Article

Fetal Programming: The influence of prenatal maternal Distress on Infant Development and Temperament

Authors:
To read the full-text of this research, you can request a copy directly from the authors.

Abstract

Entsprechend dem Konzept der Fötalen Programmierung wirkt sich pränataler Stress nachhaltig auf die Gesundheit des Nachkömmlings aus. Die Hypothalamus-Hypophysen-Nebennierenrinden-Achse wird als eine mediierende Struktur angenommen, über welche sich mütterlicher Stress in der intrauterinen Umwelt auf den Fötus auswirkt. In der vorliegenden Studie wurde an 46 Mutter-Kind-Paaren die berichtete mütterliche Stressbelastung und Kortisolausschüttung während der Schwangerschaft erfasst. Im Alter von fünf Monaten wurden das frühkindliche Temperament sowie die motorische und kognitive Entwicklung der Säuglinge untersucht. Säuglinge von Müttern mit höherer pränataler Stressbelastung zeigten erwartungsgemäß ein schwierigeres Temperament, jedoch erwartungskonträr eine bessere motorische Entwicklung. Ein schwieriges Temperament des Säuglings stellt einen Risikofaktor für eine frühe Störung der Mutter-Kind-Interaktion dar. Frühe Präventionsmaßnahmen könnten helfen, dieses Risiko zu minimieren und Schutzfaktoren zu etablieren.

No full-text available

Request Full-text Paper PDF

To read the full-text of this research,
you can request a copy directly from the authors.

... The DNA methylation, one of the most prevalent epigenetic alterations, regulates the gene activity by the addition/ binding of a methyl group on specific 5'-cytosine-guanine-3' dinucleotides (i.e., CpG sites) of the DNA sequence (Provenzi, Guida, & Montirosso, 2017;Stonawski et al., 2017). The methylation mechanism is able to change switches in the DNA activity ranging from gene activation to gene silencing (Bird, 2007;Haselbeck et al., 2013;McGowan & Szyf, 2010). It begins from the prenatal period and reaches over the lifespan, leading to long-lasting changes and constantly changing methylation patterns as well (Bird, 2007). ...
... It begins from the prenatal period and reaches over the lifespan, leading to long-lasting changes and constantly changing methylation patterns as well (Bird, 2007). During the prenatal period, as well as later in life, DNA methylation seems to depend among other things on the HPA axis activity and is therefore individual, based on individual experiences and their appraisal (Fraga et al., 2005;Haselbeck et al., 2013). A previous study exploring methylation patterns in monozygotic twins found that while the methylation of younger twin pairs was epigenetically indistinguishable, older twin pairs (over 50 years) showed remarkable differences, with 2.5 times as many DNA methylation differences and four times as many differentially expressed genes compared to their younger counterparts (Fraga et al., 2005). ...
... Likewise, as previous authors reported that methylation patterns might be reversed by positive parenting or beneficial mother-infant interaction, later mother-infant training can contribute to changing methylation patterns and preventing, for example, a possible disease onset in the child later in life (Haselbeck et al., 2013;McGowan & Szyf, 2010). ...
Thesis
Early life stress is known to influence mothers and consequently also the infant pre-, peri-, and postnatally. Both stress sensitization and inoculation theories have speculated about the conflicting previous findings of beneficial as well as impairing influences of early life stress. Findings of an impact on infant development, behavior and later vulnerability for cognitive and emotional problems, physical diseases and mental disorders, suggested the need to identify possible pathways between early life stress and infant outcome. Suggested underlying processes, such as fetal programming, were discussed. The present thesis focused on the possible impact of prenatal maternal stress on mother-infant dyadic behavior in a standardized observation paradigm, i.e. the still-face paradigm. Study I aimed to illuminate the prospective influence of psychological and physiological stress during pregnancy on mother-infant dyadic behavior in the first play episode of the still-face paradigm. In Study II, both the first play episode and the reunion episode were investigated. In Study I, the first play episode of the still-face paradigm was investigated. The findings provided evidence of an impact of psychosocial prenatal stress on mother-infant dyadic behavior during the normal mother-infant play, as it was expected for the first play episode. Mother-infant dyads with more psychosocial PS in pregnancy showed significantly more positive dyadic behavior then the less stressed dyads. The same was found for perceived maternal prenatal stress, although the effect vanished when analyses were conducted including all covariates. Hence, the findings were considered as providing only restricted evidence. No other stress index (i.e., psychopathological PS, cortisol decline and cortisol AuCg) reached significance in predicting mother-infant dyadic play behavior. In Study II, the impact of prenatal stress on mother-infant dyadic behavior in both play situations of the still-face paradigm was investigated. The dyadic behavior in the first play episode was compared with that in the reunion episode. The results provided evidence for the “still-face” and “carry-over” effect, with mother-infant dyads in both the high- and low-stress groups showing decreasing positive and increasing negative dyadic behavior in the reunion episode. Here too, mother-infant dyads with higher psychosocial prenatal stress showed significantly more positive dyadic behavior in the first play episode, but not in the reunion episode. In the latter episode, the positive behavior of the dyads with high prenatal stress decreased to approximately the same level as that of the dyads with low stress. In Study II, significant results emerged for physiological stress dimensions, with mother-infant dyads with a prenatally flat diurnal cortisol decline and low diurnal cortisol AUCg levels showing a distinctive, significant increase in negative dyadic behavior in the reunion episode. Mediation analyses run in both studies showed that maternal behavior was not a significant mediator between prenatal stress and infant behavior. The present findings contribute to inoculation theories on the impact of stress. Nevertheless, both studies provide merely a glimpse into the complex relationship of early life stress factors, maternal and environmental factors, and the infant’s development. Taken together, given the vast amount of studies reporting an impairing impact of prenatal stress on the infant, the present results should be interpreted with caution. The results add further support to the idea of individual resilience factors, suggesting that some individuals are not influenced by stressors or even benefit from them. Future research should focus on the underlying mechanisms, such as early programming, sensitive time periods in infant development, as well as possible influencing factors, in order to contribute to the explaining the mixed results, and to inform the creation of preventive programs for mothers and infants.
... Andere Studien konnten jedoch auch einen positiven Zusammenhang zwischen pränataler Stressbelastung der Mutter und kognitiver bzw. motorischer Entwicklung des Kindes feststellen (DiPietro, Novak, Costigan, Atella & Reusing, 2006;Haselbeck et al., 2013). ...
