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Postgraduate Interdisciplinary Conference on Fertility, Pregnancy
and Development
Friday 30th 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
Bethan Fulford, Cardiff University School of Psychology
Mental models of pregnancy and folic acid supplement use
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
Elinor John, HELP Trial Team
The Healthy Eating and Lifestyle in Pregnancy (HELP) Study:
Protocol
12:00 – 12:15
Gareth Thomas, Cardiff University School of Social Sciences
A Risky Business: Screening for Down’s Syndrome in Antenatal Care
12:15 – 12:30
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 (Ca2+)
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 (PIP2)
hydrolysis thus triggering the Ca2+ oscillations through the inositol 1,4,5-trisphosphate (IP3) 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
Ca2+ 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. The 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.