Establishing Pediatric and Adult RBC Reference Intervals With NHANES Data Using Piecewise Regression

OBJECTIVES: To develop age- and sex-specific RBC reference intervals using the National Health and Nutrition Examination Survey (NHANES) 1999 to 2012, a large nationally representative, population-based, cross-sectional database (n = 44,328). METHODS: Comprehensive medical data were used to define a “healthy” population. Reference intervals for RBC count, hemoglobin, hematocrit, mean cell hemoglobin, mean cell hemoglobin concentration, mean cell volume, and red cell distribution width were computed using piecewise regression, an evidence-based statistical procedure that identifies breakpoints. RESULTS: The derived reference intervals were sex specific, unlike many current standards, and more precise for individuals of different ages, especially for children, adolescents, and elderly individuals, as additional breakpoints were detected for these groups. Suggested reference values for hematocrit and hemoglobin of older adult males were substantially lower than current values. CONCLUSIONS: The reference intervals provided here, based on a large, nationally representative healthy population, contribute to the ongoing transition to precision medicine.