Feasibility of a 2-minute eye-tracking protocol to support the early identification of autism.

We tested the potential for Gazefinder eye-tracking to support early autism identification, including feasible use with infants, and preliminary concurrent validity of trial-level gaze data against clinical assessment scores. We embedded the ~ 2-min 'Scene 1S4' protocol within a comprehensive clinical assessment for 54 consecutively-referred, clinically-indicated infants (prematurity-corrected age 9-14 months). Alongside % tracking rate as a broad indicator of feasible assessment/data capture, we report infant gaze data to pre-specified regions of interest (ROI) across four trial types and associations with scores on established clinical/behavioural tools. Most infants tolerated Gazefinder eye-tracking well, returning high overall % tracking rate. As a group, infants directed more gaze towards social vs. non-social (or more vs. less socially-salient) ROIs within trials. Behavioural autism features were correlated with increased gaze towards non-social/geometry (vs. social/people) scenes. No associations were found for gaze directed to ROIs within other stimulus types. Notably, there were no associations between developmental/cognitive ability or adaptive behaviour with gaze towards any ROI. Gazefinder assessment seems highly feasible with clinically-indicated infants, and the people vs. geometry stimuli show concurrent predictive validity for behavioural autism features. Aggregating data across the ~ 2-min autism identification protocol might plausibly offer greater utility than stimulus-level analysis alone.

Categorical versus dimensional structure of autism spectrum disorder: A multi-method investigation.

Background: A key question for any psychopathological diagnosis is whether the condition is continuous or discontinuous with typical variation. The primary objective of this study was to use a multi-method approach to examine the broad latent categorical versus dimensional structure of autism spectrum disorder (ASD). Method: Data were aggregated across seven independent samples of participants with ASD, other neurodevelopmental disorders (NDD), and non-ASD/NDD controls (aggregate Ns = 512-16,755; ages 1.5-22). Scores from four distinct phenotype measures formed composite "indicators" of the latent ASD construct. The primary indicator set included eye gaze metrics from seven distinct social stimulus paradigms. Logistic regressions were used to combine gaze metrics within/across paradigms, and derived predicted probabilities served as indicator values. Secondary indicator sets were constructed from clinical observation and parent-report measures of ASD symptoms. Indicator sets were submitted to taxometric- and latent class analyses. Results: Across all indicator sets and analytic methods, there was strong support for categorical structure corresponding closely to ASD diagnosis. Consistent with notions of substantial phenotypic heterogeneity, the ASD category had a wide range of symptom severity. Despite the examination of a large sample with a wide range of IQs in both genders, males and children with lower IQ were over-represented in the ASD category, similar to observations in diagnosed cases. Conclusions: Our findings provide strong support for categorical structure corresponding closely to ASD diagnosis. The present results bolster the use of well-diagnosed and representative ASD groups within etiologic and clinical research, motivating the ongoing search for major drivers of the ASD phenotype. Despite the categorical structure of ASD, quantitative symptom measurements appear more useful for examining relationships with other factors.

The impact of sleep quality, fatigue and social well-being on depressive symptomatology in autistic older adolescents and young adults.

Depression and poor sleep quality commonly co-occur with autism, and depression has been associated with loneliness and reduced social support. In non-autistic samples, poor sleep quality and daytime fatigue also contribute to depression. However, the contribution of sleep quality and fatigue to depressive symptoms, and how they interact with social factors to influence depression in autism remain unexplored. Our aim was to examine these relationships in 114 young autistic adults aged 15-25 years (57% male) from the SASLA online, longitudinal study (baseline and 2-year follow-up). Hierarchical multiple regression models examined the association between social well-being (social integration and social contribution; T1), sleep quality (T1, T2), and fatigue (T1, T2) on depression (T1, T2). Two mediation models were conducted on T1 data predicting depression from sleep quality though fatigue and sleep quality through social well-being. Depression and fatigue scores did not change over 2 years, but sleep quality worsened. The T1 regression model was significant (R2 = 36%) with fatigue and social contribution individually predicting depression symptomatology. The longitudinal regression model was also significant (adjusted R2 = 57%) with social contribution (T1) as the only significant predictor of depression (T2). Fatigue trended towards mediating the sleep quality-depression relationship, while social well-being was a significant partial mediator of this relationship. Results highlight that sleep quality, fatigue, and social well-being contribute to depression among young autistic adults. Interestingly, fatigue and social well-being were independently associated with depression. Thus, addressing sleep quality and associated fatigue, and social well-being is important when treating depression in autistic individuals.

