Women's Health (Research Division)
|MPhil/PhD, MD(Res)
|Part Time, Full Time
Research in this group is informed by expertise in midwifery and obstetrics, social science, epidemiology and public health. The strategy is currently focusing on two main areas of Health Services Research which include inequalities and disparities in health outcomes and quality and safety in maternal health care, conducted in a range of low, medium and high income countries, and with regard to:
- Health policies and health systems, quality and safety
- Impact of service delivery and new health technologies on experiences and outcomes of care Interventions to enhance maternal physical and psychological health and well-being.
This work is underpinned by a programme of work on evidence synthesis and knowledge translation to inform maternal and infant health care.
This research stream focuses on the three inter-related areas of maternal health, fetal wellbeing and pregnancy outcomes at delivery, with the aim to improve the management of medical problems in pregnancy (antiphospholipid syndrome, pre-eclampsia, obstetric cholestasis, diabetes); fetal congenital abnormality, preterm labour, and dysfunctional labour.
The overarching goal is to implement a research strategy that will deliver new diagnostic tools, novel therapies and clinical management guidelines to improve overall outcomes for pregnant women and their children. Our strategy is centred on translating good basic science research related to parturition, inflammation, obesity and nutrition, reproductive ageing and preterm birth into novel and successful clinical outputs.
Our strengths include large multidisciplinary research team that has access to two of the largest and most socially and ethnically varied and complex populations of pregnant women in the UK that exhibits high rates of pregnancy-associated complications and social deprivation.
We have an excellent track record of developing first trimester screening tools, implementing clinical trials in pregnancy and proven experience in integrating science research goals with clinical need. Our research approach is further enhanced by cross-linking with the researchers with an interest in 'Women's Health Policy, Services and Public Health'. Collaboration will facilitate rapid evaluation of knowledge transfer, and effectiveness and safety of our research outputs in a monitored health care setting. The impact of mental health on pregnancy outcomes will also be a focused area for expansion in our research programmes.
In 1999, in a small study, we showed that antioxidants improved vascular function in women at risk of the disease, and the study showed early promise as fewer women developed pre-eclampsia. However a subsequent nationwide randomised controlled trial conducted by our unit showed no benefit of prophylactic treatment with vitamins C and E. In common with other cardiovascular diseases associated with oxidative stress it appears that antioxidants will not be able to provide an easy preventative strategy, but this does not mitigate against a role for oxidative stress, and we actively pursue research in that area. Having worked for some time in development of predictive tests for pre-eclampsia, and published patents in that area, we have recently joined the international study ‘SCOPE’ which aims to develop accurate predictive tests for pre-eclampsia, pre-term labour and fetal growth restriction. SCOPE draws upon scientific and clinical expertise from Universities across the world, and provides a unique opportunity for not only elaborating predictive tests but also through state-of-the art proteomics and bioinformatics, providing new insights into the aetiology of the three most common disorders affecting pregnant women.
Research in the unit run by Professor Andrew Shennan, is involved in a very practical problem, the accurate measurement of blood pressure in pregnant women. The last few years has seen the development of a wide range of automated instruments designed to measure blood pressure, and intended to provide replacements for the mercury sphygomanometer. Unfortunately, many have not been validated, especially for use in pregnancy. Professor Shennan’s team are accredited to validate new blood pressure measuring devices and have recently developed new devices for accurate measurement of blood pressure in the clinic, and a new, robust and inexpensive device for use in the developing world.
Clinical studies include:
- the predication, prevention and treatment of preterm labour
- improving induction and augmentation of labour
- development of new tocolytics for the treatment of preterm labour
Modern assisted reproduction technology offers both infertile women and men the potential to have a healthy child. In addition, Assisted Reproductive Technology (ART) with pre-implantation genetic diagnosis (PGD) has allowed detection in the early embryo of life threatening single gene related disorders, which through selection of unaffected embryos has enabled the delivery of healthy children to gene carrying or affected parents.
