Comprehensive Pediatric Reference Limits for High-Sensitivity Cardiac Troponin I and NT-proBNP in the CALIPER Cohort
Bibliographic record
Abstract
BACKGROUND: Cardiac biomarkers have increasing application in pediatric populations, including congenital heart disease, myocarditis, and heart failure. Clinical practice is limited by evidence gaps in pediatric reference limits to inform clinical decision-making. The current study aimed to establish comprehensive pediatric reference limits for N-terminal (NT)-pro hormone brain natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin I (hs-cTnI) in the CALIPER cohort of healthy children and adolescents. METHODS: Analytical immunoassay performance was assessed through precision, linearity, and method comparison (Abbott Alinity ci system). Subsequently, approximately 200 serum samples collected from apparently healthy children (birth to 18 years) were analyzed for hs-cTnI and NT-proBNP. Reference limits (2.5th, 97.5th, and 99th percentiles) were established as per Clinical and Laboratory Standards Institute EP-28A3c guidelines with associated 90% confidence intervals. RESULTS: Of all pediatric serum samples analyzed, 46% had detectable hs-cTnI concentrations (limit of detection: 1.3 ng/L). Both hs-cTnI and NT-proBNP demonstrated markedly elevated neonatal concentrations with 99th percentiles of 55.8 and 1785 ng/L, respectively. No statistically significant age-specific differences were observed beyond 1 year of age across all cardiac biomarkers examined. No sex-specific association was observed between hs-cTnI and NT-proBNP concentration and adolescence. CONCLUSIONS: We report age-specific reference limits for hs-cTnI and NT-proBNP in a healthy Canadian cohort of children and adolescents measured using Alinity immunoassays for the first time. These data support the need for pediatric-specific interpretation to reduce misinformed clinical decision-making and calls to action larger cohort studies such that reference limits can be more robustly defined.
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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 | 0.005 | 0.007 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".