The Utility of Natural Language Samples for Assessing Communication and Language in Infants Referred with Early Signs of Autism.

Natural Language Sampling (NLS) offers clear potential for communication and language assessment, where other data might be difficult to interpret. We leveraged existing primary data for 18-month-olds showing early signs of autism, to examine the reliability and concurrent construct validity of NLS-derived measures coded from video-of child language, parent linguistic input, and dyadic balance of communicative interaction-against standardised assessment scores. Using Systematic Analysis of Language Transcripts (SALT) software and coding conventions, masked coders achieved good-to-excellent inter-rater agreement across all measures. Associations across concurrent measures of analogous constructs suggested strong validity of NLS applied to 6-min video clips. NLS offers benefits of feasibility and adaptability for validly quantifying emerging skills, and potential for standardisation for clinical use and rigorous research design.

Brief Report: Discrete Effortful Control Skills Moderate Relations Between Childhood Behavioural Inhibition and Mental Health Difficulties in Autistic Youth.

Studies of the general population suggest that the risk for mental health difficulties conferred by dispositional behavioural inhibition (BI) may be modified by self-regulation; however, this possibility has not been explored in the context of autism. This study investigated the moderating effects of attentional-, activation-, and inhibitory control on the relationship between childhood BI and anxiety and depression among 47 autistic youths (55% male, Mage = 19.09 years, SD = 2.23). Childhood BI was associated with anxiety at low but not high levels of attentional- and activation control, and depression at low but not high levels of attentional control. However, there were no moderating effects of inhibitory control. These preliminary findings are partially consistent with those from the general population and point to avenues for future work.

Parental Imitations and Expansions of Child Language Predict Later Language Outcomes of Autistic Preschoolers.

Both the amount and responsiveness of adult language input contribute to the language development of autistic and non-autistic children. From parent-child interaction footage, we measured the amount of adult language input, overall parent responsiveness, and six discrete parent responsive behaviours (imitations, expansions, open-ended questions, yes/no questions, comments and acknowledgements) to explore which types of responsiveness predicted autistic preschoolers' language five months later, after controlling for adult language input. We found expansions and particularly imitations to be more important for later language than overall responsiveness. This study emphasises the need to capture what exactly about parent language input influences child language acquisition, and adds to the evidence that imitating and expanding early language might be particularly beneficial for autistic preschoolers.

Caregiver sensitivity predicts infant language use, and infant language complexity predicts caregiver language complexity, in the context of possible emerging autism.

While theory supports bidirectional effects between caregiver sensitivity and language use, and infant language acquisition-both caregiver-to-infant and also infant-to-caregiver effects-empirical research has chiefly explored the former unidirectional path. In the context of infants showing early signs of autism, we investigated prospective bidirectional associations with 6-min free-play interaction samples collected for 103 caregivers and their infants (mean age 12-months; and followed up 6-months later). We anticipated that measures of caregiver sensitivity/language input and infant language would show within-domain temporal stability/continuity, but also that there would be predictive associations from earlier caregiver input to subsequent child language, and vice versa. Caregiver sensitive responsiveness (from the Manchester Assessment of Caregiver-Infant interaction [MACI]) predicted subsequent infant word tokens (i.e., amount of language, coded following the Systematic Analysis of Language Transcripts [SALT]). Further, earlier infant Mean Length of Utterance (MLU; reflecting language complexity, also derived from SALT coding) predicted later caregiver MLU, even when controlling for variability in infant ages and clear within-domain temporal stability/continuity in key measures (i.e., caregiver sensitive responsiveness and infant word tokens; and infant and caregiver MLU). These data add empirical support to theorization on how caregiver input can be both supportive of, and potentially influenced by, infant capacities, when infants have social-communication differences and/or communication/language delays suggestive of possible emerging autism.

