Negative associations between maternal prenatal hair cortisol and child socioemotional problems.

Maternal prenatal distress can participate in the programming of offspring development, in which exposure to altered maternal long-term cortisol levels as measured by hair cortisol concentrations (HCC) may contribute. Yet, studies investigating whether and how maternal prenatal HCC associates with problems in child socioemotional development are scarce. Furthermore, questions remain regarding the timing and potential sex-specificity of fetal exposure to altered cortisol levels and whether there are interactions with maternal prenatal distress, such as depressive symptoms. The subjects were drawn from those FinnBrain Birth Cohort families that had maternal reports of child socioemotional problems (the Brief Infant-Toddler Social and Emotional Assessment [BITSEA] at 2 years and/or the Strengths and Difficulties Questionnaire [SDQ] at 5 years) as follows: HCC1 population: maternal mid-pregnancy HCC measured at gestational week 24 with 5 cm segments to depict cortisol levels from the previous five months (n = 321); and HCC2 population: end-of-pregnancy HCC measured 1-3 days after childbirth (5 cm segment; n = 121). Stepwise regression models were utilized in the main analyses and a sensitivity analysis was performed to detect potential biases. Negative associations were observed between maternal HCC2 and child BITSEA Total Problems at 2 years but not with SDQ Total difficulties at 5 years, and neither problem score was associated with HCC1. In descriptive analyses, HCC2 was negatively associated with Internalizing problems at 2 years and SDQ Emotional problems at 5 years. A negative association was observed among 5-year-old girls between maternal HCC1 and SDQ Total Difficulties and the subscales of Conduct and Hyperactivity/inattentive problems. When interactions were also considered, inverse associations between HCC2 and BITSEA Internalizing and Dysregulation Problems were observed in subjects with elevated prenatal depressive symptoms. It was somewhat surprising that only negative associations were observed between maternal HCC and child socioemotional problems. However, there are previous observations of elevated end-of-pregnancy cortisol levels associating with better developmental outcomes. The magnitudes of the observed associations were, as expected, mainly modest. Future studies with a focus on the individual changes of maternal cortisol levels throughout pregnancy as well as studies assessing both maternal and child HPA axis functioning together with child socioemotional development are indicated.

Latent profile analysis of diurnal cortisol patterns at the ages of 2, 3.5, and 5 years: Associations with childcare setting, child individual characteristics, and maternal distress.

This study performed latent profile analysis from more than 4000 saliva cortisol samples collected from children at the ages of 2 (T1), 3.5 (T2), and 5 years (T3). Three clearly different cortisol profiles were identified. The largest group at every age point was the Low/Regular latent profile, in which the cortisol slopes followed typical diurnal variation. A smaller proportion of the children belonged to the latent profile with relatively Low/Flat slope, and a minority belonged to the High/Fluctuating latent group, where the overall cortisol values and variations between the slopes were clearly higher than in the other groups. Most of the children who belonged to the High/Fluctuating group were cared for at home, they had higher temperamental surgency and their mothers had more depressive symptoms than in the other latent profile groups. However, only moderate intraindividual stability in diurnal cortisol profiles was observed across the follow-up period. On average, half of the children moved between the groups from T1 to T3. Neither child temperament, social competence, nor sex explained the stability or movement between the groups across age. Variations in cortisol profiles may be caused by the child's age, and diurnal cortisol rhythm becomes more regular along with development. Methodological issues regarding saliva cortisol research in young children are discussed. Also, more longitudinal research is needed to clarify mechanisms between environmental as well as individual factors and possible dysregulation in a child's HPA axis functioning.

Hair cortisol, cortisone and DHEA concentrations and the composition of microbiota in toddlers.

