Prenatal psychobiological predictors of anxiety risk in preadolescent children

Experimental animal models have demonstrated that one of the primary consequences of prenatal stress is increased fear and anxiety in the offspring. Few prospective human studies have evaluated the consequences of prenatal stress on anxiety during preadolescence. The purpose of this investigation is to determine the consequences of prenatal exposure to both maternal biological stress signals and psychological distress on anxiety in preadolescent children. Participants included 178 mother-child pairs. Maternal psychological distress (general anxiety, perceived stress, depression and pregnancy-specific anxiety) and biological stress signals were evaluated at 19, 25, and 31 gestational weeks. Anxiety was evaluated in the children at 6-9 years of age using the Child Behavior Checklist. Analyses revealed that prenatal exposure to elevated maternal cortisol, depression, perceived stress and pregnancy-specific anxiety was associated with increased anxiety in children. These associations remained after considering obstetric, sociodemographic and postnatal maternal psychological distress; factors that could influence child development. When all of the prenatal measures were considered together, cortisol and pregnancy-specific anxiety independently predicted child anxiety. Children exposed to elevated prenatal maternal cortisol and pregnancy-specific anxiety were at an increased risk for developing anxiety problems during the preadolescent period. This project identifies prenatal risk factors associated with lasting consequences for child mental health and raises the possibility that reducing maternal distress during the prenatal period will have long term benefits for child well-being.     

Prenatal exposure to maternal depression and cortisol influences infant temperament

BACKGROUND: Accumulating evidence indicates that prenatal maternal and fetal processes can have a lasting influence on infant and child development. Results from animal models indicate that prenatal exposure to maternal stress and stress hormones has lasting consequences for development of the offspring. Few prospective studies of human pregnancy have examined the consequences of prenatal exposure to stress and stress hormones. METHOD: In this study the effects of prenatal maternal psychosocial (anxiety, depression, and perceived stress) and endocrine (cortisol) indicators of stress on infant temperament were examined in a sample of 247 full-term infants. Maternal salivary cortisol and psychological state were evaluated at 18-20, 24-26, and 30-32 weeks of gestation and at 2 months postpartum. Infant temperament was assessed with a measure of negative reactivity (the fear subscale of the Infant Temperament Questionnaire) at 2 months of age. RESULTS: Elevated maternal cortisol at 30-32 weeks of gestation, but not earlier in pregnancy, was significantly associated with greater maternal report of infant negative reactivity. Prenatal maternal anxiety and depression additionally predicted infant temperament. The associations between maternal cortisol and maternal depression remained after controlling for postnatal maternal psychological state. CONCLUSIONS: These data suggest that prenatal exposure to maternal stress has consequences for the development of infant temperament.     

Prenatal and Postpartum Maternal Psychological Distress and Infant Development: A Systematic Review

Infant development plays a foundational role in optimal child development and health. Some studies have demonstrated an association between maternal psychological distress and infant outcomes, although the main emphasis has been on postpartum depression and infant-maternal attachment. Prevention and early intervention strategies would benefit from an understanding of the influence of both prenatal and postpartum maternal distress on a broader spectrum of infant developmental outcomes. We conducted a systematic review of studies assessing the effect of prenatal and postpartum maternal psychological distress on five aspects of infant development: global; cognitive; behavioral; socio-emotional; and psychomotor. These findings suggest that prenatal distress can have an adverse effect on cognitive, behavioral, and psychomotor development, and that postpartum distress contributes to cognitive and socio-emotional development.     

Variation in the Glucocorticoid Receptor Gene at rs41423247 Moderates the Effect of Prenatal Maternal Psychological Symptoms on Child Cortisol Reactivity and Behavior