Continuity of temperament subgroup classifications from infancy to toddlerhood in the context of early autism traits.

Our previous cross-sectional investigation (Chetcuti et al., 2020) showed that infants with autism traits could be divided into distinct subgroups based on temperament. This longitudinal study builds on this existing work by exploring the continuity of temperament subgroup classifications and their associations with behavioral/clinical phenotypic features from infancy to toddlerhood. 103 infants (68% male) showing early signs of autism were referred to the study by community healthcare professionals and seen for assessments when aged around 12-months (Time 1), 18-months (Time 2), and 24-months (Time 3). Latent profile analysis revealed inhibited/low positive, active/negative reactive, and sociable/well-regulated subgroups at each timepoint, and a unique reactive/regulated subgroup at Time 3. Cross-tabulations indicated a significant likelihood of children having a recurrent subgroup classification from one timepoint to the next, and no apparent patterns to the movement of children who did change from one subgroup to another over time. Temperament subgroups were associated with concurrent child social-emotional functioning and autism traits, but unrelated to child age, sex, or developmental level. These findings suggest that temperament subgroup classifications might represent a reliable and very early indicator of autism characteristics and social-emotional functioning among infants/toddlers with autism traits.

Relative predictive utility of the original and Autism-Specific Five-Minute Speech Samples for child behaviour problems in autistic preschoolers: A preliminary study.

LAY ABSTRACT: Parental Expressed Emotion refers to the intensity and nature of emotion shown when a parent talks about their child, and has been linked to child behaviour outcomes. Parental Expressed Emotion has typically been measured using the Five-Minute Speech Sample; however, the Autism-Specific Five-Minute Speech Sample was developed to better capture Expressed Emotion for parents of children on the autism spectrum. In each case, parents are asked to talk for 5 min about their child and how they get along with their child. Parents' statements are then coded for features such as number of positive and critical comments, or statements reflecting strong emotional involvement. While both the Five-Minute Speech Sample and Autism-Specific Five-Minute Speech Sample have been used with parents of autistic school-aged children, their relative usefulness for measuring Expressed Emotion in parents of preschool-aged children - including their links to child behaviour problems in this group - is unclear. We collected speech samples from 51 parents of newly diagnosed autistic preschoolers to investigate similarities and differences in results from the Five-Minute Speech Sample and Autism-Specific Five-Minute Speech Sample coding schemes. This included exploring the extent to which the Five-Minute Speech Sample and Autism-Specific Five-Minute Speech Sample, separately, or together, predicted current and future child behaviour problems. While the two measures were related, we found only the Autism-Specific Five-Minute Speech Sample - but not the Five-Minute Speech Sample - was related to child behavioural challenges. This adds support to the suggestion that the Autism-Specific Five-Minute Speech Sample may be a more useful measure of parental Expressed Emotion in this group, and provides a first step towards understanding how autistic children might be better supported by targeting parental Expressed Emotion.

Effect of Preemptive Intervention on Developmental Outcomes Among Infants Showing Early Signs of Autism: A Randomized Clinical Trial of Outcomes to Diagnosis.

