Heterogeneity of response to Early Start Denver Model: Identifying developmental trajectories and predicting cognitive outcomes

Autism is a highly heterogenous neurodevelopmental condition that, in some individuals, can significantly impair quality of life. Early identification followed by timely intervention is crucial for enhancing cognitive outcomes in children with developmental delay. Yet, marked variability in intervention response remains insufficiently understood. Characterizing this heterogeneity is essential for informing intervention strategies tailored to each childs developmental profile. Here, we aim to identify subgroups based on intervention response trajectories and investigate subgroup-specific predictors of intervention outcomes. We analyzed longitudinal data from 107 children (1.7-3.5 y.o.) receiving 1.5-2 years of Early Start Denver Model (ESDM) intervention. Children gained an average of 19 points in Developmental Quotient (DQ), significantly improved their adaptive skills and showed less autism features. Using latent class regression model, we identified 3 classes: Progressive Group A (35.5% of participants), which had the highest baseline cognitive scores (mean DQ: 78) and gained 27 DQ points in average throughout the intervention; Progressive Group B (34.6% of participants), which showed significant developmental delay at baseline (mean DQ: 62) and gained 25 DQ points; and the Stable Group (29.9% of participants), which also started with significant developmental delay (mean DQ: 47) and showed steady and modest improvement in cognitive scores throughout the intervention. Among the subgroup-specific predictors of better cognitive outcome were younger age for the Progressive Groups and fewer restrictive and repetitive behaviors for the Stable Group. Our results support previous findings of ESDMs efficacy, replicated in a larger sample of 107 children and reveal the association of subgroup-specific baseline factors with cognitive evolution, offering a first step towards personalizing interventions. Lay SummaryO_LIIn a group of 107 autistic children receiving Early Start Denver Model intervention we observed significant gain in cognitive and adaptive skills as well as reduced level of autism features. C_LIO_LIWe identified three subgroups of response with different developmental trajectories. Different factors at baseline were selected as predictors of the cognitive outcome for each subgroup. For two of the subgroups, younger age at the start of intervention was linked to better cognitive outcomes. C_LI