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Postgraduate Interdisciplinary Conference on Fertility, Pregnancy and Development

Friday 30

th

November, 10am - 3pm

Funded by Cardiff University Graduate College

Speaker details

Fertility Session

10:00 – 10:15 Christine Pinkard, Cardiff University School of Psychology

What factors predict when individuals have their first child?

10:15 – 10:30 Sean Griffiths, Swansea University

Nanomechanical properties of the endometrial epithelial surface directly correlated with characteristic molecular expression patterns

10:30 – 10:45 Khalil Elgmati, Cardiff University School of Medicine

PLC

is the physiological sperm factor in mammals

10:45 – 11:00

Pregnancy Session

11:30 – 11:45 Anna Bugge Jensen, Cardiff University School of Biosciences

Examining the role of placental PHLDA2 in human growth restricted pregnancies

11:45 – 12:00

Bethan Fulford, Cardiff University School of Psychology

Mental models of pregnancy and folic acid supplement use

Elinor John, HELP Trial Team

The Healthy Eating and Lifestyle in Pregnancy (HELP) Study:

Protocol

12:00 – 12:15

12:15 – 12:30

Gareth Thomas, Cardiff University School of Social Sciences

A Risky Business: Screening for Down’s Syndrome in Antenatal Care

Arianna Di Florio, Cardiff University School of Medicine

Bipolar disorder in pregnancy and the postpartum

Development Session

13:30 – 13:45

Gráinne Mc namara, Cardiff School of Medicine

The developmentally important imprinted gene Cdkn1c and social dominance

13:45 – 14:00 Martin Edwards, Cardiff School of Medicine

Respiratory and Neurological Outcomes of late Preterm Infants

(RANOPs)

14:00 – 14:15 Rebecca Sperotto, Cardiff School of Psychology

Social and Cognitive Development of Preterm Infants in the First Two

Years of Life

14:15- 14:30 Joanna Martin, Cardiff School of Medicine

Autistic traits in children with ADHD index cognitive and developmental problems

Abstracts

What factors predict when individuals have their first child?

Christine Pinkard

Evidence concerning the predictors of having a first child and the direction of effects is inconsistent.

Furthermore, the existing research is largely biased towards healthy heterosexual couples, disregarding groups who undergo more complex processes in order to start a family, such as same-sex couples and people with genetic diseases. A systematic review and narrative analysis of longitudinal studies on the predictors of starting a family were conducted. Fourteen electronic databases were searched and 17 studies (all of high quality) were included in the narrative synthesis. The main predictors across the included studies were identified and the most frequent results and direction of effects reported. Vote-counting and an exploration of the relationships within and between studies formed the basis of the narrative synthesis. Five predictors were found to facilitate childbearing: (a) increasing age up to 39, (b) having a partner, (c) being married, (d) intending to have a child, and (e) being a woman. Two predictors were found to hinder childbearing: (a) current enrolement in education, and (b) high levels of education for women but not men. Four main variables that did not predict childbearing were identified: employment, income, parental education, and duration of relationship. The findings of the synthesis were largely consistent with Life Course Theory, the

Theory of Planned Behaviour and Miller and Pasta’s (1995) model. However, an integration of the theories was proposed in order to provide a more complete model of childbearing. The findings have implications for interventions addressing the recent postponement of childbearing which is approaching an unsustainable level. The systematic review also revealed an absence of longitudinal studies on groups undergoing more complex transitions to parenthood, such as same-sex couples and people with genetic diseases, which must be addressed by future research.

Nanomechanical properties of the endometrial epithelial surface directly correlated with characteristic molecular expression patterns

Griffiths S, Francis L W, Gonzalez D, White J O, Margarit L, Berquand A, Conlan R S.

