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Age- and sex-specific upper reference limits for cardiac biomarkers in Chinese children and adolescents: a
Kainan Dong1,2, Jinfang Xing1,2, Yanpeng Dai1,2
1Department of Laboratory Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Insights
This study establishes crucial upper reference limits for pediatric cardiac biomarkers, including high-sensitivity cardiac troponin T (hs-cTnT), creatine kinase-MB (CK-MB) mass, and N-terminal pro-B-type natriuretic peptide (NT-proBNP). These findings aid in diagnosing cardiovascular diseases in children.
Area of Science:
- Pediatric Cardiology
- Clinical Biochemistry
- Biomarker Research
Background:
- Cardiac biomarkers are vital for diagnosing myocardial injury in children, but established upper reference limits are lacking.
- Accurate reference limits are essential for effective disease diagnosis and health assessment in pediatric populations.
- Previous studies have not comprehensively defined pediatric reference limits for key cardiac biomarkers.
Purpose of the Study:
- To establish age- and gender-specific upper reference limits for hs-cTnT, CK-MB mass, and NT-proBNP in healthy children and adolescents.
- To provide a foundational dataset for the accurate interpretation of cardiac biomarker levels in pediatric cardiovascular disease screening and diagnosis.
- To address the critical knowledge gap regarding normal pediatric ranges for these essential cardiac markers.
Main Methods:
- Prospective collection of 1,797 serum samples from healthy individuals aged 0-18 years.
- Analysis of hs-cTnT, CK-MB mass, and NT-proBNP concentrations using Roche cobas e411 analyzer.
- Calculation of upper reference limits and 90% confidence intervals following Clinical and Laboratory Standards Institute C28-A3 guidelines.
Main Results:
- Established age-specific upper reference limits for hs-cTnT, CK-MB mass, and NT-proBNP in healthy children (0-18 years).
- Observed higher biomarker levels in neonates, with gradual declines in concentration with increasing age, particularly within the first year.
- Identified gender-specific differences in hs-cTnT and CK-MB mass concentrations in older children and adolescents (10-18 years), with higher levels in boys.
Conclusions:
- Successfully established the first comprehensive upper reference limits for hs-cTnT, CK-MB mass, and NT-proBNP in a healthy Chinese pediatric cohort.
- The findings provide essential age- and gender-specific reference ranges crucial for the accurate diagnosis and management of pediatric cardiovascular conditions.
- These established limits will significantly support medical institutions in the preliminary screening, diagnosis, and treatment of pediatric cardiovascular diseases.
Abstract:
Cardiac biomarkers are being increasingly applied in pediatric populations, including those with cardiogenic and non-cardiogenic myocardial injury disease. The upper reference limits of biomarkers are an important reference for disease diagnosis and health evaluation. However, the upper reference limits of pediatric cardiac biomarkers remains unknown. A total of 1,797 serum samples were collected prospectively from healthy respondents aged 0 to 18 years old. These samples were analyzed using Roche cobas e411 to determine the concentrations of hs-cTnT, CK-MB mass, and NT-proBNP. The upper reference limits and 90% confidence interval were calculated according to Clinical and Laboratory Standards Institute C28- A3 guidelines. The study successfully established the upper reference limits for hs-cTnT, CK-MB mass, and NT-proBNP in healthy children and adolescents aged 0 to 18. The hs-cTnT, CK-MB mass, and NT-proBNP levels were visibly higher in neonatal serum. With the increase in age, hs-cTnT, CK-MB mass, and NT-proBNP decline gradually. They decrease quickly in the first year after birth and decrease slowly after 1 year old. Gender differences were observed in the concentrations of hs-cTnT and CK-MB mass among healthy children and teenagers aged 10 to 18 and 13 to 18. Specifically, boys had relatively higher concentrations of hs-cTnT and CK-MB mass. However, no gender difference was found in NT-proBNP concentration. The concentrations of hs-cTnT, CK-MB mass, and NT-proBNP were simultaneously tested in healthy Chinese children for the first time. The specific upper reference limits of age and gender in pediatrics were established. The results provide comprehensive references for medical institutions specializing in children's healthcare, which are conducive to preliminary screening, diagnosis, and treatment of pediatric cardiovascular diseases.
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