Physiology of parturition

This laboratory- focused programme, led by Dr Rachel Tribe, studies the complex cellular and tissue level processes in uterine smooth muscle responsible for promoting maintenance of pregnancy and the initiation of labour. This group also have an interest in the regulation of inflammatory responses (cytokines and natural antimicrobial proteins) in the vaginal tract. Understanding how these processes are modulated gestationally by hormonal, inflammatory and mechanical signals informs our work on pathological conditions that disrupt the timing of labour. 

Recent important advances include identification of a family of potassium channels in uterine smooth muscle as a novel target for the treatment of threatened preterm labour. 

Research is funded by the BBSRC, Dr Hadwen Trust and Action Medical Research and a wide range of techniques are employed (human tissue culture, patch clamp electrophysiology, calcium imaging, in vitro tension measurement, multiplex protein assays, and molecular biology)

Preterm labour

The PIS working in this grouping are: Tribe, Shennan, North, Kametas and Nicolaides

Preterm labour continues to increase despite extensive efforts to introduce new therapies for the prevention and treatment of preterm labour, and this is in part due to a lack of clear scientific knowledge about the pathophysiological cascades preceding preterm labour. We are implementing a different strategy that integrates the scientific and clinical expertise within our clinical academic grouping in order to improve prediction of preterm labour through a greater mechanistic understanding of preterm labour. This will enable us to ultimately categorise women into risk groups according to the precipitating factors involved, and facilitate the development of targeted treatment and optimise the timing of clinical intervention.

Our efforts are underpinned by our proven clinical trial skills (at both KCH and GSTT clinical sites) and a patient base which provides access to large numbers of high risk and low risk pregnant women. Several planned and ongoing projects (Tribe and Shennan) build on a prospective study of women at risk of pre-term labour, the CLIC project (funded by Action Medical Research) which provided a valuable biobank and a clinical database to identify biomarkers for the early prediction of preterm labour. A patent application has been filed identifying the utility of two specific cervico-vaginal fluid cytokines for predicting spontaneous preterm birth. Investigations in high risk women have been expanded to incorporate samples from the international SCOPE low risk pregnancy cohort study (Tribe, Shennan and North).

Clinical evaluation of the impact of bedside tests (IL-6, IL-8 and insulin-like growth factor) and qualitative assessment of fetal fibronectin (Equipp) on management and neonatal outcome forms a major part of the patient centred research undertaken in the preterm surveillance clinic (Shennan).

In addition a new salivary progesterone test is being evaluated in high risk women in this clinic and in collaborators centres (POPPY).

Shennan is a co-PI on the UK MRC funded OPPTIMUM trial which investigates the use of progesterone for the prevention of preterm labour. Shennan is also CI on the National MAVRIC study evaluating the role of abdominal cerclage in the prevention of preterm birth in very high risk women.

Addressing the same hypothesis, Nicolaides and Kametas are conducting a randomized study of a transvaginal silicone progesterone pessary vs standard management in women at risk of premature birth. 

Impact of mental disorders on pregnancy outcome

The Perinatal Mental Health Group is led by Professor Louise Howard at the Institute of Psychiatry. Mental disorders in the perinatal period are associated with preterm delivery, stillbirths and neonatal deaths. Women are more likely to smoke if they have mental disorders, and this explains much of the association between psychiatric disorders and poor pregnancy outcomes and SIDS. Understanding how services can facilitate women with mental disorders to stop smoking will improve outcomes and we have recently been awarded a grant from FSID to investigate barriers and facilitators to smoking cessation in pregnant women with mental disorders.

Nutrition in pregnancy

Research in this grouping is led by Professor Lucilla Poston, Mrs Annette Briley, Professor Jane Sandall, and Professor Andrew Shennan.

Nutritional status in pregnancy has an important influence on pregnancy outcome, in regard to both macronutrient and micronutrient status. Obesity, arising from over consumption of calories also has a profound influence on reproductive function and is associated with poor pregnancy outcome. There is also the potential for longer term effects on the child.

Poston's group in association with Professor Tom Sanders (Division of Nutrition), and in collaboration with Professor Philip Baker (Manchester University) have recently completed a large cohort study (500 adolescents) of nutrition in teenage pregnancy, showing a strong association with folate deficiency and the incidence of fetal growth restriction, and a very high rate of poor vitamin D status.

Poston’s group (with Sandall, Shennan, Briley, Sanders) is undertaking the pilot phase of an NIHR programme grant to develop a behavioural intervention in obese pregnant women (physical activity and diet) to improve pregnancy outcome. The main project will trial the developed intervention nationally 4 centres. Additional funding is being sought to assess the impact of the programme in infertile women on fertility and pregnancy outcome (Sandall, Poston, Oteng-Ntim, Neena).

Fetal macrosomia is a recognised risk factor of adverse labour outcomes. Dr. Pasupathy is currently working with collaborators from the SCOPE study and the Karolinska Institute to improve the characterisation and prediction of fetal macrosomia. Dr Pasupathy is also currently working with collaborators in neonatology and other groups within obstetrics in KHP to evaluate the effect of obstetric care on the risk of other adverse labour outcomes.