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UCSF, Iowa Team Develops Proteomic Test for Preterm Birth

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NEW YORK (GenomeWeb) – A team led by researchers at the University of California, San Francisco and the University of Iowa has developed a proteomic test for predicting pregnant women's risk of preterm birth and preeclampsia.

In a study published this week in the Journal of Perinatology, the test identified roughly 80 percent of women who would go on to have a preterm delivery and more than 88 percent of women who would have a preterm delivery and develop preeclampsia.

The test performed particularly well in women who developed preeclampsia and delivered before 32 weeks, identifying more than 95 percent of these patients. This is an especially high-risk group of patients, said Laura Jelliffe-Pawlowski, first author on the study and director of Precision Health and Discovery with the UCSF California Preterm Birth Initiative. "These are women and babies at a huge risk, where we see really high rates of mortality in both the mom and baby around the world."

Several companies have either launched or are developing proteomic tests for preterm birth. For instance, Sera Prognostics last year launched sales of its PreTRM test through Laboratory Corporation of America. That test uses multiple-reaction monitoring mass spec to measure two proteins, insulin-like growth factors binding protein 4 (IBP4) and sex-hormone binding globulin (SHBG), to provide a percent risk of preterm birth along with a comparison of individual risk to that of the general population. The test is given at 19 weeks gestation and in validation studies has predicted preterm birth with a sensitivity and specificity of around 80 percent.

Louisville, Kentucky-based NX Prenatal is developing a proteomic preterm birth test that uses multiple-reaction monitoring mass spec to measure exosome-bound proteins linked to preterm birth. The company has published data indicating that its assays can identify women at 10 and 12 weeks of gestation who will go on to deliver prematurely with sensitivity and specificity of more than 80 percent. 

Qiagen's PartoSure test measures the protein placental alpha macroglobulin to identify women at risk of preterm delivery. However, that test, which received US Food and Drug Administration approval last month, is intended for use in symptomatic patients.

All of these tests, Jelliffe-Pawlowski noted, are focused on identifying women at risk of spontaneous preterm delivery. She and her colleagues, on the other hand, aimed to develop a test that would apply both to spontaneous deliveries and to indicated preterm births — for instance, c-sections or inductions that are performed prior to 37 weeks of gestation to protect the health of the mother or baby.

Indicated preterm births can make up between 10 percent and 25 percent of preterm deliveries, depending on the particular patient population, Jelliffe-Pawlowski said. "We wanted to create something that performed as well as those other tests that are on the market, but that included a larger phenotype."

To identify potential markers, the researchers focused their search on cytokines and markers of placental function, because "inflammation, which is indicated by cytokine [levels], and how well the placenta is functioning, are common features of both spontaneous preterm birth and preeclampsia and other [conditions leading to] indicated preterm births," Jelliffe-Pawlowski said.

Using immunoassays run on a Luminex 200 instrument, they measured 63 markers in serum collected from pregnant women at 15 to 20 weeks of gestation. They tested a total of 400 women, 200 who delivered prematurely and 200 who delivered at term, using 240 subjects in their training set and 160 in their test set. The best performing assay combined 25 markers along with maternal poverty status and whether or not she was above 34 years of age.

Jelliffe-Pawlowski said that particularly with regard to women at high risk of preterm birth ending in preeclampsia, the assay could be useful as an initial screening assay to identify patients who should have more in-depth testing, such as blood flow analyses that can be used to identify potential preeclampsia cases.

Studies have shown that treatment with aspirin starting at 16 weeks can reduce the risk of preeclampsia in these women by more than 30 percent, she said, noting that, given this, she and her colleagues would like to push the sample collection time for their test to earlier than the 15 to 20 weeks used in the Journal of Perinatology study.

Jelliffe-Pawlowski said one of the major aims of her team's research is to develop a test targeting the highest risk populations, which in the US means primarily women or color and globally means low-income countries. Despite the large number of analytes in the panel, she said the test can be run cheaply and that the Luminex platform the researchers used is widely distributed globally and relatively inexpensive.

"It's a technology that is essentially available worldwide," she said, comparing it to a gestational dating test she and her colleagues have developed for use in areas where prenatal ultrasound is not widely available. That test, she said, uses mass spectrometry due to the large number of analytes (more than 50) involved. In many case, she said, the researchers have to send samples back to the US for analysis because of a lack of access to mass spec in the countries where testing is being done.

Jelliffe-Pawlowski said she and her colleagues are now planning a larger clinical validation trial they hope to run at multiple sites across the US. She said they are also exploring possible options for commercialization including licensing the test to an established company or possibly spinning out a new company to sell the test.

"We're thinking about how we can not only roll it out into the market of those with private insurance or those who can pay for it, but how at the same time we can have it made available to the women that need it most," he said. "That really will guide whether we partner with a company or spin something out ourselves."