Why do we need this research?
Intrahepatic cholestasis of pregnancy (ICP), also known as obstetric cholestasis, is the most common liver condition that occurs during pregnancy, affecting around 1 in 140 pregnancies in the UK. The main symptom of ICP is itching, usually without a rash, and it can sometimes lead to problems for the baby, such as premature birth and stillbirth.
ICP happens when chemicals made by the liver – bile acids – leak into a woman’s bloodstream. Women who itch in pregnancy are usually offered a blood test to see whether they have raised levels of bile acids in their blood. However, around one in five women have itchy skin during pregnancy and there is currently no way to tell for certain whether these women will go on to develop ICP or not.
We need to find a better way of predicting early in pregnancy which women are most likely to develop ICP, so that treatment can start as soon as possible.
What’s happening in this project?
Our scientists have been studying a family of molecules called sulfated metabolites of progesterone, or PMS. They previously found that raised levels of PMS in blood can be used to predict the future onset of ICP. As PMS can be released into urine, the team have now been looking at whether PMS levels in urine can also be used to predict the risk of developing ICP later in pregnancy. A urine test would be preferable to a blood test, as urine is easier, quicker and cheaper for scientists to work with, and simpler for a woman to provide.
The team recruited 290 women who donated urine samples at various points during and after pregnancy. Some of these women developed ICP and others had an uncomplicated pregnancy. By comparing urine samples from the two groups of women, the team found that there were no markers in urine that could be used to predict whether a woman would develop ICP later in pregnancy. However, they found that the ratio between two chemicals in urine (a PMS called PM3S and another chemical called creatinine) could be used to diagnose ICP.
The team also looked at the urine samples to find out if they could be used to tell how well women with ICP were responding to treatment with a drug called ursodeoxycholic acid (UDCA). They found that the ratio between PM3S and creatinine fell after 2 weeks for most of the women with ICP who were treated with UDCA. It is currently very difficult to monitor how well a patient is responding to UDCA, and so this result could feed into a test that would allow drug doses to be altered as required for women with ICP. The team also want to find out whether levels of PMS in urine can be used to predict which women are most likely to respond to treatment with UDCA.
What difference will this project make?
Although our researchers found that it was not possible to use PMS in urine to predict which women would go on to develop ICP, they did find that urine could be used to diagnose ICP and to provide an easy way of telling whether treatment is working. It may also be possible to use urine to predict whether a woman will respond to treatment for ICP. This work will help doctors to diagnose and treat ICP effectively, helping to protect the health of both mother and baby.