Second-trimester blood test predicts premature birth for average-risk women

Key takeaways:

• A mid-trimester blood test identified average-risk women at risk for preterm birth.
• A treatment bundle including progesterone and low-dose aspirin reduced neonatal morbidity and hospital stay vs. usual care.

Compared with usual care, a mid-trimester blood test designed to predict preterm birth for average-risk women markedly reduced neonatal morbidity when paired with a three-step treatment bundle, researchers reported at The Pregnancy Meeting.

Preterm birth is one of the leading causes of infant death in the United States, yet March of Dimes data show the country continues to have a persistently high preterm birth rate, according to Brian K. Iriye, MD, a maternal-fetal medicine subspecialist, president of Hera Health and managing physician at the High-Risk Pregnancy Center in Las Vegas.

“In the U.S., about $18 billion is spent on maternal care and the same amount is spent on neonatal ICU for about 10% of the population,” Iriye, also a past president of the Society of Maternal Fetal-Medicine, told Healio. “It is important that we look at data like NICU admission, neonatal length of stay, neonatal morbidity and NICU length of stay.”

For the randomized controlled PRIME study, researchers analyzed data from 5,018 women with low-risk singleton pregnancies from 19 U.S. centers from 2020 through 2023. Women with a prior preterm birth, short cervix or other serious conditions were excluded. Researchers measured the ratio of maternal circulating insulin-like growth factor-binding protein 4 to sex hormone-binding globulin with a novel blood test (Sera Prognostics) during the middle of the second trimester.

“This test has been validated in the past through two studies and is a good predictor of preterm birth, with sensitivity and specificity in the range of 75%,” Iriye told Healio. “However, just because you have