BACKGROUND:Children with complex communication needs (CCN) are those who have profound language difficulties or do not use spoken language as their primary means of communication. Having CCN can lead to difficulty accessing and participating in everyday activities. AIMS:This systematic review aims to estimate the global prevalence of CCN among children with or without autism or intellectual disability (ID). METHODS AND PROCEDURES:We will include observational (cross-sectional or longitudinal) studies that have reported the prevalence of CCN among children without acquired or physical conditions. Populations, including children, can have (1) no co-occurring conditions or (2) autism or ID. This protocol for a systematic review has been developed according to the Preferred Reporting Items for Systematic Review and Meta-Analysis for Protocols (PRISMA-P) guideline. Studies published in all languages will be searched in MEDLINE, Embase, PsycINFO, ProQuest central, CINAHL, Scopus and through grey literature searches. Retrieved records will be independently screened by two authors, and relevant data will be independently extracted. Random effects model will be fitted to obtain an overall prevalence estimate. Interstudy heterogeneity will be assessed using the I2 statistic and explored through subgroup analysis. Egger's test and visual inspection of the funnel plot will be used to assess publication bias. Quality appraisal of each included study will be performed independently by two authors using Hoy risk of bias tool, and overall quality of evidence will be assessed using GRADEpro. CONCLUSIONS AND IMPLICATIONS:The findings will provide a global estimate of the prevalence of CCN and a description of the prevalence for different settings or clinical subgroups. This information is needed to optimise resource allocation for assessment and intervention, and to direct future research to fill knowledge gaps, if identified. WHAT THIS PAPER ADDS:What is already known on the subject Children with CCN are variably described as minimally verbal (MV), nonspeaking or nonverbal (NV). Few prevalence studies have included children with CCN, including studies of autistic children. The reported prevalence of CCN in children varies widely due to the use of different definitions and study exclusions. What this paper adds to the existing knowledge This paper provides a protocol for the first systematic review and meta-analysis to estimate the global prevalence of CCN in children with and without commonly associated diagnoses. What are the potential or actual clinical implications of this work? Global and up-to-date prevalence estimates are essential for allocating adequate resources and services for children with CCN and their family. Additionally, determining prevalence direct future research to fill knowledge gaps, if identified.

Background:Improvements in neonatal and paediatric care in recent decades have increased the survival of children with non-progressive neurological impairment. Respiratory disease in children with neurological impairment is common, with symptoms difficult to manage and lower respiratory tract infection occurring frequently. To reduce these, prophylactic antibiotics are being increasingly used, but the type, duration and dose of antibiotics can vary considerably, and there is limited evidence about their effectiveness in children and young people. A joint United Kingdom and Australia multicentre, randomised, double-blind, placebo-controlled trial comparing 52 weeks of azithromycin to placebo in children and young people with neurological impairment at risk of lower respiratory tract infection (PARROT) was planned to address this gap. PARROT was a multicentre, parallel group, blinded, pragmatic randomised controlled trial of 52-week duration with a planned sample size of 500 (250 in each arm) participants with neurological impairment. The primary outcome was the proportion of children and young people hospitalised with lower respiratory tract infection over the 52-week period. Results:In total, 90 children and young people (62 in Australia, 28 in the United Kingdom) aged 3-17 years, with a diagnosed non-progressive, non-neuromuscular neurological impairment, who had persistent respiratory symptoms were randomised (1 : 1) to receive azithromycin or placebo. Baseline demographic and clinical characteristics were relatively well balanced across the two treatment groups and countries. Overall, mean (standard deviation) age was 9.2 (4.4) years, with 64% of participants having cerebral palsy, 67% being non-ambulant and 54% being totally tube-fed. At baseline, mean (standard deviation) numbers of hospital admissions with lower respiratory tract infection in the preceding year were 1.8 (2.0)/year, and general practitioner attendances 3.3 (3.0)/year. The PARROT trial was closed early to recruitment due to challenges arising from the COVID-19 pandemic. Sixty-five (72%) participants (azithromycin n = 30, placebo n = 35) completed 52 weeks of treatment and were not withdrawn early from the trial. Regarding the primary outcome, 11 (36.7%) in the azithromycin group were hospitalised with lower respiratory tract infection and 9 (25.7%) in the placebo group [absolute risk reduction 0.11 (95% confidence interval -0.12 to 0.33), relative risk 1.43 (95% confidence interval 0.68 to 2.97)]. Analysis of secondary outcome data was limited by the number of missing data, but parent-reported quality of life for young person and parent, sleep amount/quality for young person and parent, and respiratory symptoms were similar between groups and countries. Limitations:As PARROT was stopped early and was consequently underpowered, it is not possible to say whether azithromycin prophylaxis is any more effective than placebo in reducing the proportion of children admitted to hospital with lower respiratory tract infection after a 52-week period. Conclusions and future work:Although we cannot comment on the effectiveness of prophylactic antibiotics in this context, we can draw some useful conclusions from this trial. Thus, the importance placed by families on hospitalisation and its prevalence in both treatment groups, even during the pandemic, would suggest that this is an appropriate primary outcome measure for future trials in this high-risk group of children and young people. Furthermore, the high attrition rate and large numbers of missing data, specifically for questionnaire-based outcomes at later follow-up points, should encourage researchers to be mindful of minimising trial burden to families for any future trials wherever possible. Funding:This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme as award number 16/17/01.

