Adrenalin, noradrenalin and heart rate responses to psychosocial stress in young adults born preterm at very low birthweight.

OBJECTIVE: Adults born preterm at very low birthweight (VLBW; ≤ 1500 g) have high levels of cardiovascular risk factors and altered responses to psychosocial stress including higher blood pressure and lower cortisol. Our aim was to investigate adrenalin (A), noradrenalin (NA) and heart rate (HR) responses to psychosocial stress in adults born preterm at VLBW. DESIGN AND PARTICIPANTS: We studied 50 young adults, aged 19-27 years, born at VLBW and 39 term-born controls, group-matched for age, sex and birth hospital. They underwent a standardized psychosocial stress test, the Trier Social Stress Test (TSST). MEASUREMENTS: During TSST, A, NA (baseline and 0, 10 and 90 min after stress) and HR were measured. Data were analysed with mixed-effects and linear regression models, adjusted for age, sex, body mass index, hormonal contraception, time of day and highest parental educational attainment. RESULTS: Baseline concentrations, peak after stress, increments and area under the curve for A and NA were similar in VLBW and control groups. In women, NA concentrations were 27.7% lower (95% CI; 3.1-52.2) in VLBW compared with control women; in men, there was no significant difference. A concentrations were similar for VLBW and control groups in both sexes. Mean HR at baseline, task and HR reactivity was also similar in VLBW and control groups. CONCLUSIONS: Very low-birthweight women seem to have a lower NA response to stress compared with term-born peers. If replicated, this could be a protective characteristic for cardiovascular diseases.

Blunted hypothalamic-pituitary-adrenal axis and insulin response to psychosocial stress in young adults born preterm at very low birth weight.

BACKGROUND: Young adults born preterm at very low birth weight (VLBW, ≤1500 g) have higher levels of cardiovascular risk factors, including impaired glucose regulation, than their term-born peers. This could be mediated through altered hypothalamic-pituitary-adrenal axis (HPAA) response to stress. OBJECTIVE: To compare HPAA, glucose and insulin responses provoked by psychosocial stress in VLBW subjects versus a comparison group of term-born controls. DESIGN AND PARTICIPANTS: We studied 54 unimpaired young adults, aged 19-27 years, born at VLBW and a comparison group of 40 adults born at term, group-matched for age, sex and birth hospital, from one regional centre in southern Finland. The participants underwent a standardized psychosocial stress test (Trier Social Stress Test, TSST). MEASUREMENTS: In conjunction with TSST, we measured salivary cortisol, plasma ACTH, cortisol, glucose and insulin. Data were analysed with mixed-effects model and multiple linear regression analyses. RESULTS: Baseline concentrations for cortisol, ACTH, insulin and glucose were similar in VLBW and comparison groups. During TSST, analysed with mixed-effects model, overall concentrations of plasma cortisol were 17·2% lower (95% CI; 3·5 to 28·9) in the VLBW group. The VLBW group also had lower salivary (P = 0·04) and plasma cortisol (P = 0·02) responses to TSST. Insulin and glucose concentrations correlated with changes in cortisol concentrations. Accordingly, VLBW subjects had 26·5% lower increment in insulin (95% CI; 9·8-40·1). Analyses were adjusted for age, sex, body mass index, hormonal contraception, menstrual cycle phase, time of day and parental education. CONCLUSIONS: VLBW adults have lower HPAA responses to psychosocial stress than term-born controls. This is accompanied by a lower insulin response.

Sleep problems and cardiovascular function in children.

OBJECTIVE: To assess the associations of sleep problems with 24-hour ambulatory blood pressure and cardiovascular reactivity in children. METHODS: Sleep problems in 285 term-born, healthy 8-year-olds (mean [standard deviation] = 8.1 [0.3] years) were measured with a parent-rated Sleep Disturbance Scale for Children. Ambulatory blood pressure (n = 241) was measured for 24 hours (41% nonschool days) with an oscillometric device. The children (n = 274) underwent the Trier Social Stress Test for Children during which blood pressure, electrocardiography, and thoracic impedance were recorded and processed offline to give measures of cardiovascular and autonomic function. RESULTS: No associations were found between sleep problems and 24-hour ambulatory blood pressure. Children with sleep breathing disorders (n = 5) had higher baseline sympathetic vascular activity (p = .014) and higher heart rate (p = .044) and sympathetic cardiac activity (p = .031) in reaction to stress. Children with disorders of excessive somnolence (n = 55) had higher baseline parasympathetic activity (p = .016). None of the associations remained significant after controlling for multiple testing. CONCLUSIONS: Our results suggest that in a healthy community sample of prepubertal children, sleep problems are not associated with an unhealthy cardiovascular phenotype at this age. However, associations may be underestimated because of the low prevalence of sleep breathing disorders in this sample and may not generalize to older populations.

