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Fetal MRI Biomarkers and the Prenatal Origins of Autism Spectrum Disorder: A Narrative Review
Mariarosaria Motta1, Laura Sarno2, Dario Colacurci1
1Department of Public Health, University of Naples Federico II, 80131 Naples, Italy.
Insights
Prenatal fetal MRI may detect brain differences linked to autism spectrum disorder (ASD). These early structural and functional brain alterations suggest ASD may originate before birth, but more research is needed for clinical use.
Area of Science:
- Neuroscience
- Developmental Biology
- Radiology
Background:
- Autism spectrum disorder (ASD) is increasingly viewed as a neurodevelopmental condition with prenatal origins.
- Fetal magnetic resonance imaging (MRI) allows in vivo brain characterization before birth, offering potential biomarkers for early detection.
Purpose of the Study:
- To review existing human studies assessing fetal MRI biomarkers for association with later ASD diagnosis or autistic traits.
- To determine if prenatal neurodevelopmental divergence can be identified using fetal MRI.
Main Methods:
- A PRISMA-informed narrative review of studies using fetal MRI (structural and/or functional) with postnatal ASD outcomes.
- Searches conducted across MEDLINE, EMBASE, SCOPUS, and Web of Science.
Main Results:
- Eight studies suggest prenatal detection of ASD-associated neurodevelopmental divergence.
- Consistent prenatal volumetric alterations (e.g., insular cortex enlargement) and atypical network connectivity were observed.
- Prenatal abnormalities in high-risk conditions correlate with increased ASD risk.
Conclusions:
- Fetal MRI can identify structural and functional brain alterations preceding clinical ASD manifestation.
- Findings support a prenatal neurodevelopmental origin for ASD.
- Further large-scale, standardized, multicenter studies are necessary for clinical translation of fetal MRI biomarkers.
Abstract:
Objectives: Autism spectrum disorder (ASD) is increasingly conceptualized as a neurodevelopmental condition with prenatal origins. Advances in fetal magnetic resonance imaging (MRI), including high-resolution structural imaging and resting-state functional connectivity analysis, now enable in vivo characterization of the developing human brain before birth. This review examines whether fetal MRI biomarkers are associated with later ASD diagnosis or autistic traits. Methods: We conducted a PRISMA-informed narrative review of human studies identified through MEDLINE, EMBASE, SCOPUS, and Web of Science. Eligible studies included original human investigations using fetal MRI to assess brain structure and/or function, with postnatal ASD diagnosis or standardized autistic-trait outcomes. Results: Eight eligible studies provide converging evidence that neurodevelopmental divergence associated with ASD may be detectable in utero. Structural analyses consistently report prenatal volumetric alterations, particularly enlargement of the insular cortex between the second and third trimesters. Additional findings of regional overgrowth and hemispheric asymmetries suggest distributed deviations in cortical maturation. Functional fetal MRI studies further demonstrate atypical large-scale network organization prior to birth. Altered connectivity within cingulate, prefrontal, temporal, and cerebellar circuits has been prospectively associated with later autistic traits, indicating that network-level integration may diverge before behavioral symptoms emerge. Evidence from high-risk conditions, including isolated ventriculomegaly and tuberous sclerosis complex, reinforces the association between prenatal structural abnormalities and increased ASD risk. Conclusions: Current evidence suggests that structural and functional brain alterations identifiable by fetal MRI may precede the clinical manifestation of ASD. These findings support a model of ASD as a condition potentially rooted in prenatal neurodevelopmental divergence. However, larger, standardized, multicenter studies are required before fetal MRI biomarkers can be translated into predictive or clinical applications.
