ArticleLiterature Review

Cortisol: The Culprit Prenatal Stress Variable

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Abstract

Elevated prenatal cortisol has been associated with several negative conditions including aborted fetuses, excessive fetal activity, delayed fetal growth and development, prematurity and low birthweight, attention and temperament problems in infancy, externalizing problems in childhood, and psychopathology and chronic illness in adulthood. Given that maternal prenatal cortisol crosses the placenta and influences other aspects of the prenatal environment, these effects on the fetus and later development are not surprising. Cortisol would appear to be a mediating variable, resulting from prenatal stress in several forms including depression, anxiety, anger, and daily hassles. Cortisol effects are further complicated by its interaction with neurotransmitters such as norepinephrine, which may itself cause premature birth via intrauterine growth deprivation related to uterine artery resistance. Recent research has suggested that cortisol-reducing therapies such as massage therapy can reduce the risk of perinatal complications including prematurity and low birthweight.

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... During pregnancy, maternal cortisol is regulated by the placenta, uterine decidua, and fetal membrane, in addition to the hypothalamic-pituitary-adrenal (HPA) axis [2]. Significant increases in cortisol occur during pregnancy, classifying it as a physiologic period of hypercortisolism; however, notably, the variation of the diurnal rhythm of cortisol remains fairly consistent during pregnancy [3], though there may be seasonal effects [4]. ...
... Significant increases in cortisol occur during pregnancy, classifying it as a physiologic period of hypercortisolism; however, notably, the variation of the diurnal rhythm of cortisol remains fairly consistent during pregnancy [3], though there may be seasonal effects [4]. Due to transfer through the bloodstream of the mother and infant, as well as placental transfer, increased maternal cortisol levels result in increased cortisol exposure to the fetus [2]. Research in human and non-human animal studies have suggested that exposure to glucocorticoids during prenatal development is necessary for typical development, however, continued exposure to high levels of cortisol can have adverse impacts on development and growth, including preterm delivery, intrauterine growth restriction, and low birth weight [5][6][7]. ...
... The impact of maternal prenatal cortisol and resulting low birth weight has important implications for offspring outcomes, including increased risk of cardiovascular and metabolic disorders (e.g., hypertension, coronary heart disease, type II diabetes mellitus, insulin resistance, and hyperlipidemia), depression, schizophrenia, and autism [2]. Research suggests that these health conditions may be related to early growth patterns. ...
Article
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Fetal/infant growth affects adult obesity and morbidities/mortality and has been associated with prenatal exposure to cortisol. Bidirectional relations between maternal stress and breastfeeding suggest that they interact to influence offspring growth. No models have tested this hypothesis, particularly regarding longer-term offspring outcomes. We used a subset of the IDAHO Mom Study (n = 19–95) to examine associations among maternal prenatal cortisol (cortisol awakening response (CAR) and area under the curve), and standardized weight-for-length (WLZ) and length-for-age (LAZ) z-scores from birth-18 months, and main and interactive effects of prenatal cortisol and breastfeeding on infant growth from birth-6 months. CAR was negatively associated with LAZ at birth (r = −0.247, p = 0.039) but positively associated at 13–14 months (r = 0.378, p = 0.033), suggesting infant catch-up growth with lower birth weights, likely related to elevated cortisol exposure, continues beyond early infancy. A negative correlation between breastfeeding and 10-month WLZ (r = −0.344, p = 0.037) and LAZ (r = −0.468, p = 0.005) suggests that breastfeeding assists in managing infant growth. WLZ and LAZ increased from birth to 6 months (ps < 0.01), though this was unrelated to interactions between prenatal cortisol and breastfeeding (i.e., no significant moderation), suggesting that other factors played a role, which should be further investigated. Findings add to our understanding of the predictors of infant growth.
... Algunos estudios incluso apuntan a que el manejo inadecuado del estrés crónico, como tomar comidas poco saludables o en exceso para sentirse mejor, ha contribuido a la creciente epidemia de obesidad (Field, 2008;Ramos & Jordao, 2015;Sinha, 2008). ...
... Some studies have even suggested that inappropriate chronic stress management, such as eating unhealthy or comfort foods, has contributed to the growing obesity epidemic (Field, 2008;Ramos & Jordao, 2015;Sinha, 2008). ...
... Investigaciones recientes han sugerido que las terapias de reducción de cortisol, tales como la terapia de masaje, pueden reducir el riesgo de complicaciones perinatales, incluyendo la prematuridad y el bajo peso al nacer (Field & Diego, 2008). occupational stress was assessed before and after twelve weeks of aromatherapy massage with music and anxiety was measured before and after each massage session. ...
... The secretion of cortisol levels during pregnancy is regulated by the placenta, which, by secreting the corticotropin-releasing hormone (CRH), produces an exponential increase in cortisol from the eighth week of gestation up to three times above systemic values [5,36]. It is present in both the maternal and fetal phases but at different levels; under normal conditions, cortisol levels reach 200 ng/ml at the end of pregnancy, while fetal levels range from around 20 ng/ml [37]. ...
... As for the functions of cortisol during pregnancy, glucocorticoids (GC) have been described as participating in the processes of implantation and formation of decidua, as well as in fetal development and maturation, and initiation of childbirth [17,36,42]. Elevated levels of GC present during pregnancy are involved in the suppression of inflammation of the uterus, placenta, and fetal membranes, which contributes to maintaining the homeostasis necessary for the maintenance of pregnancy [42]. ...
... On the one hand, it has been shown that low maternal cortisol levels compromise the placenta's structure. In contrast, elevated levels can lead to miscarriages, uterine contractions from placental CRH deregulation, the elevation of fetal cortisol levels, and obstetric alterations by activation of the HPA gland axis [14,36,38,45]. In this sense, two main axes, the HPA, and the sympathetic nervous system-adrenal medulla exerts a negative effect on the reproductive system when activated in stressful situations. ...
Chapter
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Pregnancy is characterized by hormonal changes, critical for the mother’s physiological adaptation, exercising a role in the fetus’s development, maintenance, protection, and nutrition. Since born, the neuroendocrine system’s involvement is necessary to prevent the embryo from being rejected by the mother’s immune system. These changes are regulated by fluctuations in hormones such as Progesterone, Testosterone, Androstenedione, Dehydroepiandrosterone, Estradiol, Prolactin, human Placental Lactogen, human Chorionic Gonadotropin, and Thyroid hormones, which promote the mother’s development and the fetus (maternal-fetal development). Therefore, given the great importance of these hormones during pregnancy, this chapter will explain the preclinical and clinical participation of sex hormones in maternal-fetal development.
... Algunos estudios incluso apuntan a que el manejo inadecuado del estrés crónico, como tomar comidas poco saludables o en exceso para sentirse mejor, ha contribuido a la creciente epidemia de obesidad (Field, 2008;Ramos & Jordao, 2015;Sinha, 2008). ...
... Some studies have even suggested that inappropriate chronic stress management, such as eating unhealthy or comfort foods, has contributed to the growing obesity epidemic (Field, 2008;Ramos & Jordao, 2015;Sinha, 2008). ...
... Investigaciones recientes han sugerido que las terapias de reducción de cortisol, tales como la terapia de masaje, pueden reducir el riesgo de complicaciones perinatales, incluyendo la prematuridad y el bajo peso al nacer (Field & Diego, 2008). occupational stress was assessed before and after twelve weeks of aromatherapy massage with music and anxiety was measured before and after each massage session. ...
... To estimate the effects of exposure to armed conflict during pregnancy on birth weight outcomes and tackle the lack of consensus on the relative importance of the exposure timing (Lunney, 1998;Field et al., 2006;Field and Diego, 2008), we adopt the difference-in-differences (DiD) model, given by, ...
... Together with these studies, our findings provide evidence supporting the importance of the first trimester. Nevertheless, our presented results stand in contrast with papers pointing to the effects of intrauterine exposure to adverse events during the second and the third trimesters(Lunney, 1998;Field et al., 2006;Field and Diego, 2008).Our results represent the serious but less visible cost of conflict. Specifically, the deteriorating impacts on birth weight outcomes underline the detrimental ramifications of armed conflict on long-term human capital, given that poor infant health can leave lasting consequences over the life cycle such as higher susceptibility to diseases, lower educational attainment, andworsening labor market outcome (Reyes and Manalich, 2005; Black et al., 2007; Oreopoulos et al., 2008; Xie et al., 2019). ...
Article
This paper investigates the hidden yet persistent cost of conflict to birth weight outcomes for 53 developing countries experiencing conflict in the past three decades (1990-2018). Exploiting the variation across districts and conception months-years, we find that intrauterine exposure to armed conflict in the first trimester of pregnancy reduces child’s weight at birth by 2.8% and raises the incidence of low birth weight by 3.2 percentage points. Infants born to poor and low educated mothers are especially vulnerable to the adverse repercussions of armed conflict. Given the long-lasting consequences of poor infant health over the life cycle, our findings call for global efforts in the prevention and mitigation of conflict. Extra attention should be directed to children and women from disadvantaged backgrounds.
... Additionnaly, a prospective cohort study with 1,367 participants accros USA found an associationbetween high prenatal maternal stress and preterm delivery during COVID-19 pandemic (20). According to the Anglo-Saxon theory of "Prenatal early Life Stress, " there is an increase in Corticotrophin Releasing Hormon (CRH) and cortisol in stressed or depressed mothers (21). ...
... However, cortisol has a deleterious effect on obstetric parameters (prematurity, modification of fetal activity, intrauterine growth retardation) (21). It crosses the placental barrier influencing the development of the fetal nervous system and modifying the programming of the hypothalamiccorticotropic axis of the child which may later be responsible for attention and behavioral disturbances. ...
Article
Full-text available
During the COVID-19 pandemic, there were an increasing prevalence of perinatal psychiatric symptoms, such as perinatal anxiety, depression, and post-traumatic stress disorders. This growth could be caused by a range of direct and indirect stress factors related to the virus and changes in health, social and economic organization. In this review, we explore the impact of COVID-19 pandemic on perinatal mental health, and propose a range of hypothesis about their etiological mechanisms. We suggest first that the fear of being infected or infected others (intrauterine transmission, passage of the virus from mother to baby during childbirth, infection through breast milk), and the uncertainty about the effect of the virus on the fetuses and infants may have played a key-role to weakening the mental health of mothers. We also highlight that public health policies such as lockdown, limiting prenatal visits, social distancing measures, and their many associated socio-economic consequences (unemployment, loss of income, and domestic violence) may have been an additional challenge for perinatal mental health. Ground on these hypotheses, we finally purpose some recommendations to protect perinatal mental health during a pandemic, including a range of specific support based on digital technologies (video consultations, phone applications) during pregnancy and the postpartum period.
... Exposure to prenatal stress can have life-long negative impacts on offspring mental health and wellbeing, and the mechanisms underlying these risks have yet to be completely defined. Maternal immune and glucocorticoid responses have repeatedly been demonstrated to be two of the primary drivers of poor infant outcomes 49,50 , although variability in stress severity and duration of exposure make it difficult to pinpoint critical activation thresholds of these cellular and molecular signaling pathways. Expanding investigations of the maternal microbiome during stress and gestation also highlight microbes as primary mediators of immune status and infant neurodevelopment 51 . ...
... If anything, a reduction in maternal splenic production of IL-1β would indicate the opposite in our model, which is consistent with the immunosuppressive phenotype induced by restraint stress 61,62 . An activation of the HPA axis and increased circulating corticosterone observed here, which is continually described in both humans and animals during prenatal stress 49,63 , contributes to this immunosuppressive phenotype 62 . ...
Preprint
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Maternal stress during pregnancy is widespread and stress-induced fetal neuroinflammation is thought to derive from a disruption in intrauterine immune homeostasis, though the exact origins are incompletely defined. We aimed to identify divergent immune and microbial metagenome profiles of stressed gestating mice that may underlie detrimental inflammatory signaling at the maternal-fetal interface. In response to stress, maternal glucocorticoid circuit activation corresponded with diminished spleen mass and IL-1β production, reflecting systemic immunosuppression. At the maternal-fetal interface, density of placental mononuclear leukocytes decreased with stress. Yet maternal whole blood leukocyte analysis indicated monocytosis and classical M1 phenotypic shifts. Genome-resolved microbial metagenomic analyses revealed reductions in genes, microbial strains, and metabolic pathways in stressed dams that are primarily associated with pro-inflammatory function. Overall, these data indicate that stress disrupts maternal immunological and microbial regulation during pregnancy, characterized by concurrent anti- and pro-inflammatory signatures, which may displace immune equilibrium at the maternal-fetal interface.
... This may cause elevated maternal cortisol levels, which may be associated with a rise in fetal cortisol concentrations (Mulder, Mennes, & Glover, 2005). While acute cortisol response to stress is adaptive to deal with threats in the environment, excessive cortisol can negatively affect fetal development (Field & Diego, 2008). Cortisol is involved in the fetal programming of the HPA axis and can modulate cell proliferation and differentiation as well as synaptic development (Coe et al., 2003;Yu, Lee, Lee, & Son, 2004). ...
