Understanding the link between inflammation, the placenta and stillbirth

Dr Bernadette Baker, Dr Rebecca Jones, Dr Sylvie Girard, Dr Alexander Heazell, Professor Colin Sibley, Vikki Abrahams

Following earlier work funded by Tommy’s, the Medical Research Council is supporting research in Tommy’s Manchester Centre to try and find out if preventing inflammation in the placenta could stop stillbirths.

Through work funded by Tommy’s, we already know that inflammation of the placenta can directly cause stillbirth. Researchers showed that inflammation is related to the placenta not working properly in pregnant women who noticed their babies were moving less than normal. They also found that chemical signals - called DAMPs - involved in inflammation were higher several days before birth. This means that these signals could be used to tell early on if inflammation is present and the baby may be in danger. The inflammatory signals also had a direct effect on the placenta: in the future, drugs could be designed to target these signals, protecting the placenta and the baby.

Following Tommy’s work, the Medical Research Council has now funded a study to tell us once and for all if and how inflammation causes damage to the placenta, and to find the link between inflammation and stillbirth.

To understand whether placental inflammation can damage the placenta, we treated small fragments of placentas in culture with the chemical signals that we had previously identified. We found that these signals induced cell death in the placenta and increased production of inflammation. We have detected the same effects in pregnant rats treated with the same signals. These rats had pups that were growth restricted, providing evidence that these signals can adversely affect the placenta, resulting in poor outcomes for the babies. 

We have also performed studies to find out why to find out why DAMPs are elevated in the mother’s blood in high risk pregnancies. We have created culture models of placental damage that mimic the processes that happen when the placenta stops working properly during early pregnancy. These processes induce stress and hypoxia (oxygen starvation) in the placenta. When this happens, we have detected increased release of DAMPs. This provides the first evidence placental damage can cause the release of inflammatory signals from the placenta. These signals can then act on the placenta to increase the damage, potentially leading to abnormal placental function and harm to the baby. 

In summary, our research gives in-depth knowledge of the links between inflammation and placental dysfunction in high-risk pregnancies. By understanding these relationships, we will be able to find out if using drugs to try and stop placental inflammation may be a way to prevent stillbirths in the future.  

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This study takes place in a Tommy's centre and is funded by the Medical Research Council

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