Pregnancy can be a hugely exciting time for many women and their families, but for those who experience pregnancy loss, it can be devastating.

Miscarriage before the end of the first trimester (the first 12 weeks of pregnancy) occurs in about one in five pregnancies. One in 250 will sadly end in stillbirth, which is rare.

The role of the placenta

The placenta plays a vital role during pregnancy, delivering gases and nutrients to the unborn baby so that it can grow and develop normally.

In rare cases, the placenta can get ‘clogged up’ with immune cells from the mother. This makes it more difficult for the baby to get the nutrients it needs to grow. When this happens, pregnancy loss occurs in 50% of cases. Some babies may need to be delivered several months early to give them a chance of survival.

Experts still don’t fully understand all the causes, but we do know that three rare placental disorders – chronic histiocytic intervillositis (CHI), villitis of unknown ethology (VUE) and massive perilous fibrin deposition (MPFD) - can cause pregnancy loss in every trimester.

In the pregnancies that continue, there is an increased risk of extreme prematurity, which can have long-term health consequences for the children who survive. An additional challenge for women diagnosed with these conditions is that they carry a high risk of recurrence in further pregnancies, meaning that some families tragically suffer several stillbirths.

Unfortunately, these conditions can only be diagnosed once a pregnancy has already ended. Babies often appear much smaller than expected in ultrasound scans, but otherwise, there are very few warning signs.

Dr Emily Cornish, funded by Wellbeing of Women, has been studying the causes of these rare placental disorders and why certain women develop them. She and her team have also been investigating potential treatments, with promising results.

Understanding rare placental disorders

Dr Cornish, a clinical research fellow at University College London (UCL), focused her research on the rare placental disorder CHI.

By taking blood samples from 45 women with these rare placental disorders and comparing them to samples from women who’ve had healthy uncomplicated pregnancies, her team has been able to show that women with CHI have elevated levels of proteins that stimulate immune cells. This provides important clues about the mechanism of placental damage in CHI.

Researchers also discovered that samples from placentas affected by these disorders look similar to kidney transplants that have been rejected by their host’s body. This supports Dr Cornish’s theory about the role of the immune system in the development of CHI.

Working alongside an international network of collaborators, Dr Cornish has also investigated new reports that CHI can occur when a pregnant woman develops COVID-19 (as well as other infections). In this scenario, the CHI does not recur in future pregnancies.

Dr Cornish says:

“Rare placental disorders (CHI, VUE and MPFD) are devastating for affected families. There is currently no way to diagnose them until it is too late and no reliable tests to predict if they will recur in a future pregnancy. It is also hard to know who is likely to develop a rare placental disorder as they usually affect women who are fit and healthy.

“We desperately need to understand how and why these rare placental disorders occur so that we can improve our ability to help women dealing with the immense pain of recurrent pregnancy loss."

Next steps

Dr Cornish is working with scientists internationally and receiving funding from the Medical Research Council (MRC) to continue her research into the causes of these three rare placental disorders. By understanding the specific mechanisms of CHI, VUE and MPFD, researchers can start to design treatments and tests to prevent these placental disorders from occurring.

Improving our understanding of these disorders may also help us tackle other pregnancy conditions such as recurrent miscarriage.

Read Dr Cornish’s award-winning essay on unlocking the mystery of placental disorders and recurrent stillbirths.

Wellbeing of Women is funding several research projects to help improve treatment and care during pregnancy and birth, including:

• Dr Jane Cleal’s study into why some women struggle to become pregnant or experience miscarriage
• Dr John Allotey’s work to reduce the rate of stillbirth by understanding early pregnancy risk factors
• An investigation by Dr Matina Iliodromiti into how we can identify health risks in babies too small or too large during pregnancy
• Midwife Joanne Cull investigating how maternity services can empower pregnant women affected by trauma