... Elevated cortisol levels during pregnancy have been related to increased negative reactivity during infancy, and an increased stress response at school-age (Davis et al., 2007;Field & Diego, 2008;Field, Diego, Hernandez-Reif, Gil, & Vera, 2005;Gutteling, de Weerth, & Buitelaar, 2005;Nepomnaschy et al., 2006). The mechanisms responsible for these effects are still unclear; however, it has been suggested that some of the effects may be due, in part, to alterations in fetal physiology, brain glucocorticoid receptor development, and reduced uteroplacental blood flow . ...
Article
Opioid maintenance therapy (OMT) is generally recommended for pregnant opioid‐dependent women. However, much is still unknown about the potential long‐term effects of prenatal methadone and buprenorphine exposure. This study explored the long‐term effects of prenatal methadone and buprenorphine exposure in a cohort (n = 41) of children, aged 9–11 years, using the Wechsler Abbreviated Scale of Intelligence (WASI) to measure cognitive development and salivary cortisol samples to measure HPA‐axis activity. Prenatally exposed children scored significantly lower on all four subtests of WASI (vocabulary, similarities, block design, and matrix reasoning), compared to a comparison group (all p < .05). No group differences were found for salivary cortisol levels or cortisol reactivity levels (all p > .05). Cortisol levels significantly predicted matrix reasoning scores for the OMT group, β = −65.58, t(20) = 15.70, p = .02. Findings suggest that prenatal exposure to methadone or buprenorphine does not have long‐term effects on children's HPA‐axis functioning. However, since children of women in OMT scored significantly lower on tasks of cognitive function, careful follow‐up throughout the school years and across adolescence is recommended.
... After 25 weeks of gestation, the CRH levels rapidly increase to levels usually only observed during stress [30, 32, 33•]. Placental CRH stimulates release of cortisol and overcomes the HPA axis negative feedback system [32,34]. High levels of cortisol are sustained throughout pregnancy and into the postpartum period as an adaptive function to promote fetal development, conserve energy for lactation, improve the function of the immune system, and enhance maternal defense [6, 30, 31•]. ...
... However, a balance is required as the fetal brain is vulnerable to excessive exposure to glucocorticoid. Studies have noted elevated levels of cortisol predict premature delivery and psychomotor developmental problems such as growth delays and maladaptive behaviors [34]. ...
Article
Full-text available
Purpose of Review Our current understanding of the underlying mechanisms and etiologies of perinatal mood and anxiety disorders (PMADs) is not clearly identified. The relationship of stress-induced adaptations (i.e., the hypothalamic-pituitary-adrenal (HPA) axis, the autonomic nervous system (ANS), the immune system) and the microbiota are potential contributors to psychopathology exhibited in women during pregnancy and postpartum and should be investigated. Recent Findings The stress response activates the HPA axis and dysregulates the ANS, leading to the inhibition of the parasympathetic system. Sustained high levels of cortisol, reduced heart variability, and modulated immune responses increase the vulnerability to PMAD. Bidirectional communication between the nervous system and the microbiota is an important factor to alter host homeostasis and development of PMAD. Summary Future research in the relationship between the psychoneuroimmune system, the gut microbiota, and PMAD has the potential to be integrated in clinical practice to improve screening, diagnosis, and treatment.
... According to conventional wisdom, gestational stress increases the risk of pregnancy miscarriages and predisposes the mother to perinatal infections, premature labor, hemorrhages and preeclampsia [1][2][3][4][5][6][7][8][9][10][11][12]. Children are also presumed to be negatively affected by prenatal stress since it predisposes them to develop mood disorders, attention deficit disorder, perinatal infections, and obesity at early ages and cancer and/ or degenerative disorders in adulthood (e.g., cardiovascular disease, cancer, diabetes, obesity, and behavioral, cognitive, and mood disorders) [13][14][15][16][17][18]. ...
... To overcome these shortcomings, we believe that future studies must consider the dynamic nature of the HPA axis in pregnant women, understanding its true nature with its positive faces such as fetal programming and maturation [10,[58][59][60][61] and embryo/fetal immune tolerance [1,32,[61][62][63][64][65], that is, the recognition of the allostatic stress condition that promotes pregnancy and a new stress model that takes into account the interaction of what is perceived as stressful by the pregnant woman, the coping mechanisms which are launched, and the stress-related physiological states (Figure 2). This complex stress-related physiological state could not be assessed with cortisol as the unique biomarker. ...
Article
Full-text available
Gestational stress is believed to increase the risk of pregnancy failure and perinatal and adult morbidity and mortality in both the mother and her child or children. However, some contradictions might arise from methodological issues or even from differences in the philosophical grounds that guide the studies on gestational stress. Biased perspectives could lead us to use and/or design inadequate/incomplete panels of biochemical determinations and/or psychological instruments to diagnose it accurately during pregnancy, a psychoneuroimmune-endocrine state in which allostatic loads may be significant. Here, we review these notions and propose a model to evaluate and diagnose stress during pregnancy.
... Weight-for-Height Weight-for-Age Z-Score Z-Score Z-Score which also emphasize the health threat induced by the last two trimester exposure to negative shocks [40][41][42][43]. ...
... Our study adds to this literature by exploiting drought as an adverse in-utero shock to evaluate the persistent effects of prenatal conditions. Furthermore, our findings are in accordance with studies emphasizing the importance of second and third trimester exposure to child outcomes [40][41][42]. ...
Article
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This paper investigates the extent to which in-utero exposure to droughts influences the health outcomes of Bangladeshi children in early childhood. Exploiting the plausibly exogenous deviations of rainfall from the location-specific norms, we find that deficient rainfall during the prenatal period is harmful to child health. Specifically, in-utero exposure to droughts decreases the height-for-age, weight-for-height, and weight-for-age z-scores by 0.10, 0.11, and 0.11 standard deviations among children under five years old, respectively. Our heterogeneity analyses reveal that the adverse health setbacks fall disproportionately on children of disadvantaged backgrounds. Exploring the differential effects by trimesters of exposure, we further show that experiencing droughts during the second and the third trimesters leaves injurious effects on early childhood health.
... Fetal exposure to elevated cortisol levels may dysregulate fetal autonomic nervous system activity and result in a high degree of calorie expenditure by mobilizing fetal energy stores through glycogenesis [6]. Alternatively, cortisol combined with norepinephrine may induce uterine artery vasoconstriction, resulting in reduced uterine blood flow, restricting nutrient and oxygen supply to the fetus [17]. Cortisol could also affect birth weight by stimulating the production and release of placental corticotrophin releasing hormone (CRH), leading to shortened gestation [18]. ...
... Results of the exploratory analyses on associations between awakening salivary cortisol levels in mid-pregnancy and the risk of preterm birth, low birth weight, and small-for- In the same prospective cohort study of 2810 women, an association was observed between high morning cortisol levels (≥ 90th percentile) and an increased risk of SGA, concordant with our findings. Several potential pathways underlying the associations between elevated maternal cortisol levels and adverse birth outcomes have been suggested, including dysregulation of the fetal autonomic nervous system [6], vasoconstriction of the uterine artery resulting in reduced uterine blood flow [17], and stimulation of the production and release of placental CRH [18]. Specifically for SGA, an association with disturbed expression and/or activity of placental 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), an enzyme that protects the fetus from high levels of maternal cortisol, has been observed [46][47][48][49][50]. Interestingly, decreased functioning of 11β-HSD2 in SGA infants has only been observed in pregnancies with female fetuses [51]. ...
Article
Full-text available
Purpose Elevated levels of maternal cortisol have been hypothesized as the intermediate process between symptoms of depression and psychosocial stress during pregnancy and adverse birth outcomes. Therefore, we examined associations between cortisol levels in the second trimester of pregnancy and risks of three common birth outcomes in a nested case–control study. Methods This study was embedded in the PRIDE Study (n = 3,019), from which we selected all cases with preterm birth (n = 64), low birth weight (n = 49), and small-for-gestational age (SGA; n = 65), and 260 randomly selected controls, among the participants who provided a single awakening saliva sample in approximately gestational week 19 in 2012–2016. Multivariable linear and logistic regression was performed to assess the associations between continuous and categorized cortisol levels and the selected outcomes. Results We did not observe any associations between maternal cortisol levels and preterm birth and low birth weight. However, high cortisol levels (≥ 90th percentile) seemed to be associated with SGA (adjusted odds ratio 2.1, 95% confidence interval 0.9–4.8), in particular among girls (adjusted odds ratio 3.7, 95% confidence interval 1.1–11.9, based on eight exposed cases) in an exploratory analysis. Conclusion The results of this study showed no suggestions of associations between maternal awakening cortisol levels in mid-pregnancy and adverse birth outcomes, except for an increased risk of SGA.
... Dysregulation of the maternal hypothalamic-pituitary-adrenal axis (HPAA) in pregnancy has been hypothesized to impact fetal development negatively, with potentially long-term consequences. Studies have linked prenatal exposure to disrupted cortisol levels in utero to numerous maladaptive outcomes across the lifespan, including poor fetal physical development and child health problems; disrupted HPAA functioning; cortical thinning evident into childhood; poorer cognitive and motor development; elevated negative affectivity and difficult temperament in infancy and toddlerhood; greater emotional and behavior problems in childhood; and increased risk for posttraumatic stress disorder in adulthood (Brand et al., 2006;Davis et al., 2007;Davis et al., 2013;de Weerth et al., 2003;Bosquet Enlow et al., 2017;Field and Diego, 2008;Zijlmans et al., 2015). Therefore, identifying factors that influence functioning of the maternal HPAA functioning in pregnancy has important public health implications. ...
Article
Dysregulation of the maternal-fetal hypothalamic-pituitary-adrenal axis (HPAA) has been hypothesized to negatively influence various offspring physical and mental health outcomes. Limited data suggest that low maternal socioeconomic status (SES) in pregnancy may disrupt maternal HPAA functioning. Research is needed that examines how maternal SES in childhood may influence maternal HPAA functioning in pregnancy, given evidence that early life adversity can have persistent effects on physiological stress reactivity. In a sample of 343 sociodemographically diverse women, we tested whether indices of life course SES were associated with HPAA functioning across pregnancy reflected in hair cortisol collected within one week after delivery. Mothers were asked whether their parent(s) owned their home across three developmental periods, from birth through adolescence, as an indicator of their childhood SES. Measures of maternal SES in pregnancy included maternal educational attainment, annual household income, and current homeownership. Analyses revealed that indicators of lower maternal SES in childhood and in pregnancy were associated with higher cortisol levels during each trimester. In analyses adjusted for maternal race/ethnicity, pre-pregnancy body mass index, smoking in pregnancy, use of inhaled and topical corticosteroids, and mode of delivery, each indicator of maternal SES in pregnancy fully mediated maternal childhood SES effects on maternal hair cortisol levels in pregnancy. This is the first study to show an association between maternal life course SES and hair cortisol in pregnancy. The results suggest that maternal SES, starting in childhood, may have intergenerational consequences via disruption to the maternal-fetal HPAA in pregnancy. These findings have implications for elucidating mechanisms contributing to health disparities among socioeconomically disadvantaged populations.
... As a result, disturbances in the normal levels and amounts of exposure of these biological effectors can result in altered function and long-term disease risk [10]. As a common example, dysregulation of the hypothalamic-pituitary (HPA) axis during pregnancy is associated with increased levels of maternal cortisol, which elevates risks for premature delivery and low birth weight and can cross the placenta to have direct "programming" effects on fetal metabolism and physiology [11,12]. Hypertension has been shown to lead to lower birth weights, likely operating through factors like altered blood flow, along with the common co-occurrence of elevated inflammatory cytokines that can suppress growth [13,14]. ...
Article
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Adverse birth outcomes, such as early gestational age and low birth weight, can have lasting effects on morbidity and mortality, with impacts that persist into adulthood. Identifying the maternal factors that contribute to adverse birth outcomes in the next generation is thus a priority. Epigenetic clocks, which have emerged as powerful tools for quantifying biological aging and various dimensions of physiological dysregulation, hold promise for clarifying relationships between maternal biology and infant health, including the maternal factors or states that predict birth outcomes. Nevertheless, studies exploring the relationship between maternal epigenetic age and birth outcomes remain few. Here, we attempt to replicate a series of analyses previously reported in a US-based sample, using a larger similarly aged sample (n = 296) of participants of a long-running study in the Philippines. New pregnancies were identified prospectively, dried blood spot samples were collected during the third trimester, and information was obtained on gestational age at delivery and offspring weight after birth. Genome-wide DNA methylation was assessed with the Infinium EPIC array. Using a suite of 15 epigenetic clocks, we only found one significant relationship: advanced age on the epigenetic clock trained on leptin predicted a significantly earlier gestational age at delivery (β = − 0.15, p = 0.009). Of the other 29 relationships tested predicting gestational age and offspring birth weight, none were statistically significant. In this sample of Filipino women, epigenetic clocks capturing multiple dimensions of biology and health do not predict birth outcomes in offspring.
... Dysregulation of the maternal hypothalamic-pituitary-adrenal axis (HPAA) in pregnancy has been hypothesized to impact fetal development negatively, with potentially long-term consequences. Studies have linked prenatal exposure to disrupted cortisol levels in utero to numerous maladaptive outcomes across the lifespan, including poor fetal physical development and child health problems; disrupted HPAA functioning; cortical thinning evident into childhood; poorer cognitive and motor development; elevated negative affectivity and difficult temperament in infancy and toddlerhood; greater emotional and behavior problems in childhood; and increased risk for posttraumatic stress disorder in adulthood (Brand et al., 2006;Davis et al., 2007;Davis et al., 2013;de Weerth et al., 2003;Bosquet Enlow et al., 2017;Field and Diego, 2008;Zijlmans et al., 2015). Therefore, identifying factors that influence functioning of the maternal HPAA functioning in pregnancy has important public health implications. ...
