Redefining normal bone and mineral clinical biochemistry reference intervals for healthy infants in Canada

• Normative reference interval data for infants are sparse.
• Plasma minerals and alkaline phosphatase declined from 1 to 12 months of age.
• Plasma creatinine increased from 1 to 12 months of age.
• Data was pooled by age category to generate LMS smoothed centile curves.
• Age-specific reference intervals for infants will reduce misclassification.

BackgroundFew normative data exist for routine clinical chemistry in healthy term infants, that is, during a time of rapid development. Biochemical markers are significantly affected by these physiological changes and the lack of appropriate reference intervals may impede diagnostics in infants.ObjectiveTo define reference intervals for calcium, phosphate, creatinine, and alkaline phosphatase in infants from 1 to 12 months of age.Design and methodsThis was an unblinded secondary analysis of 132 breastfeeding infants participating in a vitamin D3 supplementation trial (400–1600 IU/d) followed prospectively until 1 year of age (NCT00381914). Serial non-fasting capillary and spot urine samples were collected for the measurement of plasma calcium, phosphate, creatinine, and alkaline phosphatase; urinary calcium, phosphate and creatinine (DxC600 Beckman Coulter); and whole-blood ionized calcium (ABL 725 Radiometer). All visits were conducted at McGill University in Montréal, Canada.ResultsAll analytes changed significantly over time (p < 0.05), but there was no effect of sex. From 1 to 12 months, values decreased for whole-blood ionized calcium; plasma calcium, phosphate, and alkaline phosphatase; and urinary calcium:creatinine. Plasma creatinine increased. For some analytes, particularly calcium and alkaline phosphatase, values were often above the ‘typical’ adult or older child reference limits. Smoothed centile curves (LMS method) were developed to fill existing gaps in normative data for these analytes.ConclusionsMost analytes showed a significant change from 1 to 12 months, confirming the need for age-specific reference values. These data can assist in the generation of new reference intervals for healthy term infants and ultimately improve the care of children.