Mira Moufarrej, a Bioengineering PhD Student at Stanford University talks about a blood test that may be able to predict premature births.
Interview conducted by Ivanhoe Broadcast News in September 2019.
What’s your chance of having a preemie?
MOUFARREJ: There are 15 million babies born premature every year, and the risk of premature birth is the highest cause of fetal death or infant death under the age of five – as well as complications later into life. In the U.S., 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 when you’re a woman at high-risk of preterm birth, that means for every pregnancy you have a 50/50 chance. It causes a lot of anxiety when you’re thinking about having 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.
What are some of the complications that could happen later in life?
MOUFARREJ: 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 like cerebral palsy, or just the quality of life deteriorates because babies were meant to develop in the womb until nine months. So, a lot of why premature babies survive today is because we have these fabulous NICUs, but the NICUs can’t perfectly emulate what the human body does.
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. If you are before 37 weeks, then you are considered premature. However, there are different gradations of that. If you’re very early, like 24 to 27 weeks, then the baby’s risk of death unfortunately and complications into life significantly increases. The longer the baby stays inside the womb, the less of a risk there is. 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.
Tell me about the due date. Is that a guess?
MOUFARREJ: Yes. When doctors estimate a due date, what they’re doing is looking at how long the baby is in the first trimester and then they’re extrapolating. It’ll be X long if you have a full-term pregnancy with no complications. But they tend to be off. It’s really a delivery date plus or minus two weeks. The number of babies that are born on their actual due date is the same as the number of babies who would have been born on their actual due date randomly. 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 it will take the baby to develop to full-term and not have complications like preterm birth.
How do they tell right now?
MOUFARREJ: They use ultrasound to estimate in the first trimester how long the baby is. They know that in the first trimester the relationship between the length of the baby 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. If the parents were shorter, then the baby maybe shorter in the second trimester whereas in the first trimester you’re just looking at fetal development. The organs are being built and the baby’s getting longer, so it’s much easier to predict when a baby will be due, based on length.
You have been part of the team that has developed a blood test. What makes that different?
MOUFARREJ: We have developed two blood tests. The first one predicts gestational age like ultrasound, so when a baby will be due, but does it in the second and the third trimester as opposed to the first. For women who live far away from the clinic or women who don’t know they’re pregnant until later in their pregnancy, this serves as a complement and a substitute whereas in the past there was no substitute to ultrasound. The second is that ultrasound does not tell you if there are going to be complications in a pregnancy. It just tells you if the baby’s healthy and when they’ll be born. We were able to predict the risk of premature delivery in cohorts of high-risk women. The cool part is that these women came in with a 50/50 chance of every pregnancy of delivering preterm. We were able to distinguish between the women who went on to deliver preterm and the women who did not deliver preterm but were still at risk.
And, with how much accuracy?
MOUFARREJ: With about 80% accuracy. But these were small pilot studies and so they need further validation and larger cohorts of asymptomatic women of different ethnicities and races than we had at present. But it was still an encouraging result.
How does it tell?
MOUFARREJ: It looks at seven molecules that you can measure in blood. These are a specific type of molecule. In the past, people have found that you can look at DNA which is like a blueprint molecule to predict 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. 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. So, looking at seven of those specific RNA types of molecules, they’re higher in women who deliver preterm than full-term and together they tell you about a woman’s risk of delivering preterm.
What can it tell you about that?
MOUFARREJ: It tells you up to two months in advance of delivery that this woman is very likely to deliver preterm. 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 now all we can say is we know for sure this woman is not going to deliver preterm.
What are current treatments?
MOUFARREJ: You can do progesterone injections during pregnancy. And then if a woman has a short cervix, there is something called a cervical cerclage that you can do. But, there’s a narrow group of women that fit that scope and who deliver preterm, and the treatments haven’t been shown to be that effective.
So, what’s next?
MOUFARREJ: First you’d have to validate the tests in larger cohorts of women. 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. 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, we would want to develop treatments for these risks and to do so, we have figure 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?
Since you’re taking the mother’s blood and testing that, are the seven molecules in the mother’s blood before there’s even a baby?
MOUFARREJ: 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. If you look at these molecules 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.
Is there 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.
END OF INTERVIEW
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