Prenatal maternal psychopathology affects child development, but some children seem more vulnerable than others. Genetic variance in hypothalamic-pituitary-adrenal axis genes may influence the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems. This hypothesis was tested in the Generation R Study, a population-based cohort from fetal life onward. In total, 1727 children of Northern European descent and their mothers participated in this study and were genotyped for variants in the glucocorticoid receptor (GR) gene (rs6189/rs6190, rs10052957, rs41423247, rs6195, and rs6198) and the FK506-binding protein 5 (FKBP5) gene (rs1360780). Prenatal maternal psychological symptoms were assessed at 20 weeks pregnancy and child behavior was assessed by both parents at 3 years. In a subsample of 331 children, data about cortisol reactivity were available. Based on power calculations, only those genetic variants with sufficient minor allele frequencies (rs41423247, rs10052957, and rs1360780) were included in the interaction analyses. We found that variation in GR at rs41423247 moderates the effect of prenatal maternal psychological symptoms on child emotional and behavioral problems (beta 0.41, SE 0.16, p=0.009). This prenatal interaction effect was independent of mother's genotype and maternal postnatal psychopathology, and not found for prenatal psychological symptoms of the father. Moreover, the interaction between rs41423247 and prenatal psychological symptoms was also associated with decreased child cortisol reactivity (beta -2.30, p-value 0.05). These findings emphasize the potential effect of prenatal gene-environment interaction, and give insight in possible mechanisms accounting for children's individual vulnerability to develop emotional and behavioral problems.     

Mechanisms underlying the effects of prenatal psychosocial stress on child outcomes: beyond the HPA axis

Accumulating evidence from preclinical and clinical studies indicates that maternal psychosocial stress and anxiety during pregnancy adversely affect child outcomes. However, knowledge on the possible mechanisms underlying these relations is limited. In the present paper, we review the most often proposed mechanism, namely that involving the HPA axis and cortisol, as well as other less well-studied but possibly relevant and complementary mechanisms. We present evidence for a role of the following mechanisms: compromised placental functioning, including the 11β-HSD2 enzyme, increased catecholamines, compromised maternal immune system and intestinal microbiota, and altered health behaviors including eating, sleep, and exercise. The roles of (epi)genetics, the postnatal environment and the fetus are also discussed. We conclude that maternal prenatal psychosocial stress is a complex phenomenon that affects maternal emotions, behavior and physiology in many ways, and may influence the physiology and functioning of the fetus through a network of different pathways. The review concludes with recommendations for future research that helps our understanding of the mechanisms by which maternal prenatal stress exerts its effect on the fetus.     

Prenatal anxiety predicts individual differences in cortisol in pre-adolescent children.

BACKGROUND: Animal studies suggest that prenatal stress is associated with long-term disturbance in hypothalamic-pituitary-adrenal (HPA) axis function, but evidence in humans is lacking. This study examined the long-term association between prenatal anxiety and measures of diurnal cortisol at age 10 years. METHODS: Measures of cortisol were collected at awakening, 30 min after awakening, and at 4 pm and 9 pm on 3 consecutive days in a sample of 10-year-olds (n = 74) from the Avon Longitudinal Study of Parents and Children, a prospective longitudinal cohort study of mothers and children on whom measures of anxiety and depression were collected in pregnancy and the postpartum period. Analyses examined the links between symptoms of prenatal anxiety and multiple indicators of cortisol, an index of HPA axis functioning. RESULTS: Prenatal anxiety was significantly associated with individual differences in awakening and afternoon cortisol after accounting for obstetric and sociodemographic risk (partial correlations were .32 and .25, p < .05). The effect for awakening cortisol remained significant after controlling for multiple postnatal assessments of maternal anxiety and depression. CONCLUSIONS: This study provides the first human evidence that prenatal anxiety might have lasting effects on HPA axis functioning in the child and that prenatal anxiety might constitute a mechanism for an increased vulnerability to psychopathology in children and adolescents.     

The Relations Between Maternal Prenatal Anxiety or Stress and Child’s Early Negative Reactivity or Self-Regulation: A Systematic Review

In the present review, we examine the association between maternal prenatal stress or anxiety and children’s early negative reactivity or self-regulation. The review includes 32 studies that focus on pregnancy-related anxiety, state or trait anxiety, perceived stress, and stressful life events in relation to child’s crying, temperament, or behavior during the first 2 years of life. We searched four electronic databases and 32 studies were selected based on the inclusion criteria. Twenty-three studies found an association between maternal prenatal anxiety or stress and a child’s negative reactivity or self-regulation, and typically the effect sizes varied from low to moderate. The association was found regardless of the form of prenatal stress or anxiety and the trimester in which the prenatal stress or anxiety was measured. In conclusion, several forms of prenatal anxiety and stress may increase the risk of emotional and self-regulatory difficulties during the first 2 years of life.     