Importance: Intervention for individuals with autism spectrum disorder (ASD) typically commences after diagnosis. No trial of an intervention administered to infants before diagnosis has shown an effect on diagnostic outcomes to date. Objective: To determine the efficacy of a preemptive intervention for ASD beginning during the prodromal period. Design, Setting, and Participants: This 2-site, single rater-blinded randomized clinical trial of a preemptive intervention vs usual care was conducted at 2 Australian research centers (Perth, Melbourne). Community sampling was used to recruit 104 infants aged 9 to 14 months showing early behaviors associated with later ASD, as measured by the Social Attention and Communication Surveillance-Revised. Recruitment occurred from June 9, 2016, to March 30, 2018. Final follow-up data were collected on April 15, 2020. Interventions: Infants were randomized on a 1:1 ratio to receive either a preemptive intervention plus usual care or usual care only over a 5-month period. The preemptive intervention group received a 10-session social communication intervention, iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP). Usual care comprised services delivered by community clinicians. Main Outcomes and Measures: Infants were assessed at baseline (approximate age, 12 months), treatment end point (approximate age, 18 months), age 2 years, and age 3 years. Primary outcome was the combined blinded measure of ASD behavior severity (the Autism Observation Scale for Infants and the Autism Diagnostic Observation Schedule, second edition) across the 4 assessment points. Secondary outcomes were an independent blinded clinical ASD diagnosis at age 3 years and measures of child development. Analyses were preregistered and comprised 1-tailed tests with an α level of .05. Results: Of 171 infants assessed for eligibility, 104 were randomized; 50 infants (mean [SD] chronological age, 12.40 [1.93] months; 38 boys [76.0%]) received the iBASIS-VIPP preemptive intervention plus usual care (1 infant was excluded after randomization), and 53 infants (mean [SD] age, 12.38 [2.02] months; 32 boys [60.4%]) received usual care only. A total of 89 participants (45 in the iBASIS-VIPP group and 44 in the usual care group) were reassessed at age 3 years. The iBASIS-VIPP intervention led to a reduction in ASD symptom severity (area between curves, -5.53; 95% CI, -∞ to -0.28; P = .04). Reduced odds of ASD classification at age 3 years was found in the iBASIS-VIPP group (3 of 45 participants [6.7%]) vs the usual care group (9 of 44 participants [20.5%]; odds ratio, 0.18; 95% CI, 0-0.68; P = .02). Number needed to treat to reduce ASD classification was 7.2 participants. Improvements in caregiver responsiveness and language outcomes were also observed in the iBASIS-VIPP group. Conclusions and Relevance: Receipt of a preemptive intervention for ASD from age 9 months among a sample of infants showing early signs of ASD led to reduced ASD symptom severity across early childhood and reduced the odds of an ASD diagnosis at age 3 years. Trial Registration: http://anzctr.org.au identifier: ACTRN12616000819426.

Caregiver Psychological Distress Predicts Temperament and Social-Emotional Outcomes in Infants with Autism Traits.

Child temperament and caregiver psychological distress have been independently associated with social-emotional difficulties among individuals with autism. However, the interrelationship among these risk factors has rarely been investigated. We explored the reciprocal interplay between child temperament (surgency, negative affectivity, and self-regulation) and caregiver psychological distress in the development of child internalizing and externalizing symptoms, in a cohort of 103 infants showing early autism traits. Caregivers completed questionnaires when children were aged around 12-months (Time 1 [T1]), 18-months (Time 2 [T2]), and 24-months (Time 3 [T3]). Cross-lagged path models revealed a significant pathway from T1 caregiver psychological distress through lower T2 child self-regulation to subsequently greater T3 child internalizing symptoms. No such caregiver-driven pathway was evident through T2 child negative affectivity or in the prediction of T3 child externalizing symptoms. Further, no support was found for temperament-driven pathways through caregiver psychological distress to child social-emotional difficulties. Child surgency was mostly unrelated to caregiver psychological distress and social-emotional difficulties. These findings implicate the need to support the mental health of caregivers with an infant with autism traits in order to enhance the emotion regulation and social-emotional development of their infants.

Temperament in individuals with Autism Spectrum Disorder: A systematic review.

The study of temperament in Autism Spectrum Disorder (ASD) has the potential to provide insight regarding variability in the onset, nature, and course of both core and co-morbid symptoms. The aim of this systematic review was to integrate existing findings concerning temperament in the context of ASD. Searches of Medline, PsychInfo and Scopus databases identified 64 relevant studies. As a group, children and adolescents with ASD appear to be temperamentally different from both typically developing and other clinical non-ASD groups, characterized by higher negative affectivity, lower surgency, and lower effortful control at a higher-order level. Consistent with research on typically developing children, correlational findings and emerging longitudinal evidence suggests that lower effortful control and higher negative affect are associated with increased internalizing and externalizing problems in ASD samples. Longitudinal studies suggest there may be temperamental differences between high familial risk infants who do and do not develop ASD from as early as 6-months of age. Limitations of existing research are highlighted, and possible directions for future research to capitalize on the potential afforded through the study of temperament in relation to ASD are discussed.

Differential predictors of well-being versus mental health among parents of pre-schoolers with autism.

