Randomised Trial of a Prodromal Intervention for Infants at High Risk for Autism: Longitudinal Outcomes to Age Three Years

Thursday, May 11, 2017: 1:45 PM
Yerba Buena 8 (Marriott Marquis Hotel)
J. Green1, E. Jones2, T. Gliga3, M. W. Wan4, A. Pickles5, V. Slonims6, G. Pasco7, M. Elsabbagh8, R. Bedford9, T. Charman10 and M. H. Johnson3, (1)University of Manchester, Manchester, England, United Kingdom, (2)Birkbeck, University of London, London, UNITED KINGDOM, (3)Centre for Brain and Cognitive Development, Birkbeck University of London, London, United Kingdom, (4)University of Manchester, Manchester, UNITED KINGDOM, (5)King's College London, London, UNITED KINGDOM, (6)Evelina Children's Hospital Guy's and St Thomas' NHS Foundation Trust, London, UNITED KINGDOM, (7)Institute of Psychiatry, London, UNITED KINGDOM, (8)McGill University, Montreal, PQ, Canada, (9)Kings College, London, UNITED KINGDOM, (10)Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
Background:  There has been increasing interest in the potential for pre-emptive (pre-diagnostic) interventions in the infancy prodrome of autism, but little investigation as to their effect.

Objectives: To determine the longer term developmental outcomes to age 39 months of a parent-mediated video-aided intervention between 9-14 months for infants at familial risk for autism.

Methods:  Two-site, two-arm assessor-blinded randomised controlled trial a 12-session therapist-delivered, parent-mediated social communication intervention delivered between 9 and 14 months of age (iBASIS-VIPP), against no intervention. iBASIS-VIPP is a modification for the autism prodrome of the Video Interaction for Promoting Positive Parenting (VIPP) programme. The home-based intervention uses video-feedback to help parents understand and adapt to their infant’s individual communication style so as to promote optimal social and communicative development. iBASIS-VIPP extended the original 6 session VIPP program by adding up to six planned booster sessions according to need in discussion with family, and added therapeutic procedures to address any emerging developmental atypicality. The sample was 54 infants (28 intervention, 26 non-intervention) at familial risk of autism but not otherwise selected by developmental difficulty. Assessments were at 9-month baseline, 15-month treatment endpoint, and 27 and 39-month follow-up. Primary outcome was the level of emergent autism-related behaviour (‘prodromal symptoms’), blind-rated on Autism Observation Schedule for Infants (AOSI) or Autism Diagnostic Observation Schedule (ADOS-2) across the four assessment points. Secondary outcomes were: blind-rated parent-child interaction (parent non-directiveness on the Manchester Assessment of Caregiver-Infant Interaction (MACI), parent synchrony on Dyadic Communication Measure for Autism (DCMA), child attentiveness on MACI and child initiations on DCMA). Other outcomes were child language (Mullen); non-blind parent-rated communication and socialisation (Vineland). Pre-specified intention to treat analysis combined estimates from repeated measures within correlated regressions to give an estimate of the overall effect of the infancy intervention. To summarize the treatment group differences in a principled fashion, the multiple point estimates were combined into an estimated area between the curves over time (sum of trapeziums, Figures 1 and 2). Trial registration: ISRCTN 87373263.

Results:  Effect estimates for the autism prodromal symptoms, largest at 27 months, had confidence intervals at each separate time point including the null, but showed a significant consistent reduction when considered over time (ES=0.32; 95% CI 0.04, 0.60; p=0.026; Figure 1a). Significant overall effects through time were also seen on proximal intervention targets of parent non-directiveness/synchrony (ES=0.33; CI 0.04, 0.63; p=0.013; Figure 1c) and child attentiveness/communication initiation (ES=0.36; (95% CI 0.04, 0.68; p=0.015; Figure 1b). There was no effect on categorical diagnostic outcome, nor on other developmental or language measures (Figure 2a-d).

Conclusions: To our knowledge this is the first study of prodromal intervention for infants at risk, which has focused on emerging autism-related prodromal symptom trajectories and other dyadic treatment targets through 3 years. We demonstrate evidence of a treatment effect, extending after intervention, consisting of significant reduction in the overall level of emergent autism-related behaviours over time and enhanced parent-child dyadic social communication. The study highlights the value for early intervention trials of extended follow-up and repeated assessments within extended follow-up.