Measurement of Salivary Cortisol for Revealing Age-Specific Dependence of Cortisol Levels on Time, Feeding, and Oxygen Metabolism in Newborn Infants

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Salivary cortisol is widely used to assess stress and circadian rhythms, yet its control variables in neonates, particularly regarding postnatal age, remain poorly understood. To elucidate age-specific effects of clinical variables on cortisol levels, 91 neonates with a mean (standard deviation) gestational age of 34.2 (3.8) weeks and postnatal age of 38.3 (35.4) days were categorised into Early, Medium, and Late groups by quartiles (days 10 and 56). Interactions with postnatal age were evaluated by comparing Early-to-Medium or Early-to-Late differences in regression coefficients between independent variables and cortisol levels. In the whole cohort, maternal hypertensive disorders of pregnancy and morning sampling were associated with reduced cortisol levels (both p = 0.001). Mean regression coefficients (95% CI) between variables and cortisol levels were as follows: for postconceptional age, Early, −0.102 (−0.215, 0.010) and Late, 0.065 (−0.203, 0.332) (p = 0.035); for feeding duration, Early, 0.796 (−0.134, 1.727) and Late, −0.702 (−2.778, 1.376) (p = 0.010); for time elapsed since feeding, Early, −0.748 (−1.275, −0.221) and Late, −0.071 (−1.230, 1.088) (p = 0.036); and for blood lactate, Early, 0.086 (0.048 to 0.124), Medium, 0.022 (−0.063, 0.108), and Late, −0.018 (−0.106, 0.070) (p = 0.008 and <0.001 vs. Medium and Late, respectively). The influence of postconceptional age, oral feeding, and anaerobic metabolism on salivary cortisol levels was observed during the birth transition period but not beyond 10 days of life. Given the age-specific dependence of cortisol levels on clinical variables, including postconceptional age, feeding, and oxygen metabolism, caution is warranted when interpreting findings from studies on salivary cortisol in newborn infants.

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