LAY ABSTRACT: Raising a child with autism has been linked to mental health difficulties. Poor parental mental health is likely influenced by various factors - including child-, parent-, and family/socioeconomic characteristics. However, little is known about what influences and promotes well-being (as opposed to mental health) among parents of young, newly diagnosed autistic children who may be particularly vulnerable. We examined child-, parent-, and family/socioeconomic factors associated with each of mental health and well-being in a sample of 136 parents of pre-school-aged children. Parental mental health was linked to both child- (i.e. autism symptom severity) and parent-related factors (i.e. personality traits reflecting a tendency to experience negative emotions). By contrast, in additional to mental health difficulties, which were linked to well-being, only other parent-related characteristics (and not child characteristics) were related to well-being. These included personality traits reflecting a tendency to be more extraverted/sociable, and also mindfulness. Other child-related and family/socioeconomic context factors (including household income, parental education level) were not linked to parental mental health or well-being in this sample. These results support the idea that poorer mental health and well-being are not simply the opposite of one another. That is, while these two factors were related, they were linked to different personal characteristics. Perhaps most importantly, the link between well-being and mindfulness - a personal characteristic that parents can improve - suggests mindfulness-based interventions may be helpful in directly supporting parental well-being in the context of raising a young child with autism.

Performance of the Autism Observation Scale for Infants with community-ascertained infants showing early signs of autism.

LAY ABSTRACT: We investigated whether a commonly used research assessment - the Autism Observation Scale for Infants (AOSI) - accurately measures autism behaviours among infants showing early signs of autism identified within the community. The AOSI is often included in studies tracking the development of infants at increased likelihood of autism, such as the infant siblings of diagnosed children. However, the suitability of this measure has not previously been tested with community-referred infants. We administered the AOSI with infants when aged 9 to 14 months and again 6 months later. Our researchers - independent of the AOSI development team and newly trained on this measure - were able to administer the brief interactive assessment and score it accurately. The infants' AOSI scores were linked to their scores on other established and validated clinical assessments, particularly at the second visit when average age was 18 months. Stronger correspondence of AOSI and other scores at this second visit suggests early autism behaviours are better established and more consistent by 18 months of age, even though these infants showed clear enough signs of possible autism to prompt referral to our study around 12 months of age. However, the moderate association of AOSI scores over time suggests that, like infant siblings - who mostly do not develop autism - community-identified infants showing early signs may also have variable developmental pathways in early life.

Subgroups of Temperament Associated with Social-Emotional Difficulties in Infants with Early Signs of Autism.

Links between temperament and social-emotional difficulties are well-established in normative child development but remain poorly characterized in autism. We sought to characterize distinct temperament subgroups and their associations with concurrent internalizing and externalizing symptoms in a sample of 103 infants (Mage = 12.39 months, SD = 1.97; 68% male) showing early signs of autism. Latent profile analysis was used to identify subgroups of infants with distinct temperament trait configurations on the Infant Behavior Questionnaire-Revised. Derived subgroups were then compared in terms of internalizing and externalizing symptoms on the Infant-Toddler Social and Emotional Assessment. Three distinct temperament subgroups were identified: (a) inhibited/low positive (n = 22), characterized by low Smiling and Laughter, low High-Intensity Pleasure, low Vocal Reactivity, and low Approach; (b) active/negative reactive (n = 23), characterized by high Activity Level, high Distress to Limitations, high Sadness, high Fear, and low Falling Reactivity; and (c) well-regulated (n = 51), characterized by high Cuddliness, high Soothability, and high Low-Intensity Pleasure. There were no differences in infant sex ratio, mean age or developmental/cognitive ability. Inhibited/low-positive infants had significantly more behavioral autism signs than active/negative reactive and well-regulated infants, who did not differ. Inhibited/low-positive and active/negative reactive infants had higher internalizing symptoms, relative to well-regulated infants, and active/negative reactive infants also had higher externalizing symptoms. These findings align closely with those garnered in the context of normative child development, and point to child temperament as a putative target for internalizing and externalizing interventions. LAY SUMMARY: This study explored whether infants with early signs of autism could be grouped according to temperament characteristics (i.e., emotional, behavioral, and attentional traits). Three subgroups were identified that differed with respect to emotional and behavioral difficulties. Specifically, "inhibited/low-positive" infants had high emotional difficulties, "active/negative reactive" infants had high emotional and behavioral difficulties, while "well-regulated" infants had the lowest difficulties.

