Beyond Behavioral Signs: Toward a Multidomain Risk Architecture for Early Detection of Autism Spectrum

Background: Autism spectrum disorder (ASD) prevalence has increased markedly over recent decades, yet primary tools for early detection remain focused almost exclusively on observable behavioral signs in children aged 18 months and older. Instruments such as the M-CHAT-R/F, ADOS-2, and ADI-R, while clinically valuable, operate within a narrow temporal and conceptual window that systematically excludes a wide range of prenatal, perinatal, medical, environmental, and psychosocial risk factors now supported by robust empirical evidence. Objective: This paper presents a theoretically grounded critique of current early detection frameworks for ASD and proposes a Multidomain Early Risk Architecture (MERA)—a conceptual model integrating ten empirically supported domains of risk that precede or co-occur with the emergence of behavioral signs. Methods: A comprehensive narrative review of peer-reviewed literature published primarily between 2006 and 2025 was conducted across PubMed, PsycINFO, and Web of Science. Sources were organized into ten thematic domains: (1) genetic and family history, (2) prenatal and perinatal conditions, (3) prenatal substance and toxic exposures, (4) early medical conditions, (5) psychomotor and language development, (6) early social behavior, (7) restricted and repetitive behaviors, (8) atypical sensory processing, (9) feeding and gastrointestinal functioning, and (10) psychosocial and environmental factors. Results: Evidence from meta-analyses, large population-based cohorts, and longitudinal studies consistently demonstrates that ASD risk is distributed across multiple domains detectable before the classic behavioral phenotype consolidates. Across 176 peer-reviewed references, pre-behavioral domains (D1–D4) account for 38% of the total evidence base, representing risk factors systematically missed by current instruments. Conclusion: The MERA model has direct implications for screening instrument development, primary care protocols, and public health policy—particularly in settings such as Chile where diagnostic delays of two to four years remain common. Future research should validate the MERA framework prospectively and develop tiered risk-stratification instruments based on its domain structure.