Continuous reference intervals for high-sensitivity cardiac troponin T in children: a closed-form approach with zlog transformation
Inga M. Trulson, Georg Hoffmann, Khosrow Adeli, Mandy Vogel, Alexandra Kiess, Jonas Palm, Peter Ewert, Stefan Holdenrieder, Frank KlawonnAbstract
Objectives
Age-dependent physiology makes interpreting high-sensitivity cardiac troponin T (hsTnT) challenging in early childhood. Values below the analytical limit create left-censored data, complicating reference interval (RI) estimation.
Methods
We combined two paediatric cohorts (CALIPER, n=277; LIFE Child, n=1,358; ages 0–10 years) to derive continuous, age-dependent hsTnT RIs. Empirical quantiles were estimated using a sliding-window approach and fitted with four-parameter logistic functions. To address the high proportion of values below the analytical limit of detection (LOD; 3 ng/L), the 2.5th percentile was inferred from the 65th and 97.5th percentiles assuming lognormal distribution. A closed-form zlog transformation was established to standardise hsTnT values. Pointwise 95 % bootstrap confidence bands (100,000 stratified resamples) were computed for both reference limits.
Results
HsTnT concentrations declined steeply during infancy and stabilised at low levels thereafter, with 46 % of samples below the analytical limit. The closed-form approach modelled reference limits according to the following logistic equation
Conclusions
We present the first continuously modelled, closed-form RIs and corresponding zlog-transformation for paediatric hsTnT (ages 0–10 years). This framework enables direct LIS/EHR deployment without specialized software and facilitates age-independent interpretation and longitudinal monitoring in paediatric cardiology.