AIM:To reach an agreed approach to define developmental regression, to improve understanding of aetiology, prevalence, and timing of investigations, and provide standardized and consistent care. METHOD:Developmental regression is a symptom of several developmental, epileptic, genetic, and metabolic conditions (e.g. autism, Rett syndrome, childhood dementias, and Landau-Kleffner syndrome). An expert interdisciplinary clinician panel reviewed the literature for existing definitions and formulated a survey using the Delphi method. Health care clinician perspectives on key elements required for a definition were sought. The survey was completed over two rounds and consensus was defined as a minimum of 70% agreement. RESULTS:Of the 76 clinicians who completed the first-round survey, 41 completed the second round (54%). Consensus was reached on the following definition. Developmental regression refers to: (1) skill(s) loss experienced during childhood lasting a minimum of 4 weeks, and (2) occurring in at least 1 of 6 developmental domains (verbal communication, nonverbal communication, functional motor skills, cognition, social skills, and self-help skills). INTERPRETATION:A working definition of developmental regression is proposed. The intention is that this definition will undergo improvements through use and evaluation to increase its utility and uptake in clinical care and research.

OBJECTIVES:This is a protocol for a Cochrane Review (diagnostic). The objectives are as follows: Primary objectives To evaluate the diagnostic accuracy of widely used ASD diagnostic tools (specifically CARS, GARS, ADOS, ADI-R, DISCO, 3di) in preschool children, compared with multidisciplinary team clinical judgement. We aim to: summarise sensitivity, specificity, and other accuracy measures for each ASD diagnostic tool; and for studies that compare two or more tools within the same study, describe and compare their diagnostic accuracy. To identify if any combination of diagnostic tools has greater diagnostic test accuracy than each single tool. We aim to: describe combined diagnostic test accuracy within a single study; and compare combined diagnostic test accuracy to individual test accuracy from primary objective 1a. Secondary objectives To assess whether there is different diagnostic test accuracy for subgroups such as intellectual disability, language level, setting, prospective versus retrospective, DSM diagnostic classification and specific ages (within the preschool age range).