Stressful events and psychological difficulties: testing alternative candidates for sensitivity

The current study investigated the longitudinal, reciprocal associations between stressful events and psychological difficulties from early childhood to mid-adolescence. Child age, sex, prenatal maternal anxiety, and difficult temperament were tested as sources of sensitivity, that is, factors that may make children more sensitive to stressful life events. Analyses were based on data from 10,417 children from a prospective, longitudinal study of child development. At ages 4, 7, 9, 11, and 16 years, stressful events and psychological difficulties were measured. Prenatal anxiety was measured at 32 weeks of gestation and difficult temperament was measured at 6 months. Children exposed to stressful events showed significantly increased psychological difficulties at ages 7 and 11 years; there was consistent evidence of a reciprocal pattern: psychological difficulties predicted stressful events at each stage. Analyses also indicated that the associations between stressful events and psychological difficulties were stronger in girls than in boys. We found no evidence for the hypothesis that prenatal anxiety or difficult temperament increased stress sensitivity, that is, moderated the link between life events and psychological difficulties. The findings extend prior work on stress exposure and psychological difficulties and highlight the need for additional research to investigate sources of sensitivity and the mechanisms that might underlie differences in sensitivity to stressful events.     

The effects of prenatal stress on temperament and problem behavior of 27-month-old toddlers

AIM: To examine, in a prospective study, the influence of prenatal stress on infant temperament and problem behavior. METHOD: 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. RESULTS: 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). CONCLUSIONS: Increased levels of maternal prenatal stress appear to be associated with temperamental and behavioral problems in toddlers.     

The impact of maternal prenatal and postnatal anxiety on children’s emotional problems: a systematic review

Maternal mental health problems during pregnancy and the postnatal period are a major public health issue. Despite evidence that symptoms of both depression and anxiety are common during pregnancy and the postpartum, the impact of maternal anxiety on the child has received relatively less attention than the impact of maternal depression. Furthermore, the evidence base for the direct impact of maternal anxiety during pregnancy and the postpartum on children’s emotional outcomes lacks cohesion. The aim of this systematic review is to summarise the empirical evidence regarding the impact of maternal prenatal and postnatal anxiety on children’s emotional outcomes. Overall, both maternal prenatal and postnatal anxiety have a small adverse effect on child emotional outcomes. However, the evidence appears stronger for the negative impact of prenatal anxiety. Several methodological weaknesses make conclusions problematic and replication of findings is required to improve the identification of at-risk parents and children with appropriate opportunities for intervention and prevention.

     

Maternal depression and treatment gains following a cognitive behavioral intervention for posttraumatic stress in preschool children

The evidence base for cognitive behavioral therapy (CBT) to treat child emotional and behavioral symptoms following exposure to trauma in youth is compelling, but relatively few studies are available on preschool children and on moderators of treatment outcomes. This paper examines maternal and child characteristics as moderators of posttraumatic stress (PTS) treatment outcomes in preschool children. Outcome data from a previously published randomized trial in three to six year old preschool children with diagnostic interview data from participating mothers were used. Hypotheses were tested via hierarchical linear modeling. Maternal depression was associated with higher initial child posttraumatic stress disorder (PTSD) symptoms, and was associated with increasing PTSD symptom trends at follow up suggesting potential child PTSD symptom relapse. Maternal PTSD symptoms similarly predicted differential child separation anxiety symptom change but not child PTSD symptom change. Targeting dyads with child PTSD symptoms and maternal depression or PTSD symptoms with enhanced interventions may be a useful strategy to improve treatment maintenance.     

Psychoneuroendocrine effects of cognitive-behavioral stress management in a naturalistic setting--a randomized controlled trial