... Moreover, exposure to prenatal stress is commonly considered to be an important factor in the development of a number of forms of psychopathology, such as Attention Deficit Hyperactivity Disorder, schizophrenia and adult depression (Hultman et al. 1997). These situations lead to morbid states, such as pre-eclampsia, miscarriage, compromised foetal growth, pre-term induction of labour, low birthweight, delayed post-natal psychomotor development and a greater incidence of infections during pregnancy and postpartum, among other complications (Diego et al. 2006;Field/ Diego 2008). The pathogenesis of pre-eclampsia and other hypertensive states during pregnancy is associated with exacerbated inflammatory processes and poor renal function (Sargent et al. 2007), which control not only blood pressure but also the secretion of hormones, such as cortisol and noradrenaline. ...
Chapter
A normal pregnancy is defined as the physiological state of a woman from fertilization to the birth of one or more living, healthy and full-term infants. Meanwhile, the term high-risk pregnancy refers to anomalous gestational conditions (e.g. eclampsia), which increase the possibility of pathophysiological states in the mother and/or the infant. There are several biological, gynaeco-obstetric and social risk factors for a high risk pregnancy. Conditions such as malnutrition, negative emotions, perceived stress and maternal anxiety are predictors of pathological conditions in both mother and child (e.g. obesity, diabetes, different types of cancer and some neurological and cardiovascular pathology). This scenario requires a modification of the concept of ‘high-risk pregnancy’, and advocates taking into account the monitoring of stress, anxiety, depression and food quality during pregnancy as potential risk factors not only for the baby, but also for subsequent generations.
... High levels of maternal stress during pregnancy can result in fetal exposure to increased levels of cortisol in-utero resulting in low birth-weight, prematurity, and increased cortisol levels in infants (Cottrell & Seckl, 2009;Field & Diego, 2008). Furthermore, there is empirical evidence linking maternal prenatal stress levels to impediments in the development of behavioral and emotional regulation among offspring, including temperament difficulties during infancy (e.g., Bergman, Sarkar, O'connor, Modi, & Glover, 2007), negative emotionality and inhibition in the preschool years (e.g., Martin, Noyes, Wisenbaker, & Huttunen, 1999), and internalizing and externalizing problems in childhood and adolescence (e.g., Davis & Sandman, 2012). ...
Chapter
Research in the health sciences has a long tradition of considering the impact of prenatal and perinatal health on child and adolescent development generally. This same consideration has not been echoed in the field of criminology where comparatively less research has investigated the link between prenatal and perinatal health and delinquency and offending over the life-course. This chapter reviews the empirical evidence on some of the key prenatal and perinatal risk factors that have been linked to offspring behavioral problems in childhood, juvenile delinquency, and offending later in life. These include: maternal substance use and stress during pregnancy; low birth weight; prematurity; and, birth and pregnancy complications. While the empirical evidence shows these factors are associated with childhood behavioral problems, and later related outcomes such as juvenile delinquency and even adult offending in some studies, the balance of evidence suggests they are moderated by environmental factors (e.g., parent characteristics, social disadvantage), and possibly even genetic differences in offspring. From a delinquency prevention point of view, prenatal and perinatal risk factors need to be understood in a broader ecological context that accounts for individual differences in offspring, family characteristics and social disadvantage, to inform multimodal and longitudinal prevention of juvenile delinquency. Furthermore, future research on the link between prenatal and perinatal health and delinquency needs to consider a broader scope of health risk factors that have demonstrated links with adverse developmental outcomes in other domains.
... Atypical cortisol levels during pregnancy are associated with a plethora of negative perinatal outcomes, including, but not limited to, miscarriage (Nepomnaschy et al., 2006), premature birth, decreased birth weight (Field & Diego, 2008), and elevated child cortisol levels (Gutteling, Weerth, & Buitelaar, 2005). Thus, although cortisol output is expected to increase over the course of pregnancy, individual differences in HCC during pregnancy persist and may provide information regarding longer term maternal stress that influences parenting behavior in the postpartum period. ...
Article
Disrupted maternal interaction in early infancy is associated with maladaptive child outcomes. Thus, identifying early risk factors for disrupted interaction is an important challenge. Research suggests that maternal depressive symptoms and maternal cortisol dysregulation are associated with disrupted maternal interaction, but both factors have rarely been considered together as independent or interactive predictors of disrupted interaction. In a sample of 51 women, hair cortisol concentrations (HCC) and depressive symptoms were assessed during pregnancy, and depressive symptoms were assessed again at 4‐month postpartum. Maternal disrupted interaction was assessed during the Still‐Face Paradigm at 4 months. Results indicated that HCC and depressive symptoms interacted to predict both maternal withdrawing and inappropriate/intrusive interaction. Withdrawing interaction was associated with high levels of HCC in pregnancy in the context of high depressive symptoms at 4 months; inappropriate/intrusive interaction was associated with high levels of HCC in the context of low depressive symptoms. Thus, high HCC potentiated both forms of disrupted interaction. Results raised questions about the meaning of very low reported depressive symptoms, and underscored the importance of chronic stress physiology and maternal depressed mood as risk factors for distinct forms of maternal disrupted interaction, both of which are deleterious for infant development.
... The results of our study showed that there was no significant correlation between cortisol levels and PSS-14 and SCL-90 with demographic and reproductive characteristics, whereas in one study, an increase in cortisol level was associated with an increase in abortion and delayed fetal growth. [27] In another study, cortisol level was higher in the mothers with secondary schooling than less schooling. [22] In our study, cortisol levels showed no significant correlation with PSS-14 and SCL-90 scores in the two groups. ...
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Background: Postpartum period and recurrent abortion are stressful conditions that affect women's mental health. Stress and depression lead to the release of stress biomarkers that may be dangerous for the mother and fetus. The aim of this study was to determine stress in the after recurrent pregnancy loss (RPL) and normal vaginal delivery (NVD) in the north of Iran. Materials and methods: This case-control study was done on forty women with NVD and forty women with RPL. Stress was measured through measuring serum cortisol, Perceived Stress Scale-14 (PSS-14), and the revised version of the Symptom Checklist-90 (SCL-90-R). Data were analyzed using the Statistical Package for the Social Sciences (SPSS) 22.0 software. Chi-square test, independent-samples t-test, Mann-Whitney U-test, and Pearson correlation were used to analyze the data. Results: Findings showed that nonpregnant healthy women had significantly higher cortisol level than RPL women (mean ± standard deviation [SD]: 155.80 ± 84.97 ng/ml and 126.02 ± 50.44 ng/ml, P < 0.011), respectively. Furthermore, they had higher PSS-14 and SCL-90 scores than PRL women (mean ± SD: 25.87 ± 7.48 and 25.5 ± 9.19, P = 0.745, and mean ± SD: 1.27±0.63 and 1.20 ± 0.53, P = 0.624), respectively. Conclusions: High levels of cortisol reflect the acute stress caused by the care of the baby in women. Therefore, social support for the pregnant woman by the health-care team is an essential factor for reducing postpartum depression.
... PTSD occurs in about 8% of pregnant women as reported in a study from the US [5], with the rate as high as 42% for displaced/migrating women [6]. Maternal exposure to stressful situations during pregnancy may have effects on their pregnancy, fetal development and birth outcomes which might result from the maternal endocrine and immune system response to these stressful stimuli [7,8]. Research has found associations between adverse pregnancy and birth outcomes and higher risk of morbidity and mortality of the newborn, both in the short and long term [9][10][11]. ...
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Background: The northern part of the province of Khyber Pakhtunkhwa in Pakistan experienced armed conflict since September 2007 till the autumn of 2011. Conflict involved widespread insurgency activity and military intervention including in 2009 internally displacing the 2.5 million people of the valley of Swat to live in camps, with relatives, or in rented accommodation across the region for approximately 4 months. It was during this period the current study was conducted to determine whether Post-Traumatic Stress Disorder in pregnant women was independently associated with Low Birth Weight (LBW) in an area affected by conflict and militancy. Methods: A case control study was conducted in tertiary care hospitals of district Peshawar, Khyber Pakhtunkhwa. Two hundred twenty-five cases (neonates with birth weight < 2.5 kg) and 225 controls (neonates with birth weight of > 2.5 kg) were enrolled within 24 h of delivery. Post-Traumatic Stress Disorder was assessed through the MINI Neuropsychiatric Interview 5.0, a validated questionnaire along with the birth weight of the newborn. Maternal anthropometry, anemia and other sociodemographic details were also obtained during data collection. Data was analyzed using statistical package (STATA version 14). Logistic regression analysis of the association between LBW and all variables collected with a p-value of < 0.25 on uni-variate analysis were entered. Results: A total of 450 newborn and mother pairs participated in the study with 225 cases and 225 controls. On univariate analysis factors significantly associated with LBW include: less than 5 years of paternal schooling and PTSD. On logistic regression, PTSD was independently associated with low birth weight in the presence of other factors like maternal/paternal schooling, gravida, history of preterm, BMI of the mother and maternal anemia. Conclusion: PTSD was found to be independently associated with LBW. In light of the current findings and other similar literature, intervention programs should be considered for pregnant women exposed to traumatic events.
... Other available gastric findings regarding clotting gastric bleeding that may be due to ooze microbleeding caused by peripartum or delivery stress [27]. In addition, neonatal stress is also due to higher cortisol levels in blood [28]. OMT may be effective in reducing and balancing neonatal stress thereby decreasing gastric bleeding. ...
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The aim of this study was to assess the impact of osteopathic manipulative treatment (OMT) on newborn babies admitted at a neonatal intensive care unit (NICU). This was an observational, longitudinal, retrospective study. All consecutive admitted babies were analyzed by treatment (OMT vs. usual care). Treatment group was randomly assigned. Between-group differences in weekly weight change and length of stay (LOS) were evaluated in the overall and preterm populations. Among 1249 babies (48.9% preterm) recorded, 652 received usual care and 597 received OMT. Weight increase was more marked in the OMT group than in the control group (weekly change: +83 g vs. +35 g; p < 0.001). Similar trends were found in the subgroup of preterm babies. A shorter LOS was found in the OMT group vs. the usual care group both in overall population (average mean difference: −7.9 days, p = 0.15) and in preterm babies (−12.3 days; p = 0.04). In severe preterm babies, mean LOS was more than halved as compared to the control group. OMT was associated with a more marked weekly weight increase and, especially in preterm babies, to a relevant LOS reduction: OMT may represent an efficient support to usual care in newborn babies admitted at a NICU.
... When the significantly altered metabolites were identified from both experiments, it was noted that they belonged to 4 categories: 4 were amino acids, 3 were bile acids, 2 were hormones and 1 was porphyrin (Table II, Fig. 3). Alterations in these metabolites have been associated with several negative pregnancy outcomes including abortion, fetal growth abnormality, prematurity and low birth weight (19). For example, in a rat intrauterine growth restriction model, elevated maternal and fetal corticosterone levels were reported in serum and AF (20). ...
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Although monitoring and diagnosis of fetal diseases in utero remains a challenge, metabolomics may provide an additional tool to study the etiology and pathophysiology of fetal diseases at a functional level. In order to explore specific markers of fetal disease, metabolites were analyzed in two separate sets of experiments using amniotic fluid from fetuses with Down syndrome (DS) as a model. Both sets included 10‑15 pairs of controls and cases, and amniotic fluid samples were processed separately; metabolomic fingerprinting was then conducted using UPLC‑MS. Significantly altered metabolites involved in respective metabolic pathways were compared in the two experimental sets. In addition, significantly altered metabolic pathways were further compared with the genomic characters of the DS fetuses. The data suggested that metabolic profiles varied across different experiments, however alterations in the 4 metabolic pathways of the porphyrin metabolism, bile acid metabolism, hormone metabolism and amino acid metabolism, were validated for the two experimental sets. Significant changes in metabolites of coproporphyrin III, glycocholic acid, taurochenodeoxycholate, taurocholate, hydrocortisone, pregnenolone sulfate, L‑histidine, L‑arginine, L‑glutamate and L‑glutamine were further confirmed. Analysis of these metabolic alterations was linked to aberrant gene expression at chromosome 21 of the DS fetus. The decrease in coproporphyrin III in the DS fetus may portend abnormal erythropoiesis, and unbalanced glutamine‑glutamate concentration was observed to be closely associated with abnormal brain development in the DS fetus. Therefore, alterations in amniotic fluid metabolites may provide important clues to understanding the etiology of fetal disease and help to develop diagnostic testing for clinical applications.
... One maternal physiological component of prenatal stress is elevation of plasma corticosterone levels [11]. Previous work implicates corticosterone as a key mediator in effects of prenatal stress on the embryo [14] and has been shown to influence microglia [9]. Prenatal stress also elevates pro-inflammatory cytokines, including interleukin-1β (IL-1β) [15], and the embryonic brain is known to be sensitive to maternal cytokines [13,16]. ...
