Most babies are not born on time. Only about 5 percent of newborns make their first appearance on their scheduled due date, according to some estimates. The rest debut in the days or weeks surrounding the much-anticipated event, setting the stage for a lifetime of surprises.
Doctors typically predict when an expectant mother will go into labor by asking her to recall the first day of her last period and adding 280 days. That rough calculation can then be improved with a first trimester ultrasound scan. A trained specialist will approximate fetal age by measuring the short distance from the top of the fetus’s head to the bottom of its rump. Yet this gold-standard imaging test is only accurate about 48 percent of the time. When ultrasounds are done in later months of pregnancy—when many women actually receive their initial prenatal care—the projected due date is even less accurate. Fetal growth is less uniform as time goes on, which makes gauging age difficult.
Tantalizing findings from an international research team are now providing hope that a blood test could one day be swapped in to predict due dates, offering roughly the same accuracy as the first trimester ultrasound—but in later trimesters and at a much lower price. One of the lead scientists behind this new offering, Stanford University biophysicist Stephen Quake, is also responsible for the decade-old prenatal blood test for Down syndrome now routinely used by obstetricians in place of amniocentesis (a much more invasive test that requires samples of fluid from the uterus). His team says looking to mom’s blood, in addition to forecasting baby due dates, is promising for another reason: Pilot testing with a small number of women suggests blood analysis may also detect if a mother is at risk of giving birth to a premature baby (one born before 37 weeks in the womb).
The two new experimental tests require about a teaspoonful of maternal blood extracted from a mother’s arm. That blood bears free-floating fragments of genetic material (RNA) from the fetus, mother and placenta, which can provide a glimpse into fetal development. These cellular snippets tell scientists which genes are turned on, suggesting the fetus has reached specific stages of maturation. Picking up on those key points in fetal life can essentially tell scientists “when someone is ready to pull the rip cord and get out of there,” says Quake, who co-led the recent study with colleagues from Stanford and the State Serum Institute in Copenhagen, along with the universities of Pennsylvania and Alabama. “What we’ve done is a proof of principle,” he notes. “The next step will be doing this in a large, blinded clinical trial with a larger number of women to validate it. I am hoping we can get that done in two years,” he adds.
To make these new experimental blood tests, the Quake team identified and zeroed in on the activity levels of specific genes in the fetus or its placenta. They pinpointed seven genes that appear to be correlated with preterm labor risk, and nine linked with gestational age. Their findings were published this week in Science.
This is only the early days for these blood tests, Quake notes. His team’s pilot preterm labor testing was only done on pregnant women who were already known to be at high risk of this hazard—either due to prior preterm births or premature contractions, which are two of the most common causes. In that known risk group the scientists’ test was able to forecast who would have premature births up to two months in advance with up to 80 percent accuracy—much better than any current tests. That rosy figure, however, was based on a round of testing with only five women. Follow-up tests also misclassified three of 18 full-term samples as premature. If the findings can be replicated in a large clinical trial that includes women not known to be at risk, it could be a huge boon for prenatal care.
Sarah Stock, a maternal and fetal health care specialist at the University of Edinburgh in Scotland who was not involved in the work, called the prospect of the preterm tests exciting. “Most research we do is on women who have had a previous preterm birth because that is such a big risk, but the majority of women who are preterm are in their first pregnancy…so that’s where a test like this may be really helpful.” A test like this may not pick up all preterm labor cases, but it would be a valuable start, Stock says.
This experimental test does not pinpoint the exact date a preterm birth will occur—it merely tells doctors the risk of preterm birth exists. But armed with that information, Stock says, a care team could then target further care to those women including advising them give birth in a facility with more specialized resources or planning to have additional medications on hand to help the preemie.
Ashley Roman, director of the Division of Maternal Fetal Medicine at N.Y.U. Langone Health, who was also not part of the study, says the blood test for gestational aging could be a great asset for patients around the world who do not have access to pricey ultrasounds and trained specialists. But Roman says this offering would also be extremely valuable in the U.S. The best way to date a pregnancy is during the first trimester using a transvaginal ultrasound, not an abdominal ultrasound, she notes—but not every U.S. facility has the former equipment. “This is promising research,” she says. “The main concern is that this is all preliminary work and this is certainly not a test that is ready to go to market—I look forward to seeing more from these authors.”
Quake says he was drawn to this area of research because years ago his own daughter was born almost a month early. “It really sensitized me that this is such an important thing to work on,” he says. This research, he says, “marks the beginning of what we hope will be an exciting chapter in this area.”