It is assumed that chronic or extensive release of cortisol due to stress has deleterious effects on somatic and psychological health, making interventions aiming to reduce and/or normalize cortisol secretion to stress of interest. Cognitive-behavioral stress management (CBSM) has repeatedly been shown to effectively reduce cortisol responses to acute psychosocial stress. However, the effects of CBSM on psychoneuroendocrine responses during "real-life" stress have yet not been examined in healthy subjects. Eight weeks before all subjects took an important academic exam, 28 healthy economics students were randomly assigned to four weekly sessions of cognitive behavioral stress management (CBSM) training or a waiting control condition. Psychological and somatic symptoms were repeatedly assessed throughout the preparation period. Salivary cortisol (cortisol awakening response and short circadian cortisol profile) was repeatedly measured at baseline and on the day of the exam. In addition, cognitive appraisal was assessed on the day of the exam. Subjects in the CBSM group showed significantly lower anxiety and somatic symptom levels throughout the period prior to the exam. On the day of the exam, groups differed in their cortisol awakening stress responses, with significantly attenuated cortisol levels in controls. Short circadian cortisol levels did not differ between groups. Interestingly, groups differed in their associations between cortisol responses before the exam and cognitive stress appraisal, with dissociation in controls but not in the CBSM group. The results show that CBSM reduces psychological and somatic symptoms and influences the ability to show a cortisol response corresponding to subjectively perceived stress. In line with current psychoneuroendocrine models, the inability to mount a cortisol response corresponding to the cognitive appraisal in controls could be a result of a dysregulated HPA axis, probably as a consequence of longlasting stress.     

Long-term stability of maternal prenatal steroid hormones from the National Collaborative Perinatal Project: still valid after all these years

Large epidemiological samples, including the National Collaborative Perinatal Project (NCPP), in which blood/serum was collected during pregnancy and offspring followed longitudinally, offer the unique opportunity to examine neuroendocrine mechanisms underlying prenatal "programming" of adult health and disease. However, in order to conduct longitudinal analyses, it is critical to determine the validity of maternal prenatal samples stored over long periods. We investigated the validity of cortisol, testosterone, and their binding globulins (corticosteroid-binding globulin (CBG) and sex hormone-binding globulin (SHBG)) in maternal prenatal serum from the NCPP after over 40 years of storage. Study 1 included 64 maternal serum samples collected on the day of delivery; study 2 involved 1099 third trimester serum samples collected between gestational weeks 31 and 36. Across both studies, cortisol and testosterone concentrations were consistent with values from published studies of fresh samples collected at similar points in gestation. CBG and SHBG were present, but showed some differences from published studies. Results support the validity of cortisol and testosterone values following 40+ years of storage. Results also provide validation for future longitudinal tests of prenatal "programming" hypotheses within the NCPP. Stability of steroid hormones over decades suggests that stored samples from other longitudinal studies may also allow opportunities to investigate links between prenatal steroids and long-term offspring outcomes.     

Antenatal maternal anxiety and stress and the neurobehavioural development of the fetus and child: links and possible mechanisms. A review

A direct link between antenatal maternal mood and fetal behaviour, as observed by ultrasound from 27 to 28 weeks of gestation onwards, is well established. Moreover, 14 independent prospective studies have shown a link between antenatal maternal anxiety/stress and cognitive, behavioural, and emotional problems in the child. This link generally persisted after controlling for post-natal maternal mood and other relevant confounders in the pre- and post-natal periods. Although some inconsistencies remain, the results in general support a fetal programming hypothesis. Several gestational ages have been reported to be vulnerable to the long-term effects of antenatal anxiety/stress and different mechanisms are likely to operate at different stages. Possible underlying mechanisms are just starting to be explored. Cortisol appears to cross the placenta and thus may affect the fetus and disturb ongoing developmental processes. The development of the HPA-axis, limbic system, and the prefrontal cortex are likely to be affected by antenatal maternal stress and anxiety. The magnitude of the long-term effects of antenatal maternal anxiety/stress on the child is substantial. Programs to reduce maternal stress in pregnancy are therefore warranted.     

Positive life events predict salivary cortisol in pregnant women

Maternal stress during pregnancy has been repeatedly associated with problematic child development. According to the fetal programming hypothesis adverse experiences during pregnancy increase maternal cortisol, which is then assumed to exert a negative effect on fetal development. Recent studies in non-pregnant women report significant associations between positive emotionality and low cortisol levels. We tested in a sample of 60 pregnant women whether both negative and positive life events independently predicted third-trimester baseline awakening cortisol levels. While the effect of negative life events proved unrelated positive life events significantly predicted lower cortisol levels. These findings suggest that positive experiences are of relevance regarding maternal morning cortisol levels in pregnancy reflecting a resource with potentially beneficial effects for the mother and the developing fetus. It might be promising for psychological intervention programs to focus on increasing positive experiences of the expecting mother rather than exclusively trying to reduce maternal stress during pregnancy.     

