Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 Nov 1;175(11):e213298.
doi: 10.1001/jamapediatrics.2021.3298. Epub 2021 Nov 1.

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

Andrew J O Whitehouse  1   2   3 , Kandice J Varcin  1   4 , Sarah Pillar  1 , Wesley Billingham  1 , Gail A Alvares  1 , Josephine Barbaro  3   5 , Catherine A Bent  6 , Daniel Blenkley  7 , Maryam Boutrus  1   3   8 , Abby Chee  1 , Lacey Chetcuti  3   6 , Alena Clark  1 , Emma Davidson  9 , Stefanie Dimov  6 , Cheryl Dissanayake  3   5 , Jane Doyle  9 , Megan Grant  6 , Cherie C Green  6 , Megan Harrap  1 , Teresa Iacono  10 , Lisa Matys  1 , Murray Maybery  8 , Daniel F Pope  7 , Michelle Renton  1   9 , Catherine Rowbottam  9 , Nancy Sadka  5 , Leonie Segal  11 , Vicky Slonims  12 , Jodie Smith  6 , Carol Taylor  13 , Scott Wakeling  6 , Ming Wai Wan  7 , John Wray  9 , Matthew N Cooper  1 , Jonathan Green  13   14 , Kristelle Hudry  3   6
Affiliations
Randomized Controlled Trial

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

Andrew J O Whitehouse et al. JAMA Pediatr. .

Abstract

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.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: Dr Barbaro 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.

Figures

Figure 1.
Figure 1.. CONSORT Flow Diagram
Participants were aged 9 to 15 months during randomization (baseline), 15 to 21 months at the treatment end point (6 months after baseline), 21 to 27 months at the first follow-up assessment (12 months after baseline), and 33 to 39 months at the second follow-up assessment (24 months after baseline). iBASIS-VIPP indicates iBASIS–Video Interaction to Promote Positive Parenting.
Figure 2.
Figure 2.. Treatment Effect Over Time for the Primary Outcome of Autism Symptom Severity
Effect size estimate with 1-tailed 95% CIs (represented by whiskers). Autism symptom severity was measured by the Autism Observation Scale for Infants and the Autism Diagnostic Observation Schedule–Second Edition. An area between curves (shaded area) below the null indicates a greater reduction in autism symptoms in the iBASIS-VIPP group vs the usual care group. The mean age of participants at assessment points was 12 months (baseline), 18 months (6 months after baseline), 24 months (12 months after baseline), and 36 months (24 months after baseline). iBASIS-VIPP indicates iBASIS–Video Interaction to Promote Positive Parenting.
See this image and copyright information in PMC

Comment in

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. American Psychiatric Association . Diagnostic and Statistical Manual of Mental Disorders. 5th ed. American Psychiatric Association; 2013.
    1. van ‘t Hof M, Tisseur C, van Berckelear-Onnes I, et al. . Age at autism spectrum disorder diagnosis: a systematic review and meta-analysis from 2012 to 2019. Autism. 2021;25(4):862-873. doi:10.1177/1362361320971107 - DOI - PubMed
    1. Hyman SL, Levy SE, Myers SM; Council on Children With Disabilities, Section on Developmental and Behavioral Pediatrics . Identification, evaluation, and management of children with autism spectrum disorder. Pediatrics. 2020;145(1):e20193447. doi:10.1542/peds.2019-3447 - DOI - PubMed
    1. Sandbank M, Bottema-Beutel K, Woynaroski T. Intervention recommendations for children with autism in light of a changing evidence base. JAMA Pediatr. 2021;175(4):341-342. doi:10.1001/jamapediatrics.2020.4730 - DOI - PubMed
    1. Whitehouse AJO. Elizabeth Usher Memorial Lecture: rethinking the clinical pathway for autism spectrum disorder and challenging the status quo. Int J Speech Lang Pathol. 2017;19(3):208-217. doi:10.1080/17549507.2016.1276963 - DOI - PubMed

Publication types