Article
Eine wachsende Zahl an Studien dokumentiert die negativen Auswirkungen von mütterlichen psychosozialen Stressoren (z. B. mütterliche Depression) und gesundheitsrelevanten Verhaltensweisen (z. B. Nikotin- und Alkoholkonsum) während der Schwangerschaft auf den Geburtsausgang. Jedoch werden mütterliche Ressourcen in diesem Kontext noch unzureichend berücksichtigt. Das Ziel ist es daher, die Bedeutung sozialer Unterstützung als frühe Ressource im Schwangerschaftsverlauf und zum Zeitpunkt der Geburt im Hinblick auf das Gesundheitsverhalten der Schwangeren und im Hinblick auf Geburtsmaße zu untersuchen. Die Datenbanken Web of Science und PubMed wurden entsprechend nach deutsch- und englischsprachigen Beiträgen für den Zeitraum 2003 bis 2013 durchsucht. 23 Studien erfüllten die Auswahlkriterien. Die Ergebnisse verdeutlichen, dass die Befundlage sehr inkonsistent ist, was teilweise auf die unterschiedlichen Definitionen sozialer Unterstützung und die Nutzung verschiedener Erhebungsinstrumente zurückzuführen ist. Des Weiteren fehlt es an Studien zur Bedeutung sozialer Unterstützung im Kontext mütterlicher psychosozialer Stressoren und Geburtsmaßen. Es bedarf weiterer Studien an Risiko- und Allgemeinpopulationen, die auf der Basis eines fundierten Rahmenkonzeptes mögliche Effekte der sozialen Unterstützung differenziert analysieren können.
Article
Full-text available
Objective: Secure attachment style is a known protective factor regarding psychopathological development. The infant's attachment style, which is developed during the first two years of life, is therefore considered a moderating factor on the association between prenatal maternal distress and child temperament development which has repeatedly been reported in previous studies. Method: In this longitudinal study on a new sample of 51 mother-child-dyads, reported maternal distress and maternal empathy were assessed during pregnancy. Infant temperament and motor development were assessed at 12 months, while additionally controlling for the infant's attachment style as a postnatal factor. Results: Infants with secure attachment style whose mothers had experienced higher prenatal distress showed slightly better gross motor development at the age of 12 months. No association could be found between prenatal maternal distress and infant temperament. Conclusions: The results support the view that secure attachment style in children is a protective factor and softens the effects of prenatal maternal distress on difficult temperament development.
Article
Full-text available
According to the concept of fetal programming, prenatal distress has long-lasting consequences on the offspring’s health later in life. The hypothalamic-pituitary–adrenal axis is considered a mediating system by which maternal distress is transferred to the fetus in intrauterine environment. In this longitudinal explorative study on 30 mother–child-dyads, reported maternal distress and salivary cortisol were collected during pregnancy. Infant temperament, motor and cognitive development were assessed at 16 months. Additionally, infant cortisol levels throughout the day and in reaction to a psycho-social stressor where measured. As expected, infants whose mothers had experienced higher prenatal distress expressed a more difficult temperament and lower fine motor development at 16 months. No association could be shown between prenatal maternal distress and infant salivary cortisol.
Article
Full-text available
Zusammenfassung. Die elterliche Sensitivität gegenüber Kleinkindern ist eine zentrale Erziehungsfertigkeit und trägt wesentlich zur gesunden Entwicklung des Kindes bei. In der bisherigen Forschung wurden einige Risiko-und Schutzfaktoren der elterlichen Sensitivität ermittelt. Ergänzend zu bestehenden Studien wurden die Determinanten der Sensitivität von jeweils 91 Müttern und Vätern derselben Familien im Quer-und Längsschnitt erforscht. Die Datenerhebung erfolgte im Alter des Kindes von fünf und 15 Monaten mittels Fragebogen. Die Ergebnisse der Querschnitterhebung replizierten mehrheitlich die Befunde der Literatur, jedoch nur für die Mütter und nicht für die Väter. Weitere Unterschiede fanden sich zwischen den Quer-und Längsschnittergebnissen. Die Befunde lassen auf grundlegende Unterschiede in den Determinanten der Sensitivität von Müttern und Vätern schliessen. Schlüsselwörter: Determinanten, elterliche Sensitivität, Fragebogen, Querschnitt, Längsschnitt, Kleinkind Determinants of parental sensitivity Abstract. Parental sensitivity is one key skill in bringing up toddlers and contributes to healthy child development. Research has determined many risk and protective factors for parental sensitivity. In addition to those findings, in this study determinants of sensitivity were investigated in 91 mothers and fathers of the same families cross-sectionally and longitudinally. Measurement were made when the child was aged 5 months and 15 months. Cross-sectional results replicated most of the earlier findings, but only for mothers and not for fathers. Differences were also found between cross-sectional and longitudinal results. Findings indicate that the determinants of sensitivity are fundamentally different in mothers and fathers.
Article
Full-text available
Zusammenfassung. Die Epigenetik, die sich mit der Bedeutung der Gene im Kontext der menschlichen Entwicklung beschäftigt, konnte zeigen, dass genetische Wirkungen auf die Entwicklung immer auf einer Wechselwirkung zwischen Genom und Umwelt basieren. Die Annahme, der genetische Einfluss auf die (psychische) Entwicklung sei konstant und nur durch gentechnologische Maßnahmen ver-a ¨nderbar, ist demnach offenbar ein Fehlschluss. Es werden Grundbegriffe der Epigenetik und aktuelle Forschungsergebnisse erörtert. Desweiteren wird diskutiert, ob epigenetische Prozesse die Pathogenese psychischer Störungen beeinflussen und ob diese Prozesse an bestimmte Entwicklungsphasen gebunden sind. Anschließend wird die Epigenetik im Kontext der Klinischen Kinderpsychologie betrachtet. Es wird diskutiert, ob die Epigenetik die Entwicklungspsychopathologie grundlegend verändert und welche Konsequenzen die neuen epigenetischen Erkenntnisse für die Klinische Kinderpsychologie bereithalten. Epigenetics – revolutionizing developmental psychopathology? Abstract. Epigenetics, a discipline concerned with genes in the context of development, has shown that genetic influences on development are always based on an interaction between genome and environment. Therefore, the assumption that the genetic influence on (psychological) development is constant and can only be changed via genetic procedures is wrong. In this article, following a brief introduction to epigenetics, the influence of epigenetic processes on the pathogenesis of psychological disorders and whether these processes are bound to certain phases of development is reviewed. Subsequently, epigenetics is considered in the context of clinical psychology. Based on the findings presented throughout this article it is discussed whether epigenetics represents a revolution in developmental psychopathology and which consequences recent epigenetic findings have for clinical child psychology.
Article
Full-text available
Daily hassles scales are useful assessment methods to investi- gate the relationship between everyday stressors and psychosomatic and chronic diseases. Brantley, Waggoner, Jones and Rappaport presented a Daily Stress Inventory (DSI) in 1987 which has been used in several studies since. In order to provide German speaking researchers such a scale the original English version was translated and psychometrically analysed. This article describes this scale (AlltagsBelastungsFragebogen, ABF), and pres-
Article
Full-text available
This prospective, longitudinal study aimed to investigate relationships between indicators of maternal prenatal stress, infant birth outcomes and early temperament. We examined the pattern of associations and postulated pathways between physiological (cortisol plasma concentrations) and self-report indices (stress, anxiety) of maternal prenatal stress, cortisol in the amniotic fluid, birth outcomes and infant temperament at 3 months. The sample consisted of 158 women undergoing amniocentesis in the 2nd trimester of pregnancy. Questionnaire measures of maternal stress and anxiety were found to be unrelated to cortisol in plasma or amniotic fluid. Maternal cortisol was related to amniotic cortisol, which in turn was associated with lower birth weight. Birth weight predicted infant fear and distress to limitation at 3 months old. We found trend-like indirect effects of amniotic fluid on infant distress to limitation and fear via birth weight. This is one of the few studies to simultaneously assess the role of maternal and amniotic fluid cortisol on birth outcomes and infant emotional development. The results suggest that foetal cortisol may be an important predictor of infant outcomes and shed light on the mechanisms through which prenatal maternal stress affects infant psychological health.