Animal research suggests that the gut microbiota and the HPA axis communicate in a bidirectional manner. However, human data, especially on early childhood, remain limited. In this exploratory design, we investigated the connections between long-term HPA axis functioning, measured as cortisol, cortisone or dehydroepiandrosterone concentrations and their ratios from hair segments of three centimeters, and gut microbiota profiles, (measured as diversity and bacterial composition by 16 S rRNA sequencing) in healthy 2.5-year-old toddlers (n = 135) recruited from the FinnBrain Birth Cohort Study. The alpha diversity of the microbiota was studied by linear regression. Beta diversity analyses with weighted UniFrac or Bray-Curtis distances were performed using PERMANOVA. The bacterial core genus level analyses were conducted using DESeq2 and ALDEx2. These analyses suggested that hair sample concentrations of separate hormones, cortisol/cortisone and cortisol/dehydroepiandrosterone ratios were associated with various gut bacterial genera such as the Veillonella, the [Ruminococcus] torques group and [Eubacterium] hallii group, although multiple testing correction attenuated the p-values. Alpha or beta diversity was not linked with either steroid concentrations or ratios. These findings in toddlers suggest that long-term HPA axis activity may be related to genera abundancies but not to ecosystem-level measures in gut microbiota. The influence of these observed interrelations on later child health and development warrants further research.

Age and sex differences in the cortisol stress reactivity and recovery among infants exposed to prenatal psychological distress.

BACKGROUND: Altered hypothalamic-pituitary-adrenal axis (HPA) functioning is one of the potential mechanisms bridging exposure to maternal prenatal psychological distress (PPD) and later risk for offspring psychiatric illness. Research on infant cortisol stress reactivity, on scarcely studied recovery and their associations with maternal PPD is needed to clarify these mechanisms. Knowledge on sex differences in prospective settings is largely lacking. We aimed at filling these gaps by building upon our previous report showing that exposure to maternal prenatal depressive and anxiety symptoms associates with slower cortisol recovery among 10-week-old female infants. METHODS: In all, 363, 205 and 263 infants at 10 weeks, six and 14 months of age from the FinnBrain Birth Cohort Study participated in a stress test comprising of venipuncture and nasopharynx sampling. Five saliva cortisol samples were collected during each visit to measure cortisol reactivity and recovery. PPD was assessed from maternal self-reports for depressive, anxiety and pregnancy-related anxiety symptoms at gestational weeks 14, 24 and 34. RESULTS: An 11% enhanced recovery among 14-month-old females was associated with higher depressive and anxiety symptoms (95% CI=1-23%) and pregnancy-related anxiety symptoms (2-21%). No alterations in the female cortisol reactivity or male cortisol stress responses were observed. CONCLUSIONS: The opposite directions in the associations between the PPD exposure and infant cortisol recovery among 10-week-old and 14-month-old females suggest sex- and age-dependent associations between HPA axis functioning and PPD exposure among healthy infants. Follow-up is needed to characterize the impact of this altered negative feedback mechanism on later health.

Children's diurnal cortisol output and temperament in two different childcare settings at 2 and 3.5 years of age.

Prior research suggests that child temperament may play an important role in early childhood stress regulation. We compared children's diurnal cortisol and the association between cortisol and temperament in two different childcare settings. Cortisol was measured from saliva samples over 2 days in children (N = 84) attending out-of-home childcare and in children (N = 27), who were cared for at home at the age of 3.5 years. There was no difference between the childcare groups in total diurnal cortisol. However, of the individual measurements, afternoon cortisol levels were higher in the out-of-home childcare group during their childcare day when compared with their home day. Child temperament was not associated with total diurnal cortisol. Comparison with our prior measurements showed that the association between temperamental surgency/extroversion and total diurnal cortisol diminished along with the child age from 2 to 3.5 years in both childcare settings. This may indicate that more extroverted children are physiologically more reactive to environmental stimuli when they are younger, but this association does not appear as the children develop. Our results further suggest that the afternoon hours in the out-of-home childcare may be demanding and accelerate the hypothalamus-pituitary-adrenal axis activation in young children independent of their age.

Hair Cortisol Concentrations Are Associated with Dental Anxiety during Pregnancy.

