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Stressregulation in der Schwangerschaft und Effekte auf die Geburt
Abstract
Epidemiologische, klinische und experimentelle Daten legen nahe, dass der Ursprung somatischer und psychiatrischer Erkrankungen teilweise im Mutterleib zu finden ist. Ungünstige intrauterine Ein-flüsse, wie Stressbelastung, Mangelernährung und Exposition gegenüber Noxen stellen pränatale Stressfaktoren für das ungeborene Kind dar. Nach Hypothese der fetalen Programmierung können diese langandauernde Effekte auf Organogenese, Geburtsausgang und Stoffwechsellage haben und konsekutiv die physische sowie seelische Gesundheit nachhaltig und anhaltend beeinflussen. Die vorliegende Arbeit untersuchte, innerhalb der prospektiven Längsschnitt-Studie POSEIDON (Pre-, Peri- and POstnatal Stress: Epigenetic Impact on DepressiON), die Auswirkungen maternaler psycho-sozialer Stressbelastung während der Spätschwangerschaft auf den Ausgang der Geburt. Die psy-chosoziale Stressbelastung des untersuchten Studienkollektivs von N = 405 Probandinnen im letzten Trimenon der Schwangerschaft (36,77 ± 1,89 SSW p.m.) wurde über sechs schwangerschaftsspezifi-sche Stressvariablen erhoben und lieferten die Grundlage zur Stressgruppeneinteilung. Der Einfluss pränataler psychosozialer Stressbelastung auf die kindliche Entwicklung im Mutterleib wurde anhand der Geburtsparameter: Gestationsalter, Gewicht, Größe und Kopfumfang als Marker einer ungünsti-gen intrauterinen Umgebung der N = 405 Nachkommen untersucht. Zur Analyse der neuroendokrinen Stressachse respektive Aktivität der Hypothalamus-Hypophysen-Nebennierenrinden-Achsen (HHNA), als vermeidlich vermittelnde Instanz pränataler psychosozialer Stressoren, wurde die Stresshormon-konzentration (Cortisol) aus Speichelproben der Mütter und aus in utero angelegten Fingernagel-Abschnitten der Neugeborenen bestimmt. Eine hohe psychosoziale Stressbelastung in der Spätschwangerschaft konnte in der vorliegenden Arbeit mit einer Dysregulation des maternalen Cortisoltagesprofils und einem negativen Geburtsaus-gang assoziiert werden. In diesem Zusammenhang ging ein hohes Maß an milde einzustufenden psy-chosozialen Stressoren mit einer signifikanten Reduktion des Geburtsgewichtes um 217 g (-6,7 %, p = .003), der Größe um 1,2 cm (-2,3 %; p = .003) und des Kopfumfangs um 0,8 cm (-2,3 %; p < .001), auch nach Kontrolle für Störfaktoren, einher. Eine hohe psychosoziale Stressbelastung konnte zudem mit einer Abflachung des Cortisoltagesprofils im Sinne eines verminderten Abfalls der Cortisolkonzentration über den Tag (↓ Cortisol decline, p = .023) assoziiert werden, welche wiederum in Zusammenhang mit signifikant verkürzten Gestationszeiten (p = .003) stand. Darüber hinaus wurden in der vorliegenden Arbeit die Interaktion beider Steroidkonzentrationen untereinander, deren Auswirkungen auf den Geburtsausgang und der Einfluss psychosozialer Stressbelastung auf die Höhe der kindlichen Stresshormonkonzentrationen untersucht. Insgesamt unterstützen die Studienergebnisse zusammen mit Evidenzen aktueller wissenschaftlicher Literatur einen ungünstigen Einfluss pränataler psychosozialer Stressoren auf das ungeborene Kind. Ein wichtiger zugrundeliegender Pathomechanismus der pränatalen Stressübertragung scheint, zu-mindest teilweise, durch eine stressinduzierte Dysregulation der maternalen HHNA-Aktivität mit kon-sekutiver fetaler Glucocorticoid-Überexposition vermittelt zu sein. Diese können den Feten im Mutter-leib für kürzere Gestationszeiten, geringere Geburtsgewichte und deren assoziierte Erkrankungen prädispositionieren. Langanhaltende Konsequenzen der pränatalen psychosozialen Stressbelastung für die kindliche Ent-wicklung und die somatische sowie seelische Gesundheit der POSEIDON-Kinder sollen im Rahmen von Follow-up-Studien untersucht werden. Die frühzeitige Identifizierung von Nachkommen mit be-sonders hohem Risiko für pränatal programmierte Erkrankungen durch psychosoziale Stressfaktoren könnte neue Dimensionen präventiver Ansätze liefern.
This review presents the current state of research on the relationship between psychological stress and the onset and course of pregnancy. The influence of (everyday) stress on the onset of pregnancy appears to be negligible, whereas there are convincing indications for the possible impairment of the course of pregnancy by traumatic psychological stress, especially with respect to gestational hypertension and prematurity. Whether these risks are increased by the direct negative influence of stressors or by more maladaptive coping behavior of pregnant women remains to be clarified. Psychological interventions can stabilize well-being and thereby reduce the risk of stress-related pregnancy complications in a subsequent pregnancy. The review concludes with considerations for future research in the field as well as suggestions for the practice.
Although maternal stress, anxiety, and depression have been linked to negative birth outcomes, few studies have investigated preventive interventions targeting maternal mental health as a means of reducing such problems. This randomized controlled study examines whether Family Foundations (FF)-a transition to parenthood program for couples focused on promoting coparenting quality, with previously documented impact on maternal stress, depression, and anxiety-can buffer the negative effects of maternal mental health problems.