Motor functioning in developmental psychopathology: A review of autism as an example context.

BACKGROUND: Motor development research has seen substantial recent growth. However, much remains to be understood about the nature and extent of motor impairments in neurodevelopmental disorders, including their potential as early markers and/or causal determinants of downstream functioning in other domains. AIMS AND METHODS: In this narrative review, drawing primarily on the autism literature by way of example, we review current accounts of the nature and consequences of motor functioning. We consider conventional approaches to measurement and study design, and current limited approaches to tackling heterogeneity. CONCLUSIONS AND IMPLICATIONS: We argue that ongoing adherence to traditional diagnostic outcome classification stands in the face of mounting evidence that characteristics of neurodevelopmental disorders lie on a continuum with variability in the general population, and that three broad research avenues stand to offer a better understanding of motor functioning: The use of technology and advanced statistical methods for a more nuanced understanding of motor abilities; exploiting the prospective longitudinal tracking of at-risk infants to understand developmental consequences of early motor difference; and employing randomized controlled trials to test the utility of motor therapies whilst also testing causal hypotheses about the role of motor functioning.

The Role of Negative Affectivity in Concurrent Relations Between Caregiver Psychological Distress and Social-Emotional Difficulties in Infants With Early Signs of Autism.

Recent evidence suggests the link between caregiver psychological distress and offspring social-emotional difficulties may be accounted for by offspring temperament characteristics. However, existing studies have only focused on neurotypical children; thus, the current study sought to provide an initial examination of this process among children with varying levels of early autism features. Participants included 103 infants aged 9-16 months (M = 12.39, SD = 1.97; 68% male) and their primary caregiver (96% mothers) referred to a larger study by community healthcare professionals. We utilized caregiver-reported measures of psychological distress (Depression Anxiety Stress Scales), infant temperament (Infant Behavior Questionnaire-Revised) and internalizing and externalizing symptoms (Infant-Toddler Social and Emotional Assessment) and administered the Autism Observation Schedule for Infants (AOSI) at an assessment visit to quantify autism features. Infant negative affectivity was found to mediate positive concurrent relations between caregiver psychological distress and infant internalizing and externalizing symptoms, irrespective of the infants' AOSI score. While preliminary and cross-sectional, these results replicate and extend previous findings suggesting that the pathway from caregiver psychological distress to negative affectivity to social-emotional difficulties might also be apparent among infants with varying levels of autism features. More rigorous tests of causal effects await future longitudinal investigation. LAY SUMMARY: Offspring of caregivers experiencing psychological distress (i.e., symptoms of depression, anxiety, and/or stress) may themselves be at increased risk of poor mental health outcomes. Several previous studies conducted with neurotypical children suggest that this link from caregiver-to-child may be facilitated by children's temperament qualities. This study was a preliminary cross-sectional exploration of these relationships in infants with features of autism. We found that infants' elevated negative emotions were involved in the relation between caregiver heightened psychological distress and children's mental health difficulties, consistent with neurotypical development. Autism Res 2020, 13: 1349-1357. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Temperament predicts challenging behavior in children with autism spectrum disorder at age 5.

Background: Challenging behaviors during early childhood have a significant impact on cognitive and social development. The present study aimed to identify the developmental predictors of these behaviors in preschool aged children with Autism Spectrum Disorder (ASD) at 2-year follow-up. We examined temperament, which has been identified as key to emotion regulation in typical development, as well as developmental level and ASD symptom severity, as potential predictors of parent-reported challenging behavior. Method: Forty-three parents of preschool aged children with ASD from a previous study were invited to participate. Data from 26 children with ASD aged 4-6 years (M = 5, SD = .60) were available for follow-up analyses. Developmental level, ASD symptom severity, and temperamental difficulty at baseline were considered as potential predictors of frequency and severity of challenging behavior at follow-up. Results: Baseline negative affectivity was uniquely predictive of frequency of challenging behavior at follow-up. Although no individual variable was identified as a unique predictor of variance, the combined effects of temperament were predictive of the severity of challenging behavior at follow-up, contributing to 46 % of variance in scores. Conclusions: These findings highlight the potential impact of emotion-regulation related aspects of temperament on later emerging challenging behavior in young children with ASD, suggesting opportunities for early intervention. Results also identified a role for developmental level in the severity of challenging behavior, but suggest that the effect may be metered by temperament.

