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.

Prospective Association of Parenting Stress with Later Child Behavior Problems in Early Childhood Autism.

PURPOSE: Autistic children are reported to display higher levels of externalizing and internalizing behaviors than neurotypical children, and their parents report more stress than parents of neurotypical children. It is unclear whether child behavior difficulties contribute to increased parenting stress, whether parenting stress contributes to child behavior difficulties, or whether the relationship may be bidirectional. METHODS: We investigated prospective bidirectional associations between parenting stress and child externalizing and internalizing behaviors when autistic children were aged on average 3.5, 4.5, and 5.5 years. Data collected at these three timepoints were examined across two panels: Time 1 to Time 2 (n = 38 parent-child dyads) and Time 2 to Time 3 (n = 27 dyads). RESULTS: Across Time 1 to Time 2, early parenting stress was significantly associated with later child externalizing behavior, and cross-lagged panel analysis supported a uni- rather than a bidirectional association between these factors. There was some evidence of a bidirectional association between parenting stress and child internalizing behavior, though this was non-significant when the strong stability of child internalizing behavior was statistically controlled. In contrast, across Time 2 to Time 3, there were no significant prospective associations found between variables, highlighting the importance of considering the impact of parenting stress early in the course of childhood autism. CONCLUSION: Our results add to research indicating that support targeting parent characteristics, especially parenting stress, could ameliorate subsequent outcomes for both parents and children.

Developmental Skills Moderate the Association Between Core Autism Features and Adaptive Behaviour in Early Childhood.

PURPOSE: While research indicates that both the core features of autism and associated developmental skills influence adaptive behaviour outcomes, results to date suggest greater influence of the latter than the former, and little attention has been given to how the interaction of both together might impact functional disability. Seeking to expand understanding of associations between young children's core social autism features, developmental skills, and functional ability/disability, we specifically tested whether early developmental skills might have a moderating effect on the association between early social features and subsequent functional disability. METHODS: Data from 162 preschool children were available for this study. These included time-1 measures of social autism features (ADOS-Social Affect score) and developmental skills (MSEL-Developmental Quotient; DQ), and a measure of functional ability/disability (VABS-Adaptive Behaviour Composite; ABC) available at follow-up 1-year later (time-2). RESULTS: Time-1 ADOS-SA and MSEL-DQ scores were concurrently associated with one another, and both prospectively associated with time-2 VABS-ABC scores. Examination of partial correlations (i.e., controlling for MSEL-DQ) demonstrated that the association of time-1 ADOS-SA and time-2 VABS-ABC was accounted for by shared variance with DQ. Formal moderation analysis returned a non-significant overall interaction term, but showed a lower-bound region of significance whereby the association of time-1 ADOS-SA with time-2 VABS-ABC was significant for children with baseline DQ ≤ 48.33. CONCLUSION: Our results add to a body of empirical evidence consistent with an understanding of the needs of and resources available to autistic people through a 'cognitive compensation' lens.

Predictors of Developmental and Adaptive Behaviour Outcomes in Response to Early Intensive Behavioural Intervention and the Early Start Denver Model.

Many autistic children require support to meet their learning needs. Given the heterogeneity within the autism spectrum it is plausible that different types of support might be better suited to different children. However, knowledge on what interventions work best for which children is limited. We examined the outcomes of autistic preschool-aged children receiving one of two community early intervention approaches. Our main objective was to understand which baseline child characteristics might be associated with the degree of individual response to intervention-whether prognostically (i.e., irrespective of intervention received) or predictively (i.e., specifically in the context of one or other EI approach). Participants comprised two matched groups of preschool-aged autistic children receiving either Group-based Early Start Denver Model (G-ESDM; n = 42) delivered in a 1:3-4 staff:child ratio or an Early Intensive Behavioural Intervention (EIBI; n = 40) delivered in combination of 1:1 and 1:2 staff:child ratio. Over an approximate one-year follow-up period, children in both groups made significant gains in Developmental Quotient (DQ) scores, and trend-level gains in adaptive behaviour composite scores. Higher attention to a playful adult measured via an eye-tracking task was prognostically indicative of better verbal DQ and adaptive behaviour outcomes for the cohort overall. Moderation analyses indicated a single predictive effect-of pre-program sustained attention for subsequent NVDQ outcomes specific to those children receiving G-ESDM. These findings suggest that fine-grained measures of learning skills offer promise towards the selection and tailoring of intervention approaches to meet individual children's learning needs.

