Diseases of pregnant women
Diseases of pregnant women are a major health problem. Approximately 500,000 women die in pregnancy every year. Globally, many pregnant women die as a consequence of poor availability of antenatal care. In developed countries such as the UK, the majority of deaths in pregnant women are associated with pre-existing maternal medical disorders.
Professor Catherine Williamson’s research focuses on medical diseases in pregnant women and their impact on the outcome of pregnancy for the mother, the unborn baby and subsequent health of the child. Her research focuses on liver disease, endocrine tumours, pre-eclampsia and prediction of poor pregnancy outcome.
Liver disease in pregnancy: Professor Williamson has a program studying intrahepatic cholestasis of pregnancy (ICP), also called obstetric cholestasis. This is the commonest liver-specific disease of pregnancy, affecting approximately 1 in 150 pregnant women in the UK. Affected women have itchy skin and liver impairment with raised bile acids in the blood. Fortunately most women improve rapidly after they deliver. However, the condition can affect the unborn baby with an increased risk of preterm labour, fetal distress and, in the worst cases, stillbirth.
Professor Williamson’s group have identified genetic causes of ICP, including the first report of a common genetic factor found in affected women. The group is also studying the hormonal signals that cause the condition to occur in pregnancy. There are specific hormones that rise in pregnant women, and some of their breakdown products are higher in women that develop ICP. Recent work shows that these hormone breakdown products can cause genetically susceptible women to develop ICP. The Genesis Research Trust provided invaluable pump-priming money for this research. Catherine is also studying the ways that raised bile acids in the mother’s blood may cause the unborn baby to become ill. She has done collaborative work with Professor Julia Gorelik to show how bile acids may affect the heart of the unborn baby. At present, the work has used laboratory studies of heart cells and has shown that high levels of bile acids may cause the heart to beat abnormally and ultimately stop. She is now performing clinical studies of the heart rate of ICP babies in the womb with the aim of showing whether abnormal heart rhythms occur unborn baby in ICP, and to see if drug treatments for the mother can protect against potentially fatal changes in the heart rhythm of the baby. She is also investigating drugs that may protect the womb and placenta from the bile acid effects with the aim of preventing preterm labour in ICP. This work should help us to choose the best treatment to prevent the complications of preterm labour, fetal distress and stillbirth in ICP.
Diabetes in pregnancy: Diabetes in pregnancy is very common. Approximately 1 in 100 women have diabetes before they conceive and almost 1 in 10 develop diabetes in pregnancy. Professor Williamson is also studying hormonal changes that cause previously unaffected women to develop diabetes mellitus when they become pregnant. Her work involves detailed studies of changes in fat tissue (white and brown adipose tissue), the pancreas and the gut, including the impact of pregnancy on microbes in the gut. It is likely that all of these tissues are influenced by pregnancy, and therefore they should all be considered when aiming to develop new treatments for diabetes in pregnancy. Professor Williamson aims to use this knowledge to develop new therapies.
Similar to ICP, women with diabetes in pregnancy have an increased risk of stillbirth. Catherine is using some of the same techniques that she uses for ICP to study the heart of the unborn baby in diabetic pregnancies with the aim of preventing fetal distress and stillbirth in this group of pregnant women and their babies.
Future health of the children of mothers with metabolic diseases in pregnancy: Following on from her work on ICP and diabetes mellitus, Professor Williamson has shown that the 16 year old children of mothers with cholestasis are more likely to have high cholesterol and be overweight. This work was started by a Genesis Research Trust grant. Professor Williamson is now studying whether treating mothers with specific drugs in pregnancy can protect children from developing obesity and high cholesterol in later life.
Endocrine tumours: Professor Williamson is using a national database (the UK Obstetric Surveillance System) to study the influence of tumours of the pituitary or adrenal gland on the health of pregnant women and their babies. This study will evaluate the influence of pregnancy on the tumour and also whether the tumour or the drugs used to treat it have adverse effects on the health of pregnant women or their babies.
Pre-eclampsia and prediction of adverse pregnancy outcome: Professor Williamson was a member of the UK Genetics of Pre-eclampsia (GOPEC) Genetic Steering Group for many years. This national collaborative group collected a DNA resource from 1000 women with pre-eclampsia and their babies to understand the genetic causes of the disease. She is also developing a new project using blood samples from women with ICP and other important pregnancy complications (including pre-eclampsia) to identify ways of predicting women who will have disease in pregnancy. This work will involve large-scale studies and we hope it will allow researchers to identify women at risk of problems for themselves or their unborn baby at a very early stage of pregnancy so clinicians can give them treatments to prevent disease and improve maternal and fetal health.
Summary of work in a few sentences:
Understanding the commonest liver disease of pregnancy:
- First identification of mutations that cause intrahepatic cholestasis of pregnancy*
- Demonstration of the role of high concentrations of progesterone sulphates in pregnant as a cause of cholestasis*
- Work to show how high bile acids in the blood can cause abnormal heart rhythms in unborn babies
- Evidence that the 16 year old children of women with cholestasis have increased adiposity and high cholesterol*
- Currently studying the impact of the drug ursodeoxycholic acid on preterm labour, stillbirth and offspring metabolic health
Causes of stillbirth
- Focus on stillbirth in normally grown babies, in particular those whose mother has diabetes mellitus or cholestasis
- Detailed studies of models of the fetal heart to show abnormal heart rhythms and drugs that may protect the unborn baby
- Currently performing clinical studies of women with diabetes and cholestasis to see if their unborn babies have abnormal heart rhythms, and to evaluate the impact of the drug ursodeoxycholic acid to protect against this
*work initiated by a grant from the Genesis Research Trust