Age-Dependent Reference Values for hs-Troponin T and NT-proBNP and Determining Factors in a Cohort of Healthy Children (The LIFE Child Study)

Alexandra Kiess,Anja Willenberg,Wieland Kiess,Uta Ceglarek,Antje Körner,Anne Jurkutat,Andreas Hiemisch,Mandy Vogel,Jessica Green,Ingo Dähnert

doi:10.1007/s00246-022-02827-x

Abstract

This study aimed to provide reliable pediatric reference values for N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive Troponin T (hsTnT) obtained from a population of well children and investigate for associations with sex, pubertal status, body mass index (BMI), and serum lipid levels. We analyzed hsTnT and NT-proBNP values obtained from 4826 samples provided by 2522 children aged 0.25–18 years participating in a prospective longitudinal population-based cohort study, “LIFE child” in Leipzig, Germany (Poulain et al., Eur J Epidemiol 32:145–158, 2017). NT-proBNP values decreased throughout childhood from values over 400 ng/L at 3 months to 138 ng/L in females and 65 ng/L in males by 18 years of age. Values dropped rapidly with advancing pubertal stage. We found a strong association between lower NT-proBNP values and higher BMI or elevated serum lipids, the latter effect being more pronounced in males. For hsTnT levels, approximately half of the measurements were below the detection limit. However, 76% of those aged 3 months and 21% of those aged 6 months had values exceeding the adult cut-off limit. Females had slightly higher levels in the first 2 years of life but this was reversed during puberty. In males, there was an upward trend from pubertal stage 2 onward. We identified a positive association between hsTnT and BMI but a negative association with low-density lipoprotein (LDL) cholesterol and triglyceride levels in boys but not in girls. Based on a large number of healthy children, we have established reliable reference values for NT-proBNP and hsTnT for use in everyday clinical practice. We have also identified important associations between certain metabolic and cardiac markers.Clinical Trial Registration ClinicalTrial.gov (NCT02550236).

Highlights

N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive Troponin T are well-established parameters for diagnosing acute and chronic cardiac stress in adults
This study aimed to provide age- and sex-adjusted reference values for high-sensitive Troponin T (hsTnT) and NT-proBNP obtained from a large cohort of healthy infants, children, and adolescents participating in the Leipzig Research Center for Civilization Diseases (LIFE) Child Study [1]
NT-proBNP levels were measured in 4648 blood samples, 58 (1.25%) of which were below the detection limit of 5 ng/L

Summary

Introduction

N-terminal pro-brain natriuretic peptide (NT-proBNP) and high-sensitive Troponin T (hsTnT) are well-established parameters for diagnosing acute and chronic cardiac stress in adults They are commonly applied in pediatric patients, despite lacking reliable reference values for this population. Population-based studies showed consistently negative associations between NT-proBNP and metabolic markers, such as BMI and lipid levels [7–9], whereas the limited data available from pediatric cohorts have not demonstrated this correlation [10, 11]. These divergent findings could be due to different metabolic mechanisms in childhood or secondary to a sampling error from small study participant numbers. The LIFE Child cohort, a population-based cohort from Leipzig, Germany, provides both laboratory and anthropometric measurements from a large number of well children and so adds this important data resource

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