Inflammation of the placenta as a cause of stillbirth

Hayley Derricott, Dr Rebecca Jones, Professor Alex Heazell, Dr Gauri Batra, Dr Sue Greenwood

Tommy's researchers found that inflammation can change the structure of the placenta, and affect the way it works during pregnancy.

This study is now complete

Stillbirth is very closely related to problems in the placenta. However, we don't fully understand how these problems happen, and what effects they have. Often, when a baby is stillborn, there is inflammation in the placenta. This is called villitis (a type of inflammation) of unknown etiology (cause), or VUE for short. Other studies have not found a cause for this inflammation such as a bacterium or virus.

We are interested in how this inflammation relates to problems in the placenta. To study this, we looked closely at how inflammation changes the placenta and if it changes how well the placenta works. Using a 'biobank' - a collection of biological samples - we looked at placental samples from pregnancies where the baby was stillborn. Our early work has shown that the number of white blood cells, which indicate inflammation, is increased in placental tissue in cases where there were reduced fetal movements. This was especially the case in pregnancies where the baby was then stillborn. 

Tommy's researchers carried out a review of earlier studies which showed that inflammation, specifically VUE, was present in 15% of apparently normal pregnancies. They also confirmed that it was about twice as common in babies that experienced growth restriction. However, there have not been studies of enough patients to definitely associate it with stillbirth - we believe that this is worth researching further. 

We studied which types of cell were present in areas of VUE in the placentas of women who had had a stillbirth. We found that the microscopic lesions in areas of VUE are made up of specific types white blood cells. We also observed, for the first time, evidence that cells involved in the body's immune response - T cells - were present in areas of placenta that looked otherwise healthy. The location and amount of the chemical messengers that these cells make was also altered in stillbirth with VUE.

Scientists carried out an experiment that allowed us to grow fragments of placenta with T cells that had been taken from mothers’ blood samples. Culturing the placenta samples and T cells together for 4 days changed the function of the placenta: it made less of an important hormone called hCG and more signals that are associated with inflammation. Culturing tissue with these inflammatory signals also caused a decrease in hCG.

Our work has shown that the cells and signals involved in VUE can damage how well the placenta works. The new experiments can be used as a basis for further studies into the effect of inflammation in the placenta, and how it is linked to stillbirth. 

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Funding

This study was fully funded by Tommy's and took place in a Tommy's centre

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