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

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).

Keywords: Cardiac biomarkers; NT-ProBNP; Pediatric percentiles; Troponin T.

Fig. 1

New NT-proBNP percentiles in the pediatric population from the LIFE Child Study cohort (n = 2489). 5th, 50th (median), 75th, 95th, and 97.5th (cut-off) percentiles for females and males showing a significant age-dependent decline and generally higher values in females. NT-proBNP levels were determined with ECLIA, Cobas Roche (n = 4648)

Fig. 2

Influence of pubertal stage on NT-proBNP levels in the LIFE Child Study cohort. Box-plots represent the 25th and 75th percentiles (boxes) and 50th percentile (mid line). NT-proBNP levels were higher in girls than in boys with an increasing effect in advancing puberty and dropped significantly in both genders again with an increasing effect in ongoing puberty until stage 4, from where only levels in males decreased further. NT-proBNP levels were determined with ECLIA, Cobas Roche (n = 2537)

Fig. 3

New hs-Troponin T percentiles in the pediatric population from the LIFE Child Study cohort (n = 2489). 5th, 50th (median), 75th, 95th, and 97.5th (cut-off) percentiles for females and males showing a significant age-dependent decline in the first year of life and generally values below the adult cut-off, as well as a surprising rise in teenage boys. hs-Troponin T levels were determined with ECLIA, Cobas Roche (n = 4337)

Fig. 4

Influence of pubertal stage on hs-Troponin levels in the LIFE Child Study cohort. Box-plots represent the 25th and 75th percentiles (boxes) and 50th percentile (mid line). Hs-Troponin levels were lower in females with an increasing effect during puberty and rose from pubertal stage 2 onward in males. Levels were determined with ECLIA, Cobas Roche (n = 2453, levels of children older than 6 years of age)

Fig. 5

NT-proBNP and hs-Troponin T levels above the 90th percentile increase the probability of the alternate marker to be above the 90th percentile. Our study cohort showed no direct correlation between NT-proBNP and hs-Troponin T values, but an increasing probability of levels above the 90th percentile for NT-proBNP, respectively, hs-Troponin T, when the other marker was above the 97th versus the 90th percentile