Mediation of 6-year mid-childhood follow-up outcomes after pre-school social communication (PACT) therapy for autistic children: randomised controlled trial.

BACKGROUND: There are very few mechanistic studies of the long-term impact of psychosocial interventions in childhood. The parent-mediated Paediatric Autism Communication Therapy (PACT) RCT showed sustained effects on autistic child outcomes from pre-school to mid-childhood. We investigated the mechanism by which the PACT intervention achieved these effects. METHODS: Of 152 children randomised to receive PACT or treatment as usual between 2 and 5 years of age, 121 (79.6%) were followed 5-6 years after the endpoint at a mean age of 10.5 years. Assessors, blind to the intervention group, measured Autism Diagnostic Observation Scale Calibrated Severity Score (ADOS CSS) for child autistic behaviours and Teacher Vineland (TVABS) for adaptive behaviour in school. Hypothesised mediators were child communication initiations with caregivers in a standard play observation (Dyadic Communication Measure for Autism, DCMA). Hypothesised moderators of mediation were baseline child non-verbal age equivalent scores (AE), communication and symbolic development (CSBS) and 'insistence on sameness' (IS). Structural equation modelling was used in a repeated measures mediation design. RESULTS: Good model fits were obtained. The treatment effect on child dyadic initiation with the caregiver was sustained through the follow-up period. Increased child initiation at treatment midpoint mediated the majority (73%) of the treatment effect on follow-up ADOS CSS. A combination of partial mediation from midpoint child initiations and the direct effect of treatment also contributed to a near-significant total effect on follow-up TVABS. No moderation of this mediation was found for AE, CSBS or IS. CONCLUSIONS: Early sustained increase in an autistic child's communication initiation with their caregiver is largely responsible for the long-term effects from PACT therapy on autistic and adaptive behaviour outcomes. This supports the theoretical logic model of PACT therapy but also illuminates fundamental causal processes of social and adaptive development in autism over time: early social engagement in autism can be improved and this can have long-term generalised outcome effects.

Parent-mediated social communication therapy for young children with autism (PACT): long-term follow-up of a randomised controlled trial.

BACKGROUND: It is not known whether early intervention can improve long-term autism symptom outcomes. We aimed to follow-up the Preschool Autism Communication Trial (PACT), to investigate whether the PACT intervention had a long-term effect on autism symptoms and continued effects on parent and child social interaction. METHODS: PACT was a randomised controlled trial of a parent-mediated social communication intervention for children aged 2-4 years with core autism. Follow-up ascertainment was done at three specialised clinical services centres in the UK (London, Manchester, and Newcastle) at a median of 5·75 years (IQR 5·42-5·92) from the original trial endpoint. The main blinded outcomes were the comparative severity score (CSS) from the Autism Diagnostic Observation Schedule (ADOS), the Dyadic Communication Assessment Measure (DCMA) of the proportion of child initiatiations when interacting with the parent, and an expressive-receptive language composite. All analyses followed the intention-to-treat principle. PACT is registered with the ISRCTN registry, number ISRCTN58133827. FINDINGS: 121 (80%) of the 152 trial participants (59 [77%] of 77 assigned to PACT intervention vs 62 [83%] of 75 assigned to treatment as usual) were traced and consented to be assessed between July, 2013, and September, 2014. Mean age at follow-up was 10·5 years (SD 0·8). Group difference in favour of the PACT intervention based on ADOS CSS of log-odds effect size (ES) was 0·64 (95% CI 0·07 to 1·20) at treatment endpoint and ES 0·70 (95% CI -0·05 to 1·47) at follow-up, giving an overall reduction in symptom severity over the course of the whole trial and follow-up period (ES 0·55, 95% CI 0·14 to 0·91, p=0·004). Group difference in DCMA child initiations at follow-up showed a Cohen's d ES of 0·29 (95% CI -0.02 to 0.57) and was significant over the course of the study (ES 0·33, 95% CI 0·11 to 0·57, p=0·004). There were no group differences in the language composite at follow-up (ES 0·15, 95% CI -0·23 to 0·53). INTERPRETATION: The results are the first to show long-term symptom reduction after a randomised controlled trial of early intervention in autism spectrum disorder. They support the clinical value of the PACT intervention and have implications for developmental theory. FUNDING: Medical Research Council.

Behavioural markers for autism in infancy: scores on the Autism Observational Scale for Infants in a prospective study of at-risk siblings.

We investigated early behavioural markers of autism spectrum disorder (ASD) using the Autism Observational Scale for Infants (AOSI) in a prospective familial high-risk (HR) sample of infant siblings (N=54) and low-risk (LR) controls (N=50). The AOSI was completed at 7 and 14 month infant visits and children were seen again at age 24 and 36 months. Diagnostic outcome of ASD (HR-ASD) versus no ASD (HR-No ASD) was determined for the HR sample at the latter timepoint. The HR group scored higher than the LR group at 7 months and marginally but non-significantly higher than the LR group at 14 months, although these differences did not remain when verbal and nonverbal developmental level were covaried. The HR-ASD outcome group had higher AOSI scores than the LR group at 14 months but not 7 months, even when developmental level was taken into account. The HR-No ASD outcome group had scores intermediate between the HR-ASD and LR groups. At both timepoints a few individual items were higher in the HR-ASD and HR-No ASD outcome groups compared to the LR group and these included both social (e.g. orienting to name) and non-social (e.g. visual tracking) behaviours. AOSI scores at 14 months but not at 7 months were moderately correlated with later scores on the autism diagnostic observation schedule (ADOS) suggesting continuity of autistic-like behavioural atypicality but only from the second and not first year of life. The scores of HR siblings who did not go on to have ASD were intermediate between the HR-ASD outcome and LR groups, consistent with the notion of a broader autism phenotype.