INTRODUCTION:Developmental regression is when children lose one or more skills they have established. Families caring for these children need timely recognition to assist diagnosis and tailored interventions. Families also need support to develop practical skills for caregiving and strategies to promote family well-being and community participation. Given the high caring demands, flexibly delivered approaches are needed to accommodate family routines. Online delivery of health-related interventions that provide coaching, information, or both has been found to be a feasible and effective option for families. Family Focus is a new family-centred online programme, co-designed with parents and family advocates, clinicians, and researchers to support and empower primary carers. METHODS AND ANALYSIS:This study is a prospective, pragmatic randomised controlled trial comparing the effectiveness of online parent coaching plus Family Focus (Coaching+FF) to Family Focus alone (FF) for primary carers of children experiencing developmental regression. A sample of 56 families will be randomised in a 1:1 ratio. Outcomes are assessed at baseline, post-intervention and 12-month post-randomisation. The primary outcome is parental stress symptoms at post-intervention. Secondary outcomes include parental depressive and anxiety symptoms, parental engagement in health-promoting activities, family empowerment, family quality of life and child global health outcomes. The study will also examine the uptake and acceptability of specific coaching and FF components and explore the facilitators and barriers to their delivery and implementation. ETHICS AND DISSEMINATION:Ethics approvals were obtained from the participating organisations (Monash Health HREC/107806). Informed consent is obtained from parents/guardians of children prior to study enrolment. Study findings will be disseminated through peer-reviewed publications, conference presentations and lived experience agencies. TRIAL REGISTRATION NUMBER:ISRCTN25513446.

Developmental regression during childhood is inconsistently defined and measured, resulting in delayed diagnostic discovery and intervention. This study aimed to examine published definitions and measures for developmental regression. A comprehensive search strategy was applied to Medline, Embase, Cochrane, and PsycINFO databases. Reviewers independently screened relevant studies according to the Preferred Reporting Items for Systematic reviews. The number and percentages of definition use, their primary features, and measures were reported. Of 19,099 potential publications, 157 were included. Thematic analysis identified four condition groups: Neurodevelopmental disorders (n = 118); Progressive neurodegenerative conditions (n = 17); Developmental epileptic encephalopathies (n = 8); and Genetic conditions (n = 14). Most studies (n = 124, 79.0%) used an operational definition, and most specified types of skills lost (n = 147, 93.6%). Age of onset was specified in 67.5% (n = 106), and duration was specified in 34.4% (n = 54). Measures designed to specifically assess developmental regression were infrequently used (n = 5, 3.2%). We concluded that developmental regression is inconsistently defined and measured. A consistent approach is vital to ensure that all children are identified as early as possible. This will allow timely diagnostic discovery, enhance research rigor, and promote the collaboration that is needed to advance our understanding of causal mechanisms and effective interventions for affected children and their families.

Child health inequities remain a persistent challenge, with well-described long-term consequences. Advances in cross-sector administrative data linkage and causal inference methods offer powerful opportunities to transform data into evidence for addressing inequities. This article explores how linked administrative data support timely, precise, agile and coordinated policy responses and monitor their impact. We outline conditions needed to realise this potential, including sustained cross-sector data infrastructure, analytic capability and increased efforts to translate evidence into action. We argue linked administrative data can inform pathways to more equitable child health and, with investment, help deliver on lasting returns for children, families and society.

Objective: Caregivers of Autistic children commonly report reduced mental health and wellbeing in comparison to caregivers of non-autistic children. Extensive research has demonstrated that psychological interventions improve caregiver mental health. This umbrella review aimed to (1) assess the quality and validity of systematic reviews and/or meta-analyses (SRs) that evaluated the effectiveness of clinician-delivered, non-pharmacological interventions on mental health and wellbeing outcomes in caregivers of Autistic children, and (2) synthesise evidence on the overall effectiveness of these interventions. Method: The review was conducted in line with the Joanna Briggs Institute methodology for umbrella reviews. Risk of bias was assessed using the Risk of Bias in Systematic Reviews tool. Results: The search across seven databases identified 2227 potentially eligible records. Seventeen SRs were included, comprising n = 61 relevant primary studies and n = 1515 participating caregivers. Methodological quality of the included SRs was generally low. No SRs were considered authoritative sources for practice recommendations. Assessment of relevant studies from included SRs identified Acceptance and Commitment Therapy (ACT) and psychoeducation as demonstrating the most consistent positive impact on caregivers’ self-reported symptoms of anxiety, depression, and stress, as well as quality of life, and general mental health and wellbeing. Mindfulness and cognitive behaviour therapy (CBT) interventions also appeared to improve symptoms in most domains to an extent, though more inconsistently. Conclusion: Despite the poor quality of available SRs, assessment of individual studies identified ACT and psychoeducation as broad intervention modalities that strengthen caregiver psychological wellbeing. Research, practice, and policy implications are discussed.