Pre-emptive intervention versus treatment as usual for infants showing early behavioural risk signs of autism spectrum disorder: a single-blind, randomised controlled trial.

BACKGROUND: Great interest exists in the potential efficacy of prediagnostic interventions within the autism spectrum disorder prodrome, but available evidence relates to children at high familial risk. We aimed to test the efficacy of a pre-emptive intervention designed for infants showing early behavioural signs of autism spectrum disorder. METHODS: In this single-blind, randomised controlled trial done at two specialist centres in Australia, infants aged 9-14 months were enrolled if they were showing at least three early behavioural signs of autism spectrum disorder on the Social Attention and Communication Surveillance-Revised (SACS-R) 12-month checklist. Infants were randomly assigned (1:1) to receive a parent-mediated video-aided intervention (iBASIS-VIPP) or treatment as usual. Group allocation was done by minimisation, stratified by site, sex, age, and the number of SACS-R risk behaviours. Assessments were done at baseline (before treatment allocation) and at the 6 month endpoint. The primary outcome was Autism Observation Scale for Infants (AOSI), which measures early behavioural signs associated with autism spectrum disorder. Secondary outcomes were a range of infant and caregiver outcomes measured by Manchester Assessment of Caregiver-Infant interaction (MACI), Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behaviour Scales, 2nd edition (VABS-2), MacArthur-Bates Communicative Development Inventory (MCDI), and Parenting Sense of Competence (PSOC) scale. This trial is registered with Australian New Zealand Clinical Trials Registry, number ANZCTR12616000819426. FINDINGS: Between June 9, 2016, and March 30, 2018, 103 infants were randomly assigned, 50 to the iBASIS-VIPP group and 53 to the treatment-as-usual group. After the intervention, we observed no significant differences between groups on early autism spectrum disorder behavioural signs measured by the AOSI (difference estimate -0·74, 95% CI -2·47 to 0·98). We also observed no significant differences on secondary outcomes measuring caregiver non-directiveness (0·16, -0·33 to 0·65), caregiver sensitive responding (0·24, -0·15 to 0·63), and infant attentiveness (-0·19, -0·63 to 0·25) during parent-child interactions (MACI), as well as on researcher-administered measures of receptive (1·30, -0·48 to 3·08) and expressive language (0·54, -0·73 to 1·80), visual reception (0·31, -0·77 to 1·40), and fine motor skills (0·55, -0·32 to 1·41) using the MSEL. Compared with the treatment-as-usual group, the iBASIS-VIPP group had lower infant positive affect (-0·69, -1·27 to -0·10) on the MACI, but higher caregiver-reported receptive (37·17, 95% CI 10·59 to 63·75) and expressive vocabulary count (incidence rate ratio 2·31, 95% CI 1·22 to 4·33) on MCDI, and functional language use (difference estimate 6·43, 95% CI 1·06 to 11·81) on VABS. There were no significant group differences on caregiver-reported measures of MCDI infant gesture use (3·22, -0·60 to 7·04) and VABS social behaviour (3·28, -1·43 to 7·99). We observed no significant differences between groups on self-reported levels of parenting satisfaction (difference estimate 0·21, 95% CI -0·09 to 0·52), interest (-0·23, -0·62 to 0·16) and efficacy (-0·08, -0·38 to 0·22) on PSOC. INTERPRETATION: A pre-emptive intervention for the autism spectrum disorder prodrome had no immediate treatment effect on early autism spectrum disorder symptoms, the quality of parent-child interactions, or researcher-administered measures of developmental skills. However, we found a positive effect on parent-rated infant communication skills. Ongoing follow-up of this infant cohort will assess longer-term developmental effects. FUNDING: Western Australia Children's Research Fund, Autism Cooperative Research Centre, La Trobe University, and Angela Wright Bennett Foundation.