The Reproductive Medicine Unit located at the Guy's Campus comprises the Reproductive Medicine Clinic (RMC), the Assisted Conception Unit (ACU) and the centre for Pre-implantation Genetic Diagnosis (PGD). Together these provide a highly rated comprehensive fertility and reproductive medicine service with over 2000 new patients seen per annum and substantial research potential. The Unit provides the UKs largest and most successful PGD programme and has a pioneering human embryonic stem cell (hESC) research unit. It is also one of the key units for subspecialty postgraduate training in reproductive medicine in the UK.
The recent build on the 11th floor of the Guy's Tower provides state of the art clinical facilities fully compliant with the European Tissue and Cells Directive (EUTCD), as well as full GMP facilities for the production of clinically grade hESC. The Unit has a good network of collaboration between Guy's and St Thomas' NHS Foundation Trust and other national research centres (Birmingham Women's Hospital, Aberdeen, St Mary's Hospital) and other sources in the private sector for recrtuitment of patients for studies (e.g. The Lister Hospital, London). International partners include groups in Belgium, Spain and Italy.
The focus on research is improvement in the outcome of fertility treatment, developing novel efficient techniques for PGD and providing materials for establishing stem cell lines from embryos affected by clinically relevant genetic disorders, under GMP conditions.
The focus on research is improvement in the outcome of fertility treatment, developing novel efficient techniques for PGD and providing materials for establishing stem cell lines from embryos affected by clinically relevant genetic disorders, under GMP conditions.
Our strategy is to adopt a life course approach towards an understanding of the aetiology and underlying mechanisms of common metabolic, cardiovascular and neurological disorders from reproductive dysfunction, fetal and neonatal development through initiation and progression to adult disease.
Research spans the characterisation of nutritional and environmental influences on mammalian reproductive function as well as the long-term consequences of such stimuli for neurodevelopment, physiological dysfunction and subsequent risk of disease. This includes the investigation of the nutritional and hormonal influences on central regulatory pathways of the ovulatory cycle, including the elucidation of molecular components of the central 24 hr (circadian) clock and their response to ageing, the role of melatonin in circadian and homeostatic sleep mechanisms and the neural mechanisms of stress-induced dysfunction of reproductive neuroendocrine functions.
The interaction of genes and the early life environment is a central focus with particular reference to the impact of nutrition and metabolic states on both pregnancy outcome and early life origins of disease; this spans from investigation of oocyte development and function to the underlying mechanisms of adult metabolic and cardiovascular disease. Furthermore, research into reproductive and neurodevelopmental aspects of psychiatry is developing our understanding of the interactions between stress, sex hormones and gender on neurodevelopment from fetus to old age.
The group fosters translation between basic and clinical research and has key links with the Menopause Research, Reproductive Medicine and Fetal and Infant Health RDUs. Within the RDU, there are the following research themes:
- Developmental Programming of Adult Disease
- Reproductive function nutritional and environmental influences
- Reproductive and Neurodevelopmental Psychiatry.
Quantitation of gene expression: Over several years the group has built expertise and state-of-the-art facilities for gene expression analysis using qPCR and has played a major role in spreading best practice in this technique in the UK through a variety of training courses attracting participants from the UK, Europe, South America and the Middle East. I am involved with a number of projects using real-time RT-PCR to quantitate steady-state levels of gene expression in various endocrine and neural cells and tissues. One of these projects in collaboration with Dr David Klein (NIH, USA) is a detailed examination of the circadian control of the expression of the genes encoding proteins (receptors, enzymes, transcription factors etc.) known to be important for the nocturnal synthesis of melatonin. Others include studies using qPCR assays to validate microarray data..
Melanopsin: Melanopsin is a novel, retinal, opsin-like protein, first identified in skin cells (melanophores) of Xenopus leavis. Recent work shows that it acts as light detector mediating the entraining action of light on the circadian clock in the SCN, and various other effects of light. We are using a Xenopus melanophore cell line, which naturally expresses melanopsin and also responds to light with a dramatic redistribution of pigment granules, as a model system to study melanopsin photo-biology, signal transduction mechanisms and function.
