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Background: Many studies have reported that autism spectrum disorder (ASD) is associated with atypical structural and functional connectivity. However, relatively little is known about the development of these differences in infancy and on how trajectories may vary between sexes. Methods: We used the International Infant EEG Platform (EEG-IP), a high-density electroencephalogram (EEG) dataset pooled from two independent infant sibling cohorts, to characterize such neurodevelopmental deviations during the first years of life. EEG was recorded at 6, 12, and 18 months of age at typical (N=97) or high familial risk for ASD (N=98), determined by the presence of an older sibling with a confirmed ASD diagnosis. We computed the functional connectivity between cortical EEG sources during video watching using the corrected imaginary part of phase-locking values. Results: Our findings showed low regional specificity for group differences in functional connectivity but revealed different sex-specific trajectories between females and males in the group of high-risk infants. Specifically, functional connectivity was negatively correlated with ADOS calibrated severity scores, particularly at 12 months for the social affect score for females and for the restrictive and repetitive behaviors for males. Limitations: This study has been limited mostly due to issues related to the relatively small effective sample size inherent in sibling studies, particularly for diagnostic group comparisons. Conclusions: These results are consistent with sex differences in ASD observed in previous research and provide further insights into the role of functional connectivity in these differences.

Theta oscillations (spectral power and connectivity) are sensitive to the social content of an experience in typically developing infants, providing a possible marker of early social brain development. Autism is a neurodevelopmental condition affecting early social behaviour, but links to underlying social brain function remain unclear. We explored whether modulations of theta spectral power and connectivity by naturalistic social content in infancy are related to family history for autism. Fourteen-month-old infants with (family history; FH; N = 75) and without (no family history; NFH; N = 26) a first-degree relative with autism watched social and non-social videos during EEG recording. We calculated theta (4-5 Hz) spectral power and connectivity modulations (social-non-social) and associated them with outcomes at 36 months. We replicated previous findings of increased theta power and connectivity during social compared to non-social videos. Theta modulations with social content were similar between groups, for both power and connectivity. Together, these findings suggest that neural responses to naturalistic social stimuli may not be strongly altered in 14-month-old infants with family history of autism.

Autism spectrum disorder (ASD) has its origins in the atypical development of brain networks. Infants who are at high familial risk for, and later diagnosed with ASD, show atypical activity in multiple electroencephalography (EEG) oscillatory measures. However, infant‐sibling studies are often constrained by small sample sizes. We used the International Infant EEG Data Integration Platform, a multi‐site dataset with 432 participants, including 222 at high‐risk for ASD, from whom repeated measurements of EEG were collected between the ages of 3–36 months. We applied a latent growth curve model to test whether familial risk status predicts developmental trajectories of spectral power across the first 3 years of life, and whether these trajectories predict ASD outcome. Change in spectral EEG power in all frequency bands occurred during the first 3 years of life. Familial risk, but not a later diagnosis of ASD, was associated with reduced power at 3 months, and a steeper developmental change between 3 and 36 months in nearly all absolute power bands. ASD outcome was not associated with absolute power intercept or slope. No associations were found between risk or outcome and relative power. This study applied an analytic approach not used in previous prospective biomarker studies of ASD, which was modeled to reflect the temporal relationship between genetic susceptibility, brain development, and ASD diagnosis. Trajectories of spectral power appear to be predicted by familial risk; however, spectral power does not predict diagnostic outcome above and beyond familial risk status. Discrepancies between current results and previous studies are discussed. Lay Summary Infants with an older sibling who is diagnosed with ASD are at increased risk of developing ASD themselves. This article tested whether EEG spectral power in the first year of life can predict whether these infants did or did not develop ASD.

It was suggested that children's referent selection may not lay memory traces sufficiently strong to lead to retention of new word-object mappings. If this was the case we expect incorrect selections to be easily rectified through feedback. Previous work suggested this to be the case in toddlers at typical likelihood (TL) but not in those at elevated likelihood (EL) for autism spectrum disorder (ASD) (Bedford et al., ). Yet group differences in lexical knowledge may have confounded these findings. Here, TL (N = 29) and EL toddlers (N = 75) chose one of two unfamiliar objects as a referent for a new word. Both groups retained the word-referent mapping above chance when their choices were immediately reinforced but were at chance after corrective feedback. The same pattern of results was obtained when children observed another experimenter make the initial referent choice. Thus, children's referent choices lay memory traces that compete with subsequent correction; these strong word-object associations are not a result of children actively choosing potential referents for new words.

