After being neglected for many years, adverse pregnancy outcomes such as pre-eclampsia and preterm birth are now the focus of a small group of researchers and companies that are aiming to fill a much-needed gap in the clinical testing market.
Around one in five women have some sort of pregnancy complication and of these, preterm birth and pre-eclampsia are the most common. While many women and their babies survive these complications, they can have a large impact in later life.
“With preterm birth there’s cognitive function impact through middle school and beyond for the babies, and for preeclampsia, Moms have a two-to-four-fold higher risk of cardiovascular disease and stroke throughout their lifetime,” Maneesh Jain, cofounder and CEO, of San Francisco based Mirvie, a company focused on developing tests for both these complications, told Inside Precision Medicine.
To try and better predict women at risk of these adverse outcomes, Jain and colleagues have developed blood tests that can detect RNA fragments in the blood that reflect whether or not a woman is likely to give birth too early or experience pre-eclampsia so that appropriate plans can be put in place that will help minimize later health problems for both mother and child.
In a study published in January this year, the company showed its pre-eclampsia test was more accurate than standard predictive tests at predicting who would develop the condition. Another study, published this week by co-founder Stephen Quake and colleagues, also evaluates this topic. This month the company also presented data at the Society for Maternal-Fetal Medicine 42nd Annual Pregnancy Meeting showing that their RNA platform can pick up 24 signals that predict early birth due to changes in cervical tissue and even 11 very specific signals that are linked to extreme preterm birth, which can be the most dangerous situation for the baby.
“I think where this research is very exciting, is that for the first time you’re doing two things, one is you’re able to effectively predict preterm birth months before the symptoms develop, the second is that we’re actually now able to look and reveal the underlying biology that’s causing some of these changes,” says Jain.
Notably, RNA fragments in the blood and not DNA is driving the tests developed by Mirvie. Jain explained that the constantly changing nature of pregnancy means that RNA fragments in the blood can paint a better picture of the state of the pregnancy than DNA which is more fixed.
Cell-free DNA blood testing has revolutionized both cancer testing, so-called ‘liquid biopsies’, and prenatal testing for fetal genetic conditions such as Down’s syndrome and other trisomies. However, Jain says it has historically had less predictive value for conditions such as pre-eclampsia.
“Pregnancy is probably the time of the most rapid development for humans and things are evolving very dramatically. So, what is causing that change? It’s actually the RNA messages are driving the change,” explains Jain.
“We found, at least for us, that that RNA because of its dynamic nature can really get to the underlying biology, whereas DNA is less likely to be able to do that.”
Mirvie are not the only ones focused aiming to better predict maternal outcomes. Some of the companies involved in this space, such as San Francisco-headquartered medical genetics company Invitae, which has both NIPT and carrier tests on the market, are also exploring how they can add maternal health testing to their prenatal testing portfolio.
Nathan Slotnick, an experienced obstetric geneticist now working as a medical advisor for Invitae, told Inside Precision Medicine: “One of the projects that I’m working on right now is trying to find out whether currently available prenatal pregnancy tests… can be used to identify patients at risk for other obstetric conditions, preterm labor, preeclampsia, or others issues to do with placentation.”
“If I can define a maternal cardiac risk, then I know that that patient will be followed more closely and can have a much better outcome, not just for the pregnancy, but also for the rest of her life.”
Mirvie is one of many companies in the medical diagnostics space that is using artificial intelligence, in this case machine learning, to help analyse the complex data collected by its platform.
Jain explained that as Mirvie are collecting information on how RNA expression changes during pregnancy across many thousands of genes, machine learning is very helpful to detect and record complex patterns.
“When you get to the scale of data that is tens of millions of data points, that’s when I think that tool becomes quite powerful because it truly is statistically, its powered to make a lot of sense out of that kind of data set and give you true predictive patterns and signatures.”
Recent developments in technology and knowledge seem to be driving these developments in an area of medicine that has long been neglected. “I think there’s definitely a rise in maternal health awareness,” agrees Jain.
“For one thing, I think we have one of the worst rates of maternal morbidity and mortality in the West in the US… I think that’s staggering. We have a great health inequity across underrepresented populations, that’s another big unmet need. I think there’s increasing awareness of that. I also think that we’re at a point in healthcare where I think consumers and women are taking more ownership of what’s important, and really pushing that a little bit more.”