Development of cortisol circadian rhythm in infancy

Early Hum Dev. 2003 Aug;73(1-2):39-52. doi: 10.1016/s0378-3782(03)00074-4.


Background and aims: Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not agree on the age of appearance of the circadian rhythm (varying between 2 weeks till the age of 9 months) nor on whether it is related to the appearance of the sleep-wake circadian rhythm. The object of the present study was to find evidence of the age of appearance of the diurnal rhythm of cortisol and to compare the results obtained by several different analysis methods on a new data set.

Design and measures: Cortisol was determined in salival samples of 14 normally developing infants who were followed monthly between the ages of 2 and 5 months. The data were analyzed with several previously published analysis methods as well as with Multilevel Analysis (Hierarchical Linear Modeling).

Results: The previously published analysis methods each produced different results when applied to the current data set. Moreover, our results indicate striking differences between young infants in both age of appearance and stability of the diurnal cortisol rhythm. Also, a link was found between the appearance of the sleep-wake circadian rhythm and the cortisol circadian rhythm. An important intraindividual variability in cortisol levels was found even after correcting for the different variables that affect cortisol (i.e. time of sampling, feeding, etc.).

Conclusions: Although the choice of analysis method influences the age of appearance obtained, our use of HLM shows that the infants' own variability in onset and stability of the cortisol circadian rhythm greatly contributes to the different results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Clocks / physiology*
  • Circadian Rhythm / physiology*
  • Female
  • Humans
  • Hydrocortisone / analysis
  • Hydrocortisone / physiology*
  • Infant
  • Male
  • Models, Statistical
  • Pregnancy
  • Saliva / chemistry
  • Sleep / physiology


  • Hydrocortisone