Emerging dimensional models of neurodevelopmental traits and mental health have the potential to more accurately characterise individual profiles in children and adolescents, addressing the limitations of categorical diagnoses. Here, we generated the first hierarchical, dimensional model of neurodevelopmental traits and mental health problems, derived from caregiver-reported measures, in a predominantly neurodivergent (71%) sample of N = 372 children and adolescents aged 7-13 years. We evaluated the criterion validity and utility of this model for predicting adaptive functioning and quality of life (QoL) outcomes compared with categorical diagnoses. Regression analyses identified five data-driven dimensions that significantly outperformed traditional diagnostic categories in predicting adaptive functioning and QoL outcomes. Our model offers an innovative framework for understanding neurodevelopmental and mental health profiles within neurodiverse youth. The model has the potential to advance the identification of multidisciplinary supports that could be tailored to every child’s individualised needs, regardless of diagnosis.

AIM:Children presenting with developmental regression are inconsistently investigated, leading to unacceptable delays to diagnosis for some children. This study sought global expert opinion to develop an agreed approach to investigate children presenting with developmental regression. METHOD:A Delphi survey collected clinician participant choice of investigations in response to case scenarios of children presenting with developmental regression and differing presenting features. Participants responded to two surveys, and consensus was achieved at 70% agreement. Results were analysed using descriptive statistics (number of responses and percentage agreement). Fifty participants completed the first-round survey, and 31 completed round two. Forty-eight percent of participants who completed both rounds had over 20 years of experience in caring for children with developmental regression. They represented four different clinician specialties and worked across five countries. RESULTS:For each of the four scenarios, there was agreement to recommend haematological, biochemical and genetic investigations as first investigations. Endocrine, metabolic and neurophysiological investigations reached consensus for scenarios based on presentation differences. INTERPRETATION:Participants agreed on first investigations to recommend for children presenting with developmental regression. This is an important initial step towards an agreed approach to investigate children with developmental regression needed to reduce inconsistencies in current care.

BACKGROUND:An increasing number of children and adolescents are prescribed second-generation antipsychotic medications, which may lead to cardiometabolic or other physical health impairments. It is unknown whether lifestyle interventions can prevent or manage these adverse effects. AIMS:To evaluate the effectiveness of lifestyle interventions for preventing or managing cardiometabolic risks and other adverse physical health outcomes in this population. METHOD:Four bibliographic databases were searched up to February 2024. Randomised controlled trials reporting a physical health outcome of children or adolescents (aged 6-17 years) taking antipsychotics and participating in a lifestyle intervention compared with treatment as usual (TAU) were eligible for inclusion. The Cochrane Risk of Bias 2 tool was used to assess risk of bias. Data were synthesised via a random-effects meta-analysis and narrative synthesis. RESULTS:Four studies with a total of 370 participants were included. Most (75%) had a high risk of bias. Lifestyle interventions resulted in moderate but statistically non-significant reductions in participants' body mass index (standard mean difference -0.70, 95% CI: -1.70 to 0.31) compared with TAU. Some studies reported improvements in other physical health outcomes favouring the intervention, although findings were inconsistent and varied across different measures. Reporting of secondary indicators of physical health, including participant or family health behaviours, was limited. CONCLUSIONS:The effectiveness of lifestyle interventions for preventing or managing the cardiometabolic risk and other adverse physical health outcomes in this population is unclear due to the limited number of available trials, small samples and high risk of bias. Larger trials are needed.