Autism spectrum disorder (ASD) has its origins in the atypical development of brain networks. Infants who are at high familial risk for, and later diagnosed with ASD, show atypical activity in multiple electroencephalography (EEG) oscillatory measures. However, infant-sibling studies are often constrained by small sample sizes. We used the International Infant EEG Data Integration Platform, a multi-site dataset with 432 participants, including 222 at high-risk for ASD, from whom repeated measurements of EEG were collected between the ages of 3-36 months. We applied a latent growth curve model to test whether familial risk status predicts developmental trajectories of spectral power across the first 3 years of life, and whether these trajectories predict ASD outcome. Change in spectral EEG power in all frequency bands occurred during the first 3 years of life. Familial risk, but not a later diagnosis of ASD, was associated with reduced power at 3 months, and a steeper developmental change between 3 and 36 months in nearly all absolute power bands. ASD outcome was not associated with absolute power intercept or slope. No associations were found between risk or outcome and relative power. This study applied an analytic approach not used in previous prospective biomarker studies of ASD, which was modeled to reflect the temporal relationship between genetic susceptibility, brain development, and ASD diagnosis. Trajectories of spectral power appear to be predicted by familial risk; however, spectral power does not predict diagnostic outcome above and beyond familial risk status. Discrepancies between current results and previous studies are discussed. LAY SUMMARY: Infants with an older sibling who is diagnosed with ASD are at increased risk of developing ASD themselves. This article tested whether EEG spectral power in the first year of life can predict whether these infants did or did not develop ASD.

Highlights • Peak alpha frequency (PAF) is thought to be a more sensitive and reliable measure of alpha band oscillatory activity. • Higher PAF has been associated with better performance on a range of cognitive tasks. • This study examines associations between PAF and non-verbal and verbal cognitive development in young infants aged 12–36 months., Although studies of PAF in individuals with autism spectrum disorder (ASD) report group differences and associations with non-verbal cognitive ability, it is not known how PAF relates to familial risk for ASD, and whether similar associations with cognition in are present in infancy. Using a large multi-site prospective longitudinal dataset of infants with low and high familial risk for ASD, metrics of PAF at 12 months were extracted and growth curves estimated for cognitive development between 12–36 months. Analyses tested whether PAF 1) differs between low and high risk infants, 2) is associated with concurrent non-verbal/verbal cognitive ability and 3) predicts developmental change in non-verbal/verbal ability. Moderation of associations between PAF and cognitive ability by familial risk status was also tested. No differences in 12-month PAF were found between low and high risk infants. PAF was associated with concurrent non-verbal cognitive ability, but did not predict change in non-verbal cognitive over development. No associations were found between PAF and verbal ability, along with no evidence of moderation. PAF is not related to familial risk for ASD, and is a neural marker of concurrent non-verbal cognitive ability, but not verbal ability, in young infants at low and high risk for ASD

Impaired face processing is proposed to play a key role in the early development of autism spectrum disorder (ASD) and to be an endophenotypic trait which indexes genetic risk for the disorder. However, no published work has examined the development of face processing abilities from infancy into the school-age years and how they relate to ASD symptoms in individuals with or at high-risk for ASD. In this novel study we investigated neural and behavioural measures of face processing at age 7 months and again in mid-childhood (age 7 years) as well as social-communication and sensory symptoms in siblings at high (n = 42) and low (n = 35) familial risk for ASD. In mid-childhood, high-risk siblings showed atypical P1 and N170 event-related potential correlates of face processing and, for high-risk boys only, poorer face and object recognition ability compared to low-risk siblings. These neural and behavioural atypicalities were associated with each other and with higher social-communication and sensory symptoms in mid-childhood. Additionally, more atypical neural correlates of object (but not face) processing in infancy were associated with less right-lateralised (more atypical) N170 amplitudes and greater social-communication problems in mid-childhood. The implications for models of face processing in ASD are discussed.