Higher levels of physical activity are associated with lower hypothalamic-pituitary-adrenocortical axis reactivity to psychosocial stress in children.

CONTEXT: Children who undertake more physical activity (PA) not only have more optimal physical health but also enjoy better mental health. However, the pathways by which PA affects well-being remain unclear. OBJECTIVE: To address this question, we examined whether objectively measured daytime PA was associated with diurnal hypothalamic-pituitary-adrenocortical axis (HPAA) activity and HPAA responses to psychosocial stress. DESIGN AND SETTING: We conducted a cross-sectional study in a birth cohort in Helsinki, Finland. PARTICIPANTS: We studied 258 8-year-old children. MAIN OUTCOME MEASURES: PA was assessed with wrist-worn accelerometers. Overall PA and percentage of time spent in vigorous PA (VPA) were categorized by sex into thirds. Salivary cortisol was measured diurnally and in response to the Trier Social Stress Test for Children. RESULTS: The children in different PA groups did not show differences in diurnal salivary cortisol (P > .10 for overall PA and VPA). Children with the highest levels of overall PA or VPA showed no, or only small, increases over time in salivary cortisol after stress (P = .10 and P =.03 for time in analyses of PA and VPA, respectively), whereas children belonging to the lowest and intermediate thirds showed significant increases over time in salivary cortisol after stress (P ≤ .002 for time in the analyses of overall PA and VPA). CONCLUSIONS: These results suggest that children with lower levels of daytime PA have higher HPAA activity in response to stress. These findings may offer insight into the pathways of PA on physical and mental well-being.

Poor sleep and cardiovascular function in children.

We investigated whether sleep quantity and quality were related to 24-hour ambulatory blood pressure and cardiovascular reactivity in children. We studied term-born, healthy 8.0-year olds (SD: 1.4 years) without sleep-disordered breathing (231 and 265 children provided valid data for analyses of ambulatory blood pressure and cardiovascular reactivity, respectively). Sleep was registered with an actigraph for 6 nights on average (SD: 1.2; range: 3 to 13 nights). Ambulatory blood pressure was measured for 24-hours (41% nonschool days) with an oscillometric device. The children underwent the Trier Social Stress Test for Children, during which blood pressure, electrocardiography, and thoracic impedance were recorded and processed offline to give measures of cardiovascular and autonomic function. Neither quantity nor quality of sleep was related to 24-hour ambulatory blood pressure or cardiovascular reactivity after accounting for major covariates (sex, age, height, body mass index, and parental education). Although lower sympathetic nervous system activation and higher cardiac activation under stress were found in the group of children who slept for short duration when they were compared with the average sleep duration group, these associations were not significant after correction for multiple testing and were not seen in linear regression models of the effects of sleep duration. These findings do not support the mainstream of epidemiological findings, derived from samples more heterogeneous in age, sociodemographic characteristics, and health, suggesting that poor sleep is associated with an unhealthy cardiovascular phenotype.

Maternal prenatal licorice consumption alters hypothalamic-pituitary-adrenocortical axis function in children.

Overexposure to glucocorticoids has been proposed as a mechanism by which prenatal adversity 'programs' the function of the hypothalamic-pituitary-adrenocortical axis (HPAA), thereby increasing the risk of adult diseases. Glycyrrhizin, a natural constituent of licorice, potently inhibits 11ß-hydroxysteroid dehydrogenase type 2, the feto-placental barrier to the higher maternal cortisol levels. We studied if maternal consumption of glycyrrhizin in licorice associates with HPAA function in children. Diurnal salivary cortisol and salivary cortisol during the Trier Social Stress Test for Children (TSST-C) were measured in children (n=321, mean age=8.1, SD=0.3 years) whose mothers consumed varying levels of glycyrrhizin in licorice during pregnancy; exposure-level groups were labeled high (≥500 mg/week), moderate (250-499 mg/week) and zero-low (0-249 mg/week). In comparison to the zero-low exposure group, children in the high exposure group had 19.2% higher salivary cortisol awakening peak, 33.1% higher salivary cortisol awakening slope, 15.4% higher salivary cortisol awakening area under the curve (AUC), 30.8% higher baseline TSST-C salivary cortisol levels, and their salivary cortisol levels remained high throughout the TSST-C protocol (P-values <0.05). These effects appeared dose-related. Our findings lend support to prenatal 'programming' of HPAA function by overexposure to glucocorticoids.

Poor sleep and altered hypothalamic-pituitary-adrenocortical and sympatho-adrenal-medullary system activity in children.

