Labour and delivery

What triggers labour

• The process of birth is thought to be controlled by hormonal factors produced by tissues within the womb. The aim of this project is to investigate one of these hormones, in particular, a metabolite of progesterone called 5-beta-dihydroprogesterone. This study will help to improve our understanding of how normal labour occurs and may provide insight into how to prevent it from occurring prematurely. Blood samples are collected from women before, during and after labour, and also from women in premature labour and before term but not in labour. Tissue samples from the womb are also collected at the delivery of babies by Caesarean section for investigation using various molecular biology techniques.

Prediction and prevention of preterm labour

• A number of factors are known to be associated with increased risk of preterm labour including the presence of certain microorganisms and the length of the cervix as measured by transvaginal ultrasound. Women known to be at higher risk of preterm labour are offered care through the preterm labour clinic. Data obtained from women attending the clinic will be used to investigate the possibility of predicting preterm labour through the development of a computer program which provides and individual risk assessment. Interventions such as cervical cerclage and vaginal progesterone supplementation to prevent preterm labour are studied through the clinic.

Endocrine control of labour and preterm birth

• Although hormones are thought to play a role in human labour and delivery, the exact pathways by which the various steroid hormones might act remain unknown. Some possible candidates for the control of myometrial contractions include progesterone and its metabolites, 20α hydroxyprogesterone, 5α dihydroprogesterone and 5β dihydroprogesterone. Possible pathways include that involving the orphan nuclear receptor, the pregnane X receptor (PXR) for which 5β dihydroprogesterone is a specific ligand. In this study, we use the molecular biology techniques real-time RT-PCR and Western blot to investigate the role of the various hormones and their related pathways in normal term human labour, functional dystocia and also preterm labour.

Prediction of pre-term labour

• The aim of this project is use proteomics to identify protein markers of spontaneous preterm labour in cervicovaginal fluid washings taken from women in spontaneous preterm labour prior to 34 weeks' gestation.

• Preterm birth is the single most important determinant of adverse neonatal outcome in normally formed infants in the developed world. Despite significant advances in perinatal medicine in recent decades, the incidence of preterm delivery has remained unchanged in developed countries. The incidence of preterm labour prior to 37 weeks gestation in the developed world is 5 - 10 %. The costs associated with preterm birth are substantial in economic, social and emotional terms. There is therefore, an urgent need to develop cost effective strategies of predicting and preventing preterm labour.

• The signals that initiate normal human parturtion are as yet unknown but the maternal-fetal interface is thought to play an important role. Remodelling of the extracellur matrix (ECM) of the amnion, chorion, decidua and myometrium occurs prior to the onset of labour. This process is activated prematurely in preterm labour. Inflammatory cytokines, prostaglandins and matrix metalloproteinases are thought to be involved in this process of remodelling. Remodelling of the EM of the decidua and chorion may lead to the disruption of the chorionic-decidual interface. This in turn may lead to the release of components of the ECM into cervicovaginal fluid. Biochemical markers of this disruption may prove to be clinically useful predictors of preterm labour.

• Proteomics permits the discovery of early disease markers through the comparison of the protein content of pathogenic cells with that of normal cells. The application of proteomics provides a powerful tool to elucidate the mechanism of human preterm labour and to identify new diagnostic markers of human preterm labour. This in turn may lead to the development and validation of effective therapeutic strategies and ultimately the prevention of preterm labour.

Failure to progress in labour - electrophysiological and molecular studies

• Failure of the muscle of the uterus to contract strongly during labour results in protracted and exhausting labour and, in a significant percentage of cases, necessitates caesarian delivery. The aim of this study is to elucidate the mechanisms that may be responsible for the weak uterine contractions that underlie ineffective labour. Failure of the uterus to contract normally at term, ineffective labour, necessitates the intervention of caesarian delivery in as many as 5-10% of first pregnancies. Administration of oxytocin may augment weak uterine contractions and resolve ineffective labour in some cases. However, in many cases, successful vaginal delivery is not achieved by oxytocin infusion. The causes of ineffective labour remain obscure. In our recent studies of uterine contractility in tissues form a subset of the in-labour group appeared to divide the ineffective labour tissues further into three groups. One group contracted weakly to applied oxytocin. In another group, contractions were anomalously suppressed by prostaglandins that are normally strongly excitatory. The smooth muscle cells in tissues of the third group had unusually negative transmembrane potentials, making contractions difficult to achieve in the face of a wide range of stimuli. Elucidation of the mechanisms underpinning the failure to contract by these tissue is the main aim of this project.

Prediction of delivery prior to 34 weeks gestation

• Fetal fibronectin is a substance produced by the uterus during pregnancy. It is normally found in vaginal fluids at term but not before this time. The presence of fetal fibronectin in vaginal fluid between 22 and 34 weeks gestation may predict the onset of preterm labour. Changes in the length and shape of the cervix (neck of the womb) may also occur in women who go into labour and deliver preterm. By assessing the length and shape of the cervix using transvaginal ultrasound and checking for the presence of fetal fibronectin, it may be able to identify those women at greater risk of preterm delivery from those who present with threatened preterm labour.