Article
Full-text available
Non-syndromic clefts of the orofacial region occur in approximately 1 per 500 to 2,500 live births, depending on geographical area and ethnicity. It can be supposed that the disruption of the normal facial structure and the long-standing pressure of treatment from birth to adulthood bring about a range of life stressors which may lead to a long-lasting impact on affected subjects throughout their lives. Therefore, the present study aimed to assess different aspects of psychosocial stress in affected individuals. The study was divided into two parts: first, the Trier Social Stress Test which involves uncontrollability and high levels of social-evaluative stress under real conditions and second, the query of various aspects of coping with psychosocial stress. The test group consisted of 30 affected adult subjects, and an equally sized control group of unaffected volunteers. Cortisol dysregulation was determined by saliva samples before and after stress induction. Meanwhile, participants were asked to complete the SVF 120 stress-coping questionnaire. The analysis of saliva samples showed a similar baseline concentration as well as a similar increase in cortisol levels after stress induction for both groups. Subsequently, the decline in cortisol concentrations was significantly faster in the CLP group (course: p<0.001; groups: p = 0.102; interaction: p = 0.167). The evaluation of the stress-coping questionnaire revealed a significantly shorter rumination about a stressful event in individuals with CLP-related malformations (p = 0.03). We conclude that adults with CLP have significantly better stress-coping strategies than their healthy peers. German Clinical Trials Organization DRKS00003466.
Article
Full-text available
We know very little about the development of rumination, the tendency to passively brood about negative feelings. Because rumination is a risk factor for many forms of psychopathology, especially depression, such knowledge could prove important for preventing negative mental health outcomes in youth. This study examined developmental origins of rumination in a longitudinal sample (N=337; 51% girls) studied in preschool (ages 3½ and 4½ years) and early adolescence (ages 13 and 15 years). Results indicated that family context and child temperament, assessed during the preschool period, were risk factors for a ruminative style in adolescence. Specifically, early family contexts characterised by over-controlling parenting and a family style of negative-submissive expressivity predicted higher levels of later rumination. These associations were moderated by children's temperamental characteristics of negative affect and effortful control. Further, the interaction of these temperament factors exerted an additional influence on later rumination. Implications for prevention and intervention efforts are discussed.
Article
Full-text available
Postpartum depression has been associated with parenting stress, impacting attachment and child development. However, the relation between antenatal depression or anxiety and postpartum parenting stress has not been investigated. We studied the effect of antenatal depression and anxiety and treatment with selective serotonin reuptake inhibitors and selective norepinephrine reuptake inhibitors (antidepressants [ADs]) on postpartum parenting stress. Ninety-four pregnant women (part of a larger study examining prenatal AD exposure on infants) were prospectively monitored for depression and anxiety during the third trimester and 3- and 6-months postpartum using the Hamilton Depression Rating Scale (HDRS) and Hamilton Anxiety Rating Scale. Parenting stress was assessed using the Parenting Stress Index-Short Form at 3- and 6-months postpartum. Both antenatal third trimester depression and anxiety were significant predictors of 3- and 6-month postpartum parenting stress, after controlling for maternal age, number of children, and exposure to prenatal ADs (all Ps < 0.001). Third trimester depression accounted for 13% to 22% of the variance in postpartum stress at 3 and 6 months. Prenatal AD use was not a significant predictor in any of the models (all Ps > 0.2). Twenty of 41 mothers on ADs achieved remission (HDRS = 7) in pregnancy and had average parenting stress scores of about 1 standard deviation lower than those who did not at 3- and 6-months postpartum (t = 3.32, df = 32, P = 0.002 and t = 2.52, df = 32, P = 0.02, respectively). Our findings indicate that antenatal depression and anxiety directly impact postpartum parenting stress, regardless of antenatal AD treatment. Ongoing maternal mental illness in pregnancy is an important predictor of postpartum parenting stress. Early recognition and treatment to remission is key.
Article
Full-text available
Prenatal maternal stress has been shown to impair functioning in nonhuman primate offspring. Little is known about the effects of prenatal stress on intellectual and language development in humans because it is difficult to identify sufficiently large samples of pregnant women who have been exposed to an independent stressor. We took advantage of a natural disaster (January 1998 ice storm in Québec, Canada) to determine the effect of the objective severity of pregnant women's stress exposure on general intellectual and language development of their children. Bayley Mental Development Index (MDI) scores and parent-reported language abilities of 58 toddlers of mothers who were exposed to varying levels of prenatal stress were obtained at 2 y of age. The hierarchical multiple regression analyses indicated that the toddlers' birth weight and age at testing accounted for 12.0% and 14.8% of the variance in the Bayley MDI scores and in productive language abilities, respectively. More importantly, the level of prenatal stress exposure accounted for an additional 11.4% and 12.1% of the variance in the toddlers' Bayley MDI and productive language abilities and uniquely accounted for 17.3% of the variance of their receptive language abilities. The more severe the level of prenatal stress exposure, the poorer the toddlers' abilities. The level of prenatal stress exposure accounted for a significant proportion of the variance in the three dependent variables above and beyond that already accounted for by non-ice storm-related factors. We suspect that high levels of prenatal stress exposure, particularly early in the pregnancy, may negatively affect the brain development of the fetus, reflected in the lower general intellectual and language abilities in the toddlers.
Article
Full-text available
To examine, in a prospective study, the influence of prenatal stress on infant temperament and problem behavior. Self-report data on stress and anxiety, and levels of cortisol in saliva were collected from nulli-parous women during pregnancy. Temperament of the child was measured at 27 months by parent report on the Infant Characteristics Questionnaire. Behavior of the child was assessed by direct observation during the administration of the Bayley Scales of Development 2-30, and by parent report on the Child Behavior Checklist 2-3. Complete data were available for 103 healthy toddlers. Logistic regression analyses were performed and results were adjusted for possible prenatal, perinatal and postnatal confounders. Perceived stress during pregnancy was a predictor of lower levels of restless/disruptive temperament (OR=0.77), more total behavioral problems (OR=1.17), and more externalizing behavioral problems (OR=1.12) in 2-year-olds. Fear of bearing a handicapped child was a predictor of higher levels of restless/disruptive temperament (OR=1.39) and more attention regulation problems in toddlers (OR=1.46). Increased levels of maternal prenatal stress appear to be associated with temperamental and behavioral problems in toddlers.
