LC-MS/MS-based reference intervals for hair cortisol in healthy children

Background: Human scalp hair is a valuable matrix for determining long-term cortisol concentrations, with wide-spread applicability in clinical care as well as research. However, pediatric reference intervals are lacking. The aim of this cross-sectional study is to establish age-adjusted reference intervals for hair cortisol in children and to gain insight into hair growth velocity in children up to 2 years old. Methods: A total of 625 healthy children were enrolled through recruitment in pregnancy, infant-welfare clinics, and school visits. Scalp hair cortisol levels were measured using liquid chromatography-tandem mass spectrometry. Age-adjusted reference intervals were established in children from birth to 18 years old. Hair growth velocity was determined in children 0−2 years of age by measuring hair length at 4- to 10-week intervals. Results: Hair cortisol levels were high (162.4 pg/mg, 2.5th-97.5th percentile: 28.8–961) after birth with a sharp fall in the first 3 months of life. This is followed by lower values until age 6 and then by graduated and subtle higher values to adult concentrations are reached at the age of 18 years (3.0 pg/mg, 2.5th-97.5th percentile: 0.53–17.8). Average hair growth velocity measured in mm/month was significantly lower in infants 0–6 months of age compared to children 12–24 months (3.5 versus 9.4, P < 0.001). Conclusions: This is the first study to provide age-adjusted reference intervals for hair cortisol in children from 0−18 years. Higher hair cortisol concentrations in infants might be explained by the significantly lower hair growth rate in the first year of life. The establishment of pediatric hair cortisol reference ranges broadens the potential applications of this biomarker in pediatric clinical care.

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