Preventing stillbirth: the role of the immune system in rejecting the placenta
Dr Chloe Brady, Professor Alexander Heazell, Laura Ford, Professor John Aplin
Start date: September 2018
End date: December 2025
Why do we need this research?
Chronic histiocytic intervillositis – or CHI – is a rare and serious condition in which the immune system reacts abnormally to pregnancy, damaging the placenta in the womb. This can prevent the baby from growing properly, and in more severe cases, can cause miscarriage, stillbirth or neonatal death. CHI often comes back in subsequent pregnancies, putting affected women and birthing people at risk of multiple pregnancy losses. It has no symptoms and can only be diagnosed by looking at the placenta after pregnancy; no treatment has been proven to cure it.
We want to know more about the causes of CHI so that we can better identify, manage and prevent it.
What’s happening in this project?
In CHI, the immune system mistakes the placenta for an alien object, causing a build-up of immune cells in the placenta and creating blood clots where the mother or birthing parent’s blood usually flows. We do not fully understand why this happens, but there are similarities with organ rejection following a transplant. Transplant doctors have managed to reduce the chances of organs being rejected by developing treatments to dampen the immune system, and it is thought that similar techniques could be used to manage CHI. As a result, CHI is usually treated with drugs that prevent blood clotting – such as aspirin and heparin – as well as drugs that reduce inflammation – such as hydroxychloroquine and prednisolone – although there is very little evidence to show how well these treatments work.
To understand the condition better, our scientists have been looking at placentas taken from women with CHI and comparing them to the placentas of women who had healthy pregnancies. Interestingly, the team found that there was no difference in the levels of a molecule called C4d – which is used to detect organ rejection – between the two different groups, meaning that CHI may not have the same cause as transplant rejection. The team also looked back at the medical records of a small group of women who had pregnancies affected by CHI and found that 7 in 10 of those who were pregnant again were treated with prednisolone and/or hydroxychloroquine, often in combination with aspirin and heparin. Importantly, treatment with prednisolone and/or hydroxychloroquine made CHI less severe and increased the chances of having a live birth, compared with aspirin and/or heparin or no treatment at all.
What difference will this project make?
Our researchers think that the combination of aspirin, heparin, prednisolone and hydroxychloroquine should be given as standard to all women and birthing people who are pregnant again after suffering from CHI and they often advise clinicians across the country about the best way to treat their patients. As we learn more about CHI, it may be possible to develop new drugs that treat it even more effectively, therefore reducing the number of families who experience the pain of miscarriage, stillbirth or neonatal death.
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