Intervention préventive versus traitement dès le dépistage précoce d'un "trouble du spectre de l'autisme": essai contrôlé randomisé en simple aveugle

Aperçu: G.M.

CONTEXTE:
L’efficacité potentielle des interventions prédiagnostiques dans le cadre du prodrome (Symptôme avant-coureur d'une maladie) des "troubles du spectre de l'autisme" (TSA) suscite un vif intérêt, mais des données factuelles sont disponibles pour les enfants à risque familial élevé. Nous avions pour objectif de tester l'efficacité d'une intervention préventive conçue pour les nourrissons présentant des signes précoces de comportement du TSA.
MÉTHODES:
Dans cet essai contrôlé randomisé en simple aveugle mené dans deux centres spécialisés en Australie, des nourrissons âgés de 9 à 14 mois ont été recrutés s'ils présentaient au moins trois signes précurseurs de TSA sur le comportement dans Social Attention and Communication Surveillance-Revised (SACS). -R) Liste de contrôle de 12 mois. 

Les nourrissons ont été assignés au hasard (1: 1) à une intervention assistée par vidéo assistée par un parent (iBASIS-VIPP) ou à un traitement habituel. L'allocation de groupe a été effectuée par minimisation, stratifiée par site, sexe, âge et nombre de comportements à risque SACS-R. 

Les évaluations ont été effectuées au départ (avant l’affectation du traitement) et au bout de 6 mois. Le critère d'évaluation principal était l'échelle d'observation de l'autisme pour les nourrissons (AOSI), qui mesure les premiers signes comportementaux associés aux TSAs. 

Les résultats secondaires étaient une gamme de résultats pour le nourrisson et le soignant mesurés par Manchester, Évaluation de l'interaction entre le soignant (MACI), l'échelle d'apprentissage précoce de Mullen (MSEL), l'échelle de comportement adaptatif de Vineland, 2e édition (VABS-2), le développement de la communication MacArthur-Bates Inventaire (MCDI) et échelles du sens des compétences parentales (PSOC). Cet essai est enregistré auprès du registre des essais cliniques australien-néo-zélandais sous le numéro ANZCTR12616000819426.
RESULTATS:
Entre le 9 juin 2016 et le 30 mars 2018, 103 nourrissons ont été assignés au hasard, 50 au groupe iBASIS-VIPP et 53 au groupe de traitement habituel. Après l’intervention, nous n’avons observé aucune différence significative entre les groupes de signes comportementaux précoces de TSA  mesurés par l’AOSI (différence estimée -0,74, IC95% -2-27 à 47). 

Nous n'avons également observé aucune différence significative entre les résultats secondaires, mesurant la non-directivité du fournisseur de soins (0-16 ans, -0,33% à 0,65 ans), la sensibilité du fournisseur de soins (0,24, -0,15 à 0,063) et la présence de nourrissons.

Lancet Child Adolesc Health. 2019 Jul 15. pii: S2352-4642(19)30184-1. doi: 10.1016/S2352-4642(19)30184-1.

Pre-emptive intervention versus treatment as usual for infants showing early behavioural risk signs of autism spectrum disorder: a single-blind, randomised controlled trial

Whitehouse AJO¹, Varcin KJ², Alvares GA², Barbaro J³, Bent C⁴, Boutrus M⁵, Chetcuti L³, Cooper MN², Clark A², Davidson E⁶, Dimov S⁴, Dissanayake C³, Doyle J⁶, Grant M⁴, Iacono T⁷, Maybery M⁸, Pillar S², Renton M⁹, Rowbottam C⁶, Sadka N⁴, Segal L¹⁰, Slonims V¹¹, Taylor C¹², Wakeling S⁴, Wan MW¹³, Wray J⁶, Green J¹⁴, Hudry K⁴.

Author information

1

Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Indooroopilly, QLD, Australia. Electronic address: andrew.whitehouse@telethonkids.org.au.

2

Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia.

3

Cooperative Research Centre for Living with Autism (Autism CRC), Indooroopilly, QLD, Australia; Olga Tennison Autism Research Centre, School of Psychology and Public Health, La Trobe University, Bundoora, VIC, Australia.

4

Olga Tennison Autism Research Centre, School of Psychology and Public Health, La Trobe University, Bundoora, VIC, Australia.

5

Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia; Cooperative Research Centre for Living with Autism (Autism CRC), Indooroopilly, QLD, Australia; School of Psychological Science, University of Western Australia, Crawley, WA, Australia.

6

Child and Adolescent Health Service, Child Development Service, West Perth, WA, Australia.

7

La Trobe Rural Health School, Bendigo, VIC, Australia.

8

School of Psychological Science, University of Western Australia, Crawley, WA, Australia.

