Pre-eclampsia: what goes wrong inside the placenta?

Up to ten per cent of pregnant women worldwide develop a serious condition called pre-eclampsia.¹ There is no way to halt the progression of the illness, so babies often have to be delivered prematurely in an attempt to save their mother’s life and their own. Researchers are investigating what causes pre-eclampsia, focusing on possible links to the death of cells in the placenta. They hope their work will ultimately save lives by leading to earlier diagnosis and improved treatment.

What's the problem and who does it affect?

A danger to both mothers and babies

Up to five percent of pregnant women in the UK develop a serious condition called pre-eclampsia.^2,3 Several hundred babies and around six women die each year in the UK after developing the condition.⁴

Women with the most severe disease can suffer high blood pressure, convulsions, strokes, liver and kidney failure, and life-threatening bleeds. In the UK, the most serious symptoms are rare, but worldwide the condition remains a major cause of death in mothers.¹

Treatment can help tackle some symptoms, lowering blood pressure and reducing the risk of convulsions. However, it does not slow the underlying progression of the disease.

In fact, the only way to cure pre-eclampsia currently is to deliver the baby early. An early birth can prove life saving, not just for mothers, but also for their babies, as pre-eclampsia can cause stillbirth.⁵

However, premature births bring their own risks. As well as being premature, the babies also tend to be worryingly small, because they do not always grow very well in the womb. Evidence suggests they might even be at increased risk of developing diabetes, high blood pressure and heart disease in later life. Better treatments are urgently needed.

What is the project trying to achieve?

Why do cells in the placenta die?

Despite the severity and frequency of pre-eclampsia, the biology behind it remains poorly understood. No-one knows exactly what causes the condition. The researchers are hoping to help fill this information gap.

Pre-eclampsia is thought to result from problems with the placenta, which feeds and nourishes the baby throughout pregnancy. Early in pregnancy, the placenta embeds itself within the wall of the womb. Cells from the placenta invade the lining of the womb and alter the structure of the mother’s blood vessels, so that nutrients and oxygen can pass from the mother’s blood, through the placenta, to the baby. Evidence suggests that this process sometimes goes wrong, and that this might cause pre-eclampsia.

The researchers suspect two key factors might contribute to pre-eclampsia:

• cells from the placenta, which are supposed to invade the lining of the womb, might be more likely to die, because they are more sensitive to signals that cause them to self-destruct
• the lining of the womb might be more likely to secrete substances that prompt cells in the placenta to self-destruct.

The researchers are investigating their ideas in the laboratory, using samples donated by around 100 women.

What are the researchers' credentials?

The researchers have many years’ experience in the study of pre-eclampsia. Their highly productive work has provided a deeper understanding of how problems within the placenta can lead to complications during pregnancy. The team has a very high standing in this area of research.

The project leader, Professor Guy Whitley, and his colleague Dr Judith Cartwright are highly skilled scientists. They have developed several new laboratory techniques, which are specially designed to help them study the molecular processes that take place within the placenta during pregnancy.

The third team member, Professor Baskaran Thilaganathan, is a hospital consultant with many years’ experience of treating pregnant women who have developed pre-eclampsia.

The researchers use state-of-the-art imaging techniques both at the bed side and in the laboratory. They have refined a way of using sophisticated ultrasound scans during the first three months of pregnancy to assess a woman’s chances of developing pre-eclampsia. They are leaders in this technique.

The combined approach of using ultrasound to asses a woman’s risk of developing pre-eclampsia, and up-to-date laboratory techniques to study what’s going wrong inside the placenta, is unique to these researchers and will be instrumental in making their study a success.

Who stands to benefit from this research and how?

Benefiting both mother and baby alike

The researchers hope to provide an important insight into what causes pre-eclampsia. Longer term, they believe this could lead to improved diagnosis and treatment.

The researchers hope their work will lead to better ways to predict who is most likely to develop pre-eclampsia. Women who are told they are not at high risk may find they worry a lot less during pregnancy, especially if they have suffered from pre-eclampsia before. Those who are at high risk could benefit from appropriate monitoring and treatment sooner.

Women who do develop pre-eclampsia can find the condition extremely frightening. They often have to stop work early and have frequent monitoring. Most are ultimately admitted to hospital and deliver their babies early.

Worldwide, the condition remains a leading cause of death and illness in both mothers and babies.¹ It puts babies at risk of stillbirth and premature birth, and even increases their chances of developing heart disease, high blood pressure and diabetes during adulthood.

The researchers hope their work will ultimately lead to a better treatment for pre-eclampsia. This could bring huge benefits to expectant mothers and their babies, both during pregnancy and throughout their lives.

References

1. Geographic variation in the incidence of hypertension in pregnancy. World Health Organization International Collaborative Study of Hypertensive Disorders of Pregnancy. Am J Obstet Gynecol 1988;158:80-83.
2. Vatten LJ and Skjærven R. Is pre-eclampsia more than one disease? BJOG: An International Journal of Obstetrics & Gynaecology 2004;111:298-302.
3. Trogstad L, Magnus P, Moffett A and Stoltenberg C. The effect of recurrent miscarriage and infertility on the risk of pre-eclampsia. BJOG: An International Journal of Obstetrics & Gynaecology 2009;116:108-113.
4. NHS Choices. Your health, your choices. Pre-eclampsia. Introduction. http://www.nhs.uk/conditions/Pre-eclampsia/Pages/Introduction.aspx
5. Confidential Enquiry into Maternal and Child Health (CEMACH), Perinatal Mortality, 2007, June 2009. http://www.cmace.org.uk/getattachment/1d2c0ebc-d2aa-4131-98ed-56bf8269e529/Perinatal-Mortality-2007.aspx