ICP Support started life as a support and information line in 1991. In the way many charities begin, it evolved out of personal tragedy. In my case, that tragedy was two stillbirths and the diagnosis of a liver condition of pregnancy called intrahepatic cholestasis of pregnancy (ICP), which less than a handful of health professionals in the UK knew about at the time.
When I learnt why my two daughters had died and that women were advised that itching (the predominant symptom in ICP) in pregnancy was normal, I felt a huge obligation to raise awareness among women and health professionals. Back then, knowledge of the condition was relatively scant; it was generally thought that delivering the baby by 38 weeks of pregnancy (an idea fuelled by research in Australia in the 1980s) to avoid stillbirth was all that was needed. I thought my task would be simple and quick: raise awareness, help change practice so that unborn babies were delivered by 38 weeks', support women until obstetric practices changed, then get back to a ‘normal’ life.
I had no idea how long raising awareness takes and that without evidence, change in practice will not happen. But I was lucky: the obstetrician who diagnosed me supported research into the condition and I met her colleague, a hepatologist, who also had a special interest in ICP. I began raising awareness through pregnancy magazines, and women started to ring the information and support line. In 1997, I met Catherine Williamson, an obstetric physician and scientist who had decided to focus her work around cholestasis of pregnancy. We have been working together ever since.
Catherine is a huge advocate of women's voices. She listened to what I wanted to do and advised what I could do to help her. In the 1990s, patient and public involvement in research was not the buzzword that it is now, but Catherine was ahead of her time and knew that the women with the condition were the voices to listen to. I also knew that many of those women, like me, would want to facilitate research into ICP, as the more research that was conducted, the faster we would get results and change practice—it was a win-win situation. With the help of women and supportive health professionals, ICP Support evolved.
Today, researchers know that ICP is much more complex than was first thought. Studies have shown that the condition may have a longer-term impact on the health of the woman and her children, (increased risk of liver disease, type 2 diabetes and possibly cardiovascular disease) (Papacleovoulou et al, 2013; Wikström Shemer et al, 2015). Research has identified that there are several genetic changes implicated in ICP (Dixon and Williamson, 2008) with newly discovered variants that are just about to be published. The mechanism for stillbirth has still not been proven, although hypotheses include bile acids having a detrimental effect on the fetal heart and the placenta (Gorelik et al, 2003; Geenes et al, 2011; Miragoli et al, 2011).
There is also no standardised care for women with ICP, and we know from what they tell us in the support groups we run that this leaves them confused, frustrated and very anxious about the risk of stillbirth.
What is ICP?
ICP is the most common liver disease specific to pregnancy. It affects just under 5500 women per year in the UK and is caused by a combination of:
The main symptom is itching, usually on the hands and feet, which typically presents in the third trimester of pregnancy. This is an area of conflicting information, as there will be some women who do not experience itching, as well as those who itch before 28 weeks of pregnancy. Women may therefore be refused testing because they don't fit the typical profile for ICP. Other symptoms include dark urine, pale stools and right upper quadrant pain.
Diagnosis is a process of exclusion. Blood tests should include bile acids (another area of confusion, as hospitals use different reference ranges), liver function test, autoimmune hepatitis, hepatitis C serology and automitochondrial antibodies.
Once diagnosis is confirmed, regular bile acids are considered vital. This is based on research (Ovadia et al, 2019) that shows the risk of stillbirth from ICP increases when bile acids rise beyond 100 µmol/L. Liver function tests should also be included (although around 20% of women with ICP will have normal liver function—another reason why bile acid tests are important).
Blood tests are another hurdle for women as many are refused bile acid testing once they are diagnosed, despite the correlation of bile acid levels with fetal risk (Ovadia et al, 2019). Many hospitals also take up to 5 days to return results. This is of little use when trying to assess fetal risk, as bile acids can rise steeply and rapidly.
Treatment
Treatment includes the use of medication, including ursodeoxycholic acid (UDCA) and possibly rifampicin. However, in a large UK trial (Chappell et al, 2018), UDCA was shown to be ineffective for the majority of women with ICP, and health professionals will need to to reconsider what has been its routine prescription. Similarly, rifampicin can worsen liver function and be dangerous for the woman, so requires specialist advice in its use. Other treatment options include regular blood tests and possibly an early birth, depending on bile acid levels.
Because of the association of stillbirth with ICP, women have often been induced early (Geenes et al, 2016). The research (Ovadia et al, 2019) now means that many women can be reassured about the safety of the baby up to 39 weeks' (there were insufficient numbers in the data beyond this gestation to advise 40 weeks'). However, regular monitoring of bile acids is required, especially in the cohort of women whose bile acids rise >100 µmol/L and who may require delivery as early as 35 weeks'.
Postnatal management
After the birth, liver function and bile acid tests should be repeated at around 6–12 weeks to provide a definitive diagnosis. Abnormal results may need further investigation by a hepatologist but repeating the tests before referral is generally a good idea, as levels (particularly ALT) can take a little longer than 12 weeks to resolve.
There is no research into the use of oral contraception. It makes sense to avoid using contraception that contains hormones, although anecdotal evidence shows that some women may be able to tolerate the combined pill and more women the progesterone-only (mini) pill. If considering these as an option, women must first have a normal liver function test result. Any subsequent itching (not to be confused with cyclical itch that can occur just before ovulation and the onset of menstruation) may mean that the woman is not tolerating the pill and she will need to stop it.
Recurrence of ICP in further pregnancies is thought to be around 80% (more commonly quoted as 60–90%) (Williamson and Geenes, 2014). As research has identified a longer-term impact of ICP on women's health, it seems sensible for women to have an annual liver function test, but this is not yet standard practice.
The work of ICP Support
It is not hard to see why there is conflicting information being given to women. Some of this article, such as the information on contraception and the need for an annual blood check, is based on anecdotal evidence and some guidelines (Royal College of Obstetricians and Gynaecologists, 2011) were last revised in 2011 (although these are being updated).
But the landscape for ICP is changing. New research (Ovadia et al, 2019) means that health professionals can reassure more women about the safety of their babies, and although the results of the PITCHES trial (Chappell et al, 2018) means that a new drug to treat ICP needs to be found, it does mean that the information given to women is now clearer and evidence-based.
For ICP Support, working closely with health professionals to update their knowledge is key. This has been achieved by producing a module on ICP for the Royal College of Midwifery's iLearn programme, and a similar programme for GPs is planned. ICP Support works closely with other health organisations such as NHS Choices to ensure that information is updated as new data emerges. The charity also attends conferences, and midwives in particular are often keen to learn more about ICP. We work closely with other charities because we believe that collaboration is key —in particular, we have worked with Tommy's to ensure that the information they have is up-to-date.
Finally, the charity works closely with researchers to advise on the design of studies into ICP, and to share what it is like to have the condition. We hope that this will improve management and understanding of the condition for women who have ICP, and that our children, who may also develop ICP or pass on the genetics for the condition, will not have to face the same uncertainty and anxiety. We cannot guarantee to end all stillbirths because of ICP, but we want to prevent as many as we can, because we know only too well the heartache that the death of a baby can bring.