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Maternal stress during pregnancy is associated with an increased risk of psychopathology in offspring. Resident immune cells of the brain, microglia, may be mediators of prenatal stress and altered neurodevelopment. Here, we demonstrate that neither the exogenous pro-inflammatory cytokine, interleukin-1β (IL-1β), nor the glucocorticoid hormone, corticosterone, recapitulated the full effects of prenatal stress on the morphology of microglial cells in the cortical plate of embryonic mice; IL-1β effects showed greater similarity to prenatal stress effects on microglia. Unexpectedly, oil vehicle alone, which has antioxidant properties, moderated the effects of prenatal stress on microglia. Microglia changes with prenatal stress were also sensitive to the antioxidant, N-acetylcysteine, suggesting redox dysregulation as a mechanism of prenatal stress.
... Indeed, through an alteration in the hypothalamic-pituitary-adrenal axis, early life or chronic stress may lead to atypical cerebral lateralization and to neurodevelopmental or psychiatric disorders (Berretz et al., 2020). Following this view, Davis et al. (2022) showed that prematurity, which is related to early life stress (Field & Diego, 2008), exhibits atypical functional lateralization. ...
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Genetics are undoubtedly implicated in the ontogenesis of laterality. Nonetheless, environmental factors, such as the intrauterine environment, may also play a role in the development of functional and behavioral lateralization. The aim of this study was to test the Left‐Otolithic Dominance Theory (LODT; Previc, 1991) by investigating a hypothetical developmental pattern where it is assumed that a breech presentation, which is putatively associated with a dysfunctional and weakly lateralized vestibular system, can lead to weak handedness and atypical development associated with language and motor difficulties. We used the ALSPAC cohort of children from 7 to 10 years of age to conduct our investigation. Our results failed to show an association between the vestibular system and fetal presentation, nor any influence of the latter on hand preference, hand performance, or language and motor development. Bayesian statistical analyses supported these findings. Contrary to our LODT‐derived hypotheses, this study offers evidence that fetal presentation does not influence the vestibular system's lateralization and seems to be a poor indicator for handedness. Nonetheless, we found that another non‐genetic factor, prematurity, could lead to atypical development of handedness. This article is protected by copyright. All rights reserved
... Fortunately, the placenta attenuates fetal exposure to stress hormones by converting cortisol into its inactive metabolites but if stress is very intense or becomes chronic, this mechanism is insufficient (471,472). Owing to rapid and genomic actions of stress hormones [especially cortisol (128)], gestational stress (GS) can disrupt fetal brain development. As a result, stressful life events, depression, and anxiety experienced by the mother during pregnancy are well-documented risk factors for neurological disorders in children and adults (62,186,241,436,459,467,468). ...
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As our understanding of respiratory control evolves, we appreciate how the basic neurobiological principles of plasticity discovered in other systems shape the development and function of the respiratory control system. While breathing is a robust homeostatic function, there is growing evidence that stress disrupts respiratory control in ways that predispose to disease. Neonatal stress (in the form of maternal separation) affects “classical” respiratory control structures such as the peripheral O2 sensors (carotid bodies) and the medulla (e.g. nucleus of the solitary tract). Furthermore, early life stress disrupts the paraventricular nucleus of the hypothalamus (PVH), a structure that has emerged as a primary determinant of the intensity of the ventilatory response to hypoxia. Although underestimated, the PVH’s influence on respiratory function is a logical extension of the hypothalamic control of metabolic demand and supply. Here, we review the functional and anatomical links between the stress neuroendocrine axis and the medullary network regulating breathing. We then present the persistent and sex-specific effects of neonatal stress on respiratory control in adult rats. The similarities between with respiratory phenotype of stressed rats and clinical manifestations of respiratory control disorders such as sleep disordered breathing and panic attacks are remarkable. These observations are in line with the scientific consensus that the origins of adult disease are often found among developmental and biological disruptions occurring during early life. These observations bring a different perspective on the structural hierarchy of respiratory homeostasis and point to new directions in our understanding of the etiology of respiratory control disorders.
... The placenta, a highly differentiated maternal-fetal organ intended exclusively for offspring's development, is a linking tissue between the mother and the fetus. Besides being essential for embryo nutrition and development, it also acts as a barrier, preventing high levels of hormones or other peptides from reaching the fetal circulation [1,2]. During placental development and in a sequence of complex events, cytotrophoblast cells differentiate into multinucleated syncytiotrophoblasts and also aggregate to form anchoring villi [3], which will later give rise to extravillous trophoblasts (EVTs), with an invasive phenotype [4,5]. ...
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Several stimuli can change maternal hormone levels during pregnancy. These changes may affect trophoblastic cells and modulate the development of the embryo and the placental tissue itself. Changes in cortisol levels are associated with impaired trophoblast implantation and function, in addition to other pregnancy complications. This study aims to analyze the effects of low and high doses of cortisol on an extravillous trophoblast cell line, and the effects of various exposures to this hormone. SGHPL-4 cells were treated with cortisol at five doses (0–1000 nM) and two exposures (continuous: 24 h/day; and intermittent: 2 h/day). In intermittent treatment, cortisol acted mainly as an anti-inflammatory hormone, repressing gene expression of kinin B1 receptors, interleukin-6, and interleukin-1β. Continuous treatment modulated inflammatory and angiogenic pathways, significantly repressing angiogenic factors and their receptors. Cortisol affected cell migration and tube-like structures formation. In conclusion, both continuous and intermittent exposure to cortisol repressed the expression of inflammatory genes, while only continuous exposure repressed the expression of angiogenic genes, suggesting that a sustained increase in the levels of this hormone is more harmful than a high short-term increase. Cortisol also impaired tube-like structures formation, and kinin receptors may be involved in this response.
... The present study indicated a significant relationship between the history of underlying diseases, stress, anxiety, and depression, which was consistent with the findings of Hosseinabadi that were performed on nurses during the Covid-19 pandemic [33]. Various studies revealed that PHEM personnel experienced elevated levels of catecholamine and cortisol because of emotional stress and missions in unfamiliar environments and different shift work [34], which might affect their mental health state. Furthermore, PHEM personnel cannot control their stress and anxiety problems for prolonged periods, which will increase the likelihood of stress, anxiety, and depression among them (poor mental health) [35]. ...
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Background Pre-hospital emergency medicine (PHEM) personnel are at risk of developing psychological disorders during the Covid-19 pandemic. This study aimed to investigate depression, anxiety, and stress levels of the Iranian PHEM personnel during the Covid-19 pandemic. Methods This descriptive cross-sectional study was performed on 544 PHEM personnel chosen by purposive sampling in North Khorasan, Khorasan-Razavi, South Khorasan, Sistan-Baluchestan, and Kerman provinces in eastern Iran from August to September 2021. Data collection tools included a demographic information questionnaire and the standardized 21-item Depression, Anxiety, and Stress Scale (DASS-21). Data were analyzed in SPSS 16 using one-way analysis of variance and linear regression. Results The mean scores of depression, anxiety, and stress were 8.7 ± 9.2, 7.0 ± 7.8, and 11.6 ± 9.2, respectively. Depression, stress, and anxiety were more prevalent in the age group of 41-55 years, people with master’s and higher degrees, people with a history of underlying diseases, and people with over 10 years of work experience( p < 0.05). Depression and stress also showed a significant relationship with the type of employment. Stress alone was also significantly associated with working less than 35 hours a week and living separately from family( p < 0.05). Conclusions PHEM personnel suffer from significant levels of depression, anxiety, and stress during the Covid-19 pandemic. Therefore, in order to improve the mental condition, it is recommended that the work schedule and services provided to these people be designed in such a way that they have more time for rest and communication with their family members. The personnel should also have easier access to the expert team in the fields of counseling and psychiatry.
... In humans, several studies found an association between SIS and depression [25,37,38]. Heightened inflammatory response [39][40][41] and prenatal cortisol levels (HPA dysfunction) [42,43] are known outcomes in depressed pregnant women. Indeed, antenatal depression has been linked to high rates of PTB [44,45] and preeclampsia [46]. ...
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Prenatal stressors have been linked to adverse pregnancy outcomes; including preterm birth (PTB). Recent work demonstrates that social isolation in mothers represents a silent stressor contributing to PTB risk. Here; we investigate the association of inflammatory and stress markers with PTB risk in Long–Evans rats exposed to social isolation stress (SIS) during preconception and pregnancy across four generations (F0-F3). Gestational length; blood glucose; corticosterone levels; and maternal and offspring weights were assessed in two SIS paradigms: transgenerational (TG) and multigenerational (MG) exposure. Maternal uterine tissues were collected 21 days after the dams gave birth. Exposure to SIS reduced pregnancy lengths in the parental generation and neonatal birth weights in the F1 and F2 generations. Interleukin (IL)-1β (Il1b) mRNA levels increased in F0 animals but decreased in the offspring of both stress lineages. Protein levels of IL-1β decreased in the TG lineage. Corticotrophin-releasing hormone receptor 1 (Crhr1) expression decreased in SIS-exposed F0 animals and increased in the TG-F2 and MG-F1 offspring. Expression of enzyme 11-β hydroxysteroid dehydrogenase-2 (11bHSD2) was enhanced in F1 animals. These findings suggest SIS has adverse consequences on the F0 mothers; but their F1–F3 progeny may adapt to this chronic stress; thus supporting the fetal programming hypothesis.
... As a result, disturbances in the normal levels and amounts of exposure of these biological effectors can result in altered function and long-term disease risk [10]. As a common example, dysregulation of the hypothalamic-pituitary (HPA) axis during pregnancy is associated with increased levels of maternal cortisol, which elevates risks for premature delivery and low birth weight and can cross the placenta to have direct "programming" effects on fetal metabolism and physiology [11,12]. Hypertension has been shown to lead to lower birth weights, likely operating through factors like altered blood flow, along with the common co-occurrence of elevated inflammatory cytokines that can suppress growth [13,14]. ...
Article
Epigenetic clocks quantify regular changes in DNA methylation that occur with age, or in relation to biomarkers of ageing, and are strong predictors of morbidity and mortality. Here, we assess whether measures of fetal nutrition and growth that predict adult chronic disease also predict accelerated biological ageing in young adulthood using a suite of commonly used epigenetic clocks. Data come from the Cebu Longitudinal Health and Nutrition Survey (CLHNS), a long-running cohort followed since birth in metropolitan Cebu, Philippines. Past work has shown that birth weight (BW) and the mother's arm fat during pregnancy (a measure of pregnancy energy status) relate inversely to health outcomes in the CLHNS but primarily in males. Genome-wide DNA methylation was assessed in whole blood using the Infinium EPIC array. Participants included males (n=895) and females (n=803) measured in 2005 (20.8-22.5 years). Clocks included the Hannum and Horvath clocks trained on chronological age, the DNAmPhenoAge and DNAmGrimAge clocks trained on clinical biomarkers, the Dunedin pace of ageing (DunedinPACE) clock trained on longitudinal changes in ageing biomarkers, and the DNAmTL clock trained on leukocyte telomere length. In males, lower BW predicted advanced biological ageing using the Hannum, DNAmPhenoAge, DunedinPoAm, and DNAmTL clocks. In contrast, BW did not predict any clock in female participants. Participants' mothers' pregnancy arm fat only predicted DNAmTL in males. These findings suggest that epigenetic clocks are a useful tool for gauging long-term outcomes predicted by fetal growth, and add to existing evidence in the CLHNS for sex differences in these relationships.
... Stress increases the levels of cortisol and norepinephrine in the blood [10,11]. Among them, cortisol is a powerful steroid, and it is known that high concentrations of cortisol can cause neuronal cell death, synaptic function deterioration, and cognitive decline in with 70% ethanol at 60 • C for 2 h. ...
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Stress is an important neurological input for successful life. However, chronic stress and stress hormones could be a cause of various neurological disorders including anxiety disorders. Therefore, there have been many efforts to find effective materials for curing stress-induced neurological disorders. In this study, we examined the effect of Hydrangea macrophylla (HM) on corticosterone-induced neurotoxicity, stress-induced anxiety in mice and suggested a possible active ingredient of HM. HM protected cortical neurons against neurotoxicity of corticosterone (CORT), a stress hormone. HM also blocked CORT-induced hippocampal synaptic deficit via regulating Akt signaling. Oral administration of HM improved chronic restraint stress-induced anxiety in Elevated Plus maze test along with reduction of plasma corticosterone and TNF-α levels. Moreover, HM reduced stress-induced neuroinflammation and oxidative stress. Thunberginol C, an active ingredient of HM, also prevented CORT-induced neuronal cell death and restraint stress-induced anxiety. Moreover, thunberginol C reduced plasma TNF-α level and neuroinflammation and oxidative stress. Collectively, HM could be a good candidate for preventing stress-induced neurological disorders and thunberginol C may be an active ingredient of HM for this purpose.
... There is also a need for human model systems to identify gene regulation specific to humans, especially investigating uniquely human diseases such as MDD. In addition, cortisol does have the ability to cross the placenta [41], and these data would likely be relevant to models of maternal stress and brain development. ...
