Mira Moufarrej, bioengineering graduate student at Stanford University, talks about how a blood test could help determine how to treat a pregnancy earlier to avoid a preterm delivery.
OK. So first of all, let’s go with the stats again. How many preemies are born? What’s your chance of having a preemie?
MOUFARREJ: So there are 15 million babies born premature every year, and the risk of premature birth is that it is the highest cause of fetal death or infant death under the age of five, as well as complications later into life. In the US, African American women, unfortunately, have twice as high of a rate of having premature babies as white women. And I think the nuance here is that, when you’re a woman at high risk of preterm birth, that means that for every pregnancy you have a 50/50 chance. And so it causes a lot of anxiety when you’re thinking about, you know, you’re going to have a baby and you’re not sure if this baby is going to come at full term and be healthy or not, and you know that well in advance of ever having been pregnant.
And so what are some of the complications that could happen later in life?
MOUFARREJ: Yeah.
You think you make it, you’re two years old and you have lived…
MOUFARREJ: Yeah. Because the babies are born so early, often their lungs don’t have time to develop. And so later in life, sometimes they will have lung complications. Sometimes because other organs haven’t developed they have other complications, for instance, like cerebral palsy. Or just the quality of life deteriorates because babies were meant to develop in the womb until nine months. And in this case, they weren’t able to make it that far. And so a lot of why premature babies survive today is because we have these fabulous NIQs. But the NIQs can’t perfectly emulate what the human body does.
And so what is the definition of a preemie?
MOUFARREJ: It’s somewhat arbitrary, but full term is 37 weeks of gestation, which is very close to nine months. And if you are before 37 weeks, then you’re considered premature. But there are different gradations of that. If you’re very early, like 24 to 27 weeks, then your risk of – the baby’s risk of death, unfortunately, and complications into life significantly increases. So the longer the baby stays inside the womb, the less of a risk there is. But when we’re talking about premature birth, frequently we’re talking about these very early cases of 27 to 33 weeks gestation as opposed to 37 weeks gestation.
Then you were talking about the due date. Tell me – that’s a guess?
MOUFARREJ: Yeah. So when doctors estimate a due date, what they’re doing is they’re looking at how long the baby is in the first trimester and then they’re extrapolating – OK, the baby is this long right now, it’ll be X long if you have a full-term pregnancy with no complications. But they tend to be off. So it’s really a delivery date plus or minus two weeks – a delivery month. And the number of babies that are born on their actual due date is the same as the number of babies who would’ve been born on their actual due date randomly. And so, really, we’re not that good at predicting the exact date. We’re good at predicting around when a woman’s going to deliver absent of any complications. It’s more of an estimate of how long will it take the baby to develop to full-term and not of complications like preterm birth.
And how do they tell right now?
MOUFARREJ: Yeah, they use ultrasound to estimate in the first trimester how long the baby is. And they know that, in the first trimester, the relationship between the length of the baby now and due date is a linear relationship. Now, if you measure the baby in the second trimester or the third trimester, that’s not necessarily the case because, at that point, differences in humans come into play. So if the parents were shorter, then the baby may be shorter in the second trimester. Whereas in the first trimester you’re really just looking at fetal development. The organs are come – are being built, the baby’s getting longer, and so it’s much easier to predict how long the baby will be at birth – or, sorry, when a baby will be due based on length.
And so you have been part of the team that has developed a blood test. What makes that different?
MOUFARREJ: Yeah, so we developed two blood tests. The first one predicts gestational age similar to ultrasound – so when a baby will be due. But it does it in the second and the third trimester as opposed to the first. So for women who live far away from the clinic or women who don’t know they’re pregnant until later in life, this serves as a complement and a substitute whereas, in the past, there was no substitute to ultrasound. That was the only thing that could tell you anything about a baby. And the second is that ultrasound does not tell you about if there are going to be complications in a pregnancy. It just tells you, if the baby’s healthy, when they’ll be born. And so we were able to predict the risk of premature delivery in cohorts of high-risk women. And the really cool part is that these women came in with a 50/50 chance of every pregnancy of delivering preterm, and we were able to distinguish between the women who went on to deliver preterm of those who are at risk and the women who did not deliver preterm but were still at risk.
With how much accuracy?
MOUFARREJ: With about 80% accuracy. But these were small pilot studies, and so they need further validation and larger cohorts. Cohorts of asymptomatic women, women of different ethnicities and races than we had at present. But it was still an encouraging result.
And how does it tell?
MOUFARREJ: It looks at seven molecules that you can measure in blood. These are a specific type of molecule. So in the past, people have found that you can look at DNA, which is, like, a blueprint molecule, to predict – to see if a child has Down syndrome very early on in pregnancy. And this was great because you didn’t have to stick a needle into the womb and do an amniocentesis. But that molecule DNA is just like a blueprint of a house, it doesn’t tell you about dynamics. We look at another molecule, RNA, which tells you more about what’s going on in the process of building a baby and what might go wrong. It’s more about, you know, like, ordering parts for a house or something like that. And so looking at seven of those specific RNA types of molecules, they’re higher in women who deliver preterm than full-term, and so together they tell you about a woman’s risk of delivering preterm.