Parent-Child Interactions May Help to Explain Relations Between Parent Characteristics and Clinically Observed Child Autistic Behaviours.

The importance of supporting parent-child interactions has been noted in the context of prodromal autism, but little consideration has been given to the possible contributing role of parental characteristics, such as psychological distress. This cross-sectional study tested models in which parent-child interaction variables mediated relations between parent characteristics and child autistic behaviour in a sample of families whose infant demonstrated early signs of autism (N = 103). The findings suggest that associations between parent characteristics (psychological distress; aloofness) and child autistic behaviours may be mediated by the child's inattentiveness or negative affect during interactions. These findings have important implications in developing and implementing interventions in infancy which target the synchrony of parent-child interaction with the goal to support children's social communication development.

Estimated Therapy Costs and Downstream Cost Consequences of iBASIS-Video Interaction to Promote Positive Parenting Intervention vs Usual Care Among Children Displaying Early Behavioral Signs of Autism in Australia.

Importance: The growing global prevalence of autism spectrum disorder (ASD) is associated with increasing costs for support services. Ascertaining the effects of a successful preemptive intervention for infants showing early behavioral signs of autism on human services budgets is highly policy relevant. Objective: To estimate the net cost impact of the iBASIS-Video Interaction to Promote Positive Parenting (iBASIS-VIPP) intervention on the Australian government. Design, Setting, and Participants: Infants (aged 12 months) showing early behavioral indicators of autism were recruited through community settings into the multicenter Australian iBASIS-VIPP randomized clinical trial (RCT), a 5- to 6-month preemptive parent-mediated intervention, between June 9, 2016, and March 30, 2018, and were followed up for 18 months to age 3 years. This economic evaluation, including cost analysis (intervention and cost consequences) and cost-effectiveness analyses of iBASIS-VIPP compared with usual care (treatment as usual [TAU]), modeled outcomes observed at age 3 through to 12 years (13th birthday) and was conducted from April 1, 2021, to January 30, 2023. Data analysis was conducted from July 1, 2021, to January 29, 2023. Exposures: iBASIS-VIPP intervention. Main Outcomes and Measures: To project the diagnostic trajectory and associated disability support costs drawing on the Australian National Disability Insurance Scheme (NDIS), the main outcome was the differential treatment cost of iBASIS-VIPP plus TAU vs TAU and disability-related government costs modeled to age 12 years, using a clinical diagnosis of ASD and developmental delay (with autism traits) at 3 years. Costs were calculated in Australian dollars and converted to US dollars. Economic performance was measured through the following: (1) differential net present value (NPV) cost (iBASIS-VIPP less TAU), (2) investment return (dollars saved for each dollar invested, taking a third-party payer perspective), (3) break-even age when treatment cost was offset by downstream cost savings, and (4) cost-effectiveness in terms of the differential treatment cost per differential ASD diagnosis at age 3 years. Alternate values of key parameters were modeled in 1-way and probabilistic sensitivity analysis, the latter identifying the likelihood of an NPV cost savings. Results: Of the 103 infants enrolled in the iBASIS-VIPP RCT, 70 (68.0%) were boys. Follow-up data at age 3 years were available for 89 children who received TAU (44 [49.4%]) or iBASIS-VIPP (45 [50.6%]) and were included in this analysis. The estimated mean differential treatment cost was A $5131 (US $3607) per child for iBASIS-VIPP less TAU. The best estimate of NPV cost savings was A $10 695 (US $7519) per child (discounted at 3% per annum). For each dollar invested in treatment, a savings of A $3.08 (US $3.08) was estimated; the break-even cost occurred at age 5.3 years (approximately 4 years after intervention delivery). The mean differential treatment cost per lower incident case of ASD was A $37 181 (US $26 138). We estimated that there was an 88.9% chance that iBASIS-VIPP would deliver a cost savings for the NDIS, the dominant third-party payer. Conclusions and Relevance: The results of this study suggest that iBASIS-VIPP represents a likely good-value societal investment for supporting neurodivergent children. The estimated net cost savings were considered conservative, as they covered only third-party payer costs incurred by the NDIS and outcomes were modeled to just age 12 years. These findings further suggest that preemptive interventions may be a feasible, effective, and efficient new clinical pathway for ASD, reducing disability and the costs of support services. Long-term follow-up of children receiving preemptive intervention is needed to confirm the modeled results.

