Does arrhythmia cause stillbirth in the babies of women with liver disease?

Professor Lucy Chappell, Dr Peter Dixon, CLN research midwives, Dr Caroline Ovadia, Professors Fiona Broughton-Pipkin and Jim Thornton, Professor Julia Gorelik, Professor Bill Fifer

Tommy’s are supporting research looking at whether a liver condition called ICP can affect a baby’s heart rate, and in turn increase the risk of stillbirth.

Around 4,000 babies are stillborn every year in the UK. Half of these have no obvious cause. Finding these reasons is immensely important to the thousands of women who suffer loss every year.

This means it is of vital important to Tommy’s, too.

There are some factors that can increase the risk of 'unexplained' stillbirth. These include age – particularly if a mother is either under 20 or over 35. They also include certain diseases. One of these is called ICP, or ‘intrahepatic cholestasis of pregnancy’. ICP is the most common liver disease that women can experience during pregnancy. Women with this disease itch more than normal, and have high levels of chemicals made by the liver, called bile acids, in their blood.

Scientists have shown in the laboratory that bile acids can affect cells in the baby’s heart. This could make the heart beat irregularly, a condition called arrhythmia. We think that arrhythmia in a baby’s heart could lead to stillbirth. However, we have also found that a drug – ursodeoxycholic acid (or UDCA) – might be able to stop arrhythmia from happening.

To find out if this is true, we are asking pregnant women to wear a portable monitor to measure the rhythm of their baby’s heart. This will let us see how often arrhythmia happens in the babies of women with ICP, compared to healthy women. We will then study women who took part in a clinical trial of UDCA (the PITCHES trial) to see if we can prevent arrhythmia in the babies of women with ICP.

We have now recruited 16 women with ICP, and 34 without. We have collaborated with Professor Broughton-Pipkin of Nottingham University, who has also recruited a similar number of women. Throughout 2017, we have been comparing the impact of mild and severe ICP and treatment with UDCA on the maternal and fetal heartbeat. We have collaborated with Professor Fifer of Columbia University to analyse this data. Our initial results suggest that severe ICP has detrimental effects on fetal heart activity. However, these changes in fetal heart activity do not seem to be present when the mother has been treated with UDCA. These results are very promising. We will continue to analyse our data to enable us to know for certain whether UCDA or other ‘anti-arrhythmic’ drugs could be of benefit to pregnant women with ICP.

At the same time, the PITCHES trial has been looking at whether UDCA can protect against arrhythmia in women with ICP. If it can, we can then work to understand whether UDCA can also protect against other causes of arrhythmia and stillbirth.

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Funding

This study takes place in a Tommy's centre and is funded by Tommy's and the John Coates Charitable Trust

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