Q&A: RNA platform predicts severe fetal growth restriction months before birth

Key takeaways:

• Severe fetal growth restriction during pregnancy is the largest risk factor for stillbirth.
• The platform identified a molecular signature independent of other risk factors.

An RNA platform successfully predicted fetal growth restriction within the second trimester of pregnancy, independent of other risk factors, according to a presentation at The Pregnancy Meeting.

“Using Mirvie’s unique RNA platform is starting to expedite the amount of conditions we can identify very early in the pregnancy to help identify those at most risk,” Kara Rood, MD, maternal-fetal medicine specialist and clinical associate professor of obstetrics and gynecology at Ohio State University Wexner Medical Center, told Healio. “It is a critical tool for OB/GYNs to help predict these pregnancy complications and, hopefully, with that in combination with health care professionals and patients, we can shift how care is delivered, hopefully resulting in fewer stillbirths and healthier lives for moms and for babies.”

Rood and colleagues evaluated more than 5,000 geographically and demographically diverse pregnancies and assessed millions of maternal, fetal and placental RNA messages using Mirvie’s RNA platform. Overall, researchers successfully predicted 60% of pregnancies with severe fetal growth restriction at 18 to 22 weeks’ gestation and the RNA platform identified a unique RNA signature independent of preeclampsia, chronic hypertension and gestational diabetes.

Healio spoke with Rood about her presentation, the RNA platform used, and what these findings mean for physicians and pregnant women.

Healio: How common is fetal growth restriction and what can the consequences be on the infant’s health?

Rood: Fetal growth restriction complicates a significant proportion of pregnancies ranging from 8% to 10% in term pregnancies and upward of even higher from 20% to 25% in some of our preterm deliveries. The reason we care about it so much is because it can have a significant increase for some of the adverse pregnancy outcomes. The one that we worry the most about, and the dreaded one, is stillbirth. But also, there can be significant early childhood, and even later childhood, adverse outcomes that are affected from inside the uterine environment. This affects long-term and as well as short-term health outcomes for the baby.

Healio: Could you summarize the RNA platform used in this research?

Rood: Mirvie’s RNA platform is very innovative and quite novel. It’s one of those things that is starting to become more of a main thought process of personalizing patient care. It’s been studied historically in cancer and some other medical conditions, but really the platform here that we’re talking about is really unlocking the biology of pregnancy. We’ve already used this in preeclampsia and spontaneous preterm birth, and now we’re starting to tackle severe fetal growth restriction as well. From a single blood sample, we’re able to generate significant information from the cell-free RNA that can come from mom, the fetus and the placenta. There are specific molecular structures and signaling that comes from that RNA that, when we look into our large database, can help predict things like preeclampsia, preterm birth and now severe growth restriction.

Healio: Could you discuss the molecular signature identified with the RNA platform and what it means for physicians?

Rood: When we talk about unique molecular signature, and what is important for our research, it was not ones that are dependent on preeclampsia and some of those maternal risk factors for babies being small. It stood alone as a predictive tool. So, we have something that we can analyze and give a result in quick turnaround time to say, “Your pregnancy is at a higher risk for your baby being significantly small,” and we know that significantly small babies have a higher risk for stillbirth. We can employ some of our testing, more frequent ultrasound evaluation and monitoring of the baby, and we can even alter the timing of delivery to try to decrease the chances of stillbirth and decrease the chances of some of those other short- and long-term complications.

Most of the time it’s not something that the mom has done or hasn’t done that results in fetal growth restriction. But we do know that surveillance really is the big thing to decrease chances of stillbirth, because then we can start to see subtle changes. Surveillance isn’t something we do in every pregnancy due to the increased amount of testing, the cost associated with the increased testing and there’s always that chance of a false positive, meaning that that testing tells us something, and then we deliver a baby that really wasn’t at that high risk. Giving more concrete prediction tools, like Mirvie’s RNA platform, early in pregnancy allows us to start early to try to prevent bad things from happening, but also to prevent unnecessary interventions for somebody who isn’t at high risk.

Healio: What further research is needed in this area?

Rood: In true fashion, when we figure one thing out, there are 25 other questions that ensue from that first initial question.

Being able to further classify exactly which person is at the highest risk to make sure that we’re able to provide them the targeted testing and the targeted screening and care plan is the next best step. Another step is to make this test something that would be available to help health care professionals and pregnant women know the risks and adjust accordingly, especially since it’s one of these things that we can identify so much earlier in the pregnancy than some other tests for other medical conditions that happen much later in pregnancy.

For more information:

Kara Rood, MD, can be reached at kara.rood@osumc.edu.

Reference:

• Rood K. Prediction of severely small-for-gestational-age infants using a novel cell-free RNA model. Presented at: The Pregnancy Meeting; Jan. 27-Feb. 1, 2025; Denver.