Dental anxiety (DA) and hair cortisol concentrations (HCC) are associated with psychological symptoms and vary during pregnancy. We aimed to examine the association between HCC and DA at two points of pregnancy. Participants were pregnant mothers (n = 533) drawn from the FinnBrain Birth Cohort Study donating a hair sample at gestational week (gwk) 24 (n = 442) and/or at delivery (n = 176) and completed questionnaires on DA. Two groups, HCC1 and HCC2, treated as separate in the analyses, were formed according to the hair sample donation time i.e., gwk24 and delivery. 85 subjects were included in both groups. MDAS, EPDS, and SCL-90 were used to measure DA, depressive and anxiety symptoms, respectively, at gwk14 for the HCC1 group and gwk34 for the HCC2 group. The association between DA and HCC was studied with a binary logistic regression model, adjusted for anxiety and depressive symptoms, age, BMI, and smoking status. Individuals with high DA had lower HCC levels at gwk24 (OR = 0.548; 95% CI = 0.35-0.86; p = 0.009), but the association was not statistically significant at the delivery (OR = 0.611; 95% CI = 0.28-1.33; p = 0.216). The independent association between HCC and DA in pregnant women suggests that long-term cortisol levels could play a role in the endogenous etiology of DA. Further studies are however, needed.

Gut microbiota diversity but not composition is related to saliva cortisol stress response at the age of 2.5 months.

Human brain and intestinal microbes reportedly maintain a constant bidirectional connection through diverse neural, endocrine, immune, and metabolic pathways. Increasing evidence indicates that this communication system, referred to as microbiota-gut-brain axis, enables the gut microbes to influence several aspects of brain function and behavior, including hypothalamic-pituitary-adrenal (HPA) axis stress responses, and on the other hand, stress can affect gut microbiota. However, the role of gut microbiota in the HPA axis functioning in humans remains to be specified especially in early life. This study aimed at identifying the potential link between the cortisol stress response and the gut microbiota at the age of 2.5 months. Fecal microbiota profiles were acquired by 16S rRNA gene sequencing, while salivary cortisol responses after an exposure to a mild acute stressor represented the HPA axis reactivity. We observed that a blunted cortisol stress response was weakly associated with a diverse gut microbiota diversity at the age of 2.5 months. Gut microbiota composition was not associated with cortisol stress responsiveness, but rather with covariates, i.e. factors that influence gut microbiota composition and colonization.LAY SUMMARYThis exploratory study aimed at identifying possible links between cortisol stress responses and fecal microbiota composition in early infancy. In a well-characterized study population of 2.5-month-old infants, we observed that an attenuated cortisol stress responsiveness after a mild stressor was weakly associated with a diverse fecal microbiota. Our results suggest that the gut microbiota composition is associated with environmental factors, such as delivery mode and number of siblings, rather than with cortisol stress responsiveness, in this age group.

Child Temperament and Total Diurnal Cortisol in Out-of-Home Center-Based Child Care and in At-Home Parental Care.

The association between child temperament characteristics and total diurnal saliva cortisol in 84 children (M = 2.3 years, SD = 0.6) attending out-of-home, center-based child care and 79 children (M = 2.0 years, SD = 0.5) attending at-home parental care was examined. Saliva samples were collected during two consecutive days, that is, Sunday and Monday, with four samples taken per day. While children higher in surgency had higher total diurnal cortisol production, we did not find evidence that temperament moderated the associations between child-care context and total diurnal cortisol. Negative affectivity and effortful control were not related to cortisol output. Our findings suggest that temperamental surgency may be associated with higher total cortisol production in early childhood across child-care settings.

Sex differences in the associations between maternal prenatal distress and infant cortisol reactivity and recovery.