Research from Professor David Barker’s unit at Southampton University over the last 20 years has sparked a remarkable resurgence in interest into the physiology of fetal nutrition. Working in collaboration with the Southampton Unit and colleagues at Cambridge and Nottingham universities, our Unit has developed several rodent models to probe the mechanisms underlylng the developmental origins of adulthood disease. Our focus has not been on undernutrition, but on overnutrition as we have shown that a maternal diet rich in fat and calories can also lead to development of disease in the offspring. We have shown that rats and mice exposed in utero to a diet rich in fat and simple sugars develop hypertension, insulin resistance and obesity.
The observation that maternal obesity and a hypercalorific diet in rodents can ‘programme’ obesity in the developing child has generated considerable interest, not to mention concern, should it be proven that this also occurs in human pregnancy. Indeed, some observational studies from other groups working with women and their children have provided some evidence to support a similar transmission of an obesogenic trait from mother to baby.
We are now pursuing our animal models with a view to understanding the underlying mechanisms, with particular focus on the hypothesis that the maternal nutritional environment may permanently ‘rewire’ the appetite control centres of the developing hypothalamus. Unravelling the epigenetic mechanisms which ensure persistent alteration of physiological and biochemical function from the in utero and early post natal environment, through to adult life presents a terrific challenge Some insight has been gained from recent work in our group which has suggested that the mitochondrion may carry the ‘memory’ and be causative in the later development of disease.
In pregnant women we are carrying out an NIHR funded intervention study to improve pregnancy outcome . Having developed and piloted a physical activity and dietary intervention we shall carry out a large national randomised study. As well as improving pregnancy outcome we anticipate that this study will provide valuable information in regard to the developmetal origins of obesity.
The Urogynaecology Unit at Kings College Hospital NHS Foundation Trust is the largest tertiary referral centre in London and has an established national and international reputation for active clinical research, clinical practice, teaching and training. It currently employs three full-time Consultant Urogynaecologists (Cardozo, Robinson, Bidmead), one subspecialty trainee, two clinical research fellows, two senior urogynaecology nurse specialist, one specialist nurse and two women's health physiotherapists.
Current research funding is from industry grants, competitive grants and private sponsorship. Grants and funding pay for the salaries and overheads of research fellows and specialist additional equipment.
The Menopause Research Unit was established in 1991 by Professor Rymer and commenced with a collaborative study with the Guy's Osteoporosis Unit to investigate the first "nonbleeding" hormone replacement therapy (HRT), the primary outcome being bone density. This 15-year follow up study was the longest running HRT trial in the UK. The Unit collaborates with many other disciplines in GSTFT: radiology, nuclear medicine, neuropharmacology, cardiology, cytology, histopathology, breast medicine, oncology, biochemistry and psychiatry. Research fellows in the unit have focussed on the following areas: HRT and osteoporosis, HRT as add back therapy with GnRH analogues, and cardiovascular effects of different nonbleeding HRTs. A major collaboration with the Institute of Psychiatry is ongoing, investigating the effect of sex hormones on brain function. The Unit has been involved in many pharmaceutical multicentre trials.Current research includes a trial on women who have had premature ovarian failure (POF). If the women choose to have treatment they are randomised to HRT or the oral contraceptive pill. The primary outcome measure is bone density. We are also collaborating with the Daisy Network (a support group for POF sufferers). The research fellow responsible for the trial (her MD project) has also started up an innovative NHS Premature Ovarian Failure Clinic with support from the Guy's & St Thomas' Charity and has established a database. This is an example of a research idea evolving into the delivery of a specialty clinic that is both service and research-orientated.
In the laboratory setting, Professor Kevin O'Byrne is studying the neural mechanisms underlying hot flushes, using a radio-telemetry system to monitor rat tail skin temperature (TST); a relevant animal model, which has been extensively validated. His is the only unit in Europe with this capability and are currently studying the effects of selective ER-alpha and ER-beta agonists and antagonists on the vasomotor disturbances that underlie hot flushes. We are also interested in the potential use of phytoestrogens as "alternative" therapies for hot flushes.