Article
A distinct rise in cortisol levels that occurs after morning awakening is increasingly used as an indicator of adrenocortical activity which is associated with different pathologies. Although it was previously assumed that the transition from sleep to wake is essential for the occurrence of the cortisol morning rise, this has never been tested. Here, we examined 16 healthy young men (20–33 yrs) between 2300 and 0800 h under sleep laboratory conditions. Serum cortisol and plasma adrenocorticotropin (ACTH) as well as salivary cortisol levels (after subjects were woken up at 0700 h) were repeatedly assessed. In a supplementary study condition, salivary cortisol levels in the first hour after awakening were measured at the subjects’ home on two consecutive days. Comparison of pre- and post awakening measurements revealed significantly steeper increases in cortisol and ACTH after awakening. The rise in cortisol upon awakening under laboratory conditions did not significantly differ from that observed at home. We conclude that the cortisol increase after awakening is a response to morning awakening that is distinct from the circadian rise in hypothalamo-pituitary-adrenal (HPA) activity in the morning hours. Although the cortisol awakening response is modulated by circadian influences, it primarily reflects phasic psychophysiological processes specific to the sleep–wake transition.
Article
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.
Article
The article aims to study mother-child and father-child interactions with 24-month-old children during feeding, considering the possible influence of time spent by the parent with the child, the infantile temperament, and the parental psychological profile. The families were recruited from 12 preschools in Italy (N = 77 families). Through an observation of the feeding [Scala di Valutazione dell'Interazione Alimentare (SVIA - Feeding Scale; I. Chatoor et al., ; L. Lucarelli et al., )], self-reporting [Symptom Checklist-90-Revised (SCL-90-R; L.R. Derogatis, ), and report-form questionnaires [Italian Questionnaires on Temperament (QUIT; G. Axia, )], and information provided by the parents about the amount of time spent with their children, results showed that the overall quality of father-child interactions during feeding is lower than that of mother-child interactions. Fathers showed higher psychological symptoms than did mothers. No associations were found between the fathers' psychopathological risk and the quality of interactions with their children during feeding. Mothers' psychopathological risks predicted less contingent exchanges interactions with their children during feeding. Children's temperaments significantly influence mother-child interactions, but no association exists between maternal involvement and the quality of interactions with their children. Paternal involvement predicts a better quality of father-infant interactions when associated with a child's higher scores on Social Orientation. The quality of parents' interactions with their children during feeding are impacted by different issues originating from the parent's psychological profile, the degree of involvement, and from the child's temperament. © 2014 Michigan Association for Infant Mental Health.
Article
The aim of this study was to assess the cognitive and behavioural development of children with healthy birth outcomes whose mothers were exposed to prenatal stress but did not experience pregnancy complications. In this prospective study, self-reported data, including the Prenatal Life Events Checklist about stressful life events (SLEs) during different stages of pregnancy, were collected at 32 to 34 weeks' gestation. Thirty-eight healthy females (mean age 27y 8mo, SD 2y 4mo) who were exposed to severe SLEs in the first trimester were defined as the exposed infant group, and 114 matched comparison participants were defined as the unexposed infant group (1:3). Maternal postnatal depressive symptoms were assessed with the Edinburgh Postnatal Depression Scale. The Bayley Scales of Infant Development and the Toddler Temperament Scale were used to evaluate the cognitive development and temperament characteristics of the infants with healthy birth outcomes when they were 16 to 18 months old. A randomized block multivariate analysis of covariance showed that the mental development index scores of the infants of mothers with prenatal exposure to SLEs in the first trimester averaged seven points (95% confidence interval 3.23-10.73 points) lower than those of the unexposed infants. Moreover, the infants in the exposed group achieved higher scores for regularity (adjusted mean [SD] 2.77 [0.65] vs 2.52 [0.78], F(5,146) =5.27, p=0.023) and for persistence and attention span (adjusted mean 3.61 [0.72] vs 3.35 [0.52], F(5,146) =5.51, p=0.020). This study provides evidence that lower cognitive ability and less optimal worse behavioural response in infants might independently result from prenatal maternal stress.
Article
Der frühzeitigen Prävention kommt eine immer größere Bedeutung zu. Auf der Basis zunehmender Kenntnisse über normale und abweichende Entwicklungsverläufe lassen sich altersspezifische und entwicklungsbezogene Präventionsprogramme besser begründen und schließlich erfolgreich umsetzen. Ein besonderer Fokus liegt auf Fördermaßnahmen, die bereits im Kindergartenalter ansetzen, wie etwa die Stärkung der sozial-emotionalen Kompetenzen. Jedoch haben sich mittlerweile auch schulbasierte Programme etabliert.
Article
Zusammenfassung. Externalisierende Verhaltensstörungen entwickeln sich zumeist bereits in der frühen Kindheit. Befunde aus der Säuglingsforschung und Neurobiologie weisen darauf hin, welche Risiken in der Genese früh auftretender Verhaltensprobleme beteiligt sind und über welche Mechanismen sie wirken. Aufgrund der enormen Plastizität des kindlichen Gehirns repräsentiert die pränatale und frühkindliche Entwicklungsperiode eine Phase erhöhter Vulnerabilität gegenüber stressinduzierenden widrigen Erfahrungen, die durch Merkmale der Beziehungsgestaltung zwischen dem Kind und seinen primären Bezugspersonen kompensiert oder verstärkt werden kön-nen. Für die klinische Praxis ergibt sich, dass Präventions-und Interventionsmaßnahmen mit dem Einsetzen der Schwangerschaft erfolgen und sich stärker an der aktuellen psychosozialen Lebenssituation und dem psychischen Befinden der Mutter orientieren sollten. Summary. Externalizing disorders often develop in infancy. Findings from infant research and neurobiological studies provide important evidence on early risks for the development of behavior problems in infants and the mechanisms involved. During the pre-, peri-and early postnatal development, the high plasticity of the brain increases the vulnerability towards the exposure to noxious stimuli and adverse experiences. The impact of early stress experiences is moderated by the quality of parent-child relationship. It is concluded that clinical assessment, prevention and intervention efforts should start during pregnancy and have a major focus on the living conditions and mental health status of the mother.
Article
Zusammenfassung: Fragestellung: Eine deutschsprachige Adaptation des Infant Behavior Questionnaire von Rothbart wird hinsichtlich der internen Konsistenzen der Skalen, der Skaleninterkorrelationen und Stabilität untersucht. Mögliche Zusammenhänge der Skalen mit der Depressivität und Ängstlichkeit der beurteilenden Mutter werden geprüft. Methode: Untersucht werden unabhängige Stichproben 6-8- und 10-12-monatiger Säuglinge (n = 149 resp. n = 109) und deren Bezugspersonen. Eine Stichprobe von 101 Mutter-Säugling-Paaren wird im Längsschnitt, im Alter der Säuglinge von vier, acht und 12 Monaten untersucht. Ergebnis: Die fünf Skalen des Fragebogens sind in den beiden Altersgruppen zufriedenstellend intern konsistent und unabhängig voneinander. Die Stabilitätskoeffizienten entsprechen denen der amerikanischen Version des Verfahrens. Schlussfolgerung: Damit liegt ein in der Forschung und Praxis verwendbares deutschsprachiges Verfahren zur Messung frühkindlicher Temperamentsmerkmale im Elternurteil vor.
