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Validity of establishing pediatric reference intervals based on hospital patient data: a comparison of the modified
Julie L V Shaw1, Ashley Cohen2, Danijela Konforte1
1Clinical Biochemistry Division, Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, University of Toronto, Toronto, ON, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada.
Insights
Pediatric reference intervals derived from hospital data were generally wider than those from healthy children. Hospital-derived intervals may serve as a guide but do not replace healthy population data for establishing pediatric reference ranges.
Area of Science:
- Clinical chemistry
- Pediatric laboratory medicine
- Reference interval determination
Background:
- Establishing accurate pediatric reference intervals is crucial for diagnosing and monitoring health conditions in children.
- The CALIPER study provided a comprehensive set of pediatric reference intervals based on healthy community samples.
- Hospital-based patient data offers a readily available alternative source for calculating reference intervals.
Purpose of the Study:
- To compare pediatric reference intervals derived from hospital-based patient data with those established by the CALIPER study using healthy children.
- To evaluate the utility of hospital data for generating pediatric reference intervals.
Main Methods:
- Utilized hospital-based data for 13 analytes (e.g., calcium, creatinine, bilirubin) measured on the Vitros 5600 analyzer.
- Applied statistical methods including outlier removal (Tukey method), cumulative distribution function (cdf) analysis, and piecewise regression (R software).
- Calculated reference intervals using the inverse cdf of a standard Gaussian distribution and compared them to CALIPER intervals using 90% confidence intervals and Reference Change Value (RCV).
Main Results:
- Reference intervals calculated from hospital data were generally wider than those from the CALIPER study.
- None of the hospital-derived reference intervals fully fell within the 90% confidence intervals established by CALIPER.
- Validation using reference samples measured on the Vitros 5600 analyzer was performed.
Conclusions:
- Pediatric reference intervals derived from hospital-based data can be a useful guide in certain situations.
- These hospital-derived intervals are unlikely to fully replace the need for reference intervals established from healthy pediatric populations.
- Further investigation into the application of hospital data for reference interval calculation is warranted.
Objectives:
To compare pediatric reference intervals calculated using hospital-based patient data with those calculated using samples collected from healthy children in the community as part of the CALIPER study.
Methods:
Hospital-based data for 13 analytes (calcium, phosphate, iron, ALP, cholesterol, triglycerides, creatinine, direct bilirubin, total bilirubin, ALT, AST, albumin and magnesium), measured on the Vitros 5600, collected between 2007 and 2011 were obtained. The data for each analyte were partitioned by age and gender as previously defined by the CALIPER study. Outliers in each partition were removed using the Tukey method. The cumulative distribution function (cdf) was then determined for each analyte value following which, the inverse cdf values of a standard Gaussian distribution were calculated. The analyte values were plotted against the inverse cdf of the standard Gaussian distribution. Piece-wise regression determined the linear portion of the resulting graph using the statistical software R. Linear regression determined an equation for the linear portion in each partition and reference intervals were calculated by extrapolating to identify the 2.5th and 97.5th centiles in each partition based on the inverse cdf values (which would correspond to the values -1.96 and 1.96 of the Gaussian distribution). Using the 90% confidence intervals for the reference intervals defined by CALIPER and the Reference Change Value (RCV) as the criteria, these calculated reference intervals were compared to those reported previously by CALIPER. Reference samples were also measured on the Vitros 5600 analyzer in an attempt to validate the calculated reference intervals.
Results:
In general, the reference intervals calculated from hospital-based data were generally wider than those calculated by CALIPER. None of the reference intervals calculated using the Hoffmann approach fell completely within the 90% confidence intervals calculated by CALIPER.
Conclusions:
These results suggest that calculating pediatric reference intervals from hospital-based data may be useful, as a guide, in some cases but will likely not replace the need to establish reference intervals in healthy pediatric populations.
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