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

Abstract

ObjectiveTo 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).DesignThis study reports findings from a prospective birth cohort. Saliva cortisol concentrations were measured prevaccination and postvaccination, and in the morning and evening, at 4 months chronological age.SettingInfants born at a single Scottish hospital.Participants45 term-born, 42 very preterm and 16 extremely preterm infants.OutcomesCortisol stress response to vaccination (postvaccination minus prevaccination cortisol concentrations), diurnal slope (log-transformed morning minus log-transformed evening cortisol values) and mean log-transformed daily cortisol.ResultsCompared with infants born at term, infants born extremely preterm had a blunted cortisol response to vaccination (5.8 nmol/L vs 13.1 nmol/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 with infants born at term.ConclusionsInfants 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.

Cortisol levels are related to neonatal pain exposure in children born very preterm at age 18 months in two independent cohorts

“…Children born very preterm (≤32 weeks gestation) display altered stress regulation as indexed by cortisol output (cortisol is the primary human stress hormone released by the hypothalamic–pituitary–adrenal [HPA] axis), which has been related to behavior 1‐4 5 .…”

“…Children born very preterm (≤32 weeks gestation) display altered stress regulation as indexed by cortisol output (cortisol is the primary human stress hormone released by the hypothalamic-pituitaryadrenal [HPA] axis), which has been related to behavior. [1][2][3][4] ; Chau et al, 2017. 5 Infants born very preterm spend their first weeks to months in the neonatal intensive care unit (NICU) receiving critical care, during a time when programming of the brain and developing stress systems is occurring.…”

Glucocorticoids in preterm human milk

“…The establishment of circadian rhythm is essential to control normal sleep–wake cycles, respiratory rate, body temperature, digestion, metabolism, hormone release, and other important physiological functions ( 5 , 6 ). However, compared to full-term infants, those infant born extremely preterm (<28 weeks) have blunted cortisol reactivity to acute stress at 4 months chronological age ( 19 ) and flattened diurnal cortisol slope across the first year of life ( 20 ), possibly indicating suppression of HPA axis activity.…”

A Preliminary Study of Correlates of Premature Birth and Their Influence on Cortisol Levels in Young Children

“…In addition, cortisol levels were generally lower than the average reference curves, suggesting that children born prematurely have lower cortisol levels. Blunted (flat) cortisol-responses in both infants (4 months), children, and young adults born extremely premature might lead to an inadequate regulation of psychological stress, resulting in both internalizing and externalizing behavioral problems, as well as sensory processing disorders later in life (Bagner et al, 2010;Brummelte et al, 2015;Kaseva et al, 2014;McLean et al, 2021;Pyhälä et al, 2017;Stoye et al, 2022). Unfortunately, we did not have hospital data with clinical indications for why C-sections were performed.…”

“…Whereas evidence on basal cortisol levels is not clearcut, several recent studies show flattened cortisol-responses to (psychological) stress in both infants (4 months) and children (<9 years) born extremely premature or SGA (Brummelte et al, 2015;Hwang et al, 2019;Stoye et al, 2022). Considering the relationship between prematurity, stress and cortisol levels, the aim of this preliminary study is to investigate the influence degree of prematurity (weeks of gestation) and delivery route (C-sections versus vaginal birth) on cortisol levels in children, as a function of their HPA-axis activity.…”