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Biomarkers and neurodevelopment in perinatally HIV-infected or exposed youth: a structural equation model analysis
Suad Kapetanovic1, Ray Griner, Bret Zeldow
1aNational Institute of Mental Health, National Institutes of Health, Bethesda, Maryland bDepartment of Biostatistics, Harvard School of Public Health, Boston, Massachusetts cDepartment of Neurosciences, University of California San Diego, San Diego, California dCenter for Neural Development and Disease, University of Rochester Medical Center, Rochester, New York eUniversity of Miami Miller School of Medicine, Miami, Florida fEunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland gDivision of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida hFeinberg School of Medicine, Northwestern University, Chicago, Illinois iDepartment of Psychiatry, Boston Children's Hospital, Boston, Massachusetts, USA.
Insights
Vascular dysfunction markers, specifically fibrinogen, CRP, and IL-6, are linked to slower processing speed in youth with and without HIV. This finding highlights potential biomarkers for neurodevelopmental outcomes in these populations.
Area of Science:
- Neuroscience
- Immunology
- Pediatrics
Background:
- Perinatally HIV-infected (PHIV+) youth face unique neurodevelopmental challenges.
- Vascular dysfunction is increasingly recognized as a factor impacting brain health.
- Understanding these links is crucial for early intervention and improved outcomes.
Purpose of the Study:
- To investigate the association between vascular dysfunction markers and neurodevelopmental outcomes.
- To compare these associations in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth.
- To identify potential latent biomarkers for cognitive function in youth.
Main Methods:
- A cross-sectional analysis of 342 youth (212 PHIV+, 130 PHEU) from a US-based cohort.
- Assessment of nine vascular biomarkers (e.g., CRP, fibrinogen, IL-6, adhesion molecules).
- Factor analysis to group biomarkers and structural equation modeling (SEM) to link biomarker factors with WISC-IV cognitive scores.
Main Results:
- Nine biomarkers clustered into three factors; adiponectin showed minimal correlation.
- A significant negative association was found between Factor 1 (fibrinogen, CRP, IL-6) and processing speed.
- This association persisted after adjusting for HIV status and confounders in both total and PHIV+ cohorts.
Conclusions:
- Aggregate measures of fibrinogen, C-reactive protein (CRP), and interleukin-6 (IL-6) may represent a latent biomarker.
- This biomarker is associated with reduced processing speed in both PHIV+ and PHEU youth.
- These findings suggest potential targets for monitoring and improving cognitive function in at-risk youth.
Objective:
To examine the relationship between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected (PHIV+) and perinatally HIV-exposed but uninfected (PHEU) youth.
Design:
Cross-sectional design within a prospective, 15-site US-based cohort study.
Methods:
Neurodevelopmental outcomes were evaluated in relation to nine selected vascular biomarkers in 342 youth (212 PHIV+, 130 PHEU). Serum levels were assessed for adiponectin, C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), soluble vascular cell adhesion molecule-1 (sVCAM-1), E-selectin (sE-selectin), monocyte chemoattractant protein (sMCP-1), intercellular adhesion molecule-1 (sICAM-1), and P-selectin (sP-selectin). The Wechsler Intelligence Scale for Children-Fourth Edition (WISC-IV) was administered at entry, yielding a Full-Scale IQ score, and four index scores. Factor analysis was conducted to reduce the biomarkers to fewer factors with related biological roles. Structural equation models (SEMs) were used to measure associations between resulting factors and WISC-IV scores.
Results:
Mean participant age was 11.4 years, 54% were female, 70% black. The nine biomarkers were clustered into three factor groups: F1 (fibrinogen, CRP, and IL-6); F2 (sICAM-1 and sVCAM-1); and F3 (MCP-1, sP-selectin, and sE-selectin). Adiponectin showed little correlation with any factor. SEMs revealed significant negative association of F1 with WISC-IV processing speed score in the total cohort. This effect remained significant after adjusting for HIV status and other potential confounders. A similar association was observed when restricted to PHIV+ participants in both unadjusted and adjusted SEMs.
Conclusion:
Aggregate measures of fibrinogen, CRP, and IL-6 may serve as a latent biomarker associated with relatively decreased processing speed in both PHIV+ and PHEU youth.
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