Background Reduced executive functions (EF) are commonly associated with developmental conditions (e.g., autism spectrum disorder, ASD; attention deficit/hyperactivity disorder, ADHD), although EF seems to be typical in children with callous unemotional (CU) traits. Regulatory function (RF) is a proposed infant precursor that maps on onto factors driving later EF. Here, we first test whether RF is specifically and negatively associated with ASD and ADHD traits, but not CU traits. Second, we test whether RF can act as a protective factor, by moderating the association between infant markers and subsequent ASD and ADHD traits. Methods Participants were 79 infants at high (N = 42) and low (N = 37) familial risk for ASD. Data come from the 14-month infant visit (Autism Observational Scale for Infants; AOSI; activity level and RF from the Infant Behavior Questionnaire; IBQ) and the 7-year visit (ASD traits: Social Responsiveness Scale, SRS; ADHD traits: Conners 3, CU traits: Inventory of Callous Unemotional Traits). Results Infant RF was negatively associated with later traits of ASD (B = − 0.5, p = 0.01) and ADHD inattention (B = − 0.24, p = 0.02) but not hyperactivity (B = − 0.25, p = 0.10) or CU traits (B = 0.02, p = 0.86). RF moderated the association between infant AOSI score and ASD traits, with a significant effect in those with low RF (B = 0.10, p = 0.006), not high RF (B = 0.01, p = 0.78). Similarly, for ADHD, infant activity level was associated with later ADHD inattention in those with low (B = 0.17, p = 0.04) but not high RF (B = 0.07, p = 0.48). For ADHD hyperactivity symptoms, activity level was predictive at both high and low levels of RF. Conclusions Strong RF may allow children to compensate for other atypicalities, thus attenuating the association between infant markers and later disorder traits. Whilst infant RF was associated with both ASD and ADHD inattention traits, there was no association with ADHD hyperactivity or CU traits. This suggests that any protective effect may not be universal and emphasises the need for a better understanding of the underlying moderating mechanisms. Electronic supplementary material The online version of this article (10.1186/s11689-019-9274-0) contains supplementary material, which is available to authorized users.

We integrated multiple behavioural and developmental measures from multiple time-points using machine learning to improve early prediction of individual Autism Spectrum Disorder (ASD) outcome. We examined Mullen Scales of Early Learning, Vineland Adaptive Behavior Scales, and early ASD symptoms between 8 and 36 months in high-risk siblings (HR; n = 161) and low-risk controls (LR; n = 71). Longitudinally, LR and HR-Typical showed higher developmental level and functioning, and fewer ASD symptoms than HR-Atypical and HR-ASD. At 8 months, machine learning classified HR-ASD at chance level, and broader atypical development with 69.2% Area Under the Curve (AUC). At 14 months, ASD and broader atypical development were classified with approximately 71% AUC. Thus, prediction of ASD was only possible with moderate accuracy at 14 months.

Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

Background: Difficulties with executive functioning (EF) are common in individuals with a range of developmental disorders, including autism spectrum disorder (ASD). Interventions that target underlying mechanisms of EF early in development could be broadly beneficial, but require infant markers of such mechanisms in order to be feasible. Prospective studies of infants at high familial risk (HR) for ASD have revealed a surprising tendency for HR toddlers to show longer epochs of attention to faces than low-risk (LR) controls. In typical development, decreases in look durations towards the end of the first year of life are driven by the development of executive attention—a foundational component of EF. Here, we test the hypothesis that prolonged attention to visual stimuli (including faces) in HR toddlers reflects early differences in the development of executive attention.Methods: In a longitudinal prospective study, we used eye-tracking to record HR and LR infants' looking behaviour to social and non-social visual stimuli at ages 9 and 15 months. At age 3 years, we assessed children with a battery of clinical research measures and collected parental report of effortful control (EC)—a temperament trait closely associated with EF and similarly contingent on executive attention.Results: Consistent with previous studies, we found an attenuated reduction in peak look durations to faces between 9 and 15 months for the HR group compared with the LR group, and lower EC amongst the HR-ASD group. In line with our hypothesis, change in peak look duration to faces between 9 and 15 months was negatively associated with EC at age 3.Conclusions: We suggest that for HR toddlers, disruption to the early development of executive attention results in an attenuated reduction in looking time to faces. Effects may be more apparent for faces due to early biases to orient towards them; further, attention difficulties may interact with earlier emerging differences in social information processing. Our finding that prolonged attention to faces may be an early indicator of disruption to the executive attention system is of potential value in screening for infants at risk for later EF difficulties and for evaluation of intervention outcomes.

