New blood test could make preeclampsia easier to predict, early study suggests
A blood test given as early as the end of the first trimester of pregnancy could help identify patients at the highest risk of preeclampsia, a potentially life-threatening condition associated with high blood pressure in pregnancy, before it occurs.
Preeclampsia dramatically raises the odds of stillbirth and preterm birth, as well as of maternal organ damage, seizures and death. There is currently no cure for preeclampsia, which can occur from 20 weeks of pregnancy to up to six weeks postpartum, and once it’s developed, delivery is the only way to prevent the worst outcomes.
Patients at high risk of the disease can lower their chance of preeclampsia by taking low-dose aspirin starting between 12 and 16 weeks of pregnancy — so by the end of the first trimester or early in the second. Doctors can predict a patient’s risk level from their medical history; having kidney disease or a history of preeclampsia raises one’s risk, for example. But reviewing only medical history can leave some at-risk patients out, meaning not all patients that need preventative aspirin are advised to take it. So some countries now do additional tests to improve doctors’ risk predictions, having them assess certain proteins in the blood and blow flow to the uterus.
However, some of these screening tests are tricky to administer or aren’t routinely given in early pregnancy, said Bernard Thienpont, head of the Laboratory for Functional Epigenetics at KU Leuven in Belgium and senior author of new research describing the blood test.
“Depending on which measures you use, you end up with different accuracy,” in terms of how many patients are accurately flagged as high risk, Thienpont told Live Science. So Thienpont and his team set out to develop a new, easy-to-give test to add to the arsenal.
“We don’t see it as something that should be applied independent of all the other tests, but more as an add-on,” he said of the new blood test, which was described in a report published Monday (Aug. 28) in the journal Nature Medicine.
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The test looks at DNA floating in the blood during pregnancy. Doctors already collect this DNA to run noninvasive prenatal screenings, the tests used to see if a fetus likely has extra or missing chromosomes.
This free-floating DNA comes from dying cells in the body, and if you’re pregnant, a fraction comes from the placenta, which is why it’s useful for prenatal screening, Thienpont explained. This could also make the DNA useful for preeclampsia screening, Thienpont’s team thought, given evidence that the condition may stem from problems with the placenta.
Preeclampsia has been linked to poor blood flow, and thus low oxygen levels, in the placenta. And in other diseases, when tissues lack oxygen, their cells can show epigenetic changes, meaning changes in the chemical tags that sit “on top of” DNA. These chemical tags include methyl groups, or molecules that latch onto genes and thus control whether they’re switched “on” or “off.”
Researchers have previously examined placentas after birth and found big differences in methylation between preeclamptic and healthy pregnancies, Thienpont said. His team wanted to see if those differences could be spotted before birth.
They analyzed this cell-free DNA previously collected from nearly 500 pregnant women and stored. About one-third of the women included in the study had developed early-onset preeclampsia, which develops before week 34 of pregnancy. Both at the time of their diagnosis and weeks earlier, preeclamptic women had different patterns of DNA methylation than the control group, and these differences were linked to cell-free DNA from the placenta, rather than from other cell types.
Affected genes included those that help cells of the placenta develop and mature, said Tu’uhevaha Kaitu’u-Lino, a professor and co-lead of the Translational Obstetrics Group at the University of Melbourne in Australia. So the work may give clues as to reasons why preeclampsia can occur, she told Live Science in an email.
This is only a theory, but “what we think is happening is that there is a delay in the development of the placenta in preeclamptic women,” Thienpont said.
Using the DNA data, the team developed a model to predict patients’ risk of preeclampsia based on free-floating DNA sampled at or after 12 weeks.
Tested on its own, the model identified 38% of patients who went on to develop preeclampsia while giving few false-positive results. That number jumped to 57% when the model was combined with maternal risk factors, such as having a family history of preeclampsia, and leapt to 72% when the team allowed for slightly more false-positive results. (The maternal risk factors, alone, captured only about 30% of the high-risk patients.)
“It may improve if additional variables are included,” Kaitu’u-Lino said, “such as some of the variables included in the Fetal Medicine Foundation test.” The first-trimester test, used in the U.K. and Australia, accounts for many risk factors and predicts preeclampsia risk with 75% accuracy with few false positives, but it’s fairly involved and requires a special ultrasound, Kaitu’u-Lino and colleagues wrote in a commentary.
Thienpont’s team is now interested in combining the new blood test with more metrics, to boost its predictive power.
“But the huge potential is that this paper identifies a convincing link between a novel measurement, and a poor pregnancy outcome,” she said. “It opens the door for a new horizon of clinical biomarker discovery.”