This systematic review evaluates the diagnostic yield of investigations requested for children with developmental regression. Online databases MEDLINE, EMBASE, CINAHL, PsycINFO, Cochrane were searched to identify published records that reported a diagnostic yield for children with developmental regression. Random effects meta-analyses were performed using R software with meta package. Our search identified 11,283 published records, of which 347 were assessed for eligibility, and 15 (596 children) were included in the final systematic review and meta-analysis. Subgroup analysis assessed the diagnostic yield for investigating children with different presentations and developmental regression. Diagnostic yield results were 68% for children with neurological symptoms (two records, six children, 95%CI 32-100) and children with epileptic symptoms (two records, 56 children, 95%CI 15-100); 40% for children with neurodevelopmental delay (six records, 294 children, 95%CI 3-78); 9% for autistic children (three records, 138 children, 95%CI 0-26). Pooled analysis could not be completed for metabolic (one record, 29 children) or genetic presentations (one record, 73 children). The diagnostic yield for genetic/genomic investigations (six records, 142 children, 95%CI, 47-92) was 70%, compared with 28% for metabolic (five records, 286 children, 95%CI 0-64), 13% for neurophysiological (two records, 127 children, 95%CI 0-39) and 6% for neuroimaging (two records, 41 children, 95%CI 0-20). Investigations for children with developmental regression and neurological or epileptic symptoms resulted in the highest diagnostic yield. These results are clinically meaningful and will inform future research to advance towards an agreed investigative approach yet lack statistical significance due to small samples.

Objective To demonstrate how linked administrative data can be utilised to examine the extent to which stacking multiple policy-relevant hypothetical interventions across early childhood could potentially reduce socioeconomic inequities in children’s developmental outcomes at school entry. Methods We used longitudinal linked administrative data from 274,123 Australian children born between January 2012-July 2013 and who participated in the 2018 Australian Early Development Census (AEDC) in their first year of formal schooling. Causal mediation analysis using an interventional effects approach was used to estimate the impact of hypothetical interventions aimed at reducing socioeconomic inequities in five intervention targets over early childhood: household income (1-2 years), home reading (2-3 years), household crowding (3-4 years), child mental health (4-5 years), and preschool attendance (4-5 years). Poor child development was measured by teacher-reported vulnerability on one or more developmental domains of the AEDC. Results The analytic sample included 172,615 children (87,179 male [50.5%]) with complete data. One-sixth exhibited poor development at school entry. Children who were socioeconomically disadvantaged in infancy (bottom 25th percentile on a composite of household income, parent education, and occupation) had a higher risk of poor developmental outcomes compared to peers: absolute risk difference = 8.7% (95% CI, 8.2% to 9.1%). Intervening to reduce inequities in all five intervention targets simultaneously resulted in a 5.6% (95% CI, 5.2% to 5.9%) absolute reduction in the risk of poor developmental outcomes. Among separate interventions, the largest absolute reduction was for home reading (4.5%, 95% CI, 4.3% to 4.8%), followed by child mental health (0.6%, 95% CI, 0.5% to 0.8%) and preschool attendance (0.2%, 95% CI, 0.2% to 0.3%). Conclusion This is the first study to apply causal methods to linked administrative data for evaluating multisectoral early childhood interventions. Combining interventions reduces socioeconomic inequities in child development more than individual approaches. We show how such data can address causal policy questions otherwise infeasible, unethical, or impractical to test in trials.

AIM:To characterize autism and co-occurring tuberous sclerosis-associated neuropsychiatric disorders (TAND) in children with tuberous sclerosis complex (TSC), addressing evidence gaps by using deep developmental phenotyping in a single cohort. METHOD:This cohort study assessed autism characteristics, intelligence, adaptive function, language, and co-occurring conditions, using multidisciplinary direct assessment, in 50 children with TSC, comparing those with and without autism. RESULTS:Autistic children (28, 56%) had moderate mean scores for autistic characteristics (Autism Diagnostic Observation Schedule calibrated severity scores; social affect, 6.9 [standard deviation 2.5]; restricted and repetitive behaviour, 7.1 [standard deviation 2.3], but with considerable variation). Autistic children were more likely to be male (54% vs 18%) and have intellectual disability (79% vs 32%), language impairment (89% vs 50%), executive dysfunction (70% vs 29%), and externalizing behaviours (46% vs 14%). Inattentive attention-deficit/hyperactivity disorder (ADHD) symptoms were frequent in autistic and not-autistic children (74% vs 78%), and not influenced by intellectual ability. Language impairment occurred in 27% without autism or intellectual disability. INTERPRETATION:TAND are complex and heterogenous in children with and without autism. Formal assessment of language function and ADHD symptoms should be considered in all children with TSC, regardless of autism categorization or intellectual ability. Language function needs greater consideration within TAND levels and clusters.