9

Telethon Kids Institute, University of Western Australia, Nedlands, WA, Australia; Child and Adolescent Health Service, Child Development Service, West Perth, WA, Australia.

10

Australian Centre for Precision Health, School of Health Sciences, University of South Australia, Adelaide, SA, Australia.

11

Children's Neurosciences, Evelina London Children's Hospital, Institute of Psychiatry, Psychology & Neuroscience, Kings College London, London, UK.

12

Division of Neuroscience and Experimental Psychology, School of Biological Sciences, University of Manchester, Manchester, UK.

13

School of Health Sciences, University of Manchester, Manchester, UK.

14

Division of Neuroscience and Experimental Psychology, School of Biological Sciences, University of Manchester, Manchester, UK; Manchester Academic Health Science Centre, Manchester University NHS Foundation Trust, Greater Manchester Mental Health NHS Trust, Manchester, UK.

Abstract

BACKGROUND:

Great interest exists in the potential efficacy of prediagnostic interventions within the autism spectrum disorder prodrome, but available evidence relates to children at high familial risk. We aimed to test the efficacy of a pre-emptive intervention designed for infants showing early behavioural signs of autism spectrum disorder.

METHODS:

In this single-blind, randomised controlled trial done at two specialist centres in Australia, infants aged 9-14 months were enrolled if they were showing at least three early behavioural signs of autism spectrum disorder on the Social Attention and Communication Surveillance-Revised (SACS-R) 12-month checklist. Infants were randomly assigned (1:1) to receive a parent-mediated video-aided intervention (iBASIS-VIPP) or treatment as usual. Group allocation was done by minimisation, stratified by site, sex, age, and the number of SACS-R risk behaviours. Assessments were done at baseline (before treatment allocation) and at the 6 month endpoint. The primary outcome was Autism Observation Scale for Infants (AOSI), which measures early behavioural signs associated with autism spectrum disorder. Secondary outcomes were a range of infant and caregiver outcomes measured by Manchester Assessment of Caregiver-Infant interaction (MACI), Mullen Scales of Early Learning (MSEL), Vineland Adaptive Behaviour Scales, 2nd edition (VABS-2), MacArthur-Bates Communicative Development Inventory (MCDI), and Parenting Sense of Competence (PSOC) scale. This trial is registered with Australian New Zealand Clinical Trials Registry, number ANZCTR12616000819426.

FINDINGS:

Between June 9, 2016, and March 30, 2018, 103 infants were randomly assigned, 50 to the iBASIS-VIPP group and 53 to the treatment-as-usual group. After the intervention, we observed no significant differences between groups on early autism spectrum disorder behavioural signs measured by the AOSI (difference estimate -0·74, 95% CI -2·47 to 0·98). We also observed no significant differences on secondary outcomes measuring caregiver non-directiveness (0·16, -0·33 to 0·65), caregiver sensitive responding (0·24, -0·15 to 0·63), and infant attentiveness (-0·19, -0·63 to 0·25) during parent-child interactions (MACI), as well as on researcher-administered measures of receptive (1·30, -0·48 to 3·08) and expressive language (0·54, -0·73 to 1·80), visual reception (0·31, -0·77 to 1·40), and fine motor skills (0·55, -0·32 to 1·41) using the MSEL. Compared with the treatment-as-usual group, the iBASIS-VIPP group had lower infant positive affect (-0·69, -1·27 to -0·10) on the MACI, but higher caregiver-reported receptive (37·17, 95% CI 10·59 to 63·75) and expressive vocabulary count (incidence rate ratio 2·31, 95% CI 1·22 to 4·33) on MCDI, and functional language use (difference estimate 6·43, 95% CI 1·06 to 11·81) on VABS. There were no significant group differences on caregiver-reported measures of MCDI infant gesture use (3·22, -0·60 to 7·04) and VABS social behaviour (3·28, -1·43 to 7·99). We observed no significant differences between groups on self-reported levels of parenting satisfaction (difference estimate 0·21, 95% CI -0·09 to 0·52), interest (-0·23, -0·62 to 0·16) and efficacy (-0·08, -0·38 to 0·22) on PSOC.

INTERPRETATION:

A pre-emptive intervention for the autism spectrum disorder prodrome had no immediate treatment effect on early autism spectrum disorder symptoms, the quality of parent-child interactions, or researcher-administered measures of developmental skills. However, we found a positive effect on parent-rated infant communication skills. Ongoing follow-up of this infant cohort will assess longer-term developmental effects.

FUNDING:

Western Australia Children's Research Fund, Autism Cooperative Research Centre, La Trobe University, and Angela Wright Bennett Foundation.

Copyright © 2019 Elsevier Ltd. All rights reserved.

PMID:31324597

DOI:10.1016/S2352-4642(19)30184-1