Article
The aim of the study was to investigate biobehavioural organisation in infants with different qualities of attachment. Quality of attachment (security and disorganisation), emotional expression, and adrenocortical stress reactivity were investigated in a sample of 106 infants observed during Ainsworth’s Strange Situation at the age of 12 months. In addition, behavioural inhibition was assessed from maternal reports. As expected, securely attached infants did not show an adrenocortical response. Regarding the traditionally defined insecurely attached groups, adrenocortical activation during the strange situation was found for the ambivalent group, but not for the avoidant one. Previous ndings of increased adrenocortical activity in disorganised infants could not be replicated. In line with previous ndings, adrenocortical activation was most prominent in insecure infants with high behavioural inhibition indicating the function of a secure attachment relationship as a social buffer against less adaptive temperamental dispositions. Additional analyses indicated that adrenocortical reactivity and behavioural distress were not based on common activation processes. Biobehavioural associations within the different attachment groups suggest that biobehavioural processes in securely attached infants may be different from those in insecurely attached and disorganised groups. Whereas a coping model may be applied to describe the biobehavioural organisation of secure infants, an arousal model explanation may be more appropriate for the other groups.
Article
This paper reviews the studies that have aimed to identify genes influencing psychological traits in infancy (from birth to age 12 months). The review also addresses why genetic research in infancy is worthwhile and what genetic approaches such as genome-wide association studies and next generation sequencing could offer infant genetics. The results revealed that: (a) all studies (N=26) have employed a candidate gene association design; (b) Existing studies have most commonly focused on the Dopamine receptor D4 (DRD4) and the Serotonin transporter promoter (5-HTTLPR) gene polymorphisms; (c) Phenotypes that have been assessed are temperament, attachment, and attention. Two further studies included both temperament and electrophysiological markers; (d) Among many unreplicated findings, the most promising result appeared to be an association between the long DRD4 polymorphism and several "positive" temperament characteristics from birth to 4-months of age and at 12-months of age. It is concluded that, to date, there are limited, and mixed, findings regarding the possible association of genes with psychological phenotypes in infancy.
Article
ZusammenfassungDie Entwicklung der Hirnfunktion wird pränatal durch epigenetische Faktoren, die insbesondere mit einer fetalen Mangelversorgung oder erhöhten fetalen Stresshormonkonzentrationen einhergehen, beeinflusst. Schon eine moderate Mangelernährung hat Effekte auf die Hirnentwicklung u.a. über eine Hemmung des Systems des insulinähnlichen Wachstumsfaktors. Daneben führt sie zu einer Erhöhung von mütterlichen Kortisolkonzentrationen im fetalen Kreislauf. Erhöhte fetale Kortisolkonzentrationen, sei es aufgrund fetaler Mangelversorgung, Stress oder pränataler Gabe von Glukokortikoiden, führen ebenfalls zu Störungen der Hirnentwicklung. Darüber hinaus induzieren sie in den letzten Wochen der Schwangerschaft, wenn die kindliche Hypophysen-Hypothalamus-Nebennieren-(HHN)-Achse reift, eine dauerhafte Desensitivierung von Glukokortikoidrezeptoren im Hippokampus. Diese bewirkt eine verminderte negative Rückkopplung der HHN-Achse mit der Folge einer verstärkten Kortisolausschüttung und einer erhöhten Stressempfindlichkeit im späteren Leben. Die Störungen der Hirnentwicklung und die dauerhaft erhöhten Kortisolspiegel induzieren subtile kognitive Störungen, Verhaltensauffälligkeiten und eine Prädisposition für depressive und schizophrene Erkrankungen.
Article
There is significant current interest in the degree to which prenatal exposures, including maternal psychological factors, influence child outcomes. Studies that detect an association between prenatal maternal psychological distress and child developmental outcomes are subject to a number of interpretative challenges in the inference of causality. Some of these are common to many types of prenatal exposures that must necessarily rely on observational designs. Such challenges include the correlation between prenatal and postnatal exposures and the potential role of other sources of shared influence, such as genetic factors. Others are more specific to this area of research. These include confounding between maternal report of child outcomes and the maternal psychological attributes under study, difficulties in distinguishing maternal stress from more ubiquitous aspects of maternal personality, and the lack of association between cortisol and measures of maternal psychological stress. This article considers these methodological issues and offers an additional methodology focused on fetal neurobehavior for discerning potential mechanisms that may mediate associations between maternal psychological functioning and the developing fetal nervous system.
Article
The association between maternal anxiety during pregnancy and child development was studied prospectively in a group of 105 healthy Caucasian women and their infants. Anxiety was measured with the State-Trait Anxiety Inventory at 32 weeks’ gestation. Infant development was measured at three weeks postpartum by means of the Neonatal Behavioral Assessment Scale, and at one and two years by means of the Bayley Scales of Infant Development. Findings of the present study showed that, even when controlled for a variety of confounding variables, high maternal anxiety levels during late pregnancy were associated with lower mental developmental scores at the age of 2 years. It is suggested that especially attention related processes may be affected, and should be studied in future research. If these findings are confirmed by future research, identification of highly anxious women during gestation may provide an important opportunity to start a support program in order to optimize later infant stimulation and caretaking.
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
Prenatal stress is known to be a potential risk factor for cognitive, behavioural and motor development that even last until adolescence. A consensus of how 'prenatal stress' can be measured, in which trimester of pregnancy women should be studied and whether subjective feelings of being stressed are associated with a hormonal response is still lacking. To close this gap, a prospective longitudinal study was conducted in pregnant women. 108 subjects were asked to fill out questionnaires concerning pregnancy-related anxiety, perceived stress, marital satisfaction, critical life events and to collect salivary cortisol in each trimester of pregnancy. Fear of giving birth increases until the end of pregnancy, and marital satisfaction is highest at the end of pregnancy. Perceived stress is related to a hormonal response in cortisol only in the first (r = 0.18, p < 0.10) and second (r = 0.18, p < 0.10) trimesters of pregnancy. Critical life events are linked to raised cortisol levels in early pregnancy only (r = 0.28, p < 0.01). Prenatal stress can be operationalized by using different subjective as well as physiological stress measures. Only in the first half of pregnancy self-report and physiological stress measures seem to be associated.
Article
Animal studies have shown that postnatal rearing style can modify the association between prenatal stress exposure and offspring neurodevelopmental outcomes. However, little is known about how parenting quality impacts the association between maternal prenatal anxiety and development in human infants. This prospective study examined the impact of maternal prenatal anxiety disorder and maternal caregiving sensitivity on cognitive and psychomotor development in healthy, full-term, 7-month-old infants. Women completed a clinical interview during the third trimester of pregnancy to assess anxiety symptoms meeting DSM-IV diagnostic criteria. At infant age 7 months, maternal sensitivity to infant distress and non-distress were observed and coded during the still-face procedure. Maternal postnatal (concurrent) anxiety and depression were also assessed at this time. Infant mental and psychomotor development was assessed at infant age 7 months using the Bayley Scales of Infant Development II. Analyses were based on 77 mother-infant dyads. Maternal sensitivity to infant distress moderated the association between maternal prenatal anxiety disorder and infant mental development, F (1, 77)=5.70, p=.02. Whereas there was a significant positive association between sensitivity and mental development among infants whose mothers were anxious during pregnancy, sensitivity had little impact on mental development among infants of control (non-anxious) women. Results were independent of prenatal depression and postnatal anxiety and depression. A caregiving moderation effect was not found for infant psychomotor development, p>.10. These findings are consistent with a cumulative risk model suggesting that maternal prenatal anxiety and quality of maternal care act in concert to shape infant outcomes.