Atomic force microscopy (AFM) offers a unique contact microscopy method to functionally analyse the role of the signature molecular patterns of the endometrial epithelial cell surface. The window of implantation has been heavily characterised by molecular biology and the apical layer presented to the blastocyst is hypothesised to be functionally adhesive and heterogeneous. Objectives: To determine

(1) the mucin protein expression using an in vitro model of receptive endometrium (2) to characterise the nanomechanical and adhesion properties of the cells (3) to directly correlate MUC1 expression and associated functional characteristics of the endometrial surface. Methods: An in vitro model for endometrial receptivity has been developed using endometrial epithelial (EE) cell lines. MUC1 protein expression in the monolayer was assessed and directly/indirectly correlated with nanomechanical functional characterisation using siRNA and single molecule force spectroscopy.

Results: Hec-1-A and Hec-1-B EE cell lines exhibit differing levels of basal MUC1 expression.

AFM delineated the functional consequences of altered MUC1 expression patterns and enabled the testing of the hypothesis that MUC1 is an anti-adhesive protein during the window of implantation.

MUC1 siRNA significantly lowered the protein expression level of MUC1 and altered its monolayer distribution pattern. AFM nano-indentation and single molecule force characterisation has for the first time allowed the direct correlation of molecular expression patterns and functional adhesion properties in endometrial epithelial monolayers.

PLC

is the physiological sperm factor in mammals

Elgmati K, Nomikos M, Swann K and Lai T

In mammalian eggs, the fertilizing sperm evokes a long-lasting series of intracellular calcium (Ca 2+ ) oscillations that are essential for the initiation of egg activation and embryonic development.

Accumulating evidence suggests that sperm-specific phospholipase C zeta (PLC

) is delivered from the fertilizing sperm into the ooplasm to cause phosphatidylinositol 4,5-bisphosphate (PIP

2

) hydrolysis thus triggering the Ca 2+ oscillations through the inositol 1,4,5-trisphosphate (IP

3

) signaling pathway. Recently few clinical reports suggested strong relation between male infertility and single point mutation in the PLC

sequence. The corresponding cRNA of mutant PLC

was found to lake

Ca 2+ oscillation-inducing activity of human PLC

, when microinjected into mouse eggs. Recombinant

PLC

protein is the target of our future work which might bring a remarkable change in the treatment the infertility related to male factor.

Mental models of pregnancy and folic acid supplement use

Bethan Fulford

BACKGROUND: Despite the benefits of folic acid supplementation to maternal and neonatal health, noncompliance with supplementation recommendations is prevalent and is linked to maternal background characteristics. The mechanisms that potentiate noncompliance may be better understood by a focus on perceived insusceptibility. METHODS: A survey of women currently pregnant or planning a pregnancy in four European countries ( n = 651; 326 currently pregnant) was conducted to measure maternal characteristics, beliefs, barriers and behaviour in relation to folic acid supplementation in the context of other pregnancy preparatory behaviours. RESULTS: Overall, knowledge and uptake of folic acid during the periconceptional period is low. Poor users of folic acid uptake can be grouped into those with high perceived health and those living in conditions of

adversity, and mediation analysis showed that these groups fail to adhere to supplementation recommendations because they feel invulnerable to the health risks of folic acid deficiency. The mechanisms underpinning perceived insusceptibility may be related to beliefs about being ‘robust mums’ or of carrying ‘robust pregnancies’. CONCLUSIONS: Women need to have greater knowledge and awareness of the importance of folic acid for a healthy pregnancy. T he challenge for the practitioner is to make mental models of insusceptibility explicit by discovering patients’ beliefs about the robustness of the mother or pregnancy and, where necessary, correcting erroneous inferences about personal health or social norms that may impact on decision-making about folic acid uptake.

The Healthy Eating and Lifestyle in Pregnancy (HELP) Study: Protocol.

Elinor John

Background: Approximately 1 in 4 pregnant women in the UK are obese. Obesity is linked to pregnancy and birth complications, leading to increased NHS costs. Excess maternal weight gain during pregnancy may also lead to long-term maternal obesity. Objectives: To assess whether a theory based weight management intervention for obese pregnant women, which targets physical activity and healthy eating, is effective in reducing women’s BMI at 12 months from giving birth and at what cost. Methods / Results : The study is a cluster randomised controlled trial. 570 pregnant women (12-20 weeks pregnant with a BMI of ≥30) will be recruited across 20 maternity units.

