Development of 24-Hour Rhythms in Cortisol Secretion Across Infancy: A Systematic Review and Meta-Analysis of Individual Participant Data.
Level 3 - non-randomized controlled study
Systematic review and individual participant data meta-analysis of observational cohort studies
PubMed 39207206 · doi:10.1210/clinem/dgae590
What was done
Systematic review and individual participant data (IPD) meta-analysis assessing spontaneous, non-stress-induced salivary cortisol concentrations across the first year of life in healthy infants. From 54 identified publications with 29,177 observations, IPD was obtained from 15 cohorts comprising 1,904 infants and 17,079 measurements. Linear mixed-effects modeling (one-stage approach) and cosinor analysis were used to analyze the interaction between infant age and time of day on cortisol concentrations.
What was found
The morning-to-evening salivary cortisol ratio rose significantly from 1.7 (95% CI: 1.3–2.1) at birth to 3.7 (95% CI: 3.0–4.5) at 6 to 9 months of age (P < .0001). Cosinor analysis confirmed the gradual emergence of a 24-hour rhythm from birth, stabilizing between 6 and 9 months.
Why it matters
This defines the timeline for when the physiological 24-hour cortisol rhythm develops in healthy infants, establishing an empirical basis for optimizing the timing and dosing of hydrocortisone replacement therapy in infantile adrenal insufficiency.
Limits
Individual participant data were obtained for only 15 of 54 eligible publications (representing ~58% of total identified measurements), introducing potential selection or cohort-retrieval bias. The abstract does not detail differences in sampling protocols, infant sleep-wake schedules, feeding times, or gestational age.
Cited by
- supports A healthy human circadian rhythm is characterized by a prominent cortisol peak in the morning that gradually subsides throughout the day.