Indirect Reference Intervals of Serum Calcium in Pakistani Children Using KOSMIC, Bhattacharya, and Hoffman Approach

Background: Reference intervals (RIs) of serum calcium vary based on age, population demographics, and meth-ods of assessment. However, conventional approaches to establish serum calcium (Ca)RIs pose ethical and practi-cal challenges, especially in the pediatric population. Hence, the use of indirect approaches is beneficial. This study was carried out to estimate the RIs of serum Ca using three indirect approaches in the pediatric and adoles-cent population of Pakistan. Methods: Data mining laboratory information systems, for serum Ca results from 2013 - 2021 was done on a tar-get population ranging from birth to 18 years of age. The population was grouped into three categories based on age (birth - 1 year, 2 - 4 years, and 5 - 18 years), as defined previously by Tahmasebi et al. in the CALIPER co-hort. Pre-validated indirect algorithms, 'KOSMIC', Bhattacharya, and Hoffman, were used for analyzing the RIs. Results: A total of non-duplicate 40,914 serum Ca tests were retrieved over a period of 6 years, including 38.7% (n = 15,830) from birth - 1 year, 16.3% (n = 6,641) from > 1 - 4 years, and 45.2% (n = 18443) from > 4 - 18 years respectively. The three methods revealed comparable performance with the direct RIs reported by Tahmasebi et al. in the CALIPER cohort. Keeping a stringent total allowable error of 1 mg/dl for Serum Ca as given by Clinical Laboratory Improvement Amendments (CLIA) the KOSMIC method outperformed the other two when com-pared to Tahmasebi, Houman, et al. Conclusions: The study advocates the use of the indirect approach for calculating RIs for serum calcium in the pe-diatric population, especially to aid clinical decision making in a low resource setting, due to its ability to repro-duce results in line with the direct approach in a more economical, practical, and feasible way.