Obstetrics and gynecology (OB-GYN) professors and doctors at Stanford Medicine applauded a May 5 breakthrough study finding certain blood markers and immune signals that can predict approaching labor — but, they say, there is more to be done. The findings could serve as a jumping-off point for future study with the goal of developing prediction methods that can be used in clinical settings.

The original study analyzed 7,142 metabolic, protein and immune cell features from blood samples provided by 63 pregnant women over a two-year span. The research team, with members of Stanford’s Prematurity Research Center (PRC), detected a noticeable surge in hormone, blood clotting and immune signaling levels before delivery. The authors said the novel discovery could dramatically increase the accuracy for forecasting labor within a few years.

To take the results and use them in clinical settings requires future research on whether the findings hold true across race and ethnicity as well as a translation of the findings to spontaneous preterm pregnancies, according to the three researchers who spoke to The Daily about the results.

Indeed, David Stevenson ’71, who is listed as an author on the study, said that these results are already being applied toward future investigations. At PRC, the findings have helped researchers move forward in identifying causes and establishing prevention measures for preterm birth, while better showing the transition from the mother’s tolerance of the fetus to inflammation signaling the approach of active labor. 

Alongside this research, PRC members are investigating health disparities in pregnant women and the various causes of preterm births, such as stress, environmental factors and a high-blood pressure condition during pregnancy.

But it is unclear how soon the study results could translate to clinical tests, according to Yair Blumenfeld, an associate OB-GYN professor not affiliated with the study: “We have various ways of determining a risk of prematurity, but we cannot predict the timing of the delivery day right now,” he wrote. “Once the pregnancy starts, I cannot say on what day or week the patient will deliver. Only a very small fraction of women deliver on their due dates.”

Maurice Druzin, a professor of OB-GYN and maternal-fetal medicine, said the results are “encouraging and exciting,” as they suggest that observable shifts in protein and hormone levels can be used to narrow the window of estimates for when a person will go into labor. The standard procedures in health centers nationwide use a combination of the last menstrual period with ultrasound confirmation to formulate an estimated date of delivery that typically ranges from 37 to 42 weeks, he said.

Druzin was credited in the paper, but provides an outside perspective. A very large majority of OB-GYN doctors and PRC members at Stanford Medicine were cited as co-authors of the study.

Druzin said it is critical that additional follow-up analysis and expansion of sample size are performed, especially when it comes to race and ethnicity. In the study, the majority of the 63 women evaluated were Asian or white.

“The results need to be validated with a much larger cohort and a more diverse population,” he wrote in an email. “Before a test can become clinically valid, larger population studies are always necessary.”

Blumenfeld agreed with Druzin, saying that given the cohort size, the investigators did not have the opportunity to determine if the results held true across different races and ethnicities.

In their published study, the co-authors did acknowledge this temporary barrier, writing, “Future studies in a more diverse population and enriched for women with extreme pregnancy lengths will be needed to further test the generalizability of our findings.”

Blumenfeld said another limitation of the study was that the research team could not test any samples from the placenta or the developing baby. They had to rely solely on the parent’s blood samples, but pregnancy is a multidimensional process that involves the baby and placenta before reaching a maternal response. The better the reactions occurring in the earlier stages are measured, the more we will understand the processes that initiate labor. 

Nevertheless, he believes that the more important achievement made by the researchers is how they obtained very precise and comprehensive analyses of biological samples and laid out how these physiological mechanisms interact with each other.

Researchers said another avenue for future research could also be looking into indicators for preterm labor, which is induced by physicians in up to 30% of total preterm births. Druzin explained that while it is currently not possible to predict spontaneous preterm births, he is confident that the observations extracted from the research could make it soon feasible.

“Now that there is this analytical and biological approach, the next step will likely be to apply this to spontaneous preterm labor and see if we can understand similarities and differences between preterm and term labor,” Blumenfield said.