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.

Non-pharmacological interventions for autistic children: An umbrella review.

LAY ABSTRACT: What is already known about the topic?The delivery of evidence-based interventions is an important part of the clinical pathway for many autistic children and their families. However, parents, practitioners, and policymakers face challenges making evidence informed decisions, due to the wide variety of interventions available and the large, and often inconsistent, body of evidence regarding their effectiveness.What this paper adds?This is a comprehensive umbrella review, also known as a 'review of reviews', which examined the range of interventions available, the evidence for their effectiveness, and whether effects were influenced by factors relating to individual children (e.g. chronological age, core autism characteristics, and related skills) or the ways interventions were delivered (by whom and in what setting, format, mode, and amount). There was evidence for positive therapeutic effects for some, but not all, interventions. No single intervention had a positive effect for all child and family outcomes of interest. The influence of child and delivery characteristics on effects was unclear.Implications for practice, research, and policyThe findings provide parents, practitioners, and policymakers with a synthesis of the research evidence to inform decision-making and highlight the importance of individualised approaches in the absence of clear and consistent evidence. The findings also highlight the need to improve consistency and completeness in reporting of research studies, so that the same questions may be answered more comprehensively in the future.

Spoken Language Change in Children on the Autism Spectrum Receiving Community-Based Interventions.

We assessed the spoken language of 73 preschool aged children on the autism spectrum receiving community-based early intervention at two time points, approximately 7 months apart. Using the Spoken Language Benchmarks, there was a small non-significant change in the proportion of children transitioning from below, to at or above, Phase 3 (word combinations). Using binomial regression, a model comprising seven of nine clinician-proposed child-related predictors explained 64% of the variance. None of the predictors were individually significant, although a large effect size (OR = 16.71) was observed for children's baseline rate of communicative acts. The findings point to substantial unmet clinical need in children with minimal verbal language, but also the relevance of clinician-proposed predictors of their spoken language outcomes.

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.

Perspectives from parents of autistic children on participating in early intervention and associated research.

LAY ABSTRACT: Support for autistic children early in life should help them to lead flourishing lives. However, many of the early intervention programmes for young autistic children are time-consuming and costly for families. These programmes are also often conducted in settings that are not closely matched to real life. We spoke to 23 parents (of 22 autistic children) to understand their experiences of their children's involvement in early intervention. Parents told us they were grateful for the opportunity, that they had 'hit the jackpot', and their children had 'gained so much' from the programme. They seemed to value the service because it made them feel safe and secure during an uncertain time in their children's lives. Parents told us they trusted staff, felt that they weren't 'doing it alone', and this 'took that pressure off' and helped them feel empowered. They also spoke of feelings of safety from being linked to the university research programme which offered 'accountability' and 'integrity'. Parents' comments showed a strong commitment to the early intervention model and staff - but also common feelings of abandonment and disempowerment as their child's time with the programme came to an end and they went 'back to the real world' and needed to find new supports for their children. These parents' insights should help to inform the design and delivery of community supports for preschool-aged autistic children and their families, which match the reality of their lived experiences.

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.

Characteristics of children on the autism spectrum who benefit the most from receiving intervention in inclusive versus specialised early childhood education settings.

This study examined the factors associated with social-communicative outcomes for children on the autism spectrum receiving early intervention in inclusive versus specialised early childhood education programmes. Fifty-eight preschool-aged children randomly assigned to receive the Group-Early Start Denver Model (G-ESDM) in either inclusive or specialised (i.e., autism-specific) classrooms across one calendar year showed similar outcomes at group mean-level across measures of communication and social behaviour. We examined factors moderating outcomes across settings. Novel moderation analyses revealed that higher baseline social interest and nonverbal cognitive skills were associated with increased social communication gains for children in the inclusive classrooms, but not for those in specialised settings. Children who spend more time paying attention to people and have higher cognitive skills might benefit from receiving early intervention in inclusive settings, whilst these factors might be less relevant for children educated in specialised settings.