Article
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Major depressive disorder (MDD) is a prevalent psychiatric disorder, and exposure to stress is a robust risk factor for MDD. Clinical data and rodent models have indicated the negative impact of chronic exposure to stress-induced hormones like cortisol on brain volume, memory, and cell metabolism. However, the cellular and transcriptomic changes that occur in the brain after prolonged exposure to cortisol are less understood. Furthermore, the astrocyte-specific contribution to cortisol-induced neuropathology remains understudied. Here, we have developed an in vitro model of “chronic stress” using human induced pluripotent stem cell (iPSC)-derived astrocytes treated with cortisol for 7 days. Whole transcriptome sequencing reveals differentially expressed genes (DEGs) uniquely regulated in chronic cortisol compared to acute cortisol treatment. Utilizing this paradigm, we examined the stress response transcriptome of astrocytes generated from MDD patient iPSCs. The MDD-specific DEGs are related to GPCR ligand binding, synaptic signaling, and ion homeostasis. Together, these data highlight the unique role astrocytes play in the central nervous system and present interesting genes for future study into the relationship between chronic stress and MDD.
... 43 This hypothesis suggests that stress in pregnancy increases maternal glucocorticoid levels that are then transmitted to the fetus through the placenta. 44 These stress hormones can have profound effects on fetal neurodevelopment at sensitive periods in gestation, with long-term consequences for behavioral development. 45 This could account for the current early gestation timing effect on rhythmicity because the hippocampus, associated with behavioral regulation, develops in early gestation. ...
Article
Objective: This study examined the effects of disaster-related prenatal maternal stress on infant temperament and whether the sex of the infant or the timing of the stressor in pregnancy would moderate the effects. Methods: Mothers' objective experiences of a sudden-onset flood in Queensland, Australia, their subjective emotional reactions, and cognitive appraisal of the event were assessed. At 6 months postpartum, 121 mothers reported their infant's temperament on the 5 dimensions of the Short Temperament Scale for Infants. Results: When controlling for postnatal maternal factors, subjective prenatal maternal stress and cognitive appraisal of the disaster were associated with easier aspects of infant temperament. However, several interesting interactions emerged showing negative effects of the flood. With higher levels of objective hardship in pregnancy, boys (but not girls) received more irritable temperament ratings. When the flood occurred early in pregnancy, higher levels of objective hardship predicted more arrhythmic infant temperament. Finally, mothers whose emotional response to the flood exceeded the hardship they endured reported significantly more active-reactive infants. Conclusion: Prenatal maternal stress from a natural disaster predicted more difficult temperament ratings that were moderated by infant sex, timing of the flood in gestation, and mother's emotional response to the disaster.
... 33,34 Ancak, gebeliğin erken dönemlerinde yüksek maternal kortizol düzeylerine maruz kalmak fetal büyüme ve organ gelişimine zararlı olmakla birlikte fetüs için uzun süreli negatif etkilere de neden olmaktadır. [35][36][37] Literatürde prenatal yoganın kortizol düzeyi üzerine etkisini belirlemeye yönelik sınırlı sayıda çalışma bulunmasına rağmen olumlu etkileri olduğu belirlenmiştir. 26,28,31 Field ve ark. ...
Article
Points essentiels La pandémie de COVID-19 a un impact majeur sur la santé mentale périnatale : la prévalence des symptômes psychiatriques périnataux, en particulier l’anxiété et la dépression périnatale, a augmenté pendant la pandémie. Cet effet pourrait être provoqué par des facteurs de stress directement liés au virus (comme la peur d’être contaminé, et l’incertitude à propos de l’effet du virus sur le fœtus et le nourrisson), mais aussi indirectement par les changements de l’organisation sanitaire, sociale et économique (comme les mesures de confinement et de distanciation sociale). Les effets du confinement généralisé, et ses nombreuses conséquences en termes socioéconomiques (chômage, perte des revenus et violence domestique), constituent un défi supplémentaire pour la santé mentale périnatale. La limitation des visites prénatales et de la présence du conjoint et de la famille pendant l’accouchement et la période du post-partum précoce a également participé à fragiliser la santé mentale des parturientes. Nous recommandons la mise en place d’un accompagnement spécifique pendant la grossesse, se poursuivant pendant la période du post-partum, et s’appuyant sur l’utilisation des technologies numériques (consultations vidéos, applications connectées). Afin de limiter l’incertitude perçue, des conseils clairs et rassurants devraient systématiquement être dispensés aux mères concernant la transmission intra-utérine, le passage du virus de la mère au bébé pendant l’accouchement, et le risque d’infection par le lait maternel. Ces mesures pourraient permettre de protéger la santé mentale périnatale pendant la pandémie.
Article
This study evaluates how being prenatally exposed to rainfall shocks affects birth weight outcomes in Kyrgyzstan, one of the most climate change vulnerable countries in Central Asia. We detect detrimental impacts of rainfall shocks during the prenatal period on birth weight. In particular, a 0.1 log point increase in in-utero rainfall relative to the local norm reduces birth weight by 23.4 grams (or 0.84%). Furthermore, children whose mothers are poor and live in rural areas are disproportionately affected. The negative impacts of fetal exposure to rainfall shocks could be partly attributed to prenatal care, diseases, and nutrient intakes. Besides, the impacts tend to concentrate in the first trimester of pregnancy.
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Maternal stress during pregnancy is widespread and is associated with poor offspring outcomes, including long-term mental health issues. Prenatal stress-induced fetal neuroinflammation is thought to underlie aberrant neurodevelopment and to derive from a disruption in intrauterine immune homeostasis, though the exact origins are incompletely defined. We aimed to identify divergent immune and microbial metagenome profiles of stressed gestating mice that may trigger detrimental inflammatory signaling at the maternal–fetal interface. In response to stress, maternal glucocorticoid circuit activation corresponded with indicators of systemic immunosuppression. At the maternal–fetal interface, density of placental mononuclear leukocytes decreased with stress, yet maternal whole blood leukocyte analysis indicated monocytosis and classical M1 phenotypic shifts. Genome-resolved microbial metagenomic analyses revealed reductions in genes, microbial strains, and metabolic pathways in stressed dams that are primarily associated with pro-inflammatory function. In particular, disrupted Parasutterella excrementihominis appears to be integral to inflammatory and metabolic dysregulation during prenatal stress. Overall, these perturbations in maternal immunological and microbial regulation during pregnancy may displace immune equilibrium at the maternal–fetal interface. Notably, the absence of and reduction in overt maternal inflammation during stress indicates that the signaling patterns driving fetal outcomes in this context are more nuanced and complex than originally anticipated.
Article
Objective A single course of synthetic antenatal corticosteroids is standard care for women considered to be at risk for preterm birth before 34 weeks of gestation. While the intended target is the fetal lung, the fetal brain contains remarkably high levels of glucocorticoid receptors in structures critical in the regulation of behavior and endocrine function. Negative programming signals may occur which can lead to permanent maladaptive changes and predispose the infant/child to an increased risk in physical, mental, and developmental disorders. Methods Framed around these areas of concerns for physical, mental, and developmental disorders, this narrative review drew on studies (animal and clinical), evaluating the long-term effects of antenatal corticosteroids to present the case that a more targeted approach to the use of antenatal corticosteroids for the betterment of the fetus urgently needed. Results Studies raised concerns about the potential negative long-term consequences, especially for the exposed fetus who was born beyond the period of the greatest benefit from antenatal corticosteroids. The long-term consequences are more subtle in nature and usually manifest later in life, often beyond the scope of most clinical trials. Conclusion Continued research is needed to identify sufficient safety data, both short term and long term. Caution in the use of antenatal corticosteroids should be exercised while additional work is undertaken to optimize dosing strategies and better identify women at risk of preterm birth prior to administration of antenatal corticosteroids. Key Points
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Background: Approximately 14.2% of newborns are estimated to be born low birth weight (LBW) in South Africa. Past work has implicated maternal prenatal stress as a potent predictor of poor birth outcomes, including preterm birth, intrauterine growth restriction, and LBW. However, less is presently known about the impacts of prenatal stress during early gestation in low- and middle-income contexts, where public health burdens due to LBW are much higher. Objective: We assess the effects of psychosocial stress during the first trimester on birthweight in a large sample of women (n = 657) in Soweto, South Africa, a peri-urban township located in the Greater Johannesburg area. Methods: Data come from the Soweto First 1000 Days Cohort, a study of maternal and fetal predictors of infant birth outcomes. Multiple regression models were used to examine the impact of prenatal stress on infant birthweight. Results: The prevalence of LBW was 16.6%. Adjusting for maternal age, gestational age, fetal gender, body mass index, and parity, maternal prenatal stress during the first trimester was a borderline predictor of lower birthweight in this sample (β = 12.7, p = 0.071, 95% CI [-26.4, 1.10]). Women who reported greater levels of stress appeared to have non-significantly longer gestations, and the negative impact of maternal stress on birthweight only appeared after adjusting for this pattern. Conclusions: These results suggest that fetal growth restriction associated with first trimester maternal stress may contribute to lower birthweights in this sample. Our findings report modest relationships between maternal stress specific to early gestation as likely important to birth outcomes in this urban South African sample.
Chapter
Breast cancer (BRCA) is the most common neoplasia among women around the world. The Official Mexican Standard states that health services must provide opportune information for the prevention of BRCA. However, this information focuses on the reduction of biological, iatrogenic or environmental risk factors and those related to reproductive history, neglecting those risk factors relating to lifestyle and other psychosocial risk factors (e.g. personality type, stress management). In this chapter we point out some recent findings that link not only obesity but also dietary habits, glycaemic index, alcohol intake and sedentary lifestyle as risk factors for developing BRCA. We also highlight the importance of addressing the psychological and social aspects, such as taboos of patients, to provide a multidisciplinary approach that allows an accurate prevention and treatment of this disease.
Chapter
Die Zeit der Schwangerschaft als früheste Entwicklungsphase des Menschen kann die biologische und psychische Entwicklung des entstehenden Lebewesens bis ins Erwachsenenalter beeinflussen. Unter diesem Gesichtspunkt sind gute Bedingungen für eine optimale Entwicklung erstrebenswert. Wohlwollende Körperberührungen und Massagen haben das Potenzial, in Menschen jeden Lebensalters komplexe biochemische Reaktionen auszulösen, die sich positiv auf den körperlichen und psychischen Zustand des Behandelten auswirken. Angenehme Körperberührungen des mütterlichen Körpers im Verlauf der Schwangerschaft beeinflussen dabei sowohl die Mutter als auch den Fötus.
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Background Studies exploring the relations between maternal stress and fetal development show an association between increased maternal stress and adverse birth outcomes. A frequently proposed mechanism linking maternal prenatal stress and adverse birth outcomes is heightened concentrations of maternal cortisol. To date, studies exploring this association have reported conflicting results because of the diverse approaches taken to measuring cortisol and the wide variety of possible birth outcomes explored. To add clarity to the growing body of literature, this systematic review and meta-analysis reports empirical findings on the association between maternal prenatal salivary cortisol and newborn birth weight. Methods Searches for relevant papers published up until November 2017 were run in MEDLINE, EMBASE, PsycINFO, and CINAHL. Non-English language papers were included and experts were contacted when necessary. We included data from human observational studies that were designed or had an underlying intention to measure maternal prenatal salivary cortisol and newborn birth weight. We only included data from measurements of salivary cortisol to prevent rendering of the review unsuitable for meta-analysis. Two independent reviewers assessed study eligibility and quality. For every maternal-fetal dyad, an area under the curve with respect to ground (AUCg) of maternal cortisol was calculated to determine a Pearson’s correlation coefficient with a continuous measure of newborn birth weight. Correlation coefficients were then pooled across all stages of gestation. To examine if there are critical gestational periods in which the fetus may be more susceptible to elevated concentration of maternal salivary cortisol, a meta-analysis was performed on separate correlations calculated from gestational trimesters. Results Nine studies with a total of 1,606 maternal-fetal dyads demonstrated a negative correlation between pooled maternal salivary cortisol and birth weight (−0.24, 95% CI −0.28 to −0.20), but there was a high degree of heterogeneity between studies (I² = 88.9%). To investigate heterogeneity, subgroup analysis by trimester of the pooled correlation between salivary cortisol and birth weight was performed with the following correlations found: first trimester, −0.18 (95% CI −0.32 to −0.03, I² = 97.3%); second trimester, −0.20 (95% CI −0.28 to −0.12, I² = 98.3%); and third trimester, −0.30 (95% CI −0.33 to −0.26, I² = 85.4%). Discussion A consistently negative association was observed between maternal cortisol and infant birth weight. The review highlights specific gaps in the literature on the relationship between maternal prenatal salivary cortisol and newborn birth weight. Although a significant negative correlation was found, substantial heterogeneity of effects and the likelihood of publication bias exist. The third trimester was revealed as a possible critical gestational period for heightened maternal cortisol concentration to affect birth weight. Challenges faced in this body of research and recommendations for future research are discussed.