To assess the effects of FF, we used a randomized block design with a sample of 259 expectant mothers assigned to FF or a control condition and analyzed using propensity score models. We examine two-way interactions of condition (intervention vs. control) with maternal mental health problems (financial stress, depression, and anxiety) on birth outcomes (birth weight, days in hospital for mothers and infants). For birth weight, we assess whether intervention effects depend on length of gestation by including a third interaction term.
FF buffered (p < 0.05) the negative impact of maternal mental health problems on birth weight and both mother and infant length of post-partum hospital stay. For birth weight, assignment to FF was associated with higher birth weight for infants born before term.
These results demonstrate that a psycho-educational program for couples focused on enhancing mutual coparental support, with preventive effects on maternal mental health, can reduce incidence of birth problems among women at elevated risk. Such improvements in birth outcomes could translate into substantial reductions in public and personal healthcare costs. Future work should assess mediating mechanisms of intervention impact and cost-benefit ratio of the intervention.
The Family Foundations follow-up intervention study is currently registered with www.clinicaltrials.gov . The study identifier is NCT01907412.
Objective:
Recent studies suggest that effective social support during pregnancy may buffer adverse effects of maternal psychological distress on fetal development. The mechanisms whereby social support confers this protective advantage, however, remain to be clarified. The aim of this study was to assess whether individual differences in social support alter the covariation of psychological distress and cortisol during pregnancy.
Methods:
Eighty-two pregnant women's psychological distress and cortisol were prospectively assessed in all three trimesters using an ecological momentary assessment strategy. Appraisal of partner social support was assessed in each trimester via the Social Support Effectiveness questionnaire.
Results:
In multilevel analysis, ambulatory assessments of psychological distress during pregnancy were associated with elevated cortisol levels (unstandardized β = .023, p < .001). Consistent with the stress-buffering hypothesis, social support moderated the association between psychological distress and cortisol (unstandardized β = -.001, p = .039), such that the covariation of psychological distress and cortisol increased with decreases in effective social support. The effect of social support for women with the most effective social support was a 50.4% reduction in the mean effect of distress on cortisol and a 2.3-fold increase in this effect for women with the least effective social support scores.
Conclusions:
Pregnant women receiving inadequate social support secrete higher levels of cortisol in response to psychological distress as compared with women receiving effective social support. Social support during pregnancy may be beneficial because it decreases biological sensitivity to psychological distress, potentially shielding the fetus from the harmful effects of stress-related increases in cortisol.
Maternal stress has been linked to infant birth weight outcomes, which itself may be associated with health later in life. The placenta acts as a master regulator for the fetal environment, mediating intrauterine exposures to stress through the activity of genes regulating glucocorticoids, including the 11beta-hydroxysteroid dehydrogenase (HSD11B) types 1 and 2 genes, and so we hypothesized that variation in these genes will be associated with infant birth weight. We investigated DNA methylation levels at 6 sites across the two genes, as well as mRNA expression for each, and the relationship to infant birth weight. Logistic regressions correcting for potential confounding factors revealed a significant association between methylation at a single CpG site within HSD11B1 and being born large for gestational age (LGA). In addition, our analysis identified correlations between methylation and gene expression, including sex specific transcriptional regulation of HSD11B2. Our work is one of the first comprehensive views of DNA methylation and expression in the placenta for both HSD11B types 1 and 2, linking epigenetic alterations with the regulation of fetal stress and birth weight outcomes.
Copyright 2015 by The Society for the Study of Reproduction.
Low socioeconomic status (SES) is associated with increased psychosocial stress among low-income persons, which could contribute to differences in activity of the HPA axis (assessed by diurnal cortisol profiles). The current article investigates associations of SES from different developmental stages with cortisol profiles.
Using data from a large, socioeconomically diverse birth cohort (N = 1,490) in Cebu, Philippines, the current study compares the relative and joint contributions of SES from five developmental periods, between the prenatal/birth period and early adulthood, to adult cortisol, and examines the effects of chronic exposure to low SES.
Chronically low SES from infancy through early adulthood predicts the highest bedtime cortisol levels, lowest cortisol awakening responses (CARs), lowest total cortisol levels across the day (area under curve or AUC), and the flattest cortisol rhythms between wake up and bedtime, a profile associated with poorer health. Results indicate that cumulative economic strain (between the prenatal period and early adulthood) predicts flatter cortisol rhythms more consistently than SES from any particular period.
Interventions focusing on the psychosocial stressors associated with economic deprivation during any period from infancy to adulthood may be helpful, but targeting interventions across multiple periods may have the greatest impact. Interventions aimed at improving economic conditions between infancy and early adulthood may have implications for long-term changes in HPA axis functioning. Am. J. Hum. Biol., 2015. © 2015 Wiley Periodicals, Inc.
© 2015 Wiley Periodicals, Inc.
The goal of this study was to understand the roles of maternal history of childhood sexual abuse (CSA) and current family functioning on the cortisol awakening response (CAR) in pregnancy. Participants were 185 pregnant women (ages 18–40) who completed items from the Adverse Childhood Experiences scale to measure child maltreatment history and the Family Assessment Device to measure current family functioning. Participants provided saliva samples at wake-up and 30 min after wake-up at 25, 29, and 35 weeks gestation to measure CAR. A moderation effect was found such that participants with more severe CSA histories and poorer perceived family functioning had increasing CAR in pregnancy compared to participants with less severe CSA histories and better family functioning. These findings highlight the importance of considering stress in both childhood and current environments in predicting maternal cortisol in pregnancy.
Preterm birth is associated with 5 to 18% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous
preterm labor, a syndrome caused by multiple pathologic processes, leads to 70% of preterm births. The prevention and the
treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of
disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown
of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk
is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable
scientific challenge worthy of investment.