Brief report: bidirectional association of core autism features and cognitive abilities in early childhood.

We explored associations among the core behavioural features and developmental/cognitive abilities of 155 autistic children, assessed between ages 13-67 months and again around 1-year later to understand predictive directionality. Bidirectional, cross-domain association was apparent, albeit with stronger direction of effect from earlier cognition to later autism features (than vice versa). Exploratory sub-domain analysis showed that early non-verbal developmental/cognitive abilities (only) predicted subsequent social- and restricted/repetitive autism features, whereas early social features (only) predicted both subsequent verbal and non-verbal abilities. Although observational study design precludes causal inference, these data support contemporary notions of the developmental interconnectedness of core autism presentation and associated abilities-that behavioural autism features may influence cognitive development, but are likely also influenced by an individuals' cognitive capacity.

The utility of LENA as an indicator of developmental outcomes for young children with autism.

BACKGROUND: There is growing understanding of the potential benefits of a multi-method approach to accurately capture language skills of children on the autism spectrum. Tools such as Language ENvironment Analysis (LENA) provide an efficient means of capturing and analysing early child vocalizations (CVs) and the language learning environment. While developed to capture whole-day recordings of child language in naturalistic settings, there is potential utility in capturing, but little knowledge about, primary LENA metrics-including CVs and conversational turns (CTs)-and novel metrics, such as vocalization ratios (VRs), sampled in clinical practice settings where children are often seen. Moreover, recent research indicates that the novel VR may offer a broad indicator of children's developmental level, beyond just their language abilities, a hypothesis yet to be investigated in a large sample of children for whom the LENA was designed (i.e., pre-schoolers). AIMS: To explore the extent to which primary and novel LENA metrics collected during brief one-to-one clinical interaction was a useful indicator of developmental outcomes for children on the autism spectrum. METHODS & PROCEDURES: Participants were recruited as part of an on-going research programme evaluating early intervention outcomes (n = 99; age 14-47 months). Language samples were collected at intake (T1) using the wearable LENA Digital Language Processors during a one-to-one, play-based assessment with a clinician. Direct (Mullen Scales of Early Learning-MSEL) and parent-report (Vineland Adaptive Behavior Scales-VABS) measures of verbal and non-verbal skills were also collected at intake (T1) and again at exit (T2), approximately 12 months later. OUTCOMES & RESULTS: Few correlations were observed between child measures and CVs, a primary LENA metric. The novel VR metric was associated with concurrent direct assessment (MSEL) (and to a lesser extent parent report; VABS) measures of verbal and non-verbal skills, with moderate positive correlations found between VRs and all directly assessed subscale scores. However, VRs did not uniquely contribute to the prediction of child outcomes when baseline skills were also considered. CONCLUSIONS & IMPLICATIONS: The novel VR may provide an insight into autistic children's overall development in addition to their language ability, suggesting that even when collected in a short recording format, LENA might be a useful component of a multi-method assessment approach. WHAT THIS PAPER ADDS: What is already known on the subject To accurately capture language skills of children on the autism spectrum, multi-method approaches, including natural language sampling, are recommended. Tools such as LENA provide an efficient means of capturing and analysing naturalistic child language and the language learning environment. What this paper adds to existing knowledge This study demonstrates the potential benefits, and limitations, of using LENA to augment assessment of young children on the autism spectrum. Specifically, LENA provides a complementary, and low burden, method for capturing child language samples. What are the potential or actual clinical implications of this work? Novel metrics, such as the VR, collected during brief clinical interactions might be a useful component of a multi-method assessment approach for children on the autism spectrum.

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.

An evidence-based framework for determining the optimal amount of intervention for autistic children.

The provision of timely, effective, and socially valid non-pharmacological intervention is at the core of efforts to support the development of young autistic children. These efforts are intended to support children to develop skills, empower their caregivers, and lay the foundation for optimal choice, independence, and quality of life into adulthood. But what is the optimal amount of intervention? In this Viewpoint, we review current guidelines and consider evidence from an umbrella review of non-pharmacological interventions for autistic children aged up to 12 years. We show the lack of consensus on the issue, identify factors that might be relevant to consider, and present an evidence-based framework for determining the optimal amount of intervention for each child, along with recommendations for future research.

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.