Previous research suggests that maternal prenatal psychological distress (PPD) is related to altered cortisol reactivity in the exposed child. There are indications for the sex differences in vulnerability for prenatal adversities that depend on the exposure and child outcome. Still, it is not known whether the association between maternal PPD and infant cortisol stress response is moderated by sex. In addition, the recovery phase of the cortisol stress response has not been given as much attention as reactivity. Our aim was to study the sex differences in the associations between self-reported maternal prenatal depressive-, anxiety- and pregnancy-related anxiety symptoms through gestational weeks 14, 24 and 34 and the saliva cortisol reactivity to and recovery from the acute stress among 10-week-old infants. The study population comprised of 363 mother-infant pairs from the FinnBrain Birth Cohort Study. We found evidence for sex-dependent associations between PPD exposure and infant cortisol response. A less steep recovery slope (-10 % per one SD increase in PPD [95 % CI = -18 to -2 %] and -8 % [-16 to 0 %] depending on the exposure) and a possibly less steep reactivity slope (-14 % [95 % CI = -25 to 0 %] and -10 % [-21 to 3 %]) were associated with higher PPD exposure in females. Of the PPD measures, the strongly intercorrelated, and thus combined, depressive and anxiety symptom score provided the most robust prediction of infant cortisol recovery. Our results demonstrate sexually dimorphic alterations in the functioning of the infant hypothalamus-pituitary-adrenal axis and especially in the functioning of the negative feedback loop of the axis after prenatal PPD exposure among healthy babies.

Maternal prenatal psychological distress and hair cortisol levels associate with infant fecal microbiota composition at 2.5 months of age.

BACKGROUND: Maternal prenatal stress associates with infant developmental outcomes, but the mechanisms underlying this association are not fully understood. Alterations in the composition and function of infant intestinal microbiota may mediate some of the observed health effects, a viewpoint that is supported by animal studies along with a small human study showing that exposure to prenatal stress modifies the offspring's intestinal microbiota. In the current study, we aim to investigate the associations between maternal prenatal psychological distress (PPD) and hair cortisol concentration (HCC) with infant fecal microbiota composition in a large prospective human cohort. METHODS: The study population was drawn from FinnBrain Birth Cohort Study. Maternal PPD was measured with standardized questionnaires (EPDS, SCL, PRAQ-R2, Daily Hassles) three times during pregnancy (n = 398). A measure addressing the chronicity of PPD was composed separately for each questionnaire. HCC was measured from a five cm segment at gestational week 24 (n = 115), thus covering the early and mid-pregnancy. Infant fecal samples were collected at the age of 2.5 months and analyzed with 16S rRNA amplicon sequencing. RESULTS: Maternal chronic PPD (all symptom measures) showed positive associations (FDR < 0.01) with bacterial genera from phylum Proteobacteria, with potential pathogens, in infants. Further, chronic PPD (SCL, PRAQ-R2, and Daily Hassles negative scale) associated negatively with Akkermansia. HCC associated negatively with Lactobacillus. Neither maternal chronic PPD nor HCC associated with infant fecal microbiota diversity. CONCLUSION: Chronic maternal PPD symptoms and elevated HCC associate with alterations in infant intestinal microbiota composition. In keeping with the earlier literature, maternal PPD symptoms were associated with increases in genera fromProteobacteria phylum. Further research is needed to understand how these microbiota changes are linked with later child health outcomes.

Alexithymic Traits and Hair Cortisol Concentrations in Pregnant Women.

INTRODUCTION: Alexithymia, a personality construct characterized by difficulties in identifying and expressing emotions, and an externally oriented thinking style, has been associated with a number of stress-related disorders, and physiological markers of stress. We examined the relationships of alexithymia and hair cortisol concentrations (HCC), a measure of long-term cortisol levels, in pregnant women. METHODS: Participants were 130 women from the FinnBrain Birth Cohort study. Alexithymia was measured with the Toronto Alexithymia Scale (TAS-20). Analysis of covariance and regression analyses were used to assess the associations between alexithymia and HCC. Educational level, current depressive symptoms, and body mass index (BMI) were applied as covariates. RESULTS: In the adjusted analyses, individuals with moderate to high alexithymic traits had significantly higher HCC (F = 5.11, partial η² = 0.040 , p = 0.026) compared to non-alexithymics. Regression analyses in the whole sample revealed that, of the individual dimensions of alexithymia, Difficulty Identifying Feelings (DIF) was associated with HCC (ß = 0.187, t = 2.064, p = 0.041). CONCLUSIONS: Alexithymia, and especially its dimension DIF, were associated with higher HCC and, therefore, may be linked to increased chronic physiological stress. Implications for pregnancy outcomes and infant development are discussed.

