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Continuous reference intervals for high-sensitivity cardiac troponin T in children: a closed-form approach with zlog

Inga M Trulson1, Georg Hoffmann1, Khosrow Adeli2

  • 1Munich Biomarker Research Centre, Institute of Laboratory Medicine, TUM University Hospital German Heart Center, Munich, Germany.

Clinical Chemistry and Laboratory Medicine
|June 19, 2026
PubMed

Insights

This study developed new continuous reference intervals for high-sensitivity cardiac troponin T (hsTnT) in children aged 0-10 years. A novel z-score transformation allows for age-independent interpretation of hsTnT levels in pediatric cardiology.

Area of Science:

  • Biochemistry
  • Pediatric Cardiology
  • Clinical Chemistry

Background:

  • Interpreting high-sensitivity cardiac troponin T (hsTnT) in children is challenging due to age-dependent physiology and left-censored data below the analytical limit.
  • Establishing accurate reference intervals (RIs) for hsTnT in early childhood is crucial for reliable clinical interpretation.

Purpose of the Study:

  • To derive continuous, age-dependent hsTnT reference intervals (RIs) for children aged 0-10 years.
  • To develop a standardized method for interpreting hsTnT values, addressing challenges posed by data below the limit of detection.

Main Methods:

  • Combined two pediatric cohorts (CALIPER and LIFE Child) with a total of 1,635 participants (ages 0-10 years).
  • Employed a sliding-window approach with logistic functions to estimate empirical quantiles and derive continuous RIs.
  • Inferred the 2.5th percentile from higher percentiles assuming lognormal distribution to handle left-censored data.
  • Developed a closed-form z-score transformation to standardize hsTnT values and remove age dependency.

Main Results:

  • HsTnT concentrations showed a steep decline in infancy, stabilizing at low levels, with 46% of samples below the analytical limit of detection.
  • The derived logistic model provided continuous reference limits for hsTnT across the 0-10 year age range.
  • The z-score transformation effectively normalized hsTnT values, with over 95% falling within the theoretical reference range (-1.96 to +1.96).

Conclusions:

  • Presented the first continuously modeled, closed-form reference intervals and z-score transformation for pediatric hsTnT (ages 0-10 years).
  • The developed framework facilitates direct integration into Laboratory Information Systems (LIS) and Electronic Health Records (EHR).
  • Enables age-independent interpretation and longitudinal monitoring of hsTnT in pediatric cardiology.
Abstract

Keywords:
age-dependent biomarkerscontinuous modellinghigh-sensitivity cardiac troponin Tlimit of detectionpaediatric reference intervalszlog

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