A new blood test has an 80% accuracy in predicting preterm preeclampsia, according to a study published today, Feb. 12, in the journal Nature Medicine.
The condition, which results in over 70,000 maternal deaths and 500,000 fetal deaths each year worldwide, has long been hard to predict. This makes proactive treatment challenging, according to one of the study's lead authors.
"The placenta is not something we can biopsy during pregnancy, but we believe it is integral to developing preeclampsia," said Dr. Swati Shree , a UW Medicine OB-GYN and co-corresponding author of the paper. "Doctors do look at clinical risk factors, which can work reasonably well, but it still misses a fair amount of people."
Preeclampsia is a pregnancy complication characterized by high blood pressure (hypertension) or organ dysfunction. It typically occurs in the third trimester. The condition's exact cause is unknown, but doctors suspect it is related to an abnormal interaction between the placenta and the mother's blood vessels.
Traditionally, doctors tried to discern a pregnant woman's risk based on her patient history. Risk factors for preeclampsia include first pregnancy, history of preeclampsia, history of hypertension or chronic kidney disease or both. Sometimes, however, preeclampsia develops in the absence of any of these pre-existing conditions.
Researchers have known for at least two decades that the placenta sheds DNA into maternal blood. Labs have been able to extract cell-free DNA, sequence it and use the sample to screen for fetal abnormalities such as Down syndrome.
Earlier, this testing was shipped to outside labs for processing, but in 2017, UW Medicine started doing these tests in house, one of the first healthcare systems to do so, Shree added.
UW Medicine and Fred Hutch Cancer Center teams collaborated in developing the idea to use cell-free DNA sequence data to screen for pre-eclampsia, Shree said.
Over the past two years, the investigators, led by Shree and co-corresponding author Gavin Ha , a computational biologist at Fred Hutch, used this data, which functions as a liquid biopsy, from the first trimester of pregnancy for over 1,000 pregnant individuals to develop and then validate their test.
"The innovation in this tool reinforces how important it is. Liquid biopsy tests were pioneered in pregnancy health research and is now an emerging research area in oncology," said Ha. "There are similarities in the genes we're looking at in both areas of research, which makes this study a collaboration which bridges both fields."
The samples were collected between 2017-2023. The researchers found that their approach, which uses signals stored within circulating cell-free DNA sequence data, had 80% sensitivity at predicting whether a pregnant individual would experience preterm preeclampsia or not.
Shree said that the next steps would be to improve the training model with more samples, and ultimately to conduct a trial that includes thousands of patients. The researchers hope a test like this could become an early preeclampsia prediction tool that seamlessly integrates into routine early pregnancy screening.
"Although using liquid biopsies for human diseases is largely used in the cancer area, given the frequency at which cell-free DNA screening is performed, prenatal biology truly has incredible opportunities for the discovery and application of innovative tools," she said.
Funding came from the National Institutes of Health (K22 CA237746, DP2 186 CA280624,K08 HL150169,R21 HD086620and UL1 TR002319).