Toddlers' diurnal cortisol levels affected by out-of-home, center-based childcare and at-home, guardian-supervised childcare: comparison between different caregiving contexts.

Previous research suggests that attending non-parental out-of-home childcare is associated with elevated cortisol levels for some children. We aimed to compare diurnal saliva cortisol levels between children having out-of-home, center-based childcare or those having at-home, guardian-supervised childcare in Finland. A total of 213 children, aged 2.1 years (SD = 0.6), were drawn from the ongoing Finnish birth cohort study. Saliva samples were collected over 2 consecutive days (Sunday and Monday), with four samples drawn during each day: 30 min after waking up in the morning, at 10 am, between 2 and 3 pm, and in the evening before sleep. These results suggest that the shapes of the diurnal cortisol profiles were similar in both childcare groups following a typical circadian rhythm. However, the overall cortisol levels were on average 30% higher (95% CI: [9%, 54%], p = .004) with the at-home childcare in comparison with the out-of-home childcare group. Furthermore, a slight increase in the diurnal cortisol pattern was noticed in both groups and in both measurement days during the afternoon. This increase was 27% higher ([2%, 57%], p = .031) in the out-of-home childcare group during the out-of-home childcare day in comparison with the at-home childcare day. The elevated afternoon cortisol levels were partly explained by the afternoon naps, but there were probably other factors as well producing the cortisol rise during the afternoon hours. Further research is needed to define how a child's individual characteristic as well as their environmental factors associate with cortisol secretion patterns in different caregiving contexts.

Maternal prenatal hair cortisol is associated with prenatal depressive symptom trajectories.

Maternal prenatal cortisol levels have been inconsistently associated with self-reports of prenatal psychological distress (PD). Previous research has linked hair cortisol concentration (HCC) evaluating cumulatively the previous months with cross-sectional PD measures that usually cover the past week(s), which may lead to misleading conclusions on their relations. We aimed to investigate how maternal HCC relates to cumulative PD measures across pregnancy. METHODS: Subjects (N = 595) were drawn from the FinnBrain Birth Cohort Study. Maternal HCC was measured from hair samples collected at gestational week (gwk) 24 (HCC1, n = 467) and at delivery (HCC2, n = 222). As HCC1 and HCC2 comprised mostly of different subjects, they were considered as independent populations. Maternal PD assessments at gwks 14, 24, and 34 were the Edinburgh Postnatal Depression Scale (EPDS), the anxiety subscale of the Symptom Checklist (SCL-90), the Pregnancy-Related Anxiety Questionnaire -Revised2 (PRAQ-R2), and a daily hassles scale. Cumulative PD comprised of the mean scores of two consecutive assessments (mean1 = gwks 14 and 24; mean2 = gwks 24 and 34). In addition, EPDS and SCL scores were modelled by using growth mixture modelling to identify symptom trajectory categories. Regression models were adjusted for age, body mass index, education and use of selective serotonin/serotonin-norepinephrine reuptake inhibitor medication. RESULTS: In the adjusted regression model, higher HCC2 was related to the "consistently elevated" prenatal depressive symptoms trajectory in comparison to "consistently low" (ß =.71, p =.021) and "low and increasing" (ß =.82, p = .011) symptom trajectories. Additionally, the cumulative mean (mean 1) of daily hassles in relationships was associated with HCC1 (ß = 0.25, p = .004). General or pregnancy-related anxiety symptoms were unrelated to HCC after adjustment for the covariates. CONCLUSIONS: The assessment of cumulative or trajectory measures of PD can reveal important associations with maternal prenatal HCC, even though the associations are generally weak. Of the different dimensions of PD, prenatal trajectories of depressive symptoms were most consistently linked with end-pregnancy HCC levels.

Prenatal maternal distress associates with a blunted cortisol response in rhinovirus-positive infants.

