B-120 Reference Interval (RI) Estimation for Pediatric Magnesium using an Indirect Method with Unsupervised Machine Learning Tool and Programming Language
Authors: Canali D , Vieira L , Santos B , Lopes A , Muller K , Sabino C , Dias C 
Published: October 2024

Abstract

Background
Magnesium is an important intracellular component present in all enzymatic reactions involving Adenosine Triphosphate (ATP) utilization, with the majority stored in bones. In the blood, it exists as a free fraction and another bound to proteins. Regulation occurs through renal processes, and for this reason, hypermagnesemia is associated with renal insufficiency, compromising the central nervous system. On the other hand, hypomagnesemia cases are related to pancreatitis, intestinal malabsorption, childhood malnutrition, among other factors. Following complaints from pediatric doctors that our reference intervals (RI), as suggested by the manufacturer, would yield falsely elevated results in healthy patients, we estimated a new RI in the population served

Methods
We employed data mining followed by estimation using an indirect method through the LabRI™ algorithm with parametric, non-parametric, and robust statistical treatments for outlier exclusion, implemented in the R language. Latent abnormal values of outpatient pediatric patients were considered. We defined three pediatric partitions for both sexes, aged 0 to 6 years, 7 to 12 years, and above 12 years, using the comparative RI described by the Roche manufacturer. Data were extracted from our Data Lake between January and December 2022 in the Federal District of Brazil, from a laboratory part of a large network. Exclusion criteria included: Potassium &gt; 5.5 and &lt; 3.0 mmol/L; Phosphorus &gt; 8.0 and &lt; 1.5 mg/dL; Total Calcium &gt; 12 mg/dL and &lt; 7 mg/dL; Ionized Calcium &gt; 1.5 mmol/L and &lt; 0.8 mmol/L; Creatinine &gt; 2.0 mg/dL; C-reactive protein (CRP) &gt; 10 mg/dL; Ferritin &gt; 700 ng/mL; A1C &gt; 7.0%; LDL Cholesterol &gt; 200 mg/dL; Magnesium repeated within &lt; 12 months, and samples of hospital origin.

Results
The evaluated population after exclusion criteria totaled 6,865 children, distributed as follows: 26.0% aged 0 to 6 years, 30.3% aged 7 to 12 years, and 43.7% above 12 years. Outliers were excluded in 1.5%, 0.9%, and 1.0%, respectively. In all partitions, there was a significant discrepancy compared to the reference intervals recommended by Roche. In our estimation, there was an expansion of the upper limit of the reference interval in all partitions, supporting the clinical opinion. The new reference intervals became: 0-6 yrs: from 1.7-2.3 to 2.0-2.7; 7-12 yrs: from 1.7-2.1 to 2.0-2.6; and &gt;12 yrs: from 1.7-2.2 to 1.9-2.6. The standard deviation varied between 0.19 and 0.20, and the median between 2.20 and 2.32

Conclusions
The manufacturer states in the package insert that they did not assess the RI for the pediatric population and that each laboratory should verify the RI in the population served. We approve the adoption of the estimated RI for the pediatric population calculated by the LabRI™ tool in the partitions of 0-6 years, 7-12 years, and &gt;12 years, stating in the report “Reference interval established by an indirect method in 6865 children tested in the laboratory, partitioned by age group.”