Article
Experiences during early development profoundly affect development of the central nervous system (CNS) to impart either risk for or resilience to later psychopathology. Work in the developmental neuroscience field is providing compelling data that epigenetic marking of the genome may underlie aspects of this process. Experiments in rodents continue to show that experiences during sensitive periods of development influence DNA methylation patterns of several genes. These experience-induced DNA methylation patterns represent stable epigenetic modifications that alter gene transcription throughout the lifespan and promote specific behavioral outcomes. We discuss the relevance of these findings to humans, and also briefly discuss these findings in the broader contexts of cognition and psychiatric disorder. We conclude by discussing the implications of these observations for future research.
Article
Childhood maltreatment and early trauma leave lasting imprints on neural mechanisms of cognition and emotion. With a rat model of infant maltreatment by a caregiver, we investigated whether early-life adversity leaves lasting epigenetic marks at the brain-derived neurotrophic factor (BDNF) gene in the central nervous system. During the first postnatal week, we exposed infant rats to stressed caretakers that predominately displayed abusive behaviors. We then assessed DNA methylation patterns and gene expression throughout the life span as well as DNA methylation patterns in the next generation of infants. Early maltreatment produced persisting changes in methylation of BDNF DNA that caused altered BDNF gene expression in the adult prefrontal cortex. Furthermore, we observed altered BDNF DNA methylation in offspring of females that had previously experienced the maltreatment regimen. These results highlight an epigenetic molecular mechanism potentially underlying lifelong and transgenerational perpetuation of changes in gene expression and behavior incited by early abuse and neglect.
Article
Epidemiological studies have reported associations between measures of size and weight at birth and disease risk in later life. Alteration in the regulation of the hypothalamic-pituitary-adrenal (HPA) axis in response to prenatal stress has been proposed as one underlying mechanism. The present study investigated in humans the association of prenatal psychosocial stress exposure with subsequent HPA axis regulation in adult life, with a focus on measures of response to challenge and feedback sensitivity. Healthy young adults whose mothers experienced severe stress during their pregnancy in form of major negative life events (e.g. death of someone close; prenatal stress (PS) group, n=31) and an age-matched comparison group (CG, n=30) underwent the Trier Social Stress Test (TSST) and a 1 microg ACTH(1-24) stimulation test. In addition, a diurnal cortisol profile was assessed. ACTH concentrations following a standardized behavioural challenge paradigm (TSST) were marginally significantly higher in PS subjects than in CG subjects (p=.06). Pre-TSST adrenocortical (cortisol) levels were lower (p=.007), whereas the increase in cortisol in response to the TSST was higher (p=.03) in PS subjects compared to CG subjects. Cortisol concentrations following a pharmacological stimulation test simulating pituitary activity (ACTH(1-24) test) were significantly lower in PS than in CG subjects (p=.006). No differences emerged between the two groups in basal diurnal cortisol levels. This study provides first evidence in humans of an association between prenatal psychosocial stress exposure and subsequent alterations in the regulation of the HPA axis.
Article
This paper presents evidence from three samples, two of college students and one of participants in a community smoking-cessation program, for the reliability and validity of a 14-item instrument, the Perceived Stress Scale (PSS), designed to measure the degree to which situations in one's life are appraised as stressful. The PSS showed adequate reliability and, as predicted, was correlated with life-event scores, depressive and physical symptomatology, utilization of health services, social anxiety, and smoking-reduction maintenance. In all comparisons, the PSS was a better predictor of the outcome in question than were life-event scores. When compared to a depressive symptomatology scale, the PSS was found to measure a different and independently predictive construct. Additional data indicate adequate reliability and validity of a four-item version of the PSS for telephone interviews. The PSS is suggested for examining the role of nonspecific appraised stress in the etiology of disease and behavioral disorders and as an outcome measure of experienced levels of stress.
Article
Recent findings suggest that many human fetuses have to adapt to a limited supply of nutrients and in doing so they permanently change their physiology and metabolism. These 'programmed' changes may be the origins of a number of diseases in later life, including coronary heart disease and the related disorders: stroke, diabetes and hypertension.
Article
It has been suggested that prenatal exposure to maternal stress increases the risk of subsequently developing schizophrenia. The five-day invasion and defeat of The Netherlands by the German army in May 1940 constituted a severe, well-circumscribed national stressful event. Individuals exposed and non-exposed to this stressor in the first, second and third trimester of pregnancy were followed up for lifetime schizophrenia outcome through the National Psychiatric Case Register. REGISTER: Cumulative incidence of schizophrenia was higher in the exposed cohort (risk ratio (RR): 1.15, 95% CI 1.03-1.28), especially in those exposed in the first trimester (RR: 1.28, 95% CI 1.07-1.53). Significant interaction with gender was apparent in second trimester exposed cohorts (RR men: 1.35, 95% CI: 1.05-1.74; RR women: 0.83, 95% CI: 0.61-1.12). Maternal stress during pregnancy may contribute to the development of vulnerability to schizophrenia. The apparent longer window of exposure in male foetuses may be related to the slower pace of male early cerebral development.
Article
We tested the hypothesis that maternal stress during pregnancy increases the risk of non-affective psychosis for the child. The concept of non-affective psychosis includes the ICD categories schizophrenic disorder, paranoid state and other non-organic psychosis. Data from the Dutch Psychiatric Registry were examined for an effect of the Flood Disaster of 1 February 1953. On this day, a gale caused a flood in the South-west of The Netherlands and 1835 people perished. Our study concerned the 19 villages where mortality exceeded 0.25%. The risk of non-affective psychosis for the cohort born in the period February-October 1953 was compared to the risks for the cohorts born in the corresponding periods of the previous and subsequent 2 years. The relative risk of non-affective psychosis for those exposed during gestation was 1.8 [95% Confidence Interval (CI): 0.9-3.5]. Thus, our study failed to demonstrate a significant association between prenatal exposure to maternal stress and risk of non-affective psychosis. The possible explanations for this finding are discussed.
Article
The association between coping and pregnancy-specific distress was examined in 167 pregnant women at high medical risk. A population-appropriate coping inventory and prenatal distress measure were administered in mid-pregnancy (mean of 24 weeks gestation). Subjects experienced moderately high levels of distress about preterm delivery, physical symptoms, labor and delivery, weight gain, and having an unhealthy baby. They most frequently coped with the demands and challenges of pregnancy through prayer and positive appraisal. Sociodemographic variables including age, income, education, and parity were significantly associated with ways of coping. Coping by avoidance, preparation for motherhood, and substance use were associated with greater distress, whereas coping by positive appraisal was associated with less distress. These effects differed somewhat when levels of global, non-specific distress were controlled. Findings underscore the unique nature of high-risk pregnancy as a stressful life event.