Effects of psychologic stress on fetal development and pregnancy outcome

Data from animal studies show that maternal stress is associated with disturbances in pregnancy outcomes and offspring development and behavior, possibly as a result of permanent structural and functional changes termed "early-life programming." There is growing interest in whether similar relationships are present in humans. Here we review recent significant findings from the literature on the impact of prenatal psychologic stressors on pregnancy outcome and offspring development, with a particular focus on the developing brain. Relevant papers were searched using PubMed, and reference lists from obtained articles were checked. In humans, prenatal stress is associated with pregnancy complications, developmental, cognitive, and behavioral disorders, and possible onset of psychopathology in later life. In contrast to the available research done in animals, virtually nothing is known about the effects of prenatal stress on morphologic fetal brain development, and the mechanisms underlying subsequent associated behavioral changes.     

The contribution of prenatal and postnatal maternal anxiety and depression to child maladjustment

Background: The adverse effect of both pre‐ and post‐natal maternal anxiety and depression on the development of offspring is shown by a large body of research. No published studies, however, have simultaneously: (i) controlled for co‐occurring prenatal risks that may influence maternal prenatal anxiety and depression; (ii) compared the relative contributions of prenatal and postnatal maternal anxiety and depression on child functioning; and (iii) assessed a full range of child psychopathology and functioning to determine the relative effects of prenatal and postnatal anxiety and depression in the mother. Method: Using 3,298 mother–offspring pairs, the authors examined these factors in a single‐path analytic model. Measurements of maternal anxiety and depression were collected at two time points: 32 weeks prenatal and 1.5 years postnatal. Other prenatal risks were assessed between 8 and 32 weeks of gestation. Child outcomes included (a) ordered‐categorical measures of DSM‐IV externalizing and internalizing disorders, and (b) an assessment of verbal IQ. Results: In both the prenatal and postnatal periods, maternal depression had a wider impact on different types of child maladjustment than maternal anxiety, which appeared more specific to internalizing difficulties in the child. Of note, prenatal risks were prospectively associated with child externalizing difficulties and verbal IQ, beyond the effects of prenatal and postnatal maternal anxiety and depression. Conclusion: The present results suggest that addressing both maternal anxiety and depression, in the prenatal and postnatal periods—as well as associated risk factors—may be the most effective approach to prevent adverse outcomes in the offspring. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.     

International note: Maternal warmth,behavioral control,and psychological control: Relations to adjustment of Ghanaian early adolescents

This investigation addressed the relation between maternal warmth, behavioral control, psychological control, and psychological adjustment in a sample of 119 Ghanaian adolescents (42% boys) living in an urban area (mean age = 14.19). Adolescents in the sample reported clinically elevated levels of depression and anxiety. Significant associations were found between warmth, behavioral control, and psychological control and adolescents' anxiety, physical aggression, relational aggression, positive friendship quality, and conflict with friends. Warmth moderated the effect of behavioral control on anxiety, physical aggression, and relational aggression such that higher levels of warmth in combination with higher levels of behavioral control were related to more positive adjustment. Higher levels of warmth in conjunction with higher psychological control were related to higher levels of anxiety. Boys who reported lower levels of warmth in combination with higher behavioral control reported higher levels of physical aggression. For boys reporting higher levels of warmth, higher behavioral control was associated with lower physical aggression.     

Dimensions of parenting among mothers and fathers in relation to social anxiety among female adolescents

Social anxiety is the most common anxiety disorder among youth; theoretical and empirical work suggest specific parenting behaviors may be relevant. However, findings are inconsistent, particularly in terms of maternal as compared to paternal effects. In the current study, we evaluated the indirect effects of perceived psychological control on the relation between anxious rearing behaviors and child social anxiety among 112 community-recruited girls (ages 12–15 years). In addition to self-report, adolescent participants completed a laboratory-based social stress task. In line with hypotheses, results indicated indirect effects of psychological control on the relation between anxious rearing behaviors and child social anxiety in maternal but not paternal models. Findings are discussed in terms of their theoretical and empirical implications for clarifying the role of parental relations in adolescent social anxiety.