Cognitive and adaptive behaviour abilities early in life provide important clinical prognostic information. We examined stability of such skills in children at high familial risk for ASD who either met diagnostic criteria for ASD at age 7 years (HR-ASD, n = 15) or did not (HR-non-ASD, n = 24) and low-risk control children (LR, n = 37), prospectively studied from infancy. For both HR groups, cognitive skills were consistently lower across time than those of LR children. HR-ASD children showed increasing difficulties in adaptive behaviour over time compared to LR children, while the HR-non-ASD children showed no such difficulties. This pattern of change may inform our understanding of developmental profiles of HR siblings beyond core ASD symptoms.

Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high-risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high-risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4-6-month-old infants with (high-risk, n = 24) and without (low-risk, n = 26) a sibling with ASD. Within the high-risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high-risk infants had significantly larger cerebellar and subcortical volumes at 4-6-months of age, relative to low-risk infants; and that larger volumes in high-risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors. Autism Res 2019, 12: 614-627. © 2019 The Authors. Autism Research published by International Society for Autism Research published byWiley Periodicals, Inc. LAY SUMMARY: Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4-6-month-old infants at high-risk of ASD have larger cerebellum and subcortical volumes than low-risk infants, and that larger volumes in high-risk infants are associated with more repetitive behaviors in childhood.

Dysregulation of cortical excitation/inhibition (E/I) has been proposed as a neuropathological mechanism underlying core symptoms of autism spectrum disorder (ASD). Determining whether dysregulated E/I could contribute to the emergence of behavioural symptoms of ASD requires evidence from human infants prior to diagnosis. In this prospective longitudinal study, we examine differences in neural responses to auditory repetition in infants later diagnosed with ASD. Eight-month-old infants with (high-risk: n = 116) and without (low-risk: n = 27) an older sibling with ASD were tested in a non-linguistic auditory oddball paradigm. Relative to high-risk infants with typical development (n = 44), infants with later ASD (n = 14) showed reduced repetition suppression of 40–60 Hz evoked gamma and significantly greater 10–20 Hz inter-trial coherence (ITC) for repeated tones. Reduced repetition suppression of cortical gamma and increased phase-locking to repeated tones are consistent with cortical hyper-reactivity, which could in turn reflect disturbed E/I balance. Across the whole high-risk sample, a combined index of cortical reactivity (cortical gamma amplitude and ITC) was dimensionally associated with reduced growth in language skills between 8 months and 3 years, as well as elevated levels of parent-rated social communication symptoms at 3 years. Our data show that cortical ‘hyper-reactivity’ may precede the onset of behavioural traits of ASD in development, potentially affecting experience-dependent specialisation of the developing brain.

Autism spectrum disorder (ASD) is a common, highly heritable, developmental disorder and later-born siblings of diagnosed children are at higher risk of developing ASD than the general population. Although the emergence of behavioural symptoms of ASD in toddlerhood is well characterized, far less is known about development during the first months of life of infants at familial risk. In a prospective longitudinal study of infants at familial risk followed to 36 months, we measured functional near-infrared spectroscopy (fNIRS) brain responses to social videos of people (i.e. peek-a-boo) compared to non-social images (vehicles) and human vocalizations compared to non-vocal sounds. At 4-6 months, infants who went on to develop ASD at 3 years (N = 5) evidenced-reduced activation to visual social stimuli relative to low-risk infants (N = 16) across inferior frontal (IFG) and posterior temporal (pSTS-TPJ) regions of the cortex. Furthermore, these infants also showed reduced activation to vocal sounds and enhanced activation to non-vocal sounds within left lateralized temporal (aMTG-STG/pSTS-TPJ) regions compared with low-risk infants and high-risk infants who did not develop ASD (N = 15). The degree of activation to both the visual and auditory stimuli correlated with parent-reported ASD symptomology in toddlerhood. These preliminary findings are consistent with later atypical social brain responses seen in children and adults with ASD, and highlight the need for further work interrogating atypical processing in early infancy and how it may relate to later social interaction and communication difficulties characteristic of ASD.

