Determination of reference intervals for serum total calcium in the vitamin d-Replete pediatric population

Context: Widespread vitamin D insufficiency raises concerns regarding the reliability of reference intervals for serum calcium. Objective: We sought to determine the reference intervals for serum total calcium in pediatric subjects without vitamin D [25-hydroxyvitamin D [25(OH)D]] deficiency [20 ng/mL (50 nmol/L)]. Design and Participants: This was a retrospective study of laboratory data obtained from all patients atTheChildren's Hospital of PhiladelphiafromJuly 1, 2011, through June 30, 2012. Patients in the renal unit,theendocrineunit, oracriticalcareunitwereexcluded.Totalserumcalciumwasdeterminedusing a colorimetric assay and serum 25(OH)D was determined by liquid chromatography tandem mass spectrometry. We ascertained 4629 subjects who had a serum 25(OH)D between 20 and 80 ng/mL (50-200 nmol/L) and a serum calcium level determined within 30 days of the 25(OH)D measurement. For comparison, we used data from an unselected cohort of patients (n = 106 220). Results: Parametric analyses generated age-specific reference intervals for serum total calcium for each of several age groups (0-90 d old, 91-180 d old, 181-365 d old, 1-3 y old, 4-11 y old, and 12-19 y old). A two-way ANOVA with Tukey's correction showed significant differences between the lower limits of normal (P <.001) and the normal range (P > .001) but not for the upper limit of normal for these subjects compared with unselected subjects. Student's t tests revealed significant differences at all ages between calcium concentrations in those with 25(OH)D values between 20 and 30 ng/mL and those with 25(OH)D values between 30 and 80 ng/mL. Conclusions: These reference intervals refine previous normal ranges that likely included subjects with vitamin D deficiency. (J Clin Endocrinol Metab 98: E1946-E1950, 2013)