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

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Andrew J.O. Whitehouse, Kandice J. Varcin, Sarah Pillar, Wesley Billingham, Gail A. Alvares, Josephine Barbaro, Catherine A. Bent, Daniel Blenkley, Maryam Boutrus, Abby Chee, Lacey Chetcuti, Alena Clark, Emma Davidson, Stefanie Dimov, Cheryl Dissanayake, Jane Doyle, Megan Grant, Cherie C. Green, Megan Harrap, Teresa Iacono & 16 more Lisa Matys, Murray Maybery, Daniel F. Pope, Michelle Renton, Catherine Rowbottam, Nancy Sadka, Leonie Segal, Vicky Slonims, Jodie Smith, Carol Taylor, Scott Wakeling, Ming Wai Wan, John Wray, Matthew N. Cooper, Jonathan Green, Kristelle Hudry

Original languageEnglish
Article numbere213298
Pages (from-to)E213298
JournalJAMA Pediatrics
Issue number11
Early online date1 Nov 2021
Accepted/In press2021
E-pub ahead of print1 Nov 2021
PublishedNov 2021

Bibliographical note

Funding Information: reported developing the Social Attention and Communication Surveillance–Revised outside the submitted work. Dr Blenkley reported receiving personal fees from the University of Manchester during the conduct of the study. Dr Chee reported receiving personal fees from the Child Development Service outside the submitted work. Dr Slonims reported providing input into the development of the iBASIS–Video Interaction to Promote Positive Parenting (iBASIS-VIPP) intervention. Dr Taylor reported providing input into the development of the iBASIS-VIPP intervention and manual outside the submitted work. Dr Wan reported providing input into the development of the iBASIS-VIPP intervention and manual outside the submitted work. Dr J. Green reported owning a patent for the iBASIS-VIPP intervention, being the initiator and codeveloper of the original iBASIS-VIPP manual, receiving personal fees for his role as codirector of IMPACT, and serving as a senior investigator for the United Kingdom National Institute for Health Research outside the submitted work. No other disclosures were reported. Funding/Support: This study was sponsored by the Telethon Kids Institute and supported by grants 1077966 and 1173896 from the National Health and Medical Research Council (Dr Whitehouse) and funding from the Angela Wright Bennett Foundation (Dr Whitehouse), the Telethon-Perth Children’s Hospital Research Fund (Drs Whitehouse, Wray, J. Green, and Segal), the La Trobe University Understanding Disease Research Focus Area (Drs Hudry, Dissanayake, Barbaro, Iacono, Slonims, J. Green, and Whitehouse), and the Cooperative Research Centre for Living with Autism (Autism CRC) established and supported by the Australian government’s Cooperative Research Centre Program (Drs Hudry, Whitehouse, Barbaro, Iacono, Dissanayake, and Maybery). Publisher Copyright: © 2021 American Medical Association. All rights reserved.

King's Authors


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: identifier: ACTRN12616000819426..

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