C3-Epimer Inclusion Influences Vitamin D Deficiency Classification Near Diagnostic Thresholds in Early Childhood.

Area of Science:

• Pediatric Endocrinology
• Nutritional Biochemistry
• Clinical Diagnostics

Background:

• Vitamin D deficiency in early childhood is typically diagnosed using fixed 25(OH)D thresholds (<20 ng/mL).
• The C3-epimer (3-epi-25(OH)D3) can influence total 25(OH)D measurements, potentially affecting deficiency classification in children with borderline levels.

Purpose of the Study:

• To evaluate the impact of including the C3-epimer in total 25(OH)D measurements on vitamin D deficiency classification in young children.
• To assess the diagnostic performance of epimer-resolved 25(OH)D measurements compared to total 25(OH)D.

Main Methods:

• A cross-sectional study involving 128 children aged 0-36 months.
• Quantification of vitamin D metabolites using LC-MS/MS in dried blood spot samples.
• Comparison of deficiency classification with and without C3-epimer subtraction, using Cohen's κ and McNemar's test.

Main Results:

• 57% of children were initially classified as vitamin D deficient (<20 ng/mL).
• Excluding the C3-epimer led to reclassification in 17.2% of children, with a significant systematic shift (p < 0.001).
• Misclassification was most pronounced in children with borderline 25(OH)D3 concentrations (18-22 ng/mL), where 54.5% were reclassified.

Conclusions:

• Inclusion of the C3-epimer in total 25(OH)D assays can lead to clinically relevant misclassification of vitamin D deficiency in young children, especially near diagnostic cutoffs.
• Epimer-resolved assessment of 25(OH)D may enhance diagnostic precision for identifying vitamin D status in pediatric populations with borderline concentrations.