The latest trial is investigating women with premature ovarian failure and randomising them to HRT or OCP. Main outcome measure is bone density.
Having recently established Guy's and St Thomas' as an endometriosis centre with the colorectal surgeons the potential is there to commence research into women who have severe endometriosis.
Being the lead for Reproductive and Sexual Health taching within King's College educational research has centred around the presence of medical students in the gynaecology clinic, chaperones, the introduction of the Gynaecology Teaching Associate Programme and more recently Breast Teaching Associates.
Urogynaecology is currently carried out on two sites within King’s Heath Partners, Kings College Hospital and St Thomas’ Hospital. The Urogynaecology Unit at Kings College Hospital NHS Foundation Trust is the largest tertiary referral centre in London and has an established National and International reputation for active clinical research, clinical practice, teaching and training. The Unit currently employs three full time Consultant Urogynaecologists (Cardozo, Robinson, Bidmead).
Current research funding is from industry grants, competitive grants and private sponsorship. Grants and funding pay for the salaries and overheads of research fellows and specialist additional equipment. Whilst individual grants are not large they have covered the costs of highly successful and innovative research for the last twenty five years.
Perinatal mental health has a major impact on women and their families, including maternal morbidity and mortality, obstetric complications, neonatal and infant death, and adverse outcomes for both mother, child and the family. We use mixed methods, including epidemiological and qualitative research, systematic reviews, development and evaluation of therapies, development of clinical management guidelines to improve outcomes for pregnant women and their children, analysis of the biological correlates of perinatal mental disorders, and investigation into the impact on parenting skills and long-term offspring development.
In addition we are carrying out a number of research projects on domestic violence, including examining the response of mental health services to domestic violence (LARA), carrying out systematic reviews on the prevalence of domestic violence experienced by mental health users, and epidemiological research investigating the impact of antenatal domestic violence on women's mental health antenatally and postnatally and the impact this has on child development using the ALSPAC cohort.
We evaluate complex interventions for women with mental health problems including women's crisis houses (CHOICES), mother and baby units (ALTERNATIVES study; ESMI study) and health visitor delivered non-directive counselling RESPOND. We lead on gender aspects of the South London and Maudsley NHS Foundation Trust /Institute of Psychiatry Biomedical Research Centre Stakeholder Participation Theme and are investigating the impact of stigma on women's mental health (SAPPHIRE).
Studies include
- barriers and facilitators to smoking cessation in pregnant women with mental disorders
- pregnancy decision making of women with bipolar disorder
- the effectiveness and cost-effectiveness of perinatal psychiatric services (ESMI study)
- development of outcome measures for pregnant women with mental health problems (CAN-M)
- epidemiological and biological research into foetal, infant and child outcomes including neonatal deaths, sudden infant death syndrome and childhood behaviour
- a multi-centre RCT comparing the effectiveness of antidepressants compared with a health visitor delivered psychosocial intervention for postnatal depression
- national surveys of existing perinatal mental health services
- systematic reviews of treatments for perinatal psychiatric disorders
- violence, migration and mental disorders in women
- gender differences in risk factors and outcomes in psychosis.
Current research includes: co-leading organisational case studies in Birthplace in England, a national study of birth outcomes in home, midwife led, and obstetric led units; investigating the relationship between measures of safety climate and health care quality in A and E and intrapartum care; and conducting nested process evaluations of two trials of obesity in pregnancy behavioural interventions.
I am programme director in the NIHR King's Patient Safety and Service Quality Research Centre leading a programme of work on innovations in service quality and health technologies. The programme of work on patient safety looks at both the translation of novel technologies into health care and innovative ways of organising services differently to bridge 'gaps' in care and improve quality and safety for patients. Current research includes: a) the exploration of the management of 'failure to rescue' in medical and maternity settings b) exploration of the development, diffusion, governance and patient experience of technique-centred and clinical innovation.
