Brian Iriye, MD, is a maternal and fetal medicine obstetrician-gynecologist working at Hera Women’s Health in Las Vegas dedicated to improving the prevention of preterm birth-related deaths. Nonetheless, preterm birth—defined as delivery before the 37th week of pregnancy—is still one of the leading causes of maternal death and the leading cause of infant or neonatal death in the United States. In 2023, 10.4% of babies born in the United States were preterm, and approximately six out of every 1,000 babies died, with little progress made in reducing the risk of infant or neonatal death from preterm birth over the last few decades. In addition to these numbers, experts in the field appear to agree that a reliable screening tool is not yet available.
“The issue is, we don’t have a great screening test for it,” Iriye told Inside Precision Medicine. “In the past, what we’ve done is we’ve done risk factors or demographics to be able to look at that, and when you do that, you miss 50–60% of all preterm births by doing that alone. There have been some other ways that people have gone about it, like checking people’s cervixes to look at the length of the cervix because, if you think of it, the cervix is like a fence that holds the pregnancy in: the thicker the fence, the harder it is to break through; the thinner the fence, the easier it is to break through. We need to get better at predicting preterm birth.”
For Iriye, the ideal preterm screening tool will not only identify those at risk but will also advise clinicians on how to proceed to reduce neonatal morbidity and mortality. Take the Sera PreTRM Test, for example, which measures a proteomic biomarker in maternal blood using mass spectrometry between 18 and 20 weeks of pregnancy.
Iriye explained, “Sera PreTRM has been utilized in multiple research studies for 8–10 years already and has some evidence of being able to predict preterm birth. But the issue is it really isn’t being used because what good is a test for preterm birth if you can’t stop what the test is trying to predict?”
To get at this problem, Iriye spent four-plus years at the helm of the PRIME Trial, which evaluated outcomes in a cohort of average-risk singleton pregnancies using a proteomic biomarker-based preterm birth risk stratification, followed by a bundle of interventions for those identified as at higher risk. Participants identified by PreTRM received a regimen of daily vaginal progesterone, low-dose aspirin, and weekly standardized telephonic nursing visits that went over risk factors.
“This study was about putting together a trial of a marker that we think is really good for predicting preterm birth and then putting together a bundle of treatments to be able to stop it,” said Iriye. “We’ve got this prediction now, but which one of these is it from? I don’t know. So, you’ve got to attack it with a bundle of things.”
The PRIME Trial’s data—presented at the Society for Maternal-Fetal Medicine’s (SMFM) annual meeting, The Pregnancy Meeting—is encouraging, demonstrating the significant impact of a maternal biomarker test on improving the outcomes of newborns. The large-scale, randomized, controlled study of 5,018 women showed that targeted interventions based on the Sera PreTRM test results significantly improve newborn health and decrease NICU admissions and length of stay.
Specifically, Iriye and colleagues observed a 20% reduction in the neonatal morbidity index (NMI), which measures various health issues in newborns, a 20% decrease in overall NICU admission rates for newborns, and a 6–8% reduction in the length of stay for infants who were admitted to the NICU. The number needed to screen patients to prevent one NICU day, a readout of test efficiency, was 3.1 patients.
Iriye explained, “You only need to screen and treat 3.1 patients to prevent one day in the neonatal intensive care unit for a baby—that’s huge! One NICU day costs about $3,500. The number needed to screen to prevent one NICU admission was 41. The biggest test that we have now is vaginal length screening by ultrasound. If the cervix is short to treat with progesterone, the number needed to screen to prevent one NICU admission in those cases is 150. We’re at 3.1—that’s the practicality of it.”
Toward clinical adoption
What makes that data even more convincing is that the PRIME Trial had a very clear and diverse large cohort that didn’t include singleton pregnancies or high-risk situations. Instead, it kept people who had a very low risk of giving birth early and people who had a clear treatment option or severe medical conditions that required early delivery.
To put this into context, the PRIME Trial was the third in a series of studies testing Sera PreTRM, preceded by the PREVENT and AVERT trials. While both trials demonstrated that the proteomic maternal biomarker tests statistically and clinically significantly improved neonatal health outcomes and hospital length of stay, these trials were limited in their patient diversity, experimental design, and reached endpoints. Both trials were performed in a single center—PREVENT in Utah and AVERT in Delaware—limiting patient diversity. The AVERT Trial used historical controls instead of an active-control arm, and the PREVENT Trial never made it to the finish line, closing early because of a very low preterm birth rate.
“The PREVENT trial was a prospective trial like PRIME, but it was a single center in Utah. That population is probably not as diverse, more homogeneous, and has a very low preterm birth rate. So it’s harder to tell the difference. But when looked at in a secondary analysis, it did show a difference in NICU. The AVERT trial was controlled somewhat differently—not in the general way you want to do it—where you randomized groups that had a historical control and showed a huge difference in outcomes.”
According to Iriye, the next steps for the PRIME Trial data are to continue digging into the data, looking at subgroups within the data, such as whether there are differences in outcomes in Medicaid or African-American populations. Iriye hopes that the results of the PRIME Trial encourage fellow physicians to adopt the approach with the Sera PreTRM to improve patient care (after all, Iriye has no stake in Sera and, therefore, has no financial incentives).
“Guidelines help adoption, and the science we’ve shown has some possibility here that there is some promise,” said Iriye. “It’s up to people to decide on their own at this time whether they feel it can work within their practice. It’s harder for me because I’ve gone through this study and I’ve seen the data and for me, it looks very good. We do utilize it in my practice and can do that.”