To examine accuracy of two-tiered surveillance to detect developmental disability and autism in a multicultural birth cohort; a subset of the Watch Me Grow Study. Surveillance tools were used at or soon after 18 months of age, including the Parents’ Evaluation of Developmental Status (PEDS), the Ages and Stages Questionnaire (ASQ-3), and the revised Modified Checklist for Autism in Toddlers (M-CHAT-R/F). Children with and without identified concerns were assessed between 18 and 23 months using the Mullen Scales of Early Learning (MSEL) and the Autism Diagnostic Observation Schedule-2 (ADOS-2). Sensitivity and specificity of the surveillance tools used in isolation and in combination in this cohort ranged from 51 to 87% (n = 165). Some children (n = 21) who were not identified with high likelihood of difficulties were later assessed as having probable developmental disability. Adding the M-CHAT-R/F did not significantly improve autism likelihood identification in comparison with tiered developmental surveillance. There was highly variable sensitivity and specificity of combined tools for tiered developmental surveillance in this cohort. There remains a need in Australia to improve methods of, and engagement in, developmental screening and surveillance that includes detection of concerns in community and primary healthcare settings.

Autistic children’s ability to access mental health services can be challenging due to the limited availability of therapists with autism experience, service ineligibility, and financial strain. This systematic review evaluated and synthesized literature regarding the impact of government policy levers on the access to, and utilization of, mental health services by Autistic children and their families. Interdisciplinary databases together with gray literature and supplementary searches were used to identify relevant articles. Peer-reviewed, English language studies which reported on the impact of government policy levers on the utilization of, and access to, mental health services by Autistic children and their families were included. Searches resulted in the identification of 2305 articles (database searches = 744, additional searches = 1531), six of which were included in the final review. All six articles were from the United States of America, published between 2013 and 2020, with a focus on national and state regulatory policy levers targeting insurance companies. Results indicated that most policy levers did not improve service access to, or utilization of, mental health services. Gray literature searches identified that several countries had implemented autism specific policy levers, most however had not been evaluated regarding their impact on mental health service access and utilization by Autistic children or their families. The majority of identified policy levers have not resulted in greater utilization or access of mental health services for Autistic children or their families. More global research, focusing on datasets that have allowed policies time to impact change, is needed.