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Natural disasters (NDs) experienced by women and their children during prenatal and infant growth may have long-lasting effects on offspring’s development. Handgrip strength (HGS) is one of the measures of muscular strength and an indicator of health status. This study compared HGS in children exposed to cyclone Aila in India during their prenatal and infant growth compared to a control group from a non-affected, adjacent area. The total sample involved 444 boys and 423 girls aged 7–9 years, categorised into 3 groups: prenatally exposed to Aila, exposed to Aila in infancy, and the control group, non-exposed to Aila. Results revealed that prenatally exposed children of both sexes had significantly lower HGS than the controls (at least, p < 0.001 in boys; p < 0.05 in girls). On the other hand, the postnatally exposed boys, but not the girls, showed lower HGS than the controls. A significant effect of a group factor (ND exposure) on HGS was observed even after controlling for confounding variables (age, height, BMI, birth weight, gestational age; at least, p < 0.05). Our findings indicate that prenatal or early postnatal experience of a ND may have association with impaired HGS in prepubertal children.
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Context Cortisol and dehydroepiandrosterone-sulfate (DHEA-S) are indispensable hormones for normal pregnancy. It is unclear if these hormones, specifically DHEA-S can offer value for predicting poor birth outcome. Objective To compare prenatal cortisol and DHEA-S levels among pregnant women with normal or poor birth outcome. Design-Patients Plasma and saliva were collected prospectively from women in second-third trimester of pregnancy. Women with normal birth outcome (NBO), (n=501) included live birth, no pregnancy complications and ≥ 2.5Kg infant birth weight. Women with poor birth outcome included adverse birth (ABO), (n=50) or low birth weight outcome (LBW), (n=147). Measurements ELISA was performed to measure hormone concentrations in plasma and saliva. Results Circulatory-DHEA-S levels in pregnant women with ABO were higher than women with NBO (p=0.043). Among ABO, only stillbirth cases demonstrated significant increase in circulatory-DHEA-S levels (p=0.006). Circulatory and salivary cortisol/DHEA-S ratio was lower among women with stillbirth (p=0.004) and ABO outcome (p=0.043) respectively compared to women with NBO. Consistently, increased odds of ABO were observed in pregnant women with highest circulatory-DHEA-S levels (odds ratio quartile score 1 vs 4, 2.79, p=0.027) and lowest salivary cortisol/DHEA-S ratio (score 4 vs 2, 2.83, p=0.025). Increased odds of stillbirth outcome were observed in pregnant women with highest circulatory-DHEA-S levels (odds ratio quartile score 1 vs 4, 8.47, p=0.046) and lowest circulatory cortisol/DHEA-S ratio (score 4 vs 1, 4.803, p=0.048). Associations remained significant after adjusting for confounders. Women with LBW did not demonstrate significant changes in cortisol or DHEA-S levels. Conclusion Prenatal measurement of DHEA-S or cortisol/DHEA-S ratio may offer significant value for predicting adverse birth, specifically stillbirth outcome. This article is protected by copyright. All rights reserved.
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This article examines how in-utero exposure to political violence affects early childhood health within the context of the 2003 Casablanca bombings in Morocco. Exploiting the variation across districts and birth months–years within a difference-in-differences framework, we uncover the detrimental association between in-utero exposure to the bombings and child height. Prenatally exposed children are 0.743 standard deviations shorter for their age. Children who were prenatally exposed to the bombings are 0.743 standard deviations shorter for their age. When examining the relative importance of exposure timing, we found that being exposed to the bombings during the first trimester has the most impact on a child’s height.
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Evidence about the association between maternal mental health disorders and stillbirth and infant mortality is limited and conflicting. We aimed to examine whether maternal prenatal mental health disorders are associated with stillbirth and/or infant mortality. MEDLINE, Embase, PsycINFO, and Scopus were searched for studies examining the association of any maternal prenatal (occurring before or during pregnancy) mental health disorder(s) and stillbirth or infant mortality. A random-effects meta-analysis was used to calculate pooled odds ratios (ORs) with 95% confidence intervals (CIs). The between-study heterogeneity was quantified using the I² statistic. Subgroup analyses were performed to identify the source of heterogeneity. Of 4487 records identified, 28 met our inclusion criteria with 27 contributing to the meta-analyses. Over 60% of studies examined stillbirth and 54% of them evaluated neonatal or infant mortality. Thirteen studies investigated the association between maternal depression and anxiety and stillbirth/infant mortality, pooled OR, 1.42 (95% CI, 1.16–1.73; I², 76.7%). Another 13 studies evaluated the association between severe maternal mental illness and stillbirth/infant mortality, pooled OR, 1.47 (95% CI, 1.28–1.68; I², 62.3%). We found similar results for the association of any maternal mental health disorders and stillbirth/infant mortality (OR, 1.59; 95% CI, 1.43–1.77) and in subgroup analyses according to types of fetal/infant mortality. We found no significant evidence of publication bias. Maternal prenatal mental health disorders appear to be associated with a moderate increase in the risk of stillbirth and infant mortality, although the mechanisms are unclear. Efforts to prevent and treat these disorders may reduce the scale of stillbirth/infant deaths.
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Objective Self-reported maternal prenatal stress (MPS) has been associated with earlier febrile seizure (FS) age of onset in offspring. Studies are needed to understand how the biological systems associated with exposure to psychological MPS are linked to seizure disorders in children. The aim of this study was to investigate whether placental markers of MPS are linked to FS incidence and age at first occurrence. Methods A subsample of children with FS (n = 28) and matched controls (n = 84), were drawn from the longitudinal 3D pregnancy cohort (N = 2366 mother-child dyads). Expression of placental genes associated with glucocorticoids, serotonin, and fetal/placental growth were analysed from placental tissues, compared between groups and associated with age at first FS. Results Overall placental normalized gene expression was statistically different (p<0.001). Children with FS showed overexpression of the serotonin transporter (mean difference=0.61, 95%CI=0.9-1.13), connexin 43 (mean difference=0.69, 95%CI=0.30-1.09), zonula occludens-1 (mean difference=0.84, 95%CI=0.42-1.26), and underexpression of glucocorticoid receptor β (mean difference=0.84, 95%CI=-1.49--0.19) and serotonin receptor 2B (mean difference=1.57, 95%CI=-2.35--0.78) compared to controls. Increased expression of the serotonin transporter predicted 37.2% in variation of age at first FS. The correlation matrix showed pregnancy-specific anxiety during the 2nd trimester was moderately associated with age at first FS (R=-0.38) but was not a significant predictor in the regression model. Significance Although our current result does not display a significant effect of self-reported MPS on FS, this study is the first to show placental gene biomarkers usually known to be associated with MPS display different expressions in children with FS. Specifically, our results suggest that placental genes associated with the glucocorticoid, serotonergic and fetal/placental growth systems may be candidate mechanisms leading to increased vulnerability offspring in FS. Since self-reported MPS was not found as a significant predictor in our statistical models, future studies are needed to investigate the mechanisms causing the observed changes in placental genes and their association with seizure disorders.
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Background: Trisomy 21 is a common aneuploid condition in humans and accounts for approximately one quarter of all aneuploid live births. To date, early diagnosis of Trisomy 21 remains a challenging task. Metabolomics may prove an innovative tool to study the early pathophysiology of Trisomy 21 at a functional level. Methods: Ultra-performance liquid chromatography coupled with mass spectrometer (UPLC-MS) was used for untargeted metabolomic analysis of amniotic fluid samples from women having normal and trisomy 21 fetuses. Results: Many significantly changed metabolites were identified between amniotic fluid samples from Trisomy 21 pregnancies and normal euploid pregnancies, such as generally lower levels of several steroid hormones and their derivatives, higher levels of glutathione catabolites coupled with lower levels of gamma-glutamyl amino acids, and increased levels of phospholipid catabolites, sugars, and dicarboxylic acids. The identification of a human milk oligosaccharide in amniotic fluid may worth further investigation, since confirmation of this observation may have significant implications for regulation of fetal development. Conclusions: The metabolisms in amniotic fluid from Trisomy 21 and normal pregnancies are quite different, and some of the significantly changed metabolites may be considered as candidates of early diagnostic biomarkers for Trisomy 21.
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This paper investigates the extent to which in utero exposure to temperature shocks affects birth weight outcomes in Vietnam. Exploiting the variations across districts and conception timing within districts, we show that a one standard deviation increase in temperature relative to the local norm (approximately 0.52°C) during the first trimester of pregnancy reduces the child's weight at birth by 67 g or 2.2 percent. Our heterogeneity analysis suggests that infants living in rural areas, born to poor and low‐educated mothers are especially vulnerable to temperature shocks.
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‬Introduction: Health services personnel, especially nurses, experience high levels of stress in their daily lives. Such stresses can deeply affect their health. This study aimed to examine the relationship between job stress, catecholamine and physical diseases in nurses of Bandar Abbas hospitals. Methods: This study is of descriptive and analytical type carried out on 101 nurses who were selected by cluster sampling technique from hospitals of Hormozgan University of Medical Sciences. The research instruments consist of two Steinmets job stress questionnaires and Severity of Physical Diseases Scale. Furthermore, to measure levels of catecholamine (epinephrine and norepinephrine) in the body, their main metabolites measurement, i.e. Vanillyl-mandelic acid (VMA) in 24-hour urine were measured using Eliza method and the commercial kits produced by Kavoshyar Company. The results were evaluated using descriptive statistics and Pearson method with SPSS 18 Software. Results: The result showed a significant and positive relationship between job stress with amount of VMA (main metabolite of epinephrine and norepinephrine), number and type of illnesses during the past two years that they have been infected (P<0.05). Conclusion: According to the results of this study, job stress can increase levels of Catecholamine's on general health and its negative effects seem to cause a variety of diseases.MEDICAL JOURNAL OF HORMOZGAN UNIVERSITY Key
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Objective. —This article defines stress and related concepts and reviews their historical development. The notion of a stress system as the effector of the stress syndrome is suggested, and its physiologic and pathophysiologic manifestations are described. A new perspective on human disease states associated with dysregulation of the stress system is provided.
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Preterm infants have a high prevalence of long-term cognitive and behavioral disturbances. However, it is not known whether the stresses associated with premature birth disrupt regionally specific brain maturation or whether abnormalities in brain structure contribute to cognitive deficits. To determine whether regional brain volumes differ between term and preterm children and to examine the association of regional brain volumes in prematurely born children with long-term cognitive outcomes. Case-control study conducted in 1998 and 1999 at 2 US university medical schools. A consecutive sample of 25 eight-year-old preterm children recruited from a longitudinal follow-up study of preterm infants and 39 term control children who were recruited from the community and who were comparable with the preterm children in age, sex, maternal education, and minority status. Volumes of cortical subdivisions, ventricular system, cerebellum, basal ganglia, corpus callosum, amygdala, and hippocampus, derived from structural magnetic resonance imaging scans and compared between preterm and term children; correlations of regional brain volumes with cognitive measures (at age 8 years) and perinatal variables among preterm children. Regional cortical volumes were significantly smaller in the preterm children, most prominently in sensorimotor regions (difference: left, 14.6%; right, 14.3% [P<.001 for both]) but also in premotor (left, 11.2%; right, 12.6% [P<.001 for both]), midtemporal (left, 7.4% [P =.01]; right, 10.2% [P<.001]), parieto-occipital (left, 7.9% [P =.01]; right, 7.4% [P =.005]), and subgenual (left, 8.9% [P =.03]; right, 11.7% [P =.01]) cortices. Preterm children's brain volumes were significantly larger (by 105. 7%-271.6%) in the occipital and temporal horns of the ventricles (P<. 001 for all) and smaller in the cerebellum (6.7%; P =.02), basal ganglia (11.4%-13.8%; P</=.005), amygdala (left, 20.2% [P =.001]; right, 30.0% [P<.001]), hippocampus (left, 16.0% [P =.001]; right, 12.0% [P =.007]), and corpus callosum (13.1%-35.2%; P</=.01 for all). Volumes of sensorimotor and midtemporal cortices were associated positively with full-scale, verbal, and performance IQ scores (P<.01 for all). Our data indicate that preterm birth is associated with regionally specific, long-term reductions in brain volume and that morphological abnormalities are, in turn, associated with poorer cognitive outcome. JAMA. 2000;284:1939-1947.
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The circadian rhythm of salivary cortisol was studied in 10 healthy women every 4 weeks throughout pregnancy. In addition, in 12 women the diurnal patterns of salivary cortisol, serum cortisol, plasma ACTH, plasma CRH and serum progesterone were analysed in late third trimester pregnancy and again 3-5 days after delivery. Salivary cortisol profiles exhibited a clear circadian rhythm during pregnancy with an increase in mean salivary cortisol from the 25th to 28th week onwards reaching concentrations in late pregnancy more than twice as high as in non-pregnant controls, rapidly returning to normal concentrations after delivery. The coefficient of variation of salivary cortisol profiles decreased in third trimester pregnancy due to a parallel upward shift of cortisol concentrations (40.2 +/- 3.4% vs 77.6 +/- 6.6% after delivery, P less than 0.01). A diurnal pattern was also found for plasma ACTH and serum cortisol before and after delivery with lower concentrations post-partum (P less than 0.01). In late pregnancy, progesterone concentrations were significantly higher in the evening (930 +/- 85 nmol/l vs 813 +/- 74 nmol/l at 0900 h, P less than 0.01) but showed no diurnal variation post-partum. Plasma CRH was significantly elevated in late third trimester pregnancy (1.22 +/- 0.23 micrograms/l at 0900 h) but showed no diurnal change (1.30 +/- 0.28 micrograms/l at 1900 h). Moreover, no correlation between the free cortisol increase in late pregnancy and plasma CRH was noted despite a wide range of CRH levels (0.13-3.60 micrograms/l). In contrast, a significant correlation was observed between the serum progesterone increase and the salivary cortisol increase in late pregnancy (r = 0.70, P less than 0.05). These findings demonstrate that placental CRH is not the only regulator of maternal ACTH and cortisol release. Instead, our study suggests that placental CRH has little influence on baseline maternal adrenocortical function in pregnancy. The elevated salivary cortisol levels in pregnancy may be explained by glucocorticoid resistance owing to the antiglucocorticoid action of high progesterone concentrations.
