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Maternal Blood Proteomic, Metabolomic Changes Could Predict Onset of Labor

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NEW YORK — Changes to the maternal metabolome, proteome, and immunome may portend that a pregnant woman will soon go into labor, a new study has found.

Currently, predictions of when labor will start are imprecise and based on gestational age and an average pregnancy length of 40 weeks, even though the onset of labor between week 37 and 42 of pregnancy is considered normal. Having a better idea of when labor may arrive could help with planning and managing medical concerns like fetal lung maturation.

To find early markers of labor, researchers from Stanford University School of Medicine followed more than 60 women toward the end of their pregnancies, collecting blood samples for metabolic, protein, and immune analysis. As they reported in Science Translational Medicine on Wednesday, they used this data to put together a model that can predict time to labor.

"We found a transition from 'progressing pregnancy' to a 'pre-labor' phase that happens two to four weeks before the mom goes into labor," first author Ina Stelzer, a postdoc in anesthesiology, perioperative medicine, and pain medicine at Stanford, said in a statement. "We've identified a novel way to use the maternal blood to predict when a mother will go into labor."

The researchers enrolled more than 100 pregnant women who were in their second or third trimester into their study, but restricted their analysis to samples from 53 women who went into labor spontaneously. Five of the women in the cohort delivered pre-term.

They collected a median of three blood samples from each participant within the 100 days preceding labor. Using untargeted mass spectrometry and an aptamer-based proteomic platform, the researchers tallied the levels of 3,529 metabolites and 1,317 proteins, while using a mass cytometry assay to gauge nearly 2,300 immune features over time.

By combining these datasets, the researchers began to piece together a picture of the changes that occur in the two to four weeks prior to delivery. For instance, the levels of steroid hormones like progesterone and cortisol rose dramatically. At the same time, levels of factors involved in angiogenesis fell, a change the researchers said could help weaken the connection between the uterus and the placenta, priming them for delivery.

Additional shifts affected the immune system. There was a rise in IL-1R4 levels, which inhibits the inflammatory factor IL-33, suggesting that this change may tamp down inflammatory responses that might otherwise be triggered during labor. In addition, the increase in IL-1R4 levels could serve a labor-initiation signal.

By feeding these changes into a model, the researchers developed a tool to predict when someone is about to go into labor. After training on their 53 cohort members, the researchers tested their predictor on data from a further 10 women to find that it had high accuracy in predicting the time to labor. They further noted that the model could predict both preterm and term labor.

The researchers next plan to validate their findings in a larger cohort as well as to winnow down the number of markers needed to predict labor. They further expect that their findings could be developed into a test in the next two to three years.

Co-author Virginia Winn, an associate professor of obstetrics and gynecology at Stanford, added in a statement that the findings could also help clinicians better manage labor. "If we understand what's regulating labor, we might be able to do a better job of inducing labor," she said.

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