Cortisol awakening response in infants during the first six postnatal months and its relation to birth outcome

Context: The rise of cortisol concentrations after awakening is well documented in adults and children and commonly used as easily accessible marker of hypothalamic-pituitary-adrenal (HPA) reactivity. Objective: The purpose of this study was to demonstrate the existence of a salivary cortisol awakening response (CAR) in infants, and to estimate its association with birth outcome. Setting: The study was conducted in the general community. Participants: Healthy infants up to six months age (N=64). Main outcome measures: Mothers were instructed to collect their infant’s saliva immediately and 30 min after awakening on two days within 45 days, irrespective of awakening time. Information on birth outcome was collected from medical records and questionnaires. Results: Linear mixed models analysis revealed a significant rise of infant salivary cortisol concentrations within 30 minutes after awakening (b=0.128, SE=0.024, t61=5.31, p<0.001), which was quite stable across the two sampling days (r=0.40, p=0.002). The infant CAR was predicted by length of gestation (t61=2.43, p=0.018). Conclusions: The current data demonstrate the existence of a CAR in infants as early as during the first six postnatal months; its relationship with length of gestation supports its usefulness for questions related to developmental neuroscience. Therefore, the infant CAR emerges as non-invasive biomarker of HPA axis dynamics at this early stage of life, with relevance for future research and potential clinical applications

Optimal Control of the Thermistor Problem in Three Spatial Dimensions

This paper is concerned with the state-constrained optimal control of the three-dimensional thermistor problem, a fully quasilinear coupled system of a parabolic and elliptic PDE with mixed boundary conditions. This system models the heating of a conducting material by means of direct current. Local existence, uniqueness and continuity for the state system are derived by employing maximal parabolic regularity in the fundamental theorem of Pr\"uss. Global solutions are addressed, which includes analysis of the linearized state system via maximal parabolic regularity, and existence of optimal controls is shown if the temperature gradient is under control. The adjoint system involving measures is investigated using a duality argument. These results allow to derive first-order necessary conditions for the optimal control problem in form of a qualified optimality system. The theoretical findings are illustrated by numerical results

Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation

The aim of this study was to investigate whether maternal adversities and cortisol levels during pregnancy predict cord blood DNA methylation of the oxytocin receptor (OXTR). We collected cord blood of 39 babies born to mothers participating in a cross-sectional study (N = 100) conducted in Basel, Switzerland (2007-10). Mothers completed the Inventory of Life Events (second trimester: T2), the Edinburgh Postnatal Depression Scale (EPDS, third trimester: T3), the Trier Inventory of Chronic Stress (TICS-K, 1-3 weeks postpartum) and provided saliva samples (T2, T3) for maternal cortisol profiles, as computed by the area under the curve with respect to ground (AUCg) or increase (AUCi) for the cortisol awakening response (CAR) and for diurnal cortisol profiles (DAY). OXTR DNA methylation was quantified using Sequenom EpiTYPER. The number of stressful life events (P = 0.032), EPDS score (P = 0.007) and cortisol AUCgs at T2 (CAR: P = 0.020; DAY: P = 0.024) were negatively associated with OXTR DNA methylation. Our findings suggest that distinct prenatal adversities predict decreased DNA methylation in a gene that is relevant for childbirth, maternal behavior and wellbeing of mother and offspring. If a reduced OXTR methylation increases OXTR expression, our findings could suggest an epigenetic adaptation to an adverse early environment

Decreased startle modulation during anticipation in the postpartum period in comparison to late pregnancy

Knowledge about healthy women’s psychophysiological adaptations during the large neuroendocrine changes of pregnancy and childbirth is essential in order to understand why these events have the potential to disrupt mental health in vulnerable individuals. This study aimed to compare startle response modulation, an objective psychophysiological measure demonstrated to be influenced by anxiety and depression, longitudinally across late pregnancy and the postpartum period. The acoustic startle response modulation was assessed during anticipation of affective images and during image viewing in 31 healthy women during gestational weeks 36–39 and again at 4 to 6 weeks postpartum. No startle modulation by affective images was observed at either time point. Significant modulation during anticipation stimuli was found at pregnancy assessment but was reduced in the postpartum period. The women rated the unpleasant images more negative and more arousing and the pleasant images more positive at the postpartum assessment. Self-reported anxiety and depressive symptoms did not change between assessments. The observed postpartum decrease in modulation of startle by anticipation suggests a relatively deactivated defense system in the postpartum period

Maternal Psychosocial Stress during Pregnancy and Placenta Weight: Evidence from a National Cohort Study

To study in a large-scale cohort with prospective data the associations between psychosocial stress during pregnancy and placenta weight at birth. Animal data suggest that the placenta is involved in stress-related fetal programming.; We defined a priori two types of psychosocial stress during pregnancy, life stress (perceived burdens in major areas of life) and emotional symptoms (e.g. anxiety). We estimated the associations of maternal stress during pregnancy with placenta weight at birth, controlled for length of gestation, by predicting gestational age- and sex-specific z-scores of placenta weight through multiple regression analysis, adjusted for potential confounders (N?=?78,017 singleton pregnancies). Life stress (per increase in stress score by 1, range: 0-18) during pregnancy was associated with increased placenta weight at birth (z-score, reported in 10(-3); B, 14.33; CI, 10.12-18.54). In contrast, emotional symptoms during pregnancy were not associated with placenta weight at birth.; Maternal life stress but not emotional symptoms during pregnancy was associated with increased placenta weight at birth; yet, the association-estimate was rather small. Our results may contribute to a better understanding of the role of the placenta in the regulation of intrauterine processes in response to maternal stress

Improving Ambulatory Saliva-Sampling compliance in Pregnant Women : A Randomized Controlled Study

Objective: Noncompliance with scheduled ambulatory saliva sampling is common and has been associated with biased cortisol estimates in nonpregnant subjects. This study is the first to investigate in pregnant women strategies to improve ambulatory saliva-sampling compliance, and the association between sampling noncompliance and saliva cortisol estimates. Methods: We instructed 64 pregnant women to collect eight scheduled saliva samples on two consecutive days each. Objective compliance with scheduled sampling times was assessed with a Medication Event Monitoring System and self-reported compliance with a paper-and-pencil diary. In a randomized controlled study, we estimated whether a disclosure intervention (informing women about objective compliance monitoring) and a reminder intervention (use of acoustical reminders) improved compliance. A mixed model analysis was used to estimate associations between women's objective compliance and their diurnal cortisol profiles, and between deviation from scheduled sampling and the cortisol concentration measured in the related sample. Results: Self-reported compliance with a saliva-sampling protocol was 91%, and objective compliance was 70%. The disclosure intervention was associated with improved objective compliance (informed: 81%, noninformed: 60%), F(1,60)  = 17.64, p<0.001, but not the reminder intervention (reminders: 68%, without reminders: 72%), F(1,60)  = 0.78, p = 0.379. Furthermore, a woman's increased objective compliance was associated with a higher diurnal cortisol profile, F(2,64) = 8.22, p<0.001. Altered cortisol levels were observed in less objective compliant samples, F(1,705) = 7.38, p = 0.007, with delayed sampling associated with lower cortisol levels. Conclusions: The results suggest that in pregnant women, objective noncompliance with scheduled ambulatory saliva sampling is common and is associated with biased cortisol estimates. To improve sampling compliance, results suggest informing women about objective compliance monitoring but discourage use of acoustical reminders