CONTEXT: Neuroendocrine alterations, with well-known links with health, may offer insight into why poor sleep is associated with poor health. Yet, studies testing associations between sleep and neuroendocrine activity in children are scarce. OBJECTIVE: The aim of this study was to determine whether actigraphy-based sleep pattern is associated with hypothalamic-pituitary-adrenocortical axis and sympatho-adrenal-medullary system activity in children. DESIGN AND SETTING: We conducted a cross-sectional study in a birth cohort in Helsinki, Finland. PARTICIPANTS: We studied 282 8-yr-old children. MAIN OUTCOME MEASURES: We measured diurnal salivary cortisol and salivary cortisol and alpha-amylase (a sympatho-adrenal-medullary system marker) responses to the Trier Social Stress Test for Children (TSST-C). RESULTS: Children with short (77.4%) displayed higher diurnal cortisol levels across the entire day (P < 0.03), higher cortisol levels after the TSST-C stressor (P < 0.04), and higher overall alpha-amylase levels across the entire TSST-C protocol (P < 0.05). The effects were not confounded by factors that may alter sleep or hormonal patterns. CONCLUSIONS: Poor sleep may signal altered neuroendocrine functioning in children. The findings may offer insight into the pathways linking poor sleep with poor health.

Childhood separation experience predicts HPA axis hormonal responses in late adulthood: a natural experiment of World War II.

BACKGROUND: Animal models have linked early maternal separation with lifelong changes in hypothalamic-pituitary-adrenocortical (HPA) axis activity. Although this is paralleled in human studies, this is often in the context of other life adversities, for example, divorce or adoption, and it is not known whether early separation in the absence of these factors has long term effects on the HPA axis. AIMS: The Finnish experience in World War II created a natural experiment to test whether separation from a father serving in the armed forces or from both parents due to war evacuation are associated with alterations in HPA axis response to psychosocial stress in late adulthood. METHOD: 282 subjects (M=63.5 years, SD=2.5), of whom 85 were non-separated, 129 were separated from their father, and 68 were separated from both their caregivers during WWII, were enlisted to participate in a Trier Social Stress Test (TSST), during which we measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations. We used mixed models to study whether parental separation is associated with salivary and plasma cortisol or plasma ACTH reactivity, and linear regressions to analyse differences in the baseline, or incremental area under the cortisol or ACTH curves. RESULTS: Participants separated from their father did not differ significantly from non-separated participants. However, those separated from both parents had higher average salivary cortisol and plasma ACTH concentrations across all time points compared to the non-separated group. They also had higher salivary cortisol reactivity to the TSST. Separated women had higher baselines in plasma cortisol and ACTH, whereas men had higher reactivity in response to stress during the TSST. Participants who had experienced the separation in early childhood were more affected than children separated during infancy or school age. CONCLUSIONS: Separation from parents during childhood may alter an individual's stress physiology much later in adult life.

Blood pressure responses to psychosocial stress in young adults with very low birth weight: Helsinki study of very low birth weight adults.

Young adults born prematurely with very low birth weight (

Body size at birth predicts hypothalamic-pituitary-adrenal axis response to psychosocial stress at age 60 to 70 years.

BACKGROUND: Studies in humans and animals have suggested intrauterine programming of hypothalamic-pituitary-adrenal axis (HPAA) function as an important mechanism in linking fetal life conditions with adult disease. OBJECTIVE: Our aim was to assess how body size at birth, a marker of intrauterine conditions, is associated with hypothalamic-pituitary-adrenal axis response to psychosocial stress in late adulthood. DESIGN AND SETTING: We conducted a clinical study in the Helsinki Birth Cohort. PARTICIPANTS: Two hundred eighty-seven men and women born between 1934 and 1944 whose birth measurements and gestational age came from hospital records participated in the study. MEASUREMENTS: We measured salivary cortisol and, for 215 individuals, plasma cortisol and ACTH concentrations in conjunction with a standardized psychosocial stressor (Trier Social Stress Test). RESULTS: There was a linear relationship between low birth weight and low plasma ACTH but no linear relationship with cortisol. There were, however, quadratic relationships between birth weight and salivary (mixed model P = 0.001) and plasma cortisol (P = 0.005) but not with plasma ACTH (P = 0.1). The lowest peak salivary cortisol concentrations were seen in the lowest third of birth weights (adjusted for gestational age and sex): 12.9 nmol/liter (95% confidence interval of mean 11.2-15.0), compared with 17.1 nmol/liter (14.8-19.8) in the middle and 14.1 nmol/liter (12.6-15.7) in the highest third of birth weights. Corresponding figures for plasma cortisol were 418 nmol/liter (380-459), 498 nmol/liter (455-545), and 454 nmol/liter (428-482), and for plasma ACTH 8.17 pmol/liter (6.98-9.57), 12.42 pmol/liter (10.64-14.51), and 11.50 (10.06-13.14), respectively. Results for areas under the curve were similar. CONCLUSIONS: We found an inverse U-shaped relationship between birth weight and cortisol concentrations during psychosocial stress. The lowest cortisol and ACTH concentrations were seen in subjects with the lowest birth weights. These results support the hypothesis that both hyper- and hypocortisolism may be programmed during the fetal period.