Maternal prenatal stress and fetal programming: long term biobehavioural outcomes in the child and potential placental mechanisms

Mounting evidence suggests prenatal stress can affect child development. Clinical studies of this concept, termed fetal programming, focus predominantly on early childhood. Also, little is known about the mechanisms underlying how maternal stress is transmitted to the fetus. This thesis will test if maternal anxiety during pregnancy is associated with (1) behavioural outcomes from childhood to early adolescence, (2) cortisol output in adolescence and (3) an altered placental phenotype. For Studies 1 and 2 participants were drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC). Psychometric data from 9,871 mother child pairs (5,098 males, 4,773 females) were analysed using latent growth curve analysis. A subsample of the ALSPAC children aged 15 years (n = 899) provided saliva samples on three days at waking, +35mins, after school and before bed, for later cortisol analysis. For Study 3 a new cohort of women (n= 73) was recruited. Maternal psychometric data was collected one day prior to elective caesarean section, and the placenta collected after delivery. Study 1 showed that maternal prenatal anxiety was associated with conduct and emotional problems, and symptoms of ADHD at age 13 years, after allowing for a range of confounders, including postnatal anxiety. There were marked sex differences in the developing patterns. Saliva cortisol demonstrated a marked diurnal profile with a clear sex difference at age 15. Higher maternal prenatal anxiety was associated with a reduced cortisol awakening response. High levels of maternal prenatal anxiety were associated with reduced placental expression and activity of the cortisol metabolising enzyme 11β-Hydroxy steroid dehydrogenase 2 (11β-HSD2) and also with reduced placental weight. This thesis provides evidence that maternal prenatal anxiety can affect behavioural and neuroendocrine outcomes in adolescence. It also provides preliminary evidence that maternal anxiety is associated with alterations in the function of the placenta, which may underlie some aspects of fetal programming. These findings have public health implications. Increasing awareness about the lasting effects of prenatal anxiety may ultimately benefit mothers, the care they receive and their families

Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age.

BACKGROUND: Studies of prenatal exposure to sex steroid hormones predict autistic traits in children at 18 to 24 and at 96 months of age. However, it is not known whether postnatal exposure to these hormones has a similar effect. This study compares prenatal and postnatal sex steroid hormone levels in relation to autistic traits in 18 to 24-month-old children.Fetal testosterone (fT) and fetal estradiol (fE) levels were measured in amniotic fluid from pregnant women (n = 35) following routine second-trimester amniocentesis. Saliva samples were collected from these children when they reached three to four months of age and were analyzed for postnatal testosterone (pT) levels. Mothers were asked to complete the Quantitative Checklist for Autism in Toddlers (Q-CHAT), a measure of autistic traits in children 18 to 24 months old. FINDING: fT (but not pT) levels were positively associated with scores on the Q-CHAT. fE and pT levels showed no sex differences and no relationships with fT levels. fT levels were the only variable that predicted Q-CHAT scores. CONCLUSIONS: These preliminary findings are consistent with the hypothesis that prenatal (but not postnatal) androgen exposure, coinciding with the critical period for sexual differentiation of the brain, is associated with the development of autistic traits in 18 to 24 month old toddlers. However, it is recognized that further work with a larger sample population is needed before the effects of postnatal androgen exposure on autistic traits can be ruled out. These results are also in line with the fetal androgen theory of autism, which suggests that prenatal, organizational effects of androgen hormones influence the development of autistic traits in later life.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Maternal prenatal anxiety and child COMT genotype predict working memory and symptoms of ADHD

Maternal prenatal anxiety is an important risk factor for altered child neurodevelopment but there is uncertainty concerning the biological mechanisms involved and sources of individual differences in children's responses. We sought to determine the role of functional genetic variation in COMT, which encodes catechol-O-methyltransferase, in the association between maternal prenatal anxiety and child symptoms of ADHD and working memory. We used the prospectively-designed ALSPAC cohort (n = 6,969) for our primary data analyses followed by replication analyses in the PREDO cohort (n = 425). Maternal prenatal anxiety was based on self-report measures; child symptoms of ADHD were collected from 4-15 years of age; working memory was assessed from in-person testing at age 8 years; and genetic variation in COMT at rs4680 was determined in both mothers and children. The association between maternal prenatal anxiety and child attention/hyperactivity symptoms and working memory was moderated by the child's rs4680 genotype, with stronger effects obtained for the val/val (G: G) genotype relative to val/met (A:G) (all p <0.01) and met/met (A: A) groups (all p <0.05). Similar findings were observed in the PREDO cohort where maternal prenatal anxiety interacted with child rs4680 to predict symptoms of ADHD at 3.5 years of age. The findings, from two cohorts, show a robust gene-environment interaction, which may contribute to inter-individual differences in the effects of maternal prenatal anxiety on developmental outcomes from childhood to mid-adolescence.Peer reviewe