Objectives:
We examined the impact of preconception acute and chronic stressors on offspring birth weight and racial/ethnic birth weight disparities.
Methods:
We included birth weights for singleton live first (n = 3512) and second (n = 1901) births to White, Mexican-origin Latina, other-origin Latina, and Black women reported at wave IV of the National Longitudinal Study of Adolescent Health (2007-2008; ages 24-32 years). We generated factor scores for preconception acute and chronic stressors from wave I (1994-1995; ages 11-19 years) or wave III (2001-2002; ages 18-26 years) for the same cohort of women.
Results:
Linear regression models indicated that chronic stressors, but not acute stressors, were inversely associated with birth weight for both first and second births (b = -192; 95% confidence interval = -270, -113; and b = -180; 95% confidence interval = -315, -45, respectively), and partially explained the disparities in birth weight between the minority racial/ethnic groups and Whites.
Conclusions:
Preconception chronic stressors contribute to restricted birth weight and to racial/ethnic birth weight disparities.
Objective
To evaluate the association between exposure to life-threatening rocket attacks and the risks of preterm birth (PTB) and low birth weight (LBW).
Methods
The present retrospective cohort study compared the outcomes of 1851 births by women exposed to rocket attacks and 2979 births by unexposed women. The timing, frequency, and intensity of exposure were calculated for each trimester and for the entire pregnancy period. Demographic and medical data were abstracted from the patients’ records.
Results
The rates of PTB and LBW were higher among exposed than unexposed women (PTB: 9.1% versus 6.8%, P = 0.004; LBW: 7.6% versus 5.8%, P = 0.02). The rate of infants who were small for gestational age did not differ between the groups. After controlling for potential confounders, the risks for PTB and LBW remained significantly higher in the exposed group (PTB: adjusted odds ratio 1.3 [95% confidence interval, 1.1–1.7]; LBW: adjusted odds ratio 1.3 [95% confidence interval, 1.03–1.7]). There was no linear association between the intensity of exposure and the risk of PTB or LBW.
Conclusion
Maternal exposure to intermittent but repeated life-threatening rocket attacks for a prolonged period might be associated with increased risks of PTB and LBW.
Background:
International literature has shown that Postpartum Depression (PPD) has a significant social and relational impact on mothers and their partners, on the interaction between mother and child, as well as on the cognitive and emotional development of the child. The goal of this study is to increase the epidemiological knowledge of PPD and to evaluate both risk and protective factors.
Subjects and methods:
Our study is based on the administration of three tests, Paykel's Life Events Scale, EPDS and MMPI-2, at three distinct time point (during the third trimester, 72 hours after delivery, and three months after delivery, respectively) to a sample of women recruited in the Prenatal Medicine Clinic at the Hospital of Perugia. The data collected was statistically analyzed.
Results:
The prevalence of PPD 72 hours after delivery was 11%, while the prevalence of PPD three months after delivery was 16.7%. Antepartum Depression (APD), measured using EPDS cut-offs scores of 9 and 14, was found to be a statistically significant risk factor for the development of PPD, while desired life-events during pregnancy can represent a protective factor.
Conclusions:
The prevalence of PPD that we measured, in agreement with that found in the literature, demonstrates that despite the fact that the diagnostic criteria of the DSM-IV refer to PPD only if it develops within 4 weeks after delivery, PPD can also develop after this period. Furthermore, it appears that monitoring APD and encouraging a psycho-socially serene pregnancy are important for prevention of PPD. In the case of APD it was shown that monitoring women with even light depressive symptoms is important, because these women are more likely to then develop PPD.
Objective: This study was a 20-year follow-up of offspring of depressed and nondepressed parents to determine the magnitude and continuity of the risk of parental depression to the offspring. Method: The authors followed 151 offspring of moderately to severely depressed parents or nonpsychiatrically ill comparison subjects for about 20 years, to a mean age of 35 years. Four interviews and diagnostic assessments from childhood or adolescence to adulthood were conducted by assessors blind to the parents' clinical status or the offspring's previous history. Final best-estimate diagnoses were also made by blinded psychologists or psychiatrists. Results: The risks for anxiety disorders, major depression, and substance dependence were approximately three times as high in the offspring of depressed parents as in the offspring of nondepressed parents. Social impairment was also greater. The period of highest incidence for major depressive disorder remained between ages 15 and 20 years, largely in females. The early onset of disorder seen in the high-risk group was not offset by a later onset in the low-risk group as they matured. Higher rates of medical problems and mortality in the offspring of depressed parents were beginning to emerge as the offspring entered middle age. Conclusions: The offspring of depressed parents constitute a high-risk group for psychiatric and medical problems, which begin early and continue through adulthood. Early detection seems warranted.
Biochemie in neuer Dimension
Die Zelle, ihr Stoffwechsel, ihre Kommunikation, die Molekularbiologie und die funktionelle Biochemie der Organe – die vielen Details in der Biochemie lassen sich am besten in überschaubaren Portionen lernen. Und genau so ist die Biochemie und Pathobiochemie aufgebaut:
· 74 überschaubar große Kapitel teilen den Stoff übersichtlich ein.
· Jedes Kapitel beginnt mit einer Übersicht über die Schwerpunkte.
· Rote Überschriften fassen einzelne Abschnitte kurz zusammen.
· Zusammenfassungen am Kapitelende wiederholen die wichtigsten Prinzipien.
· In einem Tafelteil sind die wichtigsten Strukturformeln zusammengestellt.
Die Kapitel der 9. Auflage wurden grundlegend überarbeitet:
· Zahlreiche Kapitel wurden komplett neu geschrieben.
