Diurnal cortisol changes in newborn infants suggesting entrainment of peripheral circadian clock in utero and at birth

J Clin Endocrinol Metab. 2013 Jan;98(1):E25-32. doi: 10.1210/jc.2012-2750. Epub 2012 Nov 12.


Background: In the rodent and human fetus, a diurnal cortisol rhythm is observed that is entrained in antiphase to the maternal rhythm. However, after birth, the adrenal circadian rhythm becomes unsynchronized with the clock time, and an adult-type, 24-h rhythm is observed only after a few months. Little is known about when and how the fetal adrenal circadian rhythm is synchronized with the day-night cycle.

Methods: To investigate the function of adrenal circadian clock in the newborn infant, eight serial saliva samples were collected every 3 h over 24 h (starting at 0900 h) in 27 newborn infants.

Results: Cortisol levels were higher during the period 1500 to earlier than 2100 h than during 0900 to earlier than 1500 h and 0300 to earlier than 0900 h (both P < 0.05). Salivary cortisol levels collected during 0 to <6, 6 to <12, and 12 to <18 hours after the clock time at birth (birth time) were higher than those collected during 18 to <24 hours after the birth time (P < 0.005, 0.05, and 0.05, respectively). The acrophase of salivary cortisol was linearly correlated with the birth time within the first 5 d of life (P < 0.005) but not thereafter.

Conclusion: In the newborn infant, diurnal increase in cortisol was observed in the late afternoon and in correspondence with the birth time. The adrenal circadian rhythm acquired in utero may be reentrained by endocrinological events at birth. Such complex regulation of the adrenal circadian clock may inhibit a swift synchronization of the circadian clock to the day-night rhythm.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Circadian Clocks / physiology*
  • Circadian Rhythm / physiology*
  • Cohort Studies
  • Female
  • Gestational Age
  • Humans
  • Hydrocortisone / metabolism*
  • Infant, Newborn / metabolism*
  • Infant, Newborn / physiology
  • Male
  • Parturition / metabolism*
  • Parturition / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Prenatal Exposure Delayed Effects / physiopathology
  • Saliva / metabolism
  • Time Factors


  • Hydrocortisone