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The possibility that hypersecretion of corticotropin-releasing factor (CRF) contributes to the hyperactivity of the hypothalamo-pituitary-adrenal axis observed in patients with major depression was investigated by measuring the concentration of this peptide in cerebrospinal fluid of normal healthy volunteers and in drug-free patients with DSM-III diagnoses of major depression, schizophrenia, or dementia. When compared to the controls and the other diagnostic groups, the patients with major depression showed significantly increased cerebrospinal fluid concentrations of CRF-like immunoreactivity; in 11 of the 23 depressed patients this immunoreactivity was greater than the highest value in the normal controls. These findings are concordant with the hypothesis that CRF hypersecretion is, at least in part, responsible for the hyperactivity of the hypothalamo-pituitary-adrenal axis characteristic of major depression.
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Introduction: Emotional stress during organogenesis could, in theory, cause congenital malformations by increasing the level of cortisone, but documentation is lacking. We undertook a follow-up study to test the hypothesis that psychosocial stress increases the prevalence of malformations, in particular malformations of the cranial neural crest. Material and methods: We defined serious life events as the death or first hospital admission for cancer or acute myocardial infarction of partners or children. All women exposed to severe life events during and up to 16 months before pregnancy in the period 1980 to 1992 were identified by means of five national registers. We studied 3560 exposed pregnancies and randomly selected 20,299 »not-exposed« pregnancies as the control cohort. Results: Women exposed to severe life events gave birth to offspring with an increased prevalence of cranial neural crest malformations, at an adjusted odds ratio of 1.54; 95% CI (1.05-2.27). For other malformations the adjusted odds ratio was 1.14-95% CI (0.94-1.42). Women exposed in two consecutive pregnancies had a higher odds ratio for cranial neural crest malformations, with an adjusted odds ratio of 2.99; 95% CI (1.06-8.43). Death of an older child during the first trimester was associated with an adjusted odds ratio of cranial neural crest malformations in the offspring of 4.75; 95% CI (1.63-13.78). Unexpected death of a child during the first trimester was associated with an adjusted odds ratio of 8.36 in the offspring, 95% CI (2.41-28.99) for cranial neural crest malformations and 3.64, 95% CI (1.29-10.32) for other kinds of malformations. Discussion and conclusion: These findings support the hypothesis that severe emotional stress during pregnancy, especially stress related to the death of a child, may cause congenital malformations, particularly those of the cranial neural crest.
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Glucocorticoids have been used for 30 years to accelerate fetal lung maturation in human pregnancy at risk of preterm delivery. Exposure to inappropriate levels of steroid, however, leads to altered maturation of the cardiovascular, metabolic and central nervous systems. The effects of betamethasone on neuronal development and function were determined in the fetal baboon brain by examination of cytoskeletal microtubule associated proteins (MAPs) and the presynaptic marker protein synaptophysin. At 0.73 gestation, commencing 28 weeks of gestation, pregnant baboons received four doses of saline (n= 8) or 87.5 µg (kg body weight)−1 betamethasone i.m. (n= 7) 12 h apart. This dose is equivalent to 12 mg betamethasone administered daily over two consecutive days to a 70 kg woman. Baboons underwent Caesarean section 12 h after the last injection. Paraffin sections of the fetal neocortex and the underlying white matter were labelled immunohistochemically against MAP1B, MAP2abc, MAP2ab and synaptophysin and stained histochemically with hematoxylin-eosin and silver. Tissue staining was quantified morphometrically. Betamethasone exposure resulted in decreased immunoreactivity (IR) of MAP1B by 34.3 % and MAP2abc by 34.1 % (P < 0.05). Loss of MAP2 IR was due to loss of IR of the juvenile isoform MAP2c (P < 0.05). MAP1B and MAP2c are involved in neuritogenesis and neuronal plasticity. Synaptophysin IR was reduced by 51.8 % (P < 0.01). These changes might reflect functional neuronal disturbances because they were not accompanied by an alteration of the density of neurofibrils or neuronal necrosis. These results are in agreement with earlier findings of alterations of cytoskeletal proteins and presynaptic terminals in the fetal sheep brain after betamethasone infusion directly to the fetus and support a common effect of inappropriate fetal exposure to glucocorticoids on neuronal cytoskeleton and synapses in mammalian species.
There is evidence that maternal anxiety or stress during pregnancy can adversely affect outcome, resulting particularly in babies born early or small for gestational age. Animal studies have shown that there can also be long-term effects on the behaviour of the offspring, including a hyperresponsive hypothalamic-pituitary-adrenal axis. Possible mechanisms for these effects have not previously been studied in women. We have shown, by assaying paired maternal and fetal blood samples, that there is a highly significant correlation in blood levels of cortisol, but not β-endorphin or noradrenaline. This suggests that the major stress hormone, cortisol, may be directly transported across the placenta in amounts sufficient to affect the fetus. We have also shown that maternal anxiety in the third trimester, as assessed by the Spielberger self-rating questionnaire, was linked with impaired blood flow (i.e. raised resistance index and notching) in the uterine arteries. As the latter are associated with pre-eclampsia and intrauterine growth restriction, this suggests a second mechanism whereby maternal anxiety may have an adverse effect in pregnancy.
Article
The purpose of this study was to examine the relation between maternal depressive symptoms and spontaneous preterm birth. From 1991 to 1993, pregnant, African-American women were prospectively enrolled at four hospital-based clinics in Baltimore, Maryland, that serve low-income areas of the city. The Center for Epidemiologic Studies Depression (CES-D) Scale was used to assess depressive symptoms. Multiple logistic regression analysis estimated the independent contribution of maternal depressive symptoms to spontaneous preterm birth, controlling for behavioral, clinical, and demographic variables. Among the 1,399 women in the sample, 117 (8.4%) had a spontaneous preterm delivery. Spontaneous preterm birth occurred among 12.7% of those with a CES-D score in the upper 10th percentile and among 8.0% of those with a lower score (relative risk = 1.59). The adjusted odds ratio for an elevated CES-D score was 1.96 (95% confidence interval: 1.04, 3.72); hence, maternal depressive symptoms in this sample of African-American women were independently associated with spontaneous preterm birth. Effective treatment of depression in pregnant women could ultimately result in a reduction of spontaneous preterm births.
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The CES-D scale is a short self-report scale designed to measure depressive symptomatology in the general population. The items of the scale are symptoms associated with depression which have been used in previously validated longer scales. The new scale was tested in household interview surveys and in psychiatric settings. It was found to have very high internal consistency and adequate test- retest repeatability. Validity was established by pat terns of correlations with other self-report measures, by correlations with clinical ratings of depression, and by relationships with other variables which support its construct validity. Reliability, validity, and factor structure were similar across a wide variety of demographic characteristics in the general population samples tested. The scale should be a useful tool for epidemiologic studies of de pression.
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Cortisol and growth hormone (GH) are released in response to a variety of pharmacologic and physiologic stimuli. Secretion of cortisol and GH are influenced by age, gender, time of day, nutrition, sleep, body composition, and fitness level. Exercise is one of the most potent stimulators for release of these hormones. A single session of exercise of sufficient intensity will result in dramatic increases in cortisol and GH concentrations in most individuals and may take a few hours to recover back to baseline levels. Cortisol and GH are necessary for optimal exercise performance, which is most evident in chronic cortisol and GH deficiency. In deficient individuals, replacement therapy with cortisol or GH restores normal exercise performance. Exercise training can substantially alter the degree of perturbation of the hypothalamic-pituitary axis. The cortisol response pattern to exercise has been considered to be predictive of an individual's adaptation to other forms of stress. This review discusses the cortisol and GH responses to exercise, the factors affecting these responses, the mechanisms of hormone release, and the clinical implications of these physiological observations.
Article
Elevated concentrations of maternal corticotrophin-releasing hormone (CRH) during the 2nd and early 3rd trimester of human pregnancy are associated with spontaneous preterm birth, but the effects of maternal CRH on the fetus are unknown. Maternal plasma was collected for analysis of CRH concentration, m = 156.24 ± 130.91 pg/ml, from 33 pregnant women during Weeks 31–33 of gestation. Immediately after collection of plasma, fetal heart rate (FHR) measures were obtained in response to a challenge with a series of vibroacoustic stimuli. Fetuses of mothers with highly elevated CRH did not respond significantly to the presence of a novel stimulus in a repeated series, p = 0.016. These effects on the FHR response were not related to parity, fetal gender, medical (antepartum) risk, or eventual birth outcomes. Impaired dishabituation in these fetuses of mothers with high concentrations of CRH suggests that neurological systems rich with CRH receptors that support learning and memory, such as parahippocampal regions, may be targets for maternal/placental CRH, with implications for fetal neurological development. © 1999 John Wiley & Sons, Inc. Dev Psychobiol 34: 163–173, 1999
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Prenatal stress impairs activity of the hypothalamo–pituitary–adrenal (HPA) axis in response to stress in adult offspring. So far, very few data are available on the effects of prenatal stress on circadian functioning of the HPA axis. Here, we studied the effects of prenatal stress on the circadian rhythm of corticosterone secretion in male and female adult rats. To evaluate the effects of prenatal stress on various regulatory components of corticosterone secretion, we also assessed the diurnal fluctuation of adrenocorticotropin, total and free corticosterone levels, and hippocampal corticosteroid receptors. Finally, in the search of possible maternal factors, we studied the effects of repeated restraint stress on the pattern of corticosterone secretion in pregnant female rats. Results demonstrate that prenatal stress induced higher levels of total and free corticosterone secretion at the end of the light period in both males and females, and hypercorticism over the entire diurnal cycle in females. No diurnal fluctuation of adrenocorticotropin was observed in any group studied. The effects of prenatal stress on corticosterone secretion could be mediated, at least in part, by a reduction in corticosteroid receptors at specific times of day. Results also show that prepartal stress alters the pattern of corticosterone secretion in pregnant females. Those data indicate that prenatally stressed rats exhibit an altered temporal functioning of the HPA axis, which, taken together with their abnormal response to stress, reinforces the idea of a general homeostatic dysfunction in those animals. © 1999 John Wiley & Sons, Inc. J Neurobiol 40: 302–315, 1999
Article
This paper will discuss the relationship between anxiety and depression. We will begin with a brief historical perspective. We will then move into the twentieth century, with a focus on the 1950s, at which time the introduction of pharmacological treatment options revolutionized the field of psychiatry. The use of psychiatric medications and the observation of treatment response provided an additional means of understanding the relationship between anxiety and depression. From the late 1970s to the 1990s, it became apparent that various medications possessed wider therapeutic profiles than were previously recognized. For example, many medications were found to be efficacious in both anxiety and depressive disorders. These expanded therapeutic profiles provided additional clues to fuel our thinking about the relationship between anxiety and depression. The two major objectives of this paper are, first, to describe and formalize a process of pharmacological dissection and, second, to consider how this process might contribute to our search for a better understanding of the relationship between anxiety and depression. Depression and Anxiety 14:94–104, 2001. © 2001 Wiley-Liss, Inc.
Objective: The study investigated the associations between self-rated financial strain and overall diurnal salivary cortisol levels, as well as secretory patterns among long-term unemployed individuals.Methods: Psychosocial and life-style variables were assessed by means of questionnaires among 85 participants (mean age 42±9 years; 56% females). Salivary cortisol was sampled on four occasions during a 24-hour period and data was analysed separately for men and women.Results: Among females, high financial strain was related to higher overall cortisol levels, and to elevated levels in the evening. These associations did not reach significance among men. Multivariate analyses showed that evening levels of cortisol were positively associated with financial strain, but largely unrelated to life-style variables and psychological distress.Conclusions: The results suggest that high financial strain influences the diurnal cortisol secretion of unemployed individuals in terms of elevated cortisol levels in the evening. The mediating mechanisms are in need of further investigation.
Article
OBJECTIVE: Our purpose was to determine whether various measures of poor psychosocial status in pregnancy are associated with spontaneous preterm birth, fetal growth restriction, or low birth weight. STUDY DESIGN: Anxiety, stress, self-esteem, mastery, and depression were assessed at 25 to 29 weeks in 2593 gravid women by use of a 28-item Likert scale. Scores for each psychosocial subscale were determined, and an overall psychosocial score was calculated. Scores were divided into quartiles, and the lowest quartile scores were used to define poor psychosocial status. The percent spontaneous preterm birth, low birth weight, and fetal growth restriction in women with low and high psychosocial scores were compared. Logistic regression analyses provided the odds ratios and 95% confidence intervals. RESULTS: Analyses revealed that stress was significantly associated with spontaneous preterm birth and with low birth weight with odds ratios of 1.16, p = 0.003, and 1.08, p = 0.02, respectively, for each point on the scale. A low score on the combined scale or on any subscale other than stress did not predict spontaneous preterm birth, fetal growth restriction, or low birth weight. After multivariate adjustment was performed for psychosocial status, substance use, and demographic traits, black race was the only variable significantly associated with spontaneous preterm birth, fetal growth restriction, and low birth weight; stress and low education were associated with spontaneous preterm birth and low birth weight. CONCLUSION: Stress was associated with spontaneous preterm birth and low birth weight even after adjustment for maternal demographic and behavioral characteristics. Black race continues to be a significant predictor of spontaneous preterm birth, fetal growth restriction, and low birth weight even after adjustment for stress, substance use, and other demographic factors. (Am J Obstet Gynecol 1996;175:1286-92.)