And what can it tell you about that preterm?
MOUFARREJ: It basically tells you up to two months in advance of delivery that this woman is very likely to, yes, deliver preterm. Other tests right now are very good at telling you, no, a woman will not deliver preterm. But if you think about what you want in the future, unfortunately, right now there aren’t very many treatments for preterm birth. You would want something that can tell you, yes, this woman is going to deliver preterm and now we can give her this treatment in order to prevent that from happening. Whereas at the moment, all we can say is we know for sure this woman is not going to deliver preterm.
And is this is what this blood test will hopefully do in the future is be able to say, OK, this is what this woman needs to not be preterm?
MOUFARREJ: What the blood test currently does is it tells you, yes, a woman will deliver preterm within two months of when she took the blood test. And what we hope is that it will get paired with a treatment and then you can prevent the preterm birth from happening.
But right now, there are no treatments.
MOUFARREJ: There are a few. They don’t work very well.
- What would those be?
MOUFARREJ: You can do progesterone injections during pregnancy. And then if a woman has a short cervix, then there’s – I think it’s called, like, cervical cerclage that you can do. But both of those are – there’s a narrow group of women that fit that scope and who deliver preterm, and they haven’t been shown to be that effective.
So what?
MOUFARREJ: So currently you can have…
0:07:13:>>INTERVIEWER: Taking your doctor this question.
MOUFARREJ: …Yeah. Yeah, exactly. So I think when people think about the tools that an obstetrician has right now to look at a pregnancy, it’s ultrasound and that’s it. You can tell a woman, if everything goes well in your pregnancy, then hopefully in nine months you’ll deliver at this state and that’s what you know. And you come back and you check in and you see, baby still looks OK, no malfunctions that we can see, but not much else. So this tool is another tool in the obstetrician’s tool kit where they can not only look and say, well, the baby looks OK, but what about those things you can’t see? What about the things like preterm delivery? Or if an organ internally isn’t developing properly? Hopefully in the future you’d be able to predict that too. And so this is one step on the way of thinking about, how can you help an obstetrician do their job best and what information can you give them so that they can better help a mom and a baby reach a healthy pregnancy and, hopefully, the baby is healthy when they’re delivered.
And will this help predict a more accurate due date?
MOUFARREJ: Yes.
Like to the day?
MOUFARREJ: At the moment, it’s comparable to ultrasound. So it’s still that delivery month. But there are studies going on right now to validate the test and hopefully improve its accuracy as well.
And what would your hopes be to get that down to? Like, due week instead of due month?
MOUFARREJ: Yeah, I think that there are hope – I’m currently not working on this. There is a startup working on it named Mirvy, and their hope is to get it down to the week or a couple of days even.
So, what’s next?
MOUFARREJ: So let’s see. Well, first you’d have to validate the tests in larger studies – in larger cohorts of women. So the tests that I described were largely done in groups of African American and Caucasian women. And the women who were preterm were very symptomatic of preterm delivery. So sometimes women don’t have any symptoms – imagine it’s her first pregnancy and then she delivers preterm. Can you predict it for those women as well? And in the future as well, developing treatments for these things – figuring out why women deliver preterm. Currently, we don’t know why they deliver preterm. So can you go from these molecules that correlate with preterm delivery to figuring out why this is happening and then developing a treatment?
So, this may be a silly question, but since you’re taking the mother’s blood and you’re testing that, is it in the mother’s blood before there’s even a baby that those seven molecules are there?
MOUFARREJ: Oh. Yeah. We think it’s associated with pregnancy, but we don’t exactly know whether it’s the mom or the baby right now. There are hypotheses that it may be something in the mom that leads to more preterm delivery, but we don’t know is the answer. But these molecules do have – if you look at them in a different way, you may be able to get an indication of where the signal is coming from. Is it mom or baby and what tissue is there? The present data we had didn’t allow us to do that. But in the future, we hope to collect data that will and use those techniques.
Anything I’m missing?
MOUFARREJ: No. Basically, the goal is to get healthier moms and healthier babies, and these are two tests that get you a little further on the way there.
Interview conducted by Ivanhoe Broadcast News.
END OF INTERVIEW
This information is intended for additional research purposes only. It is not to be used as a prescription or advice from Ivanhoe Broadcast News, Inc. or any medical professional interviewed. Ivanhoe Broadcast News, Inc. assumes no responsibility for the depth or accuracy of physician statements. Procedures or medicines apply to different people and medical factors; always consult your physician on medical matters.
If you would like more information, please contact:
Samantha Beal
650-498-7056
Sign up for a free weekly e-mail on Medical Breakthroughs called First to Know by clicking here
