By linking early genetic probability with brain-behavioral trajectories, PROGRESS advances understanding of autism-related differences before clinical diagnosis and provides an empirically grounded foundation for ethical genomic newborn screening and optimized early developmental monitoring and intervention.
Abstract
Background
Autism is most often diagnosed after the age of 3, despite evidence that neurodevelopmental differences emerge within the first 2 years of life and that genetic and familial risk can be identified at birth.
Methods
Established in September 2022 (anticipated duration of 5-7 years), the Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center is an ongoing longitudinal cohort study designed to characterize early developmental trajectories associated with autism and evaluate the impact of providing genetic information to families.
Results
Infants who undergo genomic newborn screening and enroll in PROGRESS are followed from 3 to 24 months of age and categorized into three groups: identified genetic probability (IGP), familial likelihood without identified genetic probability (Baby Siblings), and no identified genetic probability (NGP). Assessments include electroencephalography, electrocardiography, auditory, eye tracking, developmental testing, caregiver-infant interaction, and caregiver-reported measures. Autism screening is conducted at 18 months, with comprehensive diagnostic evaluation at 24 months. Caregiver psychosocial experiences of receiving early genetic information are assessed through surveys and interviews.
Conclusion
By integrating genomic probability with early neurobehavioral development and family experiences, PROGRESS provides a framework to inform ethical genomic screening, developmental monitoring, and timely access to early intervention supported by a family navigator.
IMPACT
This study presents the rationale and methods of the ongoing Prospective Genetic Risk Evaluation and Assessment (PROGRESS) in Autism Center at Columbia University, which began in September 2022 (anticipated duration of 5-7 years). PROGRESS is a prospective longitudinal cohort assessing infants with identified genetic probability, familial likelihood, or no identified genetic probability for autism from 3 to 24 months of age. By linking early genetic probability with brain-behavioral trajectories, PROGRESS advances understanding of autism-related differences before clinical diagnosis and provides an empirically grounded foundation for ethical genomic newborn screening and optimized early developmental monitoring and intervention.
Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition with complex genetic and environmental underpinnings. A clinically significant subset of children with ASD experience developmental regression (regASD), characterized by the acute loss of previously acquired skills. The mechanisms, predictors, and molecular basis of regASD remain poorly understood. We retrospectively and prospectively analyzed a cohort of 505 children diagnosed with ASD at the Center of Excellence for Autism and Neurodevelopmental Disorders (Paris, France) between 2017 and 2023. Clinical, neurodevelopmental, and genetic data were collected, including detailed developmental histories, standardized diagnostic assessments (ADI-R, ADOS-2, VABS), and chromosomal microarray analysis (CMA). Statistical analyses included classification tree algorithms and principal component analysis to identify clinical predictors of regression, and gene ontology enrichment to explore molecular pathways. Developmental regression was detected in 74 children (15%). Prior to regression, regASD children exhibited more favorable neurodevelopmental profiles, including lower rates of prematurity, higher birth weight and height, and earlier acquisition of first words, compared with nonregressive ASD (non-regASD) peers. However, after regression, regASD children had significantly more severe neurodevelopmental impairments across cognitive, adaptive, and social domains (p < 0.001). Routine clinical variables did not reliably predict the onset of regression. CMA revealed that regASD is associated with distinct genetic deletions enriched in immune, inflammatory (particularly Type I interferon), oxidative stress, angiogenesis, and synaptic pathways, with minimal overlap with non-regASD genetic profiles. Our findings are consistent with the hypothesis that regASD may represent a distinct clinical and molecular subgroup within ASD. The molecular signatures identified in regASD suggest involvement of immune and synaptic pathways, highlighting the need for further targeted research to clarify their potential therapeutic implications for this subgroup.
OBJECTIVE: Explore the association of prenatal, perinatal, and postnatal risk factors with autism risk at 5-years corrected age in very preterm (VPT) children. STUDY DESIGN: Data from a longitudinal cohort study of 315 VPT and 172 term-born children at a US-based academic medical center were analyzed, exploring antecedents of autism risk using elastic net regression. RESULTS: More children born VPT (8.9%) had a Social Communication Questionnaire score associated with autism (i.e., SCQ ≥ 15) than term-born controls (2.9%; p = 0.012). For VPT children, cerebellar abnormalities at term-equivalent age (OR = 1.339, 95% CI = 1.010–1.778) and moderate-severe histologic chorioamnionitis (OR = 4.148, CI = 1.294–13.368) were significantly associated with autism risk, in addition to male sex and social risk. VPT children with SCQ ≥ 15 had poorer adaptive, behavioral, cognitive, and executive functioning (all ps < 0.001). CONCLUSION: Early screening for children with these risk factors can facilitate early intervention for those at most risk for poorer neurodevelopmental outcomes.
Meg Stone-Heaberlin, Allison D Blackburn, Leanne Tamm et al.· Journal of Perinatology· 0 citations
Autism Spectrum Disorder (ASD) is a lifelong neurodevelopmental
condition characterized by deficits in social communication and the presence of
restricted or repetitive behaviors and interests. Increasing prevalence rates underscore
the importance of early identification and timely intervention. This review
examines current and emerging diagnostic and management approaches to ASD.
Standardized diagnostic frameworks, such as the DSM-5 criteria, remain central
to clinical assessment. Recent advances in screening tools have enhanced early
detection. Due to the heterogeneity of clinical presentations, individualized care
is necessary. Management strategies commonly integrate behavioral and developmental
interventions, educational support, family involvement, and, when appropriate,
pharmacological treatment for associated symptoms. Functional outcomes
are further improved by strategies, such as executive function training, occupational
therapy, technology-assisted therapies, and caregiver-mediated programs.
Research indicates that extensive family involvement and coordinated, interdisciplinary
care lead to improved long-term outcomes. To maximise functioning,
engagement, and quality of life, the existing literature generally supports a
comprehensive, flexible, and person-centred approach that takes into account
each person's unique needs and strengths.
D. I. Khan, Sana Jameel· Current Psychiatry Research...· 0 citations
It is argued that future early ASD detection systems should be developed as clinician-supervised decision-support tools rather than autonomous diagnostic instruments.
Wenhao Luo, Z. Yin, Jianbiao Dai· Diagnostics· 0 citations
Estimating how common autism is among children aged 2 to 9 years in Northern Uganda, to identify co-occurring neurodevelopmental conditions, and to explore factors that may increase likelihood of autism are carried out.
Ouma Simple, E. Estlin, Kennedy Kosko Okello et al.· Autism· 1 citation
This critical narrative review examines early autism identification as a pathway problem rather than as a single testing event and argues that early autism identification should be evaluated through linked quality measures: response to concern, repeated surveillance following negative or ambiguous screening, referral completion, time to diagnostic assessment, support initiation before diagnostic closure, and equity of access.
R. Kurmashev, Mavile Karaieva· Pediatric Investigation· 0 citations
We use cookies to run the site and, with your consent, for analytics and to show ads.
See our Cookie Policy.