· Mehr als 1000 Abbildungen wurden überarbeitet oder ganz neu gezeichnet.
· Sämtliche Abbildungen wurden in ein einheitliches Konzept gebracht.
Wie bedeutend die Kenntnisse von Molekülen, Mechanismen und Signalwegen für das Verständnis pathologischer Vorgänge sind, wird anhand zahlreicher spezieller Abschnitte oder eigener Kapitel zur Pathobiochemie herausgestellt. Schließlich geben spannende Exkurse und Hintergrundinfos einen Blick über den Tellerrand oder weiter in die Tiefe.
Lernen Sie die Biochemie Stück für Stück – mit Ihrem Begleiter durchs Studium!
Eine Besonderheit der Endokrinologie der Schwangerschaft ist die Tatsache, dass sie sich mit 2 Individuen befasst, die sich schon in der Übergangsphase von der Befruchtung zur Nidation gegenseitig beeinflussen, metabolische Substrate und zahlreiche Informationssignale austauschen und sich nach der Plazentation hierfür eines nur wenige Monate funktionsfähigen Organs bedienen, der Plazenta. Die dabei ablaufenden Vorgänge und – soweit bekannt – deren Regulation werden im Folgenden beschrieben.
Triple fluorescence labelling was employed to reveal the distribution of chemically identified neurons within the pontine laterodorsal tegmental nucleus and dorsal raphe nucleus which supply branching collateral input to the central nucleus of the amygdala and hypothalamic paraventricular nucleus. The chemical identity of neurons in the laterodorsal tegmental nucleus was revealed by immunocytochemical detection of choline-acetyltransferase or substance P; in the dorsal raphe nucleus, the chemical content of the neurons was revealed with antibody recognizing serotonin. The projections were defined by injections of two retrograde tracers, rhodamine-and fluorescein-labelled latex microspheres, in the central nucleus of the amygdala and paraventricular nucleus, respectively. Neurons projecting to both the central nucleus of the amygdala and the paraventricular nucleus were distributed primarily within the caudal extensions of the laterodorsal tegmental nucleus and dorsal raphe nucleus. Approximately 11% and 7% of the labelled cells in the laterodorsal tegmental nucleus and dorsal raphe nucleus projected via branching collaterals to the paraventricular nucleus and central nucleus of the amygdala. About half of these neurons in the laterodorsal tegmental nucleus were cholinergic, and one-third were substance-P-ergic; in the dorsal raphe nucleus, approximately half of the neurons containing both retrograde tracers were serotonergic. These results indicate that pontine neurons may simultaneously transmit signals to the central nucleus of the amygdala and paraventricular nucleus and that several different neuroactive substances are found in the neurons participating in these pathways. This coordinated signalling may lead to synchronized responses of the central nucleus of the amygdala and paraventricular nucleus for the maintenance of homeostasis. Interactions between different neuroactive substances at the target site may serve to modulate the responses of individual neurons.
Epidemiological evidence suggests that low birth weight is associated with an increased risk of cardiovascular, metabolic and neuroendocrine disorders in adult life. Glucocorticoid administration during pregnancy reduces offspring birth weight and alters the maturation of the lung and other organs. We hypothesised that prenatal exposure to excess glucocorticoids or stress might represent a mechanism linking foetal growth with adult pathophysiology. In rats, birth weight is reduced following prenatal exposure to the synthetic steroid dexamethasone, which readily crosses the placenta, or to carbenoxolone, which inhibits 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the physiological feto-placental 'barrier' to maternal glucocorticoids. As adults, the offspring exhibit permanent hypertension, hyperglycaemic, increased hypothalamic-pituitary-adrenal (HPA) axis activity and behaviour reminiscent of anxiety. Physiological variations in placental 11beta-HSD2 activity correlate directly with foetal weight. In humans, 11beta-HSD2 gene mutations cause low birth weight. Moreover, low-birth-weight babies have higher plasma cortisol levels throughout adult life, indicating HPA axis programming. The molecular mechanisms may reflect permanent changes in the expression of specific transcription factors, key among which is the glucocorticoid receptor (GR) itself. The differential programming of the GR in different tissues reflects effects upon one or more of the multiple tissue-specific alternate first exons/promoters of the GR gene. Overall, the data suggest that both pharmacological and physiological exposure prenatally to excess glucocorticoids programmes cardiovascular, metabolic and neuroendocrine disorders in adult life.
The vasoactive effects of corticotropin-releasing hormone (CRH) in the human fetal-placental circulation in vitro have been investigated. Single lobules of term placentae were bilaterally perfused with constant flows of Krebs' solution (maternal and fetal, 5 ml/min, 95% O2, 5% CO2, 37 degrees C, pH 7.3) and changes in fetal-placental arterial perfusion pressure measured. Effects of human (hCRH) and ovine (oCRH) CRH were examined during submaximal vasoconstriction (100-120 mmHg) of the fetal-placental vasculature induced by prostaglandin F2 alpha (PGF2 alpha), (0.7-2 mumol/L). During infusion of hCRH or oCRH (24-7000 pmol/L) a concentration-dependent vasodilatation was observed. Human CRH and oCRH were equipotent as vasodilator agents (regression analysis; P > 0.05; n = 5). The vasodilator response curves to human and ovine CRH were compared to prostacyclin (PGI2) (1.2-1180 nmol/L). Human and oCRH were 53 times more potent than PGI2 (regression analysis, P < 0.05; n = 5). These results indicate that CRH ha...