CE10011

Use the URI link below to search the Marine Institute Data Discovery Catalogue for datasets relevant to this report.Acoustic surveys on blue whiting (Micromesistius poutassou) spawning aggregations in the north east Atlantic have been carried out by the Institute of Marine Research (IMR) Norway since the early 1970s. In the early 1980s a coordinated acoustic survey approach was adopted, with both Russia and Norway participating to estimate the size of this migratory stock within the main spawning grounds to the west of Ireland and Britain. Since 2004, an International coordinated survey program has expanded to include vessels from the EU (Ireland and the Netherlands) and the Faroes. Due to the highly migratory nature of the stock a large geographical area has to be surveyed. Spawning takes place from January through to April along the shelf break from the southern Porcupine Bank area northwards to the Faroe Shetland Ridge including offshore areas as the Rosemary, Hatton and Rockall Banks. Peak spawning occurs between mid-March and mid April and acoustic surveys are timed to occur during this phase. To facilitate a more coordinated spatio-temporal approach to the survey participating countries meet annually to discuss survey methods and define target areas at the ICES led Working Group on Northeast Atlantic Pelagic Ecosystem Surveys (WGNAPES). Data from the annual spawning stock abundance survey (March/April, western waters), juvenile surveys (May, Norwegian Sea and January-March, Barents Sea trawl survey) and commercial landings data are presented annually at the ICES Working Group of Widely Distributed Stocks (WGWDS). Ultimately, combined data inputs into the management and catch advice for this international cross boundary stock. The 2010 survey was part of an International collaborative survey using the vessels RV Celtic Explorer (Ireland), RV Fridtjof Nansen (Russia), RV Tridens (Netherlands) and the RV Magnus Heinason (Faroes) and the RV G.O. Sars (Norway). The total combined area coverage extended from the Faroe Islands in the north (60.30°N) to south of Ireland (52°N), with east -west extension from 6°-18° W. International survey participants meet shortly after the survey to present data and produce a combined relative abundance and biomass index the blue whiting spawning stock in western waters. The combined survey report is presented annually at the WGNAPES meeting held in August and made available to the WGWDS assessment group

CE14016

In the southwest of Ireland and the Celtic Sea (ICES Divisions VIIaS, g & j),herring acoustic surveys have been carried out since 1989. This survey was undertaken in early October. The geographical confines of the annual 21 day survey program have been modified in recent years to include areas to the south of the main winter spawning grounds in an effort to identify the whereabouts of winter spawning fish before the annual inshore spawning migration. Spatial resolution of acoustic transects has been increased over the entire south coast survey area. The acoustic component of the survey has been further complimented since 2004 by detailed hydrographic and marine mammal and seabird surveys

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

Effects of Antenatal Maternal Depressive Symptoms and Socio-Economic Status on Neonatal Brain Development are Modulated by Genetic Risk

This study included 168 and 85 mother-infant dyads from Asian and United States of America cohorts to examine whether a genomic profile risk score for major depressive disorder (GPRSMDD) moderates the association between antenatal maternal depressive symptoms (or socio-economic status, SES) and fetal neurodevelopment, and to identify candidate biological processes underlying such association. Both cohorts showed a significant interaction between antenatal maternal depressive symptoms and infant GPRSMDD on the right amygdala volume. The Asian cohort also showed such interaction on the right hippocampal volume and shape, thickness of the orbitofrontal and ventromedial prefrontal cortex. Likewise, a significant interaction between SES and infant GPRSMDD was on the right amygdala and hippocampal volumes and shapes. After controlling for each other, the interaction effect of antenatal maternal depressive symptoms and GPRSMDD was mainly shown on the right amygdala, while the interaction effect of SES and GPRSMDD was mainly shown on the right hippocampus. Bioinformatic analyses suggested neurotransmitter/neurotrophic signaling, SNAp REceptor complex, and glutamate receptor activity as common biological processes underlying the influence of antenatal maternal depressive symptoms on fetal cortico-limbic development. These findings suggest gene-environment interdependence in the fetal development of brain regions implicated in cognitive-emotional function. Candidate biological mechanisms involve a range of brain region-specific signaling pathways that converge on common processes of synaptic development

Maternal prenatal cortisol predicts infant negative emotionality in a sex-dependent manner

Objective Prenatal stress influences fetal developmental trajectories, which may implicate glucocorticoid mechanisms. There is also emerging evidence that effects of prenatal stress on offspring development are sex-dependent. However, little is known about the prospective relationship between maternal prenatal cortisol levels and infant behaviour, and whether it may be different in male and female infants. We sought to address this question using data from a prospective longitudinal cohort, stratified by risk. Method The Wirral Child Health and Development Study (WCHADS) cohort (n = 1233) included a stratified random sub-sample (n = 216) who provided maternal saliva samples, assayed for cortisol, at home over two days at 32 weeks of pregnancy (on waking, 30-min post-waking and during the evening) and a measure of infant negative emotionality from the Neonatal Behavioural Assessment Scale (NBAS) at five weeks-of-age. General population estimates of associations among measures were obtained using inverse probability weights. Results Maternal prenatal cortisol sampled on waking predicted infant negative emotionality in a sex-dependent manner (interaction term, p = 0.005); female infants exposed to high levels of prenatal cortisol were more negative (Beta = 0.440, p = 0.042), whereas male infants were less negative (Beta = − 0.407, p = 0.045). There was no effect of the 30-min post-waking measure or evening cortisol. Discussion Our findings add to an emerging body of work that has highlighted sex differences in fetal programming, whereby females become more reactive following prenatal stress, and males less reactive. A more complete understanding of sex-specific developmental trajectories in the context of prenatal stress is essential for the development of targeted prevention strategies