INTRODUCTION: Prenatal exposure to maternal psychological distress (PD) may have programming effects on the fetus/infant hypothalamic-pituitary-adrenal (HPA) axis and subsequently on the development of the fetus' immune function. Therefore, our aim was to study whether prenatal exposure to PD is related to early infant HPA axis reactivity in the context of a subclinical rhinovirus infection that challenges infants HPA axis postnatally. METHODS: This study included 336 10-week-old infants from the nested case control Focus Cohort of the FinnBrain Birth Cohort Study. The outcome was infant HPA axis reactivity in a stress test. The acute stressor comprised of pediatric examination with venipuncture and nasal swabs for virus assessment. Saliva cortisol samples were collected at 5 time points: baseline, 0, 15, 25 and 35 min after the stressor. HPA axis reactivity was defined by the cumulative post-stressor cortisol concentration. RESULTS: HPA axis reactivity was blunted in the PD/rhinovirus + group compared to the average of control/rhinovirus+, PD/rhinovirus-, and control/rhinovirus- groups (difference: 14.7 ln [nmol/L] × min, 95% confidence interval 3.8-25.6, p = .008). HPA axis reactivity was significantly blunted only in boys with rhinovirus detected when separately tested for boys and girls (p = .04). CONCLUSION: Our finding of PD-exposed rhinovirus-positive infants having blunted cortisol secretion gives rise to a hypothesis that maternal PD during pregnancy influences infant HPA axis functioning and the functioning of the immune system. Future studies are needed to test whether this suppression of the HPA axis that co-occurs with rhinovirus infection associates with later disease development (e.g., asthma).

Hair cortisol concentration (HCC) as a measure for prenatal psychological distress - A systematic review.

Prenatal environment reportedly affects the programming of developmental trajectories in offspring and the modification of risks for later morbidity. Among the increasingly studied prenatal exposures are maternal psychological distress (PD) and altered maternal hypothalamus-pituitary-adrenal (HPA) axis functioning. Both prenatal PD and maternal short-term cortisol concentrations as markers for HPA axis activity have been linked to adverse child outcomes and it has been assumed that maternal PD affects the offspring partially via altered cortisol secretion patterns. Yet, the existing literature on the interrelations between these two measures is conflicting. The assessment of cortisol levels by using hair cortisol concentration (HCC) has gained interest, as it offers a way to assess long-term cortisol levels with a single non-invasive sampling. According to our review, 6 studies assessing the associations between maternal HCC during pregnancy and various types of maternal PD have been published so far. Measures of prenatal PD range from maternal symptoms of depression or anxiety to stress related to person's life situation or pregnancy. The aim of this systematic review is to critically evaluate the potential of HCC as a biomarker for maternal PD during pregnancy. We conclude that HCC appears to be inconsistently associated with self-reported symptoms of prenatal PD, especially in the range of mild to moderate symptom levels. Self-reports on PD usually cover short time periods and they seem to depict partly different phenomena than HCC. Thus, methodological aspects are in a key role in future studies evaluating the interconnections across different types of prenatal PD and maternal HPA axis functioning. Further, studies including repetitive measurements of both HCC and PD during the prenatal period are needed, as timing of the assessments is one important source of variation among current studies. The significance of prenatal HCC in the context of offspring outcomes needs to be further investigated.

[Oxytocin, a neuropeptide regulating affection and social behavior]. / Oksitosiini, kiintymyksen ja sosiaalisuuden neuropeptidi.

Oxytocin has been reported to modulate human behavior in many social interactions of which attachment between mother and child is the child's first social relationship. Quality of the attachment might affect the sensitivity of child's stress regulation system by modulating the development of the child's oxytocin system. This might affect social behavior in adulthood and could be one of the risk or resilience factors for mental disorders and coronary artery diseases. Oxytocin has been linked to conditions like autism and depression that significantly disturb social interaction capabilities and coping with daily life activities. Better treatment and preventative methods might be found to those diseases by investigating the effects of oxytocin to the formation of the mother-child attachment and child's development.