PEACHES: finding out how existing high blood pressure can cause pregnancy complications

Dr Kate Bramham, Dr Carolyn Gill, Mr Paul Seed, Professor Neil Dalton, Professor Fiona Broughton Pipkin, Professor Hannele Laivouri

Scientists are working to find out how chronic hypertension – high blood pressure before becoming pregnant – can make pregnancy more risky.

Women who have high blood pressure before getting pregnant are more at risk of pre-eclampsia, early birth, and giving birth to babies that are too small. At the moment, we don’t know much about why this happens. However, it is vital to try and find out. Constant high blood pressure, or chronic hypertension, is one of the most common chronic problems in women around the age they might have children (chronic illnesses are ones which exist for a long time, or keep coming back). Knowing how and why this can affect pregnancy can help us make sure that as many babies as possible are born healthy and without complications.  

Tommy’s researchers have carried out a study looking at the function of the placenta, kidneys, heart, and the lining of the blood vessels in pregnant women with pre-existing high blood pressure. They compared the results to healthy women, to look for signs that could tell us when and why high blood pressure can lead to complications. So far, they have found that women with pre-existing high blood pressure who went on to get pre-eclampsia have changes in kidney function and lower levels of a substance found in the placenta, called placental growth factor. They also make less of the protective layer that grows inside blood vessels.

High blood pressure and the kidneys

During normal pregnancy, the kidneys respond to the presence of the baby. In particular, they make sure that sodium is kept at the right level in the body. Sodium helps us control the amount of water in our blood and cells, and is also important for nerve and muscle cells to work properly. We already know that the kidneys of people with high blood pressure don’t work the same way. Scientists think that in pregnant women, this might be one of the reasons some women go on to get pre-eclampsia. We are currently looking at particular substances in the kidney to see whether they can give us clues about what is going wrong.

So far, working together with the Bill and Melinda Gates Foundation’s 'Pregnancy CoLaboratory,' researchers have found that pregnant women with existing high blood pressure had a much higher 'creatinine clearance' than those that didn’t.

Creatinine is made by muscle cells, and is one of the waste products the kidneys remove from our blood. The higher a person’s creatinine clearance, the more of this product the kidneys are taking out of the blood every minute. This means that the kidneys are filtering the blood more than normal: a condition known as hyperfiltration.

In women who developed superimposed pre-eclampsia – pre-eclampsia in women with chronic hypertension – creatinine clearance and levels of placental growth factor went down again before pre-eclampsia began. The levels of these substances could one day be used to tell whether a woman is likely to get pre-eclampsia, so we can act earlier to give the baby the best chance of survival.

High blood pressure and blood Vessels

Scientists have also found that women with pre-existing high blood pressure make less of a special layer inside our blood vessels that protects them from damage. They now plan to look at the effects of losing this layer in women with pre-eclampsia, using a new imaging technique. This will allow them to measure thickness directly in very small blood vessels. If a thinner protective layer causes complications, then we can try and develop a treatment to restore the layer, or stop it from thinning in the first place.

Researchers have also found that in women with kidney disease, there is an increase in proteins released from this protective layer of blood vessels. Plus, women who develop pre-eclampsia have an increase in proteins in the urine compared to women who do not go on to develop the condition.

Researchers have now examined protein samples in large numbers of women with kidney disease and high blood pressure in pregnancy. The next step is to assess how they can use these findings to help with diagnosis and management in the future.

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This study takes place in a Tommy's centre and is funded by Tommy's and the National Institute for Health Research's Clinical Research Network

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