Women in the intervention group will attend a weekly 1.5 hour weight management group, which targets healthy eating and physical activity, until 6 weeks postpartum. Control and intervention participants will receive usual care and a leaflet on diet and physical activity. Women will be followed up at 36 weeks gestation and 6 weeks, 6 months and 1 year postpartum. BMI at 1 year postpartum is the primary outcome. Secondary outcomes include pregnancy weight gain, quality of life, mental health, waist-hip ratio, child weight centile, diet, physical activity, pregnancy and birth complications, social support, self regulation and self efficacy. A health economic and process evaluation will also be conducted. Conclusion: If successful this intervention could significantly reduce health risks for the women, as well as NHS healthcare costs.

A Risky Business: Screening for Down’s Syndrome in Antenatal Care

Gareth M. Thomas

Prenatal screening for Down’s syndrome has become a standardised and taken-for-granted practice in antenatal care, transforming obstetric medicine whilst simultaneously invigorating the parental

imagination and shaping issues surrounding reproductive politics. Following huge technological progress in prenatal care over recent years, such practices inevitably create dilemmas, both for healthcare practitioners providing this service and for expectant parents who must choose what information they receive about their unborn baby. Drawing on the preliminary findings gathered during ethnographic observations of two healthcare institutions, I briefly explore the experiences of both parents and clinicians as active agents in the world of antenatal care. Few studies in this area have explored the concept of ‘risk’ and how it is understood, negotiated, and managed by both parents and healthcare practitioners when screening for Down’s syndrome is undertaken. I will describe how ideas surrounding risk and uncertainty play out in the everyday practice of antenatal care through statistical probabilities, distinguishing the ‘at-risk’ mother and foetus, medical ‘risks’ of harm, and the connotations of ‘risk’ as a concept. I conclude by reflecting on the implications that these findings could have for further understanding pregnancy and antenatal care.

Bipolar disorder in pregnancy and the Postpartum

Arianna Di Florio, MD

About 2-7% of women of childbearing age suffers from some form of bipolar disorder, a spectrum of disorders characterised by periods of pathological mood elation (mania). It is a severe and recurrent illness, often consisting in episodes of mania and depression alternated with periods of well being.

Although severe forms of postpartum mania have intrigued scientists for centuries, the link between childbirth and bipolar spectrum disorders is still poorly understood. The gap in knowledge is wider for the less severe, but more prevalent, forms of perinatal bipolar depression and hypomania, that have been almost neglected by research and clinical practice. Confusion in the clinical nosology has probably prevented firm and consistent conclusions on the nature of the postpartum trigger. Moreover, the research in this field relies mostly on arbitrary definitions, while more evidence-based criteria are needed. My PhD project sought to address these deficiencies. The project was organised in 2 parts, that reflect the core structure of my talk. In the first part, I will present the results of a study on the childbirth trigger conducted on over 1900 women with bipolar disorder and unipolar depression. In the second part I will introduce a prospective study on bipolar disorder in pregnancy and the postpartum period, designed and piloted as part of the Bipolar Disorder Research Network Project.

The developmentally important imprinted gene Cdkn1c and social dominance

G. I. MC NAMARA , B. A. DAVIS, R. M. JOHN, A. R. ISLES

Genes that are imprinted are subject to a developmentally determined epigenetic marking which restricts expression to a single allele, dependant on the parent of origin. A large proportion of imprinted genes are expressed in the brain and have been postulated to be important for adult behaviour. One such behaviour that has been linked to imprinted genes is social dominance. Social dominance over other animals ensures better feeding and mating opportunities and the paternally expressed Grb10 has previously been shown to negatively influence this, as indexed by increased barbering of cage mates and in the ‘tube test’. In order to determine if effects on social dominance is a feature of other brain expressed imprinted genes we tested whether the converse was true for maternally expressed imprinted genes and social behaviour. In this study we utilised a ‘loss of imprinting’ model of a maternally expressed, imprinted gene, Cdkn1c, which encodes a cell-cycle regulator and has previously been shown to be involved in midbrain dopaminergic cell development. Using this model

( Cdkn1c -BAC) allowed us to determine the effect of two-fold over-expression of Cdkn1c on social dominance behaviours. In agreement with our hypothesis, we found that Cdkn1c -BAC mice won significantly more encounters in a ‘tube test’ than their wild-type littermates. This suggests that over-expressing maternally expressed Cdkn1c enhances dominance. Using a number of other measures of social dominance, we found that the presence of an animal over expressing Cdkn1c in the home cage caused a breakdown in social cohesion. These results indicate an important role for this developmentally important gene in social dominance.