RATIONALE:Individuals with autism spectrum disorder (ASD) exhibit a wide variety of symptoms related to social interaction and behaviour. Atypical antipsychotics have been widely evaluated and prescribed to treat distressing symptoms (e.g. irritability, aggression, obsessions, repetitive behaviours, etc.) in children and adults with ASD. Still, their effects and relative efficacy remain unclear. OBJECTIVES:Primary: to assess the comparative benefits of atypical antipsychotics for irritability through network meta-analyses in children and adults with ASD at short-term follow-up. Secondary: to assess the benefits and harms of atypical antipsychotics, compared to placebo or any other atypical antipsychotic, for different symptoms (e.g. aggression, obsessive-compulsive behaviours, inappropriate speech) and side effects (e.g. extrapyramidal symptoms, weight gain, metabolic side effects) in children and adults with ASD at short-, medium- and long-term follow-up. SEARCH METHODS:We searched CENTRAL, MEDLINE, 10 other databases, and two trial registers, together with reference checking, citation searching and contact with study authors to identify studies for inclusion. The latest search was 3 January 2024. ELIGIBILITY CRITERIA:Randomised controlled trials (RCTs) comparing any atypical antipsychotic drug with placebo or another atypical antipsychotic drug for adults and children with a clinical diagnosis of ASD. OUTCOMES:Critical outcomes included irritability, aggression, weight gain, extrapyramidal side effects, obsessive-compulsive behaviours and inappropriate speech. RISK OF BIAS:We used the Cochrane RoB 2 tool to assess risk of bias in the included studies. SYNTHESIS METHODS:We performed statistical analyses using a frequentist network meta-analysis for combined estimates for the outcome irritability and a random-effects model for pairwise comparisons for other outcomes. We rated the certainty of the evidence using GRADE. INCLUDED STUDIES:We included 17 studies with 1027 randomised participants. One study evaluated adults (31 participants); the remaining 16 studies evaluated children (996 participants). The interventions were risperidone, aripiprazole, lurasidone and olanzapine. SYNTHESIS OF RESULTS:Comparative efficacy on irritability Based on the network meta-analysis, risperidone and aripiprazole may reduce symptoms of irritability compared to placebo in the short term in children with ASD (risperidone: mean difference (MD) -7.89, 95% confidence interval (CI) -9.37 to -6.42; 13 studies, 906 participants; low-certainty evidence; aripiprazole: MD -6.26, 95% CI -7.62 to -4.91; 13 studies, 906 participants; low-certainty evidence). Lurasidone probably results in little to no difference in irritability compared to placebo in the short term (MD -1.30, 95% CI -5.46 to 2.86; 13 studies, 906 participants; moderate-certainty evidence). Efficacy and safety on other outcomes We are very uncertain about the effects of atypical antipsychotics on aggression compared to placebo at short-term follow-up in children with ASD (risk ratio (RR) 1.06, 95% CI 0.96 to 1.17; 1 study, 66 participants; very low-certainty evidence). The certainty of the evidence was very low due to concerns about risk of bias and serious imprecision. We are very uncertain about the effects of atypical antipsychotics on the occurrence of weight gain (above predefined levels) compared to placebo in the short term in children with ASD (RR 2.40, 95% CI 1.25 to 4.60; 7 studies, 434 participants; very low-certainty evidence). We are also very uncertain about the effects of atypical antipsychotics on weight gain (in kilograms) compared to placebo in the short term in children with ASD (MD 1.22 kg, 95% CI 0.55 to 1.88; 3 studies, 297 participants; very low-certainty evidence). In both, the certainty of the evidence was very low due to concerns about risk of bias and serious imprecision. We are very uncertain about the effects of atypical antipsychotics on the occurrence of extrapyramidal side effects compared to placebo in the short term in children with ASD (RR 2.36, 95% CI 1.22 to 4.59; 6 studies, 511 participants; very low-certainty evidence). The certainty of the evidence was very low due to concerns about risk of bias and serious imprecision. Atypical antipsychotics may improve obsessive-compulsive behaviours compared to placebo in the short term in children with ASD (MD -1.36, 95% CI -2.45 to -0.27; 5 studies, 467 participants; low-certainty evidence). The certainty of the evidence was low due to concerns about risk of bias and heterogeneity. Atypical antipsychotics may reduce inappropriate speech compared to placebo in the short term in children with ASD (MD -1.44, 95% CI -2.11 to -0.77; 8 studies, 676 participants; low-certainty evidence). The certainty of the evidence was low due to concerns about risk of bias and heterogeneity. We were unable to evaluate the effects of other atypical antipsychotics. Furthermore, our findings on adults with autism were scarce due to the lack of available studies. AUTHORS' CONCLUSIONS:Risperidone and aripiprazole may reduce symptoms of irritability compared to placebo in children with ASD in the short term, but lurasidone probably has little to no effect on irritability compared to placebo. Other benefits and potential harms observed ranged from moderate- to very low-certainty evidence. The available data did not allow comprehensive subgroup analyses. New randomised controlled trials with larger sample sizes are needed to balance the efficacy and safety of interventions with enough certainty, which are currently scarce (or even absent in the case of the adult population). Authors should report population and intervention characteristics transparently, providing disaggregated or individual patient data when possible. Furthermore, consistent measurement methods for each outcome should be reported to avoid problems during the data synthesis process. FUNDING:This Cochrane review had no dedicated funding. REGISTRATION:Protocol available via 10.1002/14651858.CD014965.