Saliva cortisol diurnal variation and stress responses in term and preterm infants

Objectives: To determine if preterm birth is associated with adaptation of the hypothalamic-pituitary-adrenal (HPA) axis, and whether HPA axis programming relates to the degree of prematurity (defined as extremely preterm birth at <28 weeks, or very preterm birth at 28-32 weeks gestation).

Design: This study reports findings from a prospective birth cohort. Saliva cortisol concentrations were measured pre and post-vaccination, and in the morning and evening, at 4- months chronological age.

Setting: Infants born at a single Scottish hospital.

Participants: 45 term-born, 42 very preterm, and 16 extremely preterm infants.

Outcomes: Cortisol stress response to vaccination (post vaccination minus pre vaccination cortisol concentrations), diurnal slope (log-transformed morning minus log-transformed evening cortisol values), and mean log-transformed daily cortisol.

Results: Compared to infants born at term, infants born extremely preterm had a blunted cortisol response to vaccination (5.8nmol/L vs 13.1nmol/L, difference in means: -7.3 nmol/L, 95% CI: -14.0 to -0.6), and a flattened diurnal slope (difference in geometric means: -72.9%, 95% CI: -87.1 to -42.8). In contrast, the cortisol response to vaccination (difference in means -2.7 nmol/L, 95% CI: -7.4 to 2.0) and diurnal slope at 4-months (difference in geometric means: -33.6%, 95% CI: -62.0 to 16.0), did not differ significantly in infants born very preterm compared to infants born at term.

Conclusions: Infants born extremely preterm have blunted cortisol reactivity and a flattened diurnal slope. These patterns of HPA axis regulation are commonly seen after childhood adversity, and could contribute to later metabolic and neurodevelopmental phenotypes, observed in this population.