BACKGROUND: There has been increasing interest in the potential for pre-emptive interventions in the prodrome of autism, but little investigation as to their effect. METHODS: A two-site, two-arm assessor-blinded randomised controlled trial (RCT) of a 12-session parent-mediated social communication intervention delivered between 9 and 14 months of age (Intervention in the British Autism Study of Infant Siblings-Video Interaction for Promoting Positive Parenting), against no intervention. Fifty-four infants (28 intervention, 26 nonintervention) at familial risk of autism but not otherwise selected for developmental atypicality were assessed at 9-month baseline, 15-month treatment endpoint, and 27- and 39-month follow-up. PRIMARY OUTCOME: severity of autism prodromal symptoms, blind-rated on Autism Observation Schedule for Infants or Autism Diagnostic Observation Schedule 2nd Edition across the four assessment points. SECONDARY OUTCOMES: blind-rated parent-child interaction and child language; nonblind parent-rated communication and socialisation. Prespecified intention-to-treat analysis combined estimates from repeated measures within correlated regressions to estimate the overall effect of the infancy intervention over time. RESULTS: Effect estimates in favour of intervention on autism prodromal symptoms, maximal at 27 months, had confidence intervals (CIs) at each separate time point including the null, but showed a significant overall effect over the course of the intervention and follow-up period (effect size [ES] = 0.32; 95% CI 0.04, 0.60; p = .026). Effects on proximal intervention targets of parent nondirectiveness/synchrony (ES = 0.33; CI 0.04, 0.63; p = .013) and child attentiveness/communication initiation (ES = 0.36; 95% CI 0.04, 0.68; p = .015) showed similar results. There was no effect on categorical diagnostic outcome or formal language measures. CONCLUSIONS: Follow-up to 3 years of the first RCT of a very early social communication intervention for infants at familial risk of developing autism has shown a treatment effect, extending 24 months after intervention end, to reduce the overall severity of autism prodromal symptoms and enhance parent-child dyadic social communication over this period. We highlight the value of extended follow-up and repeat assessment for early intervention trials.

The aim of the current paper was to use data from a prospective study to assess the impact of early motor skills on the rate of language development in infants with an older sibling with Autism Spectrum Disorder (ASD), who are at increased risk of developing ASD themselves. Infants were tested prospectively at four points (7, 14, 24 and 36 months), and were assessed for ASD at the last visit. Latent growth curve analysis was used to model rate of language development using the Vineland Adaptive Behavior Scales between 7-36 months in infants at high and low familial risk for ASD. Motor scores from the Mullen Scales of Early Learning at 7 months were used as predictors of language growth. Gross motor scores predicted the subsequent rate of expressive, but not receptive, language development in at-risk siblings who were later diagnosed with ASD. Although the pattern was similar for fine motor skills, the relationship did not reach significance. It seems that early motor delay impacts the rate of development of expressive language, and this may be of particular importance to infants at increased risk of developing ASD.

