Scientists have developed an inexpensive blood test to predict a pregnant woman’s due date and possibly identify women who are at risk of giving birth prematurely.
The research, which is still preliminary and involved small numbers of women, was led by a prominent pioneer in the field of genetic blood testing, Stephen Quake at Stanford University, who said the test could eventually provide a low-cost method of gauging the gestational age of a developing fetus.
The test, which detects changes in RNA circulating in a pregnant women’s blood, estimated due dates within two weeks in nearly half the cases, making it as accurate as the current, more expensive method, ultrasound, and more accurate than guesses based on a woman’s last menstrual period.
Using a similar analysis of RNA in blood from eight women who delivered prematurely, the researchers were able to correctly classify six of their pregnancies as preterm. If much larger studies achieve comparable results, the test could become a tool to help prevent unnecessary induction of labor or Cesarean deliveries, and could possibly help save babies would have died because they were born too early.
Premature birth is the leading cause of newborn death in the United States. And 15 million babies a year are born prematurely around the world.
“I think it’s really a very exciting study that suggests an approach that may have a lot of potential for predicting preterm delivery,” said Dr. Louis Muglia, director of the Center for Prevention of Preterm Birth at Cincinnati Children’s Hospital Medical Center at the University of Cincinnati. “It can certainly help you understand where the baby is in maturity,” he said, which could aid doctors in gauging when to deliver babies of women who go into unexpected early labor.
In the study, published Thursday in the journal Science, the team, which was co-led by Dr. Mads Melbye, who runs the Statens Serum Institute in Denmark, analyzed the blood of 31 Danish women taken every week throughout their pregnancies, which were all full-term. The researchers studied genes linked to the placenta, the maternal immune system and the fetal liver, and found nine of those genes produce RNA signals that change distinctly as pregnancy progresses.
“RNA is what’s happening in the cells at any given moment,” said Dr. Quake, who is also co-president of the Chan Zuckerberg Biohub, which funded the study, along with the Bill and Melinda Gates Foundation and others. “We had this idea that we could make a molecular clock to see how these things change over time and it should allow you to measure gestational age and see where things are in pregnancy.”
Dr. Quake, who invented the first noninvasive prenatal blood test for Down syndrome, said the relevant genes for gestational age were in the placenta, and the test’s predictions were most reliable in the second and third trimester.
The researchers then applied the test to two groups of women at risk for preterm birth — patients at the University of Pennsylvania who had premature contractions and patients at the University of Alabama at Birmingham who had delivered prematurely in a previous pregnancy. The gestational age blood test did not do a great job of predicting which women would deliver prematurely, suggesting those particular genes “may not account for the various outlier physiological events that may lead to preterm birth,” the study said.
But in analyzing the blood of some of the women who delivered prematurely, the team identified seven other genes, mostly from the women, with RNA signals that seemed to characterize preterm birth. Dr. Quake said the team is developing plans for a large clinical trial in the general population.
Dr. Diana Bianchi, director of the Eunice Kennedy Shriver National Institute of Child Health and Human Development and an expert in prenatal genetic testing, said a trial should involve as much diversity as possible. She noted that the genes relevant for estimating gestational age were identified using healthy Caucasian Danish women with full-term pregnancies. The women in the preterm birth analysis were African-American, and they represented only two of many potential risk categories for premature delivery, which can also be caused by infection, inflammation, maternal stress and other factors, she said.
“The strength of the study is showing there are molecular milestones that are achieved by the fetus and by the placenta,” she said. And while the blood test is unlikely to replace ultrasound, which provides other important information, “I think it will add another dimension to identifying high-risk pregnancies.”
To Dr. Edith Cheng, a professor of maternal-fetal medicine and medical genetics at the University of Washington, the study’s real significance is that it “cracked the door a little bit into potentially finding out how a fetus talks to the mother, what makes a pregnancy go.”
It is almost as though the molecular message being sent by RNA “is a little bus that travels back and forth and is letting Mom know what’s going on,” Dr. Cheng said. “I bet you they’re going to find that the mother’s going to respond. There’s a conversation going on. That’s what’s cool.”