Article
Our findings in the Helsinki Influenza Study and the Danish Forty Year Study lead us to conclude that a 2nd-trimester maternal influenza infection may increase risk for adult schizophrenia or adult major affective disorder. More recently we have also reported an increase of unipolar depression among offspring who were exposed prenatally to a severe earthquake (7.8 on the Richter scale) in Tangshan, China. Among the earthquake-exposed males (but not the females), we observed a significantly greater depression response for those individuals exposed during the 2nd trimester of gestation. These findings suggest that maternal influenza infection and severe maternal stress may operate (in different ways) as teratogens, disrupting the development of the fetal brain and increasing risk for developing schizophrenia or depression in adulthood.
Article
A self-rating inventory has been developed to measure DSM-IV and ICD-10 diagnoses of major (moderate to severe) depression by the patients' self-reported symptoms. This Major Depression Inventory (MDI) can be scored both according to the DSM-IV and the ICD-10 algorithms for depressive symptomatology and according to severity scales by the simple total sum of the items. The Schedule for Clinical Assessment in Neuropsychiatry (SCAN) was used as index of validity for the clinician's DSM-IV and ICD-10 diagnosis of major (moderate to severe) depression. The sensitivity and specificity of MDI was assessed in a sample of 43 subjects covering a spectrum of depressive symptoms. The sensitivity of the MDI algorithms for major depression varied between 0.86 and 0.92. The specificity varied between 0.82 and 0.86. When using the total score of MDI the optimal cut-off score was estimated 26 and the total score was shown to be a sufficient statistic. The sample of subjects was limited. Patients with psychotic depression were not included. The MDI was found to have a sensitivity and specificity which is acceptable. The questionnaire is brief and can be scored diagnostically by the DSM-IV and ICD-10 algorithms as well as by its simple total score.
Article
Animal experiments suggest that maternal stress and anxiety during pregnancy have long-term effects on the behaviour of the offspring. To test the hypothesis that antenatal maternal anxiety predicts behavioural problems at age 4 years. Data were collected on multiple antenatal and postnatal assessments of maternal anxiety and depression, antenatal and obstetric risks, psychosocial risks and children's behavioural/emotional problems (n=7448). Antenatal maternal anxiety predicted behavioural/emotional problems in boys (OR=2.14, 95% CI 1.48-3.10) and girls (OR=1.88, 95% CI 1.3-2.69) after accounting for covariates. When covarying maternal anxiety up to 33 months postnatally, antenatal anxiety continued to predict total problems in boys (OR=1.56, 95% CI 1.02-2.41) and girls (OR=1.51, 95% CI 1.22-2.81). There could be a direct effect of maternal mood on foetal brain development, which affects the behavioural development of the child.
Article
To examine, in a prospective study, whether maternal stress during pregnancy is related to infant temperament. Self-report data on various aspects of prenatal stress were collected from nulliparous women in early pregnancy. Infant temperament was measured at 3 and 8 months by direct observation and by parent report. Complete data were available for 170 term-born infants. Pregnancy-specific anxiety explained 3.3% of the variance of attention regulation at 3 months. Perceived stress and pregnancy anxiety taken together explained 5% of the variance of attention regulation at 8 months. Perceived stress accounted for 8.2% of the variance of difficult behavior of the 3-month-old infant. All results were adjusted for covariates. Increased maternal prenatal stress seems to be associated with temperamental variation of young infants and may be a risk factor for psychopathology later in life.
Article
Study protocols in endocrinological research and the neurosciences often employ repeated measurements over time to record changes in physiological or endocrinological variables. While it is desirable to acquire repeated measurements for finding individual and group differences with regard to response time and duration, the amount of data gathered often represents a problem for the statistical analysis. When trying to detect possible associations between repeated measures and other variables, the area under the curve (AUC) is routinely used to incorporate multiple time points. However, formulas for computation of the AUC are not standardized across laboratories, and existing differences are usually not presented when discussing results, thus causing possible variability, or incompatibility of findings between research groups. In this paper, two formulas for calculation of the area under the curve are presented, which are derived from the trapezoid formula. These formulas are termed 'Area under the curve with respect to increase' (AUCI) and 'Area under the curve with respect to ground' (AUCG). The different information that can be derived from repeated measurements with these two formulas is exemplified using artificial and real data from recent studies of the authors. It is shown that depending on which formula is used, different associations with other variables may emerge. Consequently, it is recommended to employ both formulas when analyzing data sets with repeated measures.
Article
Cortisol is the final product of the hypothalamus-pituitary-adrenal (HPA) axis. It is secreted in a pulsatile fashion that displays a circadian rhythm. Infants are born without a circadian rhythm in cortisol and they acquire it during their first year of life. Studies do not agree on the age of appearance of the circadian rhythm (varying between 2 weeks till the age of 9 months) nor on whether it is related to the appearance of the sleep-wake circadian rhythm. The object of the present study was to find evidence of the age of appearance of the diurnal rhythm of cortisol and to compare the results obtained by several different analysis methods on a new data set. Cortisol was determined in salival samples of 14 normally developing infants who were followed monthly between the ages of 2 and 5 months. The data were analyzed with several previously published analysis methods as well as with Multilevel Analysis (Hierarchical Linear Modeling). The previously published analysis methods each produced different results when applied to the current data set. Moreover, our results indicate striking differences between young infants in both age of appearance and stability of the diurnal cortisol rhythm. Also, a link was found between the appearance of the sleep-wake circadian rhythm and the cortisol circadian rhythm. An important intraindividual variability in cortisol levels was found even after correcting for the different variables that affect cortisol (i.e. time of sampling, feeding, etc.). Although the choice of analysis method influences the age of appearance obtained, our use of HLM shows that the infants' own variability in onset and stability of the cortisol circadian rhythm greatly contributes to the different results.
Article
Animal studies show that prenatal maternal stress may be related to cognitive impairments in offspring. Therefore, we examined whether psychological and endocrinologic measures of stress during human pregnancy predicted developmental outcome of the infant at 3 and 8 months. Self-report data about daily hassles and pregnancy-specific anxiety and salivary cortisol levels were collected in 170 nulliparous women in early, mid- and late pregnancy in a prospective design, in which healthy infants born at term were followed up after birth. High levels of pregnancy-specific anxiety in mid-pregnancy predicted lower mental and motor developmental scores at 8 months (p < .05). High amounts of daily hassles in early pregnancy were associated with lower mental developmental scores at 8 months (p < .05). Early morning values of cortisol in late pregnancy were negatively related to both mental and motor development at 3 months (p < .05 and p < .005, respectively) and motor development at 8 months (p < .01). On average a decline of 8 points on the mental and motor development scale was found. All results were adjusted for a large number of covariates. Stress during pregnancy appears to be one of the determinants of delay in motor and mental development in infants of 8 months of age and may be a risk factor for later developmental problems. Further systematic follow-up of the present sample is needed to determine whether these delays are transient, persistent or even progressive.
