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Identification of Heterogeneous Cortical Thickness Patterns Associated with Prenatal Gestational Diabetes Exposure: A
Insights
Prenatal exposure to gestational diabetes mellitus (GDM) is linked to two distinct brain patterns in youth. These subtypes show varied associations with physical growth, psychiatric conditions, and brain development over time.
Area of Science:
- Neuroscience
- Developmental Biology
- Public Health
Background:
- Prenatal exposure to gestational diabetes mellitus (GDM) is associated with adverse outcomes in offspring.
- The heterogeneity of neuroanatomical patterns in GDM-exposed youth remains unclear.
Purpose of the Study:
- To identify distinct cortical thickness subtypes in GDM-exposed youth.
- To examine associations between these subtypes and anthropometric, neurocognitive, psychiatric/behavioral, and neuroimaging measures.
- To analyze longitudinal developmental trajectories of these subtypes.
Main Methods:
- Utilized the Adolescent Brain Cognitive Development (ABCD)® data, a multisite longitudinal study.
- Applied unsupervised machine learning (Subtype and Stage Inference - SuStaIn) to structural MRI data from 573 GDM-exposed youth and 2854 controls.
- Conducted posthoc longitudinal analyses on a subset of GDM-exposed youth with 1-, 2-, and 4-year follow-ups.
Main Results:
- Identified two distinct cortical thickness subtypes in GDM-exposed youth.
- Subtype 1 showed insula involvement, associated with greater height and weight.
- Subtype 2 exhibited frontal involvement, linked to higher ADHD prevalence, steeper cortical thinning, and a smaller decline in OCD prevalence over time.
Conclusions:
- Gestational diabetes mellitus exposure is associated with two distinct offspring cortical thickness subtypes.
- These subtypes differ in inferred regional ordering patterns and clinical associations.
- One subtype is linked to anthropometric measures, while the other is associated with psychiatric measures and accelerated cortical thinning.
Importance:
Prenatal exposure to gestational diabetes mellitus (GDM) has been associated with adverse metabolic, neurodevelopmental, and psychiatric outcomes in offspring. However, whether GDM-exposed youth exhibit heterogeneous neuroanatomical patterns remains unclear.
Objective:
To identify distinct cortical thickness subtypes among GDM-exposed youth and examine their associations with anthropometric, neurocognitive, psychiatric/behavioral and neuroimaging measures both cross-sectionally and longitudinally.
Design Setting And Participants:
This cohort study used the Adolescent Brain Cognitive Development (ABCD)®data, a multisite longitudinal population study. Subtype and Stage Inference (SuStaIn), an unsupervised machine learning framework, was applied to cross-sectional structural MRI data to identify cortical thickness patterns in 573 GDM-exposed youth and 2854 healthy controls. Posthoc longitudinal analyses included 1,853 observations from a subset of GDM-exposed youth with 1-, 2-, and 4-year follow-up visits to examine subtype differences in developmental trajectories over time.
Exposures:
Prenatal exposure to GDM.
Main Outcomes And Measures:
The primary outcomes included identification of cortical thickness subtypes and their inferred regional ordering patterns. Secondary outcomes included subtype-specific anthropometric, neurocognitive, psychiatric/behavioral and neuroimaging measures.
Results:
The GDM-exposed sample had a mean age of 119.02 ± 7.34 months and was 47.5% female. Two cortical thickness subtypes were identified. Between subtypes, Subtype 1 (63.2%) was characterized by earlier inferred insula involvement and was associated with greater height ( d = 0.36, p FDR < 0.001) and weight ( d = 0.26, p FDR = 0.007), whereas Subtype 2 exhibited earlier inferred frontal involvement and nominally higher Attention-Deficit/Hyperactivity Disorder (ADHD) prevalence ( d = 0.08, p = 0.036), steeper longitudinal cortical thinning across all six cortical regions of interest (β range: -0.05 to -0.13, all p FDR < 0.05), and a smaller decline in Obsessive-Compulsive Disorder (OCD) prevalence over time (β = -1.02, p FDR = 0.049).
Conclusions And Relevance:
GDM exposure was associated with two distinct offspring cortical thickness subtypes, each showing different inferred regional ordering patterns and clinical associations. One subtype showed an insula-cingulate-predominant pattern associated with anthropometric measures, whereas the other showed a frontal-predominant pattern associated with nominally higher psychiatric measures and faster cortical thinning over time.
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