Development of 24-Hour Rhythms in Cortisol Secretion Across Infancy: A Systematic Review and Meta-Analysis of...

Area of Science:

• Endocrinology
• Pediatric Physiology
• Chronobiology

Background:

• Cortisol exhibits a distinct 24-hour rhythm in adults, peaking in the early morning.
• The developmental emergence of this cortisol rhythm during infancy is not well-understood.
• This knowledge gap impacts hydrocortisone replacement therapy for infants with adrenal insufficiency.

Purpose of the Study:

• To characterize the daily variation in salivary cortisol concentrations throughout the first year of life.
• To determine the age at which the infant cortisol rhythm emerges.
• To inform optimal dosing strategies for pediatric hydrocortisone therapy.

Main Methods:

• Systematic review of published literature.
• Individual participant data meta-analysis of spontaneous salivary cortisol concentrations in healthy infants (0-1 year).
• Linear mixed-effects modeling to analyze age and time-of-day interactions on cortisol levels.

Main Results:

• Data from 1904 infants (17,079 measurements) were analyzed.
• The morning/evening cortisol ratio significantly increased from 1.7 at birth to 3.7 by 6-9 months.
• A 24-hour cortisol rhythm gradually emerged during infancy, confirmed by Cosinor analysis.

Conclusions:

• The early-morning cortisol peak develops progressively from birth.
• A stable morning/evening cortisol ratio is established by 6-9 months of age.
• Findings have significant implications for managing hydrocortisone replacement therapy in infants.