Abstract 4359925: Brain-Derived Exosomal Biomarkers of Neuroinflammation and Brain Iron Deficiency in Infants with Critical Congenital Heart Disease: A Pilot Study
Bibliographic record
Abstract
Background: Up to 50% of infants with critical congenital heart disease (CCHD) experience neurodevelopmental delay, potentially due in part to neuroinflammation and iron deficiency. These factors contribute to long-term neurodevelopmental disorders in preterm infants, but it is unclear whether similar mechanisms occur in CCHD and thus represent intervention targets. To address knowledge gaps about brain inflammation and iron status in CCHD, we developed a novel, non-invasive method to isolate brain-derived exosomes (BDEs) from peripheral blood using contactin-2 (CNTN2), a brain-specific glycoprotein. BDEs cross the blood-brain barrier and carry biomarkers reflecting their origin. Aim: Determine the feasibility of isolating plasma BDEs and assessing therein markers for neuroinflammation and iron status in infants with CCHD. Methods: This pilot study included infants ≤6 months old with transposition of the great arteries (TGA) or hypoplastic left heart syndrome (HLHS), using plasma from the Heart Centre Biobank (Toronto). CNTN2+ BDEs were isolated via size exclusion spin columns, enriched by immunoprecipitation, and analyzed for size, concentration, and integrity. BDE contents were assessed with a validated (for clinical use) panel of cytokines, chemokines, iron, and brain biomarkers. Analysis included data visualization and Pearson’s correlation matrix to explore relationships and compare results to published BDE values of healthy newborns from mothers with or without overweight/obesity (OWO). Results: Infants (n=11; 5 HLHS, 6 TGA) were 55% female and mean age 3.7 months. Compared to healthy newborns (Fig. 1), infants with CCHD had higher ferritin and lower transferrin and S100B. While peripheral CRP (850.16 ± 637.94 ng/mL) was elevated, BDE CRP was lower compared to healthy newborn groups. BDE Ferritin was positively correlated (Fig. 2) with PARK7, a cell metabolism marker, and TfR correlated with S100B (reflects astrocytosis). Conclusions: Assessing BDE biomarkers in infants with CCHD is feasible. In this small cohort, preliminary results showed that CCHD iron biomarker patterns aligned with those in newborns of mothers with OWO, an inflammatory condition that sequesters iron as ferritin. Further research is warranted to determine if patterns of low BDE CRP (amid systemic inflammation), reduced S100B, and higher BDNF (a nerve growth factor), are replicated in larger CCHD cohorts, and if BDE inflammation and iron biomarkers can indicate neurodevelopmental deficits.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".