Maternal Medicine
Maternal research focuses on obstetric cholestasis (OC), a common liver disease of pregnancy complicated by intrauterine death and spontaneous prematurity. The aim is to identify the role of genetic variation in OC susceptibility and treatment response. Dr Catherine Williamson has identified mutations with a functional effect in two genes that encode a biliary transporter and a bile acid receptor respectively, and are currently establishing the role of polymorphisms in the nuclear receptor FXR in treatment response. After developing in vitro models to investigate fetal death in OC, and establishing that bile acids cause abnormal contraction and calcium dynamics in cardiomyocytes, we showed in preliminary work that ursodeoxycholic acid (UDCA) and dexamethasone protect against cardiomyocyte dysfunction. Thus drugs used to treat maternal symptoms in OC are likely to protect against fetal death in addition to treating maternal symptoms; this gives insights into other causes of stillbirth. Our five-year plan is to develop a screening test for OC, and to establish in randomised clinical studies whether drugs protect the fetus from lethal dysrrhythmia. Other work in this area addresses the genetic basis for pre-eclampsia through national collaborations, as a platform on which elusive preventative therapies might be built.
Pruritus of the legs in obstetric cholestasis
Heart disease is one of the most important causes of maternal mortality in the UK. The management of pregnant women with pre-existing heart disease has been the focus of Professor Steer’s work at the Chelsea and Westminster Hospital. He has worked closely with Professor Michael Gatzoulis of the Royal Brompton Hospital, to develop up-to-date evidence based protocols that are in use throughout the UK. In addition, the large regional resource covering 600,000 deliveries recorded in the St Mary’s Maternity Information System database has proved a major international resource in quantifying maternal epidemiology and pregnancy outcomes.
Arising out of earlier studies of fetal and birth stress, Professor Vivette Glover’s work in large population cohorts has shown that maternal stress in pregnancy results in the child being anxious and more likely to have attention deficit/hyperactivity and lower developmental scores. In addition to studying long-term effects of early stress on child development, and the role of the fetal HPA axis in mediating fetal and neonatal programming, an intervention trial is planned to evaluate cognitive therapy to reduce cortisol levels in anxious or depressed pregnant women.
