Californian biotech firm Mirvie is pioneering a new approach to high risk pregnancies, by tracking a unique molecular signal associated with a leading cause of stillbirth. 

Its new platform – based on RNA, the nucleic acid present in all living cells – is the first to uncover the molecular signal for babies that are at risk of severe foetal growth restriction.

The RNA platform assesses maternal blood at 18 to 22 weeks to predict adverse pregnancy outcomes. It is able to identify high-risk pregnancies by analysing cell-free RNA, which can indicate placental and foetal health, potentially enabling early care interventions for better pregnancy outcomes.

Mirvie aims to personalise maternal care and integrate the platform into clinical practice, exploring targeted therapies based on RNA insights. Femtech World spoke to Dr. Thomas McElrath, vice president of clinical development, to find out more.

“We’ve never really had the ability to risk stratify patients for adverse outcomes in the third trimester, but this platform helps fill that gap,” says McElrath.

“As a clinician with nearly 30 years of experience, what I was taught – and what has been standard practice – is to assess someone’s risk based on their history.

“For instance, prior preterm delivery is considered a marker for high-risk pregnancy in subsequent pregnancies. However, this approach isn’t helpful for patients who haven’t experienced such problems or for those in their first pregnancy.

“This is where Mirvie’s platform comes in. It’s a blood test that identifies patterns of gene expression from the fetus, placenta, and mother. These patterns follow a highly regulated and normal progression throughout pregnancy.”

Drawing on the largest molecular study of pregnancy completed to date, researchers examined more than 5,000 geographically and demographically diverse pregnancies.

Analysing millions of maternal, foetal, and placental RNA messages using the Mirvie RNA platform, the technology was able to distinctly predict babies born with severe forms of growth restriction.

“Knowing what normal progression looks like allows us to identify deviations, enabling predictions about higher-risk outcomes.

“For example, we’ve already developed a test to predict a higher risk of preeclampsia. Our most recent test, focuses on predicting the risk of small-for-gestational-age infants. That’s the broad overview of the work we’re doing.”

Using the platform, researchers were able to successfully predict 60 per cent of babies with severe foetal growth restriction months in advance of delivery.

The Mirvie RNA platform found that severe growth restriction has a unique RNA signature independent of preeclampsia, chronic hypertension, and gestational diabetes, all of which can impact foetal growth.

McElrath says: “The key point here is that we believe we’re honing in on the pregnancies where the babies are unwell. These are babies more likely to have complications – we’re identifying 60 per cent, suggesting we’re likely detecting pregnancies where there’s already an underlying issue.

“That issue seems to lie in the functioning of the placenta. Whether it’s related to the maternal vascular supply to the placenta, an internal metabolic process within the placenta, another biochemical issue, or even something at the cellular level – that’s where the crux of the problem appears to be.

“We’re picking up signals of these issues, but there’s still much to uncover. Our next steps will involve determining exactly what’s going on. Is the issue coming from the baby itself? Is it the placenta? Or is it the maternal vascular supply? These are questions for future research.

“What we do know is that these are pregnancies that require closer monitoring. At around 18 to 20 weeks, we’re obtaining this critical information. By that stage, we’ve already performed an ultrasound to assess the baby’s size, yet we’re able to identify pregnancies that will benefit from additional follow-up in the third trimester.

“These are the ones who may need an extra couple of visits, because they’re at greater risk of having small babies – and such cases are at a significantly increased risk of stillbirth, which is devastating for any family.

“If we can use this information to identify and monitor potentially risky pregnancies before an adverse outcome occurs, it’s a win for everyone involved.”

McElrath believes that one of the challenges in obstetrics is that, historically, it has defined diseases in patients based on how they present when they walk into the clinic.

“Our definitions have been shaped by the condition at its end stage – rupture of membranes, hypertension and preeclampsia, preterm labour. We haven’t focused on defining diseases by what happens earlier in pregnancy,” he says.

“This is unlike the rest of medicine. For instance, if you’re at risk of a heart attack, we can identify high cholesterol or arterial plaques. If you’re at risk of a stroke, we can pinpoint hypercoagulability and similar factors. Most other fields of medicine work from understanding the pathology as it progresses towards the event. In obstetrics, we’ve been working backwards from the event itself.

“The advantage of this technology is that it starts to unravel those biological pathways that lead to clinical outcomes. It allows us to identify, for example, whether a baby is small due to a placental issue or a metabolic problem. We can begin to tease apart these causes, because treating every patient with the same approach isn’t as effective.

“If we can be more specific about what one patient needs compared to another, we’ll achieve far better outcomes. This is the direction obstetrics needs to move in if we want to make significant progress in improving pregnancy and maternal-foetal outcomes.”

Initially being launched in the US, Mirvie has also collaborated with research sites in the UK in order to make the platform available to all mothers everywhere as soon as possible.

“Our next initiative is to organise rollouts into various clinical settings,” says McElrath.

“We’ve received a great deal of positive feedback from clinician groups we’ve spoken to, including figures like the surgeon general for California and other public health leaders across parts of the US. They’ve shown interest in this because resources are limited – if you only have so much in your budget for maternal care, you need to know who needs it most.

“We’re seeing encouraging responses at the institutional level and are now at the stage where the platform will be introduced into a few clinical practices.”

The research is being presented at the Society for Maternal-Fetal Medicine annual meeting.