Article
Prenatal mood and biochemistry levels were assessed in women with (N=70) and without (N=70) depressive symptoms during their second trimester of pregnancy. At the neonatal period maternal and neonatal biochemistry, EEG and vagal tone levels were assessed, neonatal behavioral states were observed and the Brazelton neurobehavioral assessment was conducted. The mothers with depressive symptoms had higher prenatal cortisol levels and lower dopamine and serotonin levels. Mothers with depressive symptoms were also more likely to deliver prematurely and have low birthweight babies. The newborns of mothers with depressive symptoms had higher cortisol levels and lower dopamine and serotonin levels, thus mimicking their mothers prenatal levels. On the Brazelton Scale, the newborns of depressed mothers had less optimal habituation, orientation, motor, range of state, autonomic stability and depressed scores. A path analysis was conducted to assess the effects of prenatal depression and the mothers’ prepartum biochemistry on gestational age and birthweight. As predicted in the model proposed, prenatal depression was related to prepartum cortisol and norepinephrine levels, and cortisol levels were in turn negatively related to prematurity, and norepinephrine levels were positively related to low birthweight.
Article
Sixty-three pregnant women (36 with depression symptoms) were recruited during their last trimester of pregnancy. The depressed mothers had higher cortisol and norepinephrine levels and lower dopamine levels. Their infants subsequently had higher cortisol and norepinephrine levels and lower dopamine levels at the neonatal stage. The neonates of depressed mothers also showed inferior performance on the orientation, reflex, excitability, and withdrawal clusters of the Brazelton Neonatal Behavioral Assessment. Stepwise regression analyses revealed that the depressed mothers' prenatal norepinephrine and dopamine levels significantly predicted the newborns' norepinephrine and dopamine levels and their Brazelton scores, highlighting an early biochemical influence on neonatal outcome.
Article
Prenatal stress (PS) and maternal exposure to exogenous glucocorticoids can lead to permanent modification of hypothalamo-pituitary-adrenal (HPA) function and stress-related behaviour. Both of these manipulations lead to increased fetal exposure to glucocorticoids. Glucocorticoids are essential for many aspects of normal brain development, but exposure of the fetal brain to an excess of glucocorticoids can have life-long effects on neuroendocrine function. Both endogenous glucocorticoid and synthetic glucocorticoid exposure have a number of rapid effects in the fetal brain, including modification of neurotransmitter systems and transcriptional machinery. Such fetal exposure permanently alters HPA function in prepubertal, postpubertal and ageing offspring, in a sex-dependent manner. Prenatal stress and exogenous glucocorticoid manipulation also lead to the modification of behaviour, brain and organ morphology, as well as altered regulation of other endocrine systems. It is also becoming increasingly apparent that the timing of exposure to PS or synthetic glucocorticoids has tremendous effects on the nature of the phenotypic outcome. Permanent changes in endocrine function will ultimately impact on health in both human and animal populations.
Article
Basal corticosterone (B) levels increase with age in the rat, a result of decreased negative-feedback inhibition of hypothalamic-pituitary-adrenal (HPA) activity. Postnatal handling increases CNS negative-feedback sensitivity and appears to attenuate some of the changes occurring in the HPA axis in later life. In the experiments described here, we have examined basal HPA function in young (6-8 months) and old (22 months), handled (H) and nonhandled (NH) rats in relation to changes in corticosteroid receptor binding. Among young animals, there were no group differences in basal adrenocorticotropin (ACTH) or B levels at any point in the diurnal cycle. In contrast, plasma ACTH and B levels during the PM phase were significantly higher in old NH animals in comparison to old H animals and to both groups of young animals. The H and NH groups did not differ in in vivo adrenal responsiveness to exogenous ACTH. As expected, ACTH sensitivity was greater in all groups during the PM phase and in general, old animals showed a greater response to ACTH regardless of the treatment group. There were no differences across the groups in AM plasma corticosterone-binding globulin (CBG) levels. However, during the PM phase of the cycle, CBG levels were significantly lower and the percentage of B in the free form was significantly higher in the old NH animals. As expected, levels of free B during the PM phase of the cycle were significantly higher in the old NH animals. Thus, there is a significant increase in the PM corticoid signal in the old NH animals that occurs as a function of elevated B and decreased CBG levels; these age-related changes in basal HPA activity were not seen in the old H animals. Type I (mineralocorticoid-like) receptor binding in the hippocampus did not differ as a function of handling and was significantly reduced with age in both H and NH animals. Type II (glucocorticoid) receptor binding decreased as a function of age in both H and NH animals, but was consistently higher in the H animals. There were no differences in type II receptor binding in the hypothalamus or pituitary as a function of age or handling. These data suggest that the increase in basal HPA activity occurring in aged rats is largely restricted to the dark phase of the cycle and is attenuated by postnatal handling, a treatment that increases hippocampal type II corticosteroid receptor binding.
Plasma cortisol, adrenocorticotrophic hormone (ACTH), beta-endorphin and corticotrophin releasing hormone or factor (CRF) all rise progressively as pregnancy advances, and fall postnatally. The placenta produces large amounts of CRF in the third trimester and this is released into the maternal circulation. Present evidence suggests that it stimulates the maternal pituitary to produce ACTH while desensitizing the maternal pituitary to further stimulation with CRF. Maternal control of ACTH production is retained, allowing a persistent response to stress and a diurnal rhythm, perhaps through the secretion of vasopressin. The placenta also produces pro-opiomelanocortin peptides; however, the nature of the fragments produced from the precursor differs from that formed in the anterior pituitary of the mother and the role of these fragments in the control of maternal adrenal function is unclear. These changes in the hypothalamo-pituitary-adrenal axis during pregnancy are associated with loss of the normal suppression of cortisol by dexamethasone and elevated basal levels of cortisol with preservation of a diurnal rhythm, features also found in some patients with endogenous depression. Several studies have suggested a relationship between alterations in maternal concentrations of cortisol and beta-endorphin and the development of postnatal mood disturbances.
Article
Total and free cortisol levels are significantly elevated in pregnancy, but the reasons for this are not clear. The relationships between the diurnal variation in saliva (free) cortisol and baseline levels of total cortisol, corticosterone-binding globulin (CBG), progesterone, and estrogens were studied in several groups of women (normal nonpregnant, taking a combined oral contraceptive pill, after superovulation therapy, during early and late pregnancy, and postpartum). Saliva cortisol levels were significantly elevated in late pregnancy throughout the day, with preservation of diurnal variation. Total cortisol and CBG levels were also significantly raised in pregnancy, but total cortisol levels were normal in women taking a combined oral contraceptive pill in spite of significantly elevated CBG. There was no relationship between saliva cortisol and progesterone levels, and it is unlikely that the increase in cortisol is due to displacement of cortisol from CBG by progesterone. Cortisol levels fell slowly postpartum over several days, making it improbable that the increase in cortisol is solely due to elevated CRH levels. It appears that increased free and total cortisol levels in pregnancy are related to resetting of the sensitivity of the hypothalamic-pituitary-adrenal axis and not merely to raised CBG, progesterone, or CRH levels.
Article
The levels of immunoreactive CRH are elevated in both maternal and fetal plasma in late gestation and labor, but fall precipitously after parturition. The major source of this peptide is thought to be the placenta. We determined if the placenta and also the amnion, chorion, and decidua produce CRH, whether this material has biological activity, and whether CRH output is modulated by glucocorticoids and progesterone. In an in vitro monolayer culture system CRH was produced by the fetal membranes and decidua. Media immunoreactive CRH concentrations averaged 625 +/- 45 (SE) pg/10(5) cells in amnion, 701 +/- 56 pg/10(5) cells in chorion, and 580 +/- 60 pg/10(5) cells in decidual tissue obtained at cesarean section. This output was similar to that by the placenta (906 +/- 121 pg/10(5) cells). These values increased in tissue obtained after spontaneous labor. A single peak of CRH immunoreactivity eluting at the same position as synthetic human CRH, and possessing biological activity, was found in all tissues. There was a dose-dependent increase in CRH output by all tissue types when cells were maintained in the presence of increasing concentrations of cortisol and dexamethasone. In contrast, increasing concentrations of progesterone decreased CRH output by all tissue types. We conclude that immuno- and biologically active CRH is produced not only in the human placenta, but also in the fetal membranes. CRH output by the placenta/fetal membranes is moderated by steroids, and changes with labor. These findings raise the possibility of a regulatory system similar to that of the hypothalamic pituitary axis, but residing within the placenta and fetal membranes.
Article
The substances stimulating the release of immunoreactive corticotropin-releasing factor from cultured human placental cells were investigated. Monolayer primary cultures of trophoblast cells from pregnant women at term were used. The immunoreactive corticotropin-releasing factor released in the culture medium eluted from high-performance liquid chromatography with the same retention time as human corticotropin-releasing factor. Norepinephrine and acetylcholine increased immunoreactive corticotropin-releasing factor release into the culture medium in a dose-related manner. Epinephrine was partially active, whereas dopamine and serotonin did not induce significant changes of immunoreactive corticotropin-releasing factor release from placental cultures. Angiotensin II, interleukin-1, oxytocin, and arginine-vasopressin also increased placental immunoreactive corticotropin-releasing factor release in a dose-related manner, whereas other peptides (vasoactive intestinal peptide, substance P, somatostatin, atrial natriuretic factor, interleukin-2) were ineffective. These results showed that several neurotransmitters and peptides stimulate the release of immunoreactive corticotropin-releasing factor from placental cells, suggesting their possible involvement in the physiologic regulation of placental immunoreactive corticotropin-releasing factor release during pregnancy and parturition.
Article
Although depression is well studied in women, little information is available regarding depression during pregnancy. The purpose of this study was to determine the correlates of depressive symptoms as measured by the Center for Epidemiological Studies-Depression Scale during pregnancy. Between 1984 and 1987, 1014 women, primarily poor and of minority status, who attended the prenatal clinic at Boston City Hospital were interviewed and were asked to furnish urine samples that were then assayed for marijuana and cocaine metabolites. Scores on the Center for Epidemiological Studies-Depression Scale ranged from 0 to 57, with a median score of 16. Depressive symptoms during pregnancy were associated with increased life stress (p less than 0.001), decreased social support (p less than 0.001), poor weight gain (p less than 0.01), and the use of cigarettes (p less than 0.001), alcohol (p less than 0.001), and cocaine (p less than 0.05). These findings are important because these health behaviors have been demonstrated to have an an adverse effect on infant outcome. Interventions to change health behaviors during pregnancy should consider a woman's affective state, social context, and mental health.
Article
This article reviews the literature and presents data from our laboratories on sensory deprivation stress and supplemental stimulation of the rat pup and the preterm neonate. The data suggest that the effects of maternal deprivation in the rat pup (suppression of growth hormone release and protein synthesis) are regulated by a specific form of tactile stimulation: only brush stroking of maternally deprived rat pups returned growth parameters to normal; other forms of stimulation, including kinesthetic and vestibular stimulation, were ineffective in restoring normal functions. Other data are presented demonstrating that very small preterm neonates given tactile-kinesthetic stimulation gain more weight per day, spend more time awake and active, and show more mature habituation, orientation, motor, and range of state behaviors on the Brazelton assessment.
Article
This study was undertaken to determine the differential distribution of catecholamines, in particular L-dihydroxyphenylalanine (L-dopa) and dopamine, between the fetal and maternal compartments during human pregnancy. Amniotic fluid and fetal and maternal blood were obtained from two groups of pregnant women with uncomplicated pregnancies. One group was at 15-20 weeks of gestation and the second group was in labor after 36-41 weeks of gestation. Samples were analyzed for L-dopa, dopamine, norepinephrine, and epinephrine by radioenzymatic assays. L-Dopa constituted about 80% of the total circulating fetal catecholamines, and levels were 2- to 3-fold higher in fetal than maternal plasma. Marked increases in norepinephrine, small rises in epinephrine, but no changes in L-dopa or dopamine concentrations occurred in fetal plasma from mid- to late gestation. Maternal plasma catecholamines did not change. Towards the end of gestation, dopamine in the amniotic fluid increased 15-fold, and norepinephrine increased 5- to 6-fold; L-dopa remained high and unchanged. We conclude that L-dopa is the predominant catecholamine in fetal plasma and amniotic fluid during human pregnancy. No significant changes in its concentrations occur in either compartment between mid- and late gestation. In contrast, dopamine levels, which are 30- to 50-fold lower than those of L-dopa in amniotic fluid during midgestation, show a striking elevation toward the time of labor. Neither the sources nor the possible physiological functions of either L-dopa or dopamine during fetal life are known.