Article
Sparse information on early development of hypothalamic pituitary adrenal (HPA) axis responsivity in human infants limits our understanding of stress hormone regulation and vulnerability to psychopathology. We considered whether infant cortisol stress response (CSR) is a suitable endocrine phenotype for developmental stress research. We assessed stability of key CSR parameters across time, location, and stressor through saliva samples taken before and then 20 and 40 min following exposure to two stressors administered 1 week apart in 27 infants aged 12 to 18 months. Time-matched home samples were collected to control for circadian rhythm and to evaluate baseline stability. Baseline cortisol concentrations, peak percent change, and area under the curve (AUC) were stable across time and stressors. Following both stressors, half the infants exhibited peak cortisol concentrations at 20 min poststress; half peaked at 40 min poststress. For 56% of the infants, peak response time was inconsistent across stressors. In humans, baseline and CSR are stable by 12 to 18 months. Variation in CSR time course across stressors indicates that infant CSR should be sampled beyond 30 min. Results support using infant CSR, particularly as measured by AUC, as a valid endocrine phenotype for developmental stress research.
Article
Previous animal investigations link antenatal stress with a range of persistent behavioural abnormalities in the offspring. The current study examined if the effect was also found in humans through middle childhood. The current study is based on the Avon Longitudinal Study of Parents and Children (ALSPAC), a prospective, community-based study that has followed a cohort of women from pregnancy. Self-report measures of maternal anxiety and depression were assessed at repeated intervals in pregnancy and the postnatal period. Children's behavioural/emotional problems were assessed by parent report at age 47 and 81 months. Information on obstetric and psychosocial factors was obtained at several points in pregnancy and the postnatal period. Children whose mothers experienced high levels of anxiety in late pregnancy exhibited higher rates of behavioural/emotional problems at 81 months of age after controlling for obstetric risks, psychosocial disadvantage, and postnatal anxiety and depression (for girls, OR = 1.91, 95%CI = 1.26-2.89; for boys, OR = 2.16, 95%CI = 1.41-3.30). Furthermore, the effect at 81 months was comparable to what was previously obtained at 47 months, suggesting the kind of persistent effect proposed in the animal literature. There is evidence that antenatal stress/anxiety has a programming effect on the fetus which lasts at least until middle childhood.
Article
Associations between antenatal maternal anxiety, measured with the State Trait Anxiety Inventory, and disorders in 8- and 9-year-olds were studied prospectively in 71 normal mothers and their 72 firstborns. Clinical scales were completed by the mother, the child, the teacher, and an external observer. Hierarchical multiple regression analyses showed that maternal state anxiety during pregnancy explained 22%, 15%, and 9% of the variance in cross-situational attention deficit hyperactivity disorder symptoms, externalizing problems, and self-report anxiety, respectively, even after controlling for child's gender, parents' educational level, smoking during pregnancy, birth weight, and postnatal maternal anxiety. Anxiety at 12 to 22 weeks postmenstrual age turned out to be a significant independent predictor whereas anxiety at 32 to 40 weeks was not. Results are consistent with a fetal programming hypothesis.
Article
Depressed (n = 45) and nondepressed (n = 47) mothers were recruited prenatally at an ultrasound clinic. Their urine samples were assayed for cortisol, catecholamines (norepinephrine, epinephrine, dopamine) and serotonin. Their urines were assayed again at the neonatal period, and their newborns' urines were also assayed at that time. The depressed versus the nondepressed mothers showed significantly higher cortisol and norepinephrine and significantly lower dopamine levels across the pre- and postnatal assessments. At the postnatal assessment all levels had decreased except the serotonin levels for both groups. Regression analyses on the mother's postnatal biochemistry with the prenatal biochemistry entered as predictor variables showed highly significant, specific relationships between each of the catecholamines, cortisol, and serotonin. The newborn's biochemistry (except for epinephrine) was higher than the maternal biochemistry. Regression analyses on the neonatal biochemistry with the mother's prenatal biochemistry entered as predictor variables also suggested highly significant, specific relationships. The continuity between the mother's and the newborn's neurotransmitter/ neurohormone profiles and data showing that elevated norepinephrine and cortisol predict to low birthweight and prematurity, respectively, highlight the importance of assessing these levels during pregnancy.
Article
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.
Article
To assess whether links exist between maternal trait anxiety (STAI), perceived life event (LE) stress and depression (Edinburgh scale) and infant temperament. Women in the third trimester of pregnancy returned psychological self-report questionnaires; infant temperament was evaluated at 4 and 6 months by maternal and paternal report, while depression (concurrent Edinburgh scale) was also assessed at four and six months. As data were returned inconsistently at 4 and 6 months, we combined these two time points for simplicity of reporting and optimisation of numbers. Univariate logistic regressions on 970 subjects indicated that the pregnancy STAI (>40) scores were associated with 2.56- and 1.57-fold increases (maternal and paternal, respectively), in the odds of "difficult" infant temperament at 4 or 6 months. Concurrent Edinburgh scores (OR of 3.06 and 2.64 for maternal reports, respectively) were also predictive of infant temperament. Age, education, income, marital status, obstetric complications, infant gender and prematurity were not predictive of infant temperament. In stepwise multiple logistic regression analyses, the antenatal trait STAI (odds ratio 1.96) significantly predicted maternal reports of "difficult" temperament at 4 or 6 months independent of both antenatal and postnatal depression scores. There were similar trends for paternal reports of "difficult" temperament but these were not significant. Antenatal depression and perceived LE stress were not predictive of temperament. Finally, women (N=14) reporting domestic violence (DV) in pregnancy had highly significant increased Edinburgh and STAI scores. Maternal trait anxiety was predictive of "difficult" infant temperament, independent of "concurrent" depression and key sociodemographic and obstetric risk factors. These findings, while needing replication using objective measures of infant temperament, suggest that antenatal psychological interventions aimed at minimising anxiety may optimize infant temperament outcomes. There may be some benefit in shaping specific interventions to women reporting specific risk factors such as DV or past abuse.
Article
Maternal prenatal stress has been found to be related to over-activity and/or dysregulation of the HPA-system in the offspring. These effects are more readily apparent in response to novel situations. The aim of the present report was to examine whether pregnancy stress predicted HPA-axis reactions of children to the first day of school after the summer break. Children of mothers with more prenatal stress were compared to those of mothers with less stress. Habituation was studied by comparisons between the first school day and a second school day a week later. Finally, cortisol levels at school were compared to those of a weekend day. The participants were 29 mother-child pairs (20 girls and nine boys, mean age 5.31 years, SD = 0.50). The children's cortisol levels were determined in saliva. Multilevel analysis (hierarchical linear modelling) was used to analyze the data. Both prenatal cortisol and pregnancy anxiety were related to the children's cortisol levels as a reaction to the first school day. Children whose mothers had higher levels of morning cortisol during pregnancy, and more fear of bearing a handicapped child showed higher levels of cortisol on school days. In addition, the circadian rhythm of cortisol on school days appeared to have a steeper slope as compared to that of the circadian curve on a weekend day.