What's the problem and who does it affect? A stressful pregnancy full of uncertainty Each year in the UK, an estimated 3,500 pregnant women develop obstetric cholestasis. This liver disease is normally diagnosed after the mother-to-be notices an unusual itching, often on the palms and the soles of the feet. Fortunately, the mother's illness normally disappears outside of pregnancy. Sadly, the babies don’t always fare so well. Obstetric cholestasis can be associated with serious complications, including stillbirth, premature birth and fetal distress. Stillbirths tend to happen without warning, in the last few weeks of pregnancy. Women who have long been feeling the kicks of their unborn child, and who ought to be preparing for life with a newborn, are suddenly faced with the tragic loss of their baby. We do not understand why some babies die. It’s also unclear whether a drug called ursodeoxycholic acid (UDCA), which relieves the mothers’ itch, could also benefit babies. Some babies are delivered early, to try to avoid a stillbirth, but we lack concrete evidence that this is beneficial. This dire lack of information makes it difficult to know how best to protect babies.
What is the project trying to achieve? How does obstetric cholestasis cause stillbirth? It has long been known that pregnant women with obstetric cholestasis have abnormally high levels of bile acids in their blood, because the liver isn’t working properly. The project team suspects that these raised levels of bile acids might endanger unborn babies by causing their heart to beat abnormally, putting them at risk of a heart attack. Researchers are exploring their theory by performing a series of sophisticated laboratory studies of fetal and adult heart cells. They are measuring the changes in heart rhythms when the cells are exposed to bile acids, and investigating the precise mechanisms by which this happens. They hope to explain why an unborn baby’s heart could be more vulnerable to the effects of bile acids than that of its mother. The team is also examining whether UDCA can protect the heart cells from the effects of bile acids, again looking for a detailed explanation of how this happens.
What are the researchers' credentials? - Project leader: Dr Julia Gorelik PhD, National Heart and Lung Institute, Imperial College London
- Project team: Dr Catherine Williamson MD MRCP
- Other locations: Institute of Reproductive and Developmental Biology, Imperial College London
- Duration: 2 years
- Grant: £131,566
- Status: Ongoing
Two leading scientists, who both have track records of the highest quality, are collaborating on this exciting project. The Project Leader, Dr Julia Gorelik, is highly experienced in using a sophisticated technique called Scanning Ion Conductance Microscopy. She has pioneered the use of this technique in the study of cultured heart cells, allowing detailed investigations of the processes that lead to abnormal rhythms and heart failure. Dr Catherine Williamson is an acknowledged authority on obstetric cholestasis, heading a research group that focuses on pinning down the causes of this distressing condition and studying the influence of pregnancy and reproductive hormones on levels of bile acids. Working together, Dr Gorelik and Dr Williamson bring complementary skills in biophysics, molecular biology, cell biology and medicine. They have every chance of tackling the complex clinical problem of obstetric cholestasis successfully.
Who stands to benefit from this research and how? Helping find ways to prevent stillbirth Researchers hope their work will help explain why some women with obstetric cholestasis have stillborn babies – whether raised levels of bile acids in the blood lead to heart problems that cause the babies to die so suddenly in the womb. Eventually, all expectant mothers with obstetric cholestasis, and their babies, may benefit. The research team estimates that 1 in 200 pregnant women with obstetric cholestasis has a stillborn baby. They also estimate that the condition is linked with complications, such as premature birth, in up to 1000 babies each year in the UK. Revealing the exact mechanisms that cause stillbirth will facilitate the design of new ways to prevent it. In particular, the results of this project may indicate whether UDCA has the potential to prevent stillbirth – currently it is only used to treat the mothers’ symptoms. Much more work will be needed, but the ultimate aim is to find a successful new treatment for obstetric cholestasis. The goal is a treatment that frees expectant mothers from worries that their condition may harm their baby, and helps avoid the heartbreak of stillbirth, by saving babies’ lives. References 1. Abedin P, Weaver JB, Egginton E. Intrahepatic cholestasis of pregnancy: prevalence and ethnic distribution. Ethn Health. 1999 Feb-May;4(1-2):35-7. 2. Office for National Statistics. Health Statistics Quarterly 35 (Autumn 2007), 3. Glantz A, Marschall HU, Mattsson LA. Intrahepatic cholestasis of pregnancy: Relationships between bile acid levels and fetal complication rates. Hepatology 2004; 40: 467-474. |
