Penn Medicine’s Michal Elovitz discusses detecting ‘messages’ in a mother’s blood from genes expressed by the baby and placenta, their potential to date pregnancies, and whether a simple blood test could provide clinicians more answers on who is at risk for spontaneous preterm birth.
Michal Elovitz is a professor of obstetrics and gynecology at the Perelman School of Medicine and director of the Maternal and Child Health Research Center. (Photo: Christian Peacock)
The field has moved closer to an answer, with work published this week in Science about a non-invasive blood test that can potentially determine gestational age and predict preterm delivery. Elovitz, a professor of obstetrics and gynecology at the Perelman School of Medicine and director of Penn’s Maternal and Child Health Research Center, contributed data to the research and conducted a scientific review of the just-released paper.
Penn Today spoke with Elovitz about biomarkers in the bloods known as cell-free RNA, the effect of these biomarkers on pregnancy, and their potential for helping predict women at risk for delivering early.
How do we typically determine a baby’s gestational age?
The most basic way is by a woman’s last period. For women with regular cycles, that is fairly accurate, but we also use early ultrasound. If you do an ultrasound in the first trimester, it’s usually accurate to within five days. If you do it in the second trimester, it can be in the range of two weeks, and in the third trimester, about three weeks. There is variation because of individual growth curves by population, by demographic, and for each woman based on her race, ethnicity, stature, and other factors.
How does the new blood test work?
Actually, this technology is not new, but it’s being applied now to obstetrics for the first time. Here, the team of researchers looked at what’s called cell-free RNA, which is like picking up gene expression from all different parts of the body. In this case, the study looked for cell-free RNA expressed from the placenta or fetus. Because this RNA “floats” around in the maternal blood, we can then detect—systemically in the mother—what might be happening to the pregnancy. We already know that the placenta releases particles into the bloodstream. At the most basic level, we also know that the baby and mom exchange blood because we can detect fetal DNA in maternal blood and we know mom’s immune system sees fetal DNA. So, it’s not a big leap to assume that as the fetus and placenta grow those genes being expressed would show up more or less in the maternal blood.
The paper in Science reports on two studies, one with a group of women whose pregnancies went full-term, another with those who delivered early. What did the researchers learn?
In the first study, they looked at 521 samples from 31 healthy women whose pregnancies went to term. The idea was to determine whether expression of certain genes (using cell-free RNA) goes along with gestational age and changes over time until delivery. They found there are about nine that correspond to that gestational time clock. The researchers then applied those same nine to preterm and found they didn’t work, which to me is one of the key findings of the study.
One question out there in the scientific community is whether spontaneous preterm birth is a malfunction of the gestational clock. In other words, everything that happens normally at 37, 38, 39 weeks for some reason gets turned on and happens too early, like at 28 weeks. What the researchers found, however, argues that that’s not what is happening. This study—understanding that more work and validation are needed—suggests that whatever is marking the clock of gestation for term delivery is not the same for women who ultimately have a spontaneous preterm birth.
But we still don’t know what causes that spontaneous preterm birth?
I’ve spent 18 years trying to figure it out. That’s why the research team did the second part of the study related to preterm delivery. They did find seven cell-free RNA associated with preterm birth, and these are not the ones associated with term delivery.
What happens if a pregnant woman has these seven biomarkers? What can be done?
We don’t have therapeutics right now because we still don’t fully understand preterm births. It’s not that nothing can be done. If you identify someone at risk, you can move her to an area where her infant can get the best care, so that’s important. Secondly, we do have one drug that changes outcome. If you really had a biomarker that accurately predicted who was at risk, you could use steroids to decrease morbidity and mortality for that newborn. So, you are not really changing the preterm birth risk, but you might be improving outcomes for once the baby is born. As far as a direct therapeutic to reduce risk of preterm delivery, we are not there yet, unfortunately.
Do you think that could eventually happen?
I hope so. I really hope so.
For that to be more of a reality, what needs to occur?
For this to make it to the clinical realm, it needs to be validated. It’s very interesting, it’s promising, but it must be validated in a much larger cohort, with more and well-characterized patients. That being said, it is interesting that you can pick up something systemically. Systemically, by most other measures, these moms who deliver early are fine. This technology enables us to ask not just what’s happening in the mother but what’s going on at the level of the reproductive tissues and at the fetus and the placenta. This is unique.
How does this fit into your overall research interests?
I do both translational and clinical research. My goal has been to first understand what may cause preterm birth, so we can then develop effective and precise therapeutic agents to reduce the outcomes. Our goal is not just to treat women in preterm labor, not just to improve the neonatal outcomes, but also to focus on preventing it from happening in the first place.
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