Face recognition difficulties are frequently documented in children with autism spectrum disorders (ASD). It has been hypothesized that these difficulties result from a reduced interest in faces early in life, leading to decreased cortical specialization and atypical development of the neural circuitry for face processing. However, a recent study by our lab demonstrated that infants at increased familial risk for ASD, irrespective of their diagnostic status at 3 years, exhibit a clear orienting response to faces. The present study was conducted as a follow-up on the same cohort to investigate how measures of early engagement with faces relate to face-processing abilities later in life. We also investigated whether face recognition difficulties are specifically related to an ASD diagnosis, or whether they are present at a higher rate in all those at familial risk. At 3 years we found a reduced ability to recognize unfamiliar faces in the high-risk group that was not specific to those children who received an ASD diagnosis, consistent with face recognition difficulties being an endophenotype of the disorder. Furthermore, we found that longer looking at faces at 7 months was associated with poorer performance on the face recognition task at 3 years in the high- risk group. These findings suggest that longer looking at faces in infants at risk for ASD might reflect early face-processing difficulties and predicts difficulties with recognizing faces later in life.

Recently, evidence of poor or atypical motor skills in Autism Spectrum Disorder (ASD) has led some to argue that motor impairment is a core feature of the condition. The current study uses a longitudinal prospective design to assess the development of motor skills of twenty children at increased risk of developing ASD, who were recruited and tested at 9 and 40 months old, on the basis of having an older sibling diagnosed with the condition. All children completed a range of motor, face processing, IQ and diagnostic assessments at a follow-up visit (aged 5-7 years), providing a detailed profile of development in this group from a number of standardised, parental report and experimental measures. A higher proportion of children than expected demonstrated motor difficulties at the follow-up visit, and those highlighted by parental report as having poor motor skills as infants and toddlers were also more likely to have lower face processing scores and elevated autism-related social symptoms at 5-7 years, despite having similar IQ levels. These data lend support to the argument that early motor difficulties may be a risk factor for later motor impairment as well as differences in social communication and cognition, traits that are related to ASD.

The aim was to build a profile of motor development in infant siblings of children diagnosed with autism. Infants at high familial risk of developing autism spectrum disorder and those at low-risk were tested longitudinally between 6 and 24 months. Data were analysed from the gross and fine motor scales of the Mullen Scales of Early Learning and the Vineland Adaptive Behavior Scales at three age points. Low-risk and at-risk infants differed significantly on motor scales at all three visits, with significantly lower motor scores in the at-risk group evident from the age of 6 months based on parental report. Poorer gross and fine motor skills in the at-risk group were only evident on the direct standardised assessment from 12 months. Only gross motor scores were highly correlated across the two measures. A combination of standardised assessments and parental reports may therefore provide the best method for early identification of motor atypicalities in the broader autism phenotype.

BACKGROUND: Recent models of the early emergence of autism spectrum disorder (ASD) propose that infant intrinsic risk susceptibilities in behaviour may be amplified by interaction within the early social environment into an increasingly atypical developmental trajectory. This study examines whether 6- and 12-month parent-infant interactions in at-risk siblings differ from those with low-risk and whether--in at-risk siblings--such interactions predict later 3-year classification of ASD or no ASD. METHOD: Within the British Autism Study of Infant Siblings (BASIS), 6-min videotaped episodes of parent-infant free play in infants at 6-10 months (45 at-risk siblings and 47 low-risk siblings) and 12-15 months (43 at-risk siblings and 48 low-risk siblings) in a laboratory setting were rated on the Manchester Assessment of Caregiver-Infant Interaction (MACI), blind to participant information. Standard tests were administered for concurrent behavioural signs of ASD features and developmental level. Systematic consensus diagnostic classification of ASD was made at 3 years for the at-risk siblings. RESULTS: Parent nondirectiveness and sensitive responsiveness differed in relation to ASD/risk status (at-risk ASD, at-risk no-ASD and low-risk) at both 6 and 12 months. At 6 months, infant liveliness was lower in the at-risk groups; at 12 months, infant attentiveness to parent and positive affect were lower in the at-risk group later diagnosed with ASD. Dyadic mutuality and intensity of engagement showed a group effect at 12 months. Dyadic mutuality, infant positive affect and infant attentiveness to parent at 12 months (but not 6 months) predicted 3-year ASD outcome, whereas infant ASD-related behavioural atypicality did not. CONCLUSIONS: This is the first prospective evidence that early dyadic interaction between at-risk infants and their parents is associated with later diagnostic outcome in ASD. Possible explanations for these findings and their theoretical implications are considered.