Steroidhormone bilden eine umfangreiche Gruppe von Hormonen, die sich vom Cholesterin ableiten. Sie werden v. a. in der Nebennierenrinde, den Hoden sowie den Ovarien synthetisiert. Alle Steroidhormone wirken über nucleäre Rezeptoren. Ihr Wirkungsspektrum reicht von der Beeinflussung des Intermediär- und Knochenstoffwechsels bis zur Regulation der männlichen bzw. weiblichen Sexualentwicklung und -funktion.
Der Hypothalamus ist mit der Hypophyse über das Infundibulum verbunden; hieraus ergibt sich eine anatomische und funktionale Einheit, die als übergeordnetes Zentrum die hierarchisch organisierten Hormonachsen steuert.
The relationships between severity, chronicity, and timing of maternal depressive symptoms and child outcomes were examined in a cohort of 4,953 children. Mothers provided self-reports of depressive symptoms during pregnancy, immediately postpartum, and when the child was 6 months old and 5 years old. At the age 5 follow-up, mothers reported on children's behavior and children completed a receptive vocabulary test. Results suggest that both the severity and the chronicity of maternal depressive symptoms are related to more behavior problems and lower vocabulary scores in children. The interaction of severity and chronicity of maternal depressive symptoms was significantly related to higher levels of child behavior problems. Timing of maternal symptoms was not significantly related to child vocabulary scores, but more recent reports of maternal depressive symptoms were associated with higher rates of child behavior problems.
Fetal programming of the hypothalamus-pituitary-adrenal (HPA) axis was proposed as one mechanism underlying the link between prenatal stress, adverse birth outcomes (particularly low birth weight) and an enhanced vulnerability for several diseases later in life. In recent studies, birth weight was significantly related to basal cortisol levels as well as to cortisol responses to pharmacological stimulation. In order to investigate the association between cortisol responses to psychological challenge, birth weight and length of gestation, 106 young healthy males were exposed to the ‘Trier Social Stress Test’. Salivary cortisol responses to the stress exposure were significantly and inversely related to the subjects' birth weight, while the analysis of the impact of gestational age yielded inconsistent results. This finding is consistent with the concept of fetal programming of the HPA axis and provides the first preliminary evidence for an association between birth weight and adrenocortical responses to psychosocial stress. As the investigated subjects were twins, possible implications of this sample characteristic for the present findings are discussed.
Aim: To investigate the prevalence rate of attention deficit hyperactivity disorder (ADHD) in children and family risk factors of ADHD so as to provide evidence for the treatment of ADHD. Methods: Self-made Pupil Behavior Questionnaire and Family Environment Questionnaire were applied among 1726 pupils of grade 1 to 6 in Quanzhou Experimental Elementary School, and 1675 shares of Questionnaires were reclaimed. The ADHD cases were diagnosed by employing the diagnostic criteria of American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders, Third Revised Edition (DSM-III-R), Attention-deficit Surveying Instrument and Neuropsychological Examination so as to analyze the family risk factors of ADHD. Results: Totally 75 pupils were diagnosed for ADHD cases in the detection rate of 4.48%, and prevalence rate in boys (6.03%) was significantly higher than that in girls (2.54%) (χ2 = 11.80, P < 0.01). The older the pupils was, the higher was the prevalence rate of ADHD in boys (χ2tendency = 4.70, P < 0.05), but the lower was in girls (χ2tendency = 7.43, P < 0.01). The lower the fathers or mothers educated grade was, the higher was the prevalence rate of ADHD in children (χ2tendency = 6.96, P < 0.05; χ2tendency = 21.27, P < 0.01. The prevalence rate of ADHD in the children whose fathers or mothers were "cadres" was significantly lower than that in the children whose fathers or mothers were "non-cadres" (χ2 = 4.69, P < 0.05; χ2 = 12.5, P < 0.01). The risk factors of ADDH were during 12 and 13 years old (P = 0.000 5) and mother "non-cadres" professions (P = 0.029 5) in the boys. The risk factors of ADDH were during 7 and 8 years olds (P = 0.000 0), mothers' educated grade under middle education (P = 0.024 1) and father or mother "non-cadres" professions (P = 0.002 4, P = 0.078 4) in the girls. Conclusion: The prevalence rate of ADHD in schoolboys was significantly higher than that in the schoolgirls. The risk factors of ADDH are different between the boys and the girls. The maladjustment to study in grade 1 of primary school raises prevalence rate of ADHD in pupils, and so does the heavy study burden. There is significant relation between prevalence rate of ADHD and parental (especially maternal) educated grades and professions. So, it should pay enough attention and intervention when ADHD is diagnosed and treated.
Objective: Prenatal exposure to inappropriate levels of glucocorticoids (GCs) and maternal stress are putative mechanisms for the fetal programming of later health outcomes. The current investigation examined the influence of prenatal maternal cortisol and maternal psychosocial stress on infant physiological and behavioral responses to stress.
Methods: The study sample comprised 116 women and their full term infants. Maternal plasma cortisol and report of stress, anxiety and depression were assessed at 15, 19, 25, 31 and 36 + weeks' gestational age. Infant cortisol and behavioral responses to the painful stress of a heel-stick blood draw were evaluated at 24 hours after birth. The association between prenatal maternal measures and infant cortisol and behavioral stress responses was examined using hierarchical linear growth curve modeling.
Results: A larger infant cortisol response to the heel-stick procedure was associated with exposure to elevated concentrations of maternal cortisol during the late second and third trimesters. Additionally, a slower rate of behavioral recovery from the painful stress of a heel-stick blood draw was predicted by elevated levels of maternal cortisol early in pregnancy as well as prenatal maternal psychosocial stress throughout gestation. These associations could not be explained by mode of delivery, prenatal medical history, socioeconomic status or child race, sex or birth order.