Respiratory and Neurological Outcomes of late Preterm Infants (RANOPs)

Martin Edwards

In some industrialised countries, the rate of preterm birth (<37 weeks gestation) has risen markedly in recent years. In the USA, the rate of preterm birth has increased from 9.5% in 1981 to 12.7% in 2005, of which 80% are late preterm births occurring at 32-36 weeks gestation (Goldberg et al; Lancet,

2008). Perinatal respiratory morbidity is increasingly recognised in late preterm infants. Using the

Avon Longitudinal Study of Parents and Children (ALSPAC) cohort, our data shows that lung function is decreased in 8-9 year old late preterm born children compared to term-born similarly-aged children.

In this study, I hypothesise that children born late preterm have increased respiratory symptoms and increased hospitalisation due to respiratory disease compared to those born at term. Using the welllinked health databases in Wales, I shall send questionnaires to preterm-born children now aged 1, 2,

3, 5, 7 and 9 years old and to matched term-born children. We aim to send out 24,000 questionnaires to families across Wales. Over the last 12 months I have gained ethical and R&D approval. We are now working with NHS Wales Informatics Service (NWIS) to create a data base so that we can start mailing questionnaires in January 2013.

Social and Cognitive Development of Preterm Infants in the First Two Years of Life

Rebecca G. Sperotto, Alice Winstanley, Marc H. Bornstein, & Merideth Gattis

Preterm birth (before 37 completed weeks of gestation) occurs in around 7% of deliveries in the UK.

Many researchers have documented different types of developmental problems and delays (involving motor, behavioural, cognitive and sensory domains) occurring in infants, children, and adults born preterm. Concurrently, the literature has shown that preterm birth does not necessarily lead to developmental impairments.

The aim of this short-term longitudinal study is to investigate social and cognitive development of infants born preterm during the first two years of life. Our focus is not only on infants but also the adults who make up their early social world as well as the resultant social interactions of these premature infants. To help us disentangle the consequences of preterm birth rather than associated medical conditions, our sample is constituted only by healthy late preterms (i.e., born between 30 and

36 weeks of gestation). A range of questionnaires, behavioural tasks and observations of parent-infant interactions are used in four data waves: following the infant’s birth; at 5; 13 and 18 months of age. In particular, we address questions about development of joint attention, imitation, language and their relation to parent-child interactions.

Autistic traits in children with ADHD index cognitive and developmental problems

Joanna Martin

Traits of autistic spectrum disorders (ASD) occur frequently in children with attention deficit hyperactivity disorder (ADHD), but the significance of their presence in relation to associated cognitive and developmental features is not properly understood. In this study, children meeting research diagnostic criteria for ADHD with no known diagnosis of ASD (N=711) were administered a battery of psychological assessments and assessed (via parent report) on measures of autistic traits

(using the Social Communication Questionnaire (SCQ)) and general developmental problems.

Multivariate regression analyses examined the association of SCQ scores with cognitive and developmental outcomes, adjusting for putative confounders. Post-hoc analyses explored levels of

differential association of the three ASD sub-domains (social deficits, communication deficits and restrictive/repetitive behaviours (RRBs)) with significant outcomes. Results show that increasing

ASD symptoms within ADHD are associated with lower full-scale IQ, specific working memory deficits and general motor problems. ASD sub-domain scores did not show unique contributions to these outcomes, except that RRBs independently predicted motor problems. These results suggest that autistic traits in children with ADHD index higher levels of associated cognitive and developmental problems. This finding has important implications for research into the overlap between these conditions as well as treatment strategies for children with features of both.

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