When effects were then restricted to exclude those at high risk of detection bias, only one significant summary effect was estimated-naturalistic developmental behavioral interventions on measures of diagnostic characteristics of autism (0.30, 0.03 to 0.57; P=0.03). Adverse events were poorly monitored, but possibly common.
CONCLUSION
The available evidence on interventions to support young autistic children has approximately doubled in four years. Some evidence from randomized controlled trials shows that behavioral interventions improve caregiver perception of challenging behavior and child social emotional functioning, and that technology based interventions support proximal improvements in specific social communication and social emotional skills. Evidence also shows that developmental interventions improve social communication in interactions with caregivers, and naturalistic developmental behavioral interventions improve core challenges associated with autism, particularly difficulties with social communication. However, potential benefits of these interventions cannot be weighed against the potential for adverse effects owing to inadequate monitoring and reporting.
Topics: Child; Humans; Child, Preschool; Autistic Disorder; Behavior Therapy; Early Intervention, Educational; Social Skills; Adaptation, Psychological
PubMed: 37963634
DOI: 10.1136/bmj-2023-076733 -
The Cochrane Database of Systematic... Jul 2018Autism spectrum disorder (ASD) is a behaviourally diagnosed condition. It is defined by impairments in social communication or the presence of restricted or repetitive... (Review)
Review
BACKGROUND
Autism spectrum disorder (ASD) is a behaviourally diagnosed condition. It is defined by impairments in social communication or the presence of restricted or repetitive behaviours, or both. Diagnosis is made according to existing classification systems. In recent years, especially following publication of the Diagnostic and Statistical Manual of Mental Disorders - Fifth Edition (DSM-5; APA 2013), children are given the diagnosis of ASD, rather than subclassifications of the spectrum such as autistic disorder, Asperger syndrome, or pervasive developmental disorder - not otherwise specified. Tests to diagnose ASD have been developed using parent or carer interview, child observation, or a combination of both.
OBJECTIVES
Primary objectives1. To identify which diagnostic tools, including updated versions, most accurately diagnose ASD in preschool children when compared with multi-disciplinary team clinical judgement.2. To identify how the best of the interview tools compare with CARS, then how CARS compares with ADOS.a. Which ASD diagnostic tool - among ADOS, ADI-R, CARS, DISCO, GARS, and 3di - has the best diagnostic test accuracy?b. Is the diagnostic test accuracy of any one test sufficient for that test to be suitable as a sole assessment tool for preschool children?c. Is there any combination of tests that, if offered in sequence, would provide suitable diagnostic test accuracy and enhance test efficiency?d. If data are available, does the combination of an interview tool with a structured observation test have better diagnostic test accuracy (i.e. fewer false-positives and fewer false-negatives) than either test alone?As only one interview tool was identified, we modified the first three aims to a single aim (Differences between protocol and review): This Review evaluated diagnostic tests in terms of sensitivity and specificity. Specificity is the most important factor for diagnosis; however, both sensitivity and specificity are of interest in this Review because there is an inherent trade-off between these two factors.Secondary objectives1. To determine whether any diagnostic test has greater diagnostic test accuracy for age-specific subgroups within the preschool age range.
SEARCH METHODS
In July 2016, we searched CENTRAL, MEDLINE, Embase, PsycINFO, 10 other databases, and the reference lists of all included publications.
SELECTION CRITERIA
Publications had to: 1. report diagnostic test accuracy for any of the following six included diagnostic tools: Autism Diagnostic Interview - Revised (ADI-R), Gilliam Autism Rating Scale (GARS), Diagnostic Interview for Social and Communication Disorder (DISCO), Developmental, Dimensional, and Diagnostic Interview (3di), Autism Diagnostic Observation Schedule - Generic (ADOS), and Childhood Autism Rating Scale (CARS); 2. include children of preschool age (under six years of age) suspected of having an ASD; and 3. have a multi-disciplinary assessment, or similar, as the reference standard.Eligible studies included cohort, cross-sectional, randomised test accuracy, and case-control studies. The target condition was ASD.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed all studies for inclusion and extracted data using standardised forms. A third review author settled disagreements. We assessed methodological quality using the QUADAS-2 instrument (Quality Assessment of Studies of Diagnostic Accuracy - Revised). We conducted separate univariate random-effects logistical regressions for sensitivity and specificity for CARS and ADI-R. We conducted meta-analyses of pairs of sensitivity and specificity using bivariate random-effects methods for ADOS.
MAIN RESULTS
In this Review, we included 21 sets of analyses reporting different tools or cohorts of children from 13 publications, many with high risk of bias or potential conflicts of interest or a combination of both. Overall, the prevalence of ASD for children in the included analyses was 74%.For versions and modules of ADOS, there were 12 analyses with 1625 children. Sensitivity of ADOS ranged from 0.76 to 0.98, and specificity ranged from 0.20 to 1.00. The summary sensitivity was 0.94 (95% confidence interval (CI) 0.89 to 0.97), and the summary specificity was 0.80 (95% CI 0.68 to 0.88).For CARS, there were four analyses with 641 children. Sensitivity of CARS ranged from 0.66 to 0.89, and specificity ranged from 0.21 to 1.00. The summary sensitivity for CARS was 0.80 (95% CI 0.61 to 0.91), and the summary specificity was 0.88 (95% CI 0.64 to 0.96).For ADI-R, there were five analyses with 634 children. Sensitivity for ADI-R ranged from 0.19 to 0.75, and specificity ranged from 0.63 to 1.00. The summary sensitivity for the ADI-R was 0.52 (95% CI 0.32 to 0.71), and the summary specificity was 0.84 (95% CI 0.61 to 0.95).Studies that compared tests were few and too small to allow clear conclusions.In two studies that included analyses for both ADI-R and ADOS, tests scored similarly for sensitivity, but ADOS scored higher for specificity. In two studies that included analyses for ADI-R, ADOS, and CARS, ADOS had the highest sensitivity and CARS the highest specificity.In one study that explored individual and additive sensitivity and specificity of ADOS and ADI-R, combining the two tests did not increase the sensitivity nor the specificity of ADOS used alone.Performance for all tests was lower when we excluded studies at high risk of bias.
AUTHORS' CONCLUSIONS
We observed substantial variation in sensitivity and specificity of all tests, which was likely attributable to methodological differences and variations in the clinical characteristics of populations recruited.When we compared summary statistics for ADOS, CARS, and ADI-R, we found that ADOS was most sensitive. All tools performed similarly for specificity. In lower prevalence populations, the risk of falsely identifying children who do not have ASD would be higher.Now available are new versions of tools that require diagnostic test accuracy assessment, ideally in clinically relevant situations, with methods at low risk of bias and in children of varying abilities.
PubMed: 30075057
DOI: 10.1002/14651858.CD009044.pub2