Blood test suggests preeclampsia risk using RNA

Preeclampsia can lead to many pregnancy complications including death, but it can be hard to detect early in gestation. A new blood test could help doctors identify those at risk of developing the condition months before symptoms start.

“We can narrow it down to about 1 in 4 pregnancies that are truly at high risk, and that’s a big step,” says Maneesh Jain at Mirvie, a California-based health start-up.

Preeclampsia is a type of hypertensive disorder of pregnancy (HDP) that occurs when something – scientists aren’t sure precisely what – goes awry during the placenta’s development. This leads to high blood pressure, which can cause cardiovascular disease, organ damage, seizures and even death. It can also harm the developing fetus.

Catching preeclampsia and other HDPs can be difficult, however, because symptoms usually don’t show up until at least 20 weeks into pregnancy. Sometimes, the signs go undetected until labour. And monitoring placental development is tough because taking a tissue sample from the organ is extremely invasive.

The new blood test is relatively non-invasive, and uses RNA markers to predict whether someone is likely to develop an HDP. Specifically, the test focuses on certain genes, including PAPPA2 and CD163, the overexpression of which has previously been linked to HDPs. The researchers wanted to see whether they could detect this overexpression in blood samples.

Their validation study of more than 9000 pregnant people suggests they can: Jain says the test was able to determine with over 99 per cent accuracy whether or not someone without pre-existing risk factors overexpressed the genes and was therefore at high risk of preeclampsia or another HDP. Roughly one-quarter of the participants without pre-existing HDP risk factors overexpressed the genes.

People in certain demographics – for example, those with pre-existing high blood pressure or a family history of preeclampsia – are known to have a moderately higher risk of developing the condition, says Morten Rasmussen at Mirvie. But for many, it comes seemingly out of the blue.

Once someone knows they are at high risk of preeclampsia, they can take action to prevent it. Common interventions include taking drugs like aspirin, switching to a Mediterranean diet and monitoring blood pressure daily.

However, the new test only looked at people who were between 17.5 weeks and 22 weeks into pregnancy. “Ideally, aspirin has to be started prior to 16 weeks,” says Kathryn Gray at the University of Washington in Seattle. “So we’ve missed that window already by the time most people would be getting the results of this test.”

Mirvie plans to make the blood test commercially available soon. Once it is on the market, the team hopes other scientists will use it to develop drugs specifically targeted to the expression of genes like PAPPA2. Such molecular pinpointing “gives a much better chance for the treatment to show effect”, says Rasmussen.

Gray would also like to see researchers use Mirvie’s bank of RNA data to further nail down the genes behind preeclampsia risk for specific people. Narrowing the search profile could help lower the cost of the test, making it affordable for more people, she says.