Conclusions: These data suggest that exposure to maternal cortisol and psychosocial stress exerts programming influences on the developing fetus with consequences for infant stress regulation.
The long-term consequences of exposure to excess stress, particularly during sensitive developmental windows, on the initiation and progression of many complex, common physical and mental disorders that confer a major global burden of disease are well established. The period of intrauterine life represents among the most sensitive of these windows, at which time the effects of stress may be transmitted inter-generationally from a mother to her as-yet-unborn child. As explicated by the concept of fetal or developmental programming of health and disease susceptibility, a growing body of evidence supports the notion that health and disease susceptibility is determined by the dynamic interplay between genetic makeup and environment, particularly during intrauterine and early postnatal life. Except in extreme cases, an adverse intrauterine exposure may not, per se, ‘cause’ disease, but, instead, may determine propensity for disease(s) in later life (by shaping phenotypic responsivity to endogenous and exogenous disease-related risk conditions). Accumulating evidence suggests that maternal psychological and social stress during pregnancy represents one such condition that may adversely affect the developing child, with important implications for a diverse range of physical and mental health outcomes.
In this paper we review primarily our own contributions to the field of maternal stress during pregnancy and child mental and physical health-related outcomes. We present findings on stress-related maternal-placental-fetal endocrine and immune/inflammatory processes that may mediate the effects of various adverse conditions during pregnancy on the developing human embryo and fetus. We enunciate conceptual and methodological issues related to the assessment of stress during pregnancy and discuss potential mechanisms of intergenerational transmission of the effects of stress. Lastly, we describe on-going research and some future directions of our program.
The hypothalamo-pituitary-adrenal axis (HPA) is responsible for stimulation of adrenal corticosteroids in response to stress. Negative feedback control by corticosteroids limits pituitary secretion of corticotropin, ACTH, and hypothalamic secretion of corticotropin-releasing hormone, CRH, and vasopressin, AVP, resulting in regulation of both basal and stress-induced ACTH secretion. The negative feedback effect of corticosteroids occurs by action of corticosteroids at mineralocorticoid receptors (MR) and/or glucocorticoid receptors (GRs) located in multiple sites in the brain and in the pituitary. The mechanisms of negative feedback vary according to the receptor type and location within the brain-hypothalmo-pituitary axis. A very rapid nongenomic action has been demonstrated for GR action on CRH neurons in the hypothalamus, and somewhat slower nongenomic effects are observed in the pituitary or other brain sites mediated by GR and/or MR. Corticosteroids also have genomic actions, including repression of the pro-opiomelanocortin (POMC) gene in the pituitary and CRH and AVP genes in the hypothalamus. The rapid effect inhibits stimulated secretion, but requires a rapidly rising corticosteroid concentration. The more delayed inhibitory effect on stimulated secretion is dependent on the intensity of the stimulus and the magnitude of the corticosteroid feedback signal, but also the neuroanatomical pathways responsible for activating the HPA. The pathways for activation of some stressors may partially bypass hypothalamic feedback sites at the CRH neuron, whereas others may not involve forebrain sites; therefore, some physiological stressors may override or bypass negative feedback, and other psychological stressors may facilitate responses to subsequent stress. © 2015 American Physiological Society. Compr Physiol 5:1161-1182, 2015.
To examine whether a pre-gestational diagnosis of depression is a risk factor for adverse obstetric and neonatal outcome.
A retrospective cohort study investigating maternal characteristics, obstetrical and perinatal outcomes in singleton pregnancies of women with and without a diagnosis of depression was conducted. A pre-gestational diagnosis of depression was made by a psychiatrist or family physician and was recorded in the patients' chart. Multiple logistic regression models were used to control for possible confounders.
During the study period, 256312 deliveries occurred. Out of which, 221 women (0.1%) had a pre-gestational diagnosis of depression. When examining obstetric outcomes, women with a diagnosis of depression were older (32.05±5.772 VS 28.56±5.851) and smokers (7.2% VS 1.1%), had a higher rate of preterm deliveries (37.99±2.989 VS 39.02±2.249) and cesarean sections (28.5% VS 13.6%) in comparison to the control group. When examining neonatal outcomes, neonates of women diagnosed with depression had a lower birth mean weight (3.038.47±649.6 VS 3183.44±551.8) and increased rates of perinatal mortality (3.2% VS 1.3%). Using a multiple logistic regression model, with perinatal mortality as the outcome variable to control for cofounders such as maternal age, preterm birth, chronic hypertension and gestational diabetes mellitus, a diagnosis of depression was not found to be an independent risk factor for perinatal mortality. Another multiple logistic regression model found advanced maternal age, smoking, preterm birth and labor induction to be associated with a diagnosis of depression.
Pregnant women diagnosed with depression are at an increased risk for preterm birth, low birth weight, and cesarean sections. However, it was not associated with increased rates of perinatal mortality.
The cortisol level in fingernails may reflect the hormone's cumulative production over a long period, but the notions have not been fully established. In this study, we investigated the association of cortisol in fingernails with cortisol accumulation over a long period (hair cortisol) and over a relatively short period (salivary cortisol). In study 1, hair and fingernail samples were collected from 58 middle-aged and elderly men. The cortisol level in hair samples was moderately associated with the level in fingernail samples (r=0.29, p<0.05 and rs=0.36, p<0.01). In study 2, 37 workers provided 4 saliva samples over the course of one day (at awakening, 30min after awakening, before lunch, and after work) and another set a month later. Further, the workers were asked to provide fingernail samples during a six-month period. We found that the cortisol level in saliva over the whole day (area under the curve for cortisol) was moderately associated with the cortisol level measured in fingernail samples that were collected 4 months (r=0.43, p<0.05 and rs=0.50, p<0.01) and 5 months later (r=0.45, p<0.05 and rs=0.53, p<0.01). These results indicated that the cortisol level in fingernail samples might retrospectively represent hormone production during a given period. The cortisol level in fingernail samples may be useful in the investigation of the link between psychosocial stress and health.
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Background:
Altered functioning of the hypothalamic-pituitary-adrenal axis (HPA-axis) has been associated with depression, but findings have been inconsistent. Among older depressed persons, both hyperactivity and hypo-activity of the HPA-axis were demonstrated. However, most studies were population-based studies, with single cortisol measurements, lacking insight into diurnal patterns of HPA-axis functioning. We aim to provide insight into functioning of the HPA-axis, assessed by various salivary cortisol samples, in depressed older adults and non-depressed controls.
Methods:
Data were derived from the Netherlands Study of Depression in Older Persons. Cortisol levels of older persons without a lifetime diagnosis of depression and/or anxiety (n=109) were compared with older persons with a 6-month major depression diagnosis (n=311). ANCOVA analyses and random coefficient analysis on the four morning cortisol samples were performed. A possible U-shaped association between cortisol and depression status was examined.
Results:
Depressed older persons showed higher morning cortisol levels at awakening (T1) and a less dynamic awakening response compared to non-depressed older persons. Dexamethasone suppression did not differ across groups. No U-shaped association between HPA-axis activity and depression was observed.
Conclusion:
We demonstrated a hypercortisolemic state and a diminished ability to respond to the stress of awakening among depressed older persons. Previously it was shown, that hypercortisolemic states may indicate a lifelong biological vulnerability for depression. Our findings expand on previous literature by demonstrating that in older persons the HPA-axis may become less responsive to stress, culminating in a further dysregulation of the diurnal cortisol-rhythm, superimposed on - possibly lifelong - hypercortisolemic states.
In utero exposure of fetuses to tobacco is associated with reduced birth weight. We hypothesized that this may be due to the toxic effect of carbon monoxide (CO) from tobacco, which has previously been described to damage mitochondria in non-pregnant adult smokers. Maternal peripheral blood mononuclear cells (PBMCs), newborn cord blood mononuclear cells (CBMCs) and placenta were collected from 30 smoking pregnant women and their newborns and classified as moderate and severe smoking groups, and compared to a cohort of 21 non-smoking controls. A biomarker for tobacco consumption (cotinine) was assessed by ELISA (enzyme-linked immunosorbent assay). The following parameters were measured in all tissues: mitochondrial chain complex IV [cytochrome c oxidase (COX)] activity by spectrophotometry, mitochondrial DNA levels by reverse transcription polymerase chain reaction, oxidative stress by spectrophotometric lipid peroxide quantification, mitochondrial mass through citrate synthase spectrophotometric activity and apoptosis by Western blot parallelly confirmed by TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling) assay in placenta. Newborns from smoking pregnant women presented reduced birth weight by 10.75 percent. Materno-fetal mitochondrial and apoptotic PBMC and CBMC parameters showed altered and correlated values regarding COX activity, mitochondrial DNA, oxidative stress and apoptosis. Placenta partially compensated this dysfunction by increasing mitochondrial number; even so ratios of oxidative stress and apoptosis were increased. A CO-induced mitotoxic and apoptotic fingerprint is present in smoking pregnant women and their newborn, with a lack of filtering effect from the placenta. Tobacco consumption correlated with a reduction in birth weight and mitochondrial and apoptotic impairment, suggesting that both could be the cause of the reduced birth weight in smoking pregnant women.
Fetal development is a critical period for shaping the lifelong health of an individual. However, the fetus is susceptible to internal and external stimuli that can lead to adverse long-term health consequences. Glucocorticoids are an important developmental switch, driving changes in gene regulation that are necessary for normal growth and maturation. The fetal hypothalamic-pituitary-adrenal (HPA) axis is particularly susceptible to long-term programming by glucocorticoids; these effects can persist throughout the life of an organism. Dysfunction of the HPA axis as a result of fetal programming has been associated with impaired brain growth, altered behaviour and increased susceptibility to chronic disease (such as metabolic and cardiovascular disease). Moreover, the effects of glucocorticoid-mediated programming are evident in subsequent generations, and transmission of these changes can occur through both maternal and paternal lineages.
Prenatal exposure to maternal anxiety and inappropriate levels of glucocorticoids may influence intrauterine growth and affect later health outcomes. We examined the relationship between maternal anxiety, maternal serum, and fetal cord blood cortisol.
Eighty-four pregnant women with gestational age above 37 weeks admitted for elective caesarian section were studied. The Spielberger State-Trait Anxiety Inventory was used to assess maternal anxiety. Maternal blood was sampled immediately before caesarean section. Cord blood sample was taken immediately after birth. Multiple regression analysis was performed.
Maternal trait anxiety score, maternal serum cortisol, and neonatal weight were associated with the fetal cord blood cortisol (r = 0.21, P = 0.04). Bivariate correlation analysis revealed a positive correlation between maternal trait anxiety and fetal cord blood cortisol (r = 0.21, P = 0.03).
These data suggested that high maternal trait anxiety increases fetus cord blood cortisol and may regulate fetal growth.
Background
Previous studies concerning the association between maternal anxiety during pregnancy and adverse birth outcomes have provided controversial findings.
Methods
In this systematic review, a meta-analysis was utilized to investigate the association between maternal anxiety and preterm birth (PTB) and/or low birth weight (LBW). Literature was searched until June 2013. Only prospective cohort studies that reported data on maternal anxiety during pregnancy with PTB and/or LBW were included. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using fixed or random effects models depending on the size of heterogeneity.
Results
Twelve studies totaling 17,304 pregnant women reported PTB data; and six studies totaling 4948 pregnant women reported LBW data. Maternal anxiety during pregnancy was associated with significant increased risk of PTB (pooled RR=1.50, 95% CI=1.33–1.70) and LBW (pooled RR=1.76, 95% CI=1.32–2.33).
Limitations
Potential moderators could not be adequately considered due to insufficient information. In addition, the effects of different types of anxiety disorder on the risk of these adverse birth outcomes could not be investigated.
Conclusions
The results suggested that maternal anxiety during pregnancy was positively related to an increased risk of PTB and LBW. Healthcare providers should give close attention to anxiety in pregnant women and provide appropriate mental health support in order to improve outcomes for both mothers and infants.
Glucocorticoids are widely used for their unsurpassed anti-inflammatory and immunomodulatory effects. However, the therapeutic use of glucocorticoids is almost always limited by substantial adverse outcomes such as osteoporosis, diabetes, and obesity. These unwanted outcomes are a major dilemma for clinicians because improvements in the primary disorder seem to be achievable only by accepting substantial adverse effects that are often difficult to prevent or treat. To understand the pathogenesis of glucocorticoid-induced osteoporosis, it is necessary to consider that the actions of glucocorticoids on bone and mineral metabolism are strongly dose and time dependent. At physiological concentrations, endogenous glucocorticoids are key regulators of mesenchymal cell differentiation and bone development, with additional regulatory roles in renal and intestinal calcium handling. However, at supraphysiological concentrations, glucocorticoids affect the same systems in different and often unfavourable ways. For many years, these anabolic and catabolic actions of glucocorticoids on bone were deemed paradoxical. In this Review, we highlight recent advances in our understanding of the mechanisms underlying the physiology and pathophysiology of glucocorticoid action on the skeleton and discuss present and future management strategies for glucocorticoid-induced osteoporosis.
Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis is accepted as one of the fundamental biological mechanisms that underlie major depression. This hyperactivity is caused by diminished feedback inhibition of glucocorticoid (GC)-induced reduction of HPA axis signaling and increased corticotrophin-releasing hormone (CRH) secretion from the hypothalamic paraventricular nucleus (PVN) and extra-hypothalamic neurons. During chronic stress-induced inhibition of systemic feedback, cytosolic glucocorticoid receptor (GR) levels were significantly changed in the prefrontal cortex (PFC) and hippocampus, both structures known to be deeply involved in the pathogenesis of depression.
Exposures to environmental contaminants can pose risks to pregnant women's health, their developing fetuses, children, and adults later in their lives. Assessing risks to this potentially susceptible population requires a sound understanding of the physiological and behavioral changes that occur during pregnancy and lactation. Many physiological and anatomical changes occur in a woman's organ systems during the course of pregnancy and lactation. For example, blood volume and cardiac output increase during pregnancy, and other metabolic functions are altered to provide for the demands of the fetus. During lactation, nutritional demands are greater than during pregnancy. There are also changes in behavior during both pregnancy and lactation. For example, water consumption during pregnancy and lactation increases. These behavioral and physiological changes can lead to different environmental exposures than these women might otherwise experience in the absence of pregnancy or lactation. This paper provides a summary of information from the published literature related to behavioral and physiological changes in pregnant and lactating women that may affect their exposure or susceptibility to environmental contaminants, provides potentially useful exposure factor data for this population of women, and highlights data gaps.Journal of Exposure Science and Environmental Epidemiology advance online publication, 15 January 2014; doi:10.1038/jes.2013.92.
Alteration in the HPA axis is a robust biomarker of anxiety and depression in adults, but questions remain about this association in pregnancy. We examined the longitudinal links between diurnal cortisol and mood symptoms from self-report questionnaire and diagnostic interview in an ethnically diverse, psychosocially at-risk sample of 101 women at mid-pregnancy and early third trimester. There were modest but significant associations between depression and elevated cortisol, indexed by a decreased morning level and diminished diurnal decline; the effects were strongest for diagnostic data from clinical interview. These effects were independent of socio-demographic factors and sleep disturbance. Associations with anxiety and trauma were generally non-significant. These findings extend prior work by showing that significant mood symptoms in pregnancy are associated with altered diurnal cortisol in pregnancy, which may have implications for maternal and child health.
Objectives:
Immigrant women living in Canada present with higher rates of prenatal depressive symptomatology than Canadian-born women; however, the associated psychosocial correlates remain understudied. Antenatal depression and stress negatively affect maternal health and infant development, in part through changes in maternal hypothalamic-pituitary-adrenal (HPA) axis activity. We aimed to examine the factors associated with prenatal depressive symptoms, including altered HPA axis function, in an ethnically diverse community sample of Canadian immigrant women.
Methods:
Seventy-eight pregnant immigrant women were recruited from the community at 19 weeks' gestation and provided information on health, mood, stressful life events (SLEs), and social support. Fifty-seven of these women also provided saliva samples for measurement of the cortisol awakening response and nighttime cortisol levels.
Results:
Seventeen per cent of the sample had a high level of prenatal depressive symptoms, and these women reported more perceived stress, more somatic symptoms, lower social support, and were less often working or attending school during pregnancy. Controlling for wake time, parity, and region of origin, high levels of prenatal depressive symptoms were associated with elevated nighttime cortisol levels, whereas SLEs were not associated with any measures of HPA axis activity.
Conclusions:
High levels of prenatal depressive symptoms are common in immigrant women living in Canada, and are associated with identifiable factors. Preliminary evidence suggests a similar pattern of HPA axis activity characterizing depressive symptomatology in this subpopulation as previously seen in clinically depressed patients.