Reference Interval Corner
Cardiac Troponin in Pediatrics
Shannon Haymond, PhD, DABCC
Director, Clinical Chemistry and Mass Spectrometry, Ann & Robert H. Lurie Children’s Hospital of Chicago
The indications for measurement of cardiac troponin (cTn) in pediatrics include evaluation of chest pain (in patients who were previously healthy and those with known history of cardiac disease) and monitoring for cardiac injury in patients administered cardiotoxic drugs and those undergoing cardiac surgery. The most common reasons for chest pain in pediatrics are not cardiac in origin; however, ruling out cardiac causes is necessary and this may warrant measurement of cTn. Additionally as assays improve and more data is collected using high sensitivity cTn (hs-cTn) assays, it is clear that the presence of detectable cTn in blood is not necessarily pathologic or reflective of myocyte injury (1).
What is an elevated cTn in children?
Few cTn reference range studies exist but large, longitudinal pediatric reference interval studies using current and state-of-the-art assays are beginning to investigate this question (2,3,4). A previous study has also shown that there is age dependence, where cTn is highest in newborns and decreases over the first several months of life (5). In a survey on utilization of cTn, 24 pediatric hospitals indicated that 55% use a cutoff validated internally, 40% use the 99th% cutoff defined by their assay manufacturer and 5% use the 10% CV defined by their assay manufacturer (unpublished results). The third universal definition of myocardial infarction describes the cutoff for increased cTn concentration as a value exceeding the 99th percentile of a normal reference population (6). An obvious question is whether or not the 99th% values are applicable to a pediatric population, since there were likely few pediatric patients included in the method validation set and reports are clear that the selection of the population is critical to establishing a relevant cutoff (7,8,9). Recent data from the CALIPER study using a cTnI assay is shown in Table 1 (4). There was no difference between genders but an age-dependent increase was observed. Calculation of the 99th% in this population shows that the 99th% cutoff provided in the manufacturer’s package insert for the assay used in the study is reasonable for children older than 3 months. Data reported from the Australian LOOK study using a hs-cTnI assay, highlights the importance of population selection on establishing the 99th% cutoff and reveals that transient illness in otherwise healthy children (8, 10 and 12 y) caused elevations in hs-cTnI above the 99th% cutoff (2). These authors further examined the distribution of hs-cTnI after exclusion of 2 data points due to transient illness and found that in both males and females, the distribution was Gaussian (3). The authors conclude that there is a background physiological release of troponin and that in a truly healthy population concentrations of hs-cTnI can be described by a Gaussian distribution. This suggests that a traditional 95% reference interval may be applicable for cTn in children. In current practice, there is a high degree of variability around how cutoffs are being defined for cTn in pediatrics but as data is collected from large cohorts of healthy children, we will continue to understand what is ‘normal’ for cTn in children. This information will be of particular importance given the fact that elevations in cTn indicating myocyte damage will be rare in the pediatric population with chest pain. Many pediatric hospital labs are using cutoffs that exceed the 99th% because of this reason, so transitions to lower cutoffs will need to be evaluated and managed carefully.
Table 1. Reference ranges for cTnI using Abbott ARCHITECT i2000 assay in healthy children of the CALIPER study. (Clin Chem. 2013 Sep;59(9):1393-405.)
** Corresponding 99th percentiles for TnI obtained by linear interpolation: 968 ng/L (5 days to <15 days); 59 ng/L (15 days to <3 months); 21 ng/L (3 months to <19 years).
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