Touching Lives - March 2003
Treating the mother -- protecting the baby
Action Medical Research gave a grant of £84,000 to Dr Catherine Williamson, Professor Richard Boyd and their team to find out more about the condition — and they are making remarkable strides.
It’s thought that one in 200 pregnancies may be affected by obstetric cholestasis (OC), a liver disease characterised by severe itching during pregnancy. For the mother the itching can be a real nuisance, but if undiagnosed it can be catastrophic for the unborn infant, leading to prematurity, foetal distress and even stillbirth.
Over the past two years Dr Williamson and her team, funded by Action Medical Research, have made some exciting discoveries that will ultimately help in the treatment and management of women with OC.
They wanted to know whether the drugs currently given to women to treat the itching can also offer protection to the unborn child. They have looked at whether babies can inherit a predisposition to the condition from their mothers and also at what part the transport of bile acids from baby to mother plays in the disease. Women and babies with OC have high levels of bile — a waste product of the liver which helps to break down fats during digestion.
With others, the team has established that there is, in fact, a genetic link to the disease. Certain ethnic groups are more predisposed to it and there are family traits that suggest a gene being handed down from one generation to the next. If that is the case, babies may well inherit the condition from their mothers. Indeed, Dr Williamson’s group has found mutations in one specific gene in a sub group of affected women.
The transport of bile acids between mother and baby is also significant. Before a baby is born, it cannot excrete bile acids through faeces. Instead they are transported across the placenta and eliminated by the mother.
Studies suggest that 50 per cent of unborn babies may be at risk because they cannot properly control their bile acid levels. Dr Williamson’s team is now working to establish whether some babies have an inefficient transport of these bile acids across the placenta and how this might put them at risk.
She said: “We spent a considerable amount of time looking at the placentas of women who have had normal pregnancies and those with obstetric cholestasis to try to understand the role that different genes may play in causing the foetal complications of obstetric cholestasis. We found three genes that were expressed differently in the placentas of those diagnosed with the condition, and one of those genes has mutations, so this was a very exciting find.
“Now we are looking at placentas from women diagnosed with OC who have been treated with drugs to see if their babies’ gene expression and transport of bile acids is affected. We are growing cultures to mimic OC to see how it influences the transport of bile acids in placenta in collaboration with Professor Boyd’s group in Oxford.
“An interesting aside is that the disease may also be influenced by environmental factors — for example, there are many more cases in the winter, which may have something to do with UV rays from the sun.”
Dr Williamson added: “We have some way to go but have had some excellent results. Hopefully soon we will get answers on whether the drugs given to women affect the foetus and give it some protection.
“In the past, the drugs have only been given to treat the mother and no-one has known if they improve the transport of bile acids across the placenta. If they do it will be very likely that they protect the unborn child from foetal distress and stillbirth, and this knowledge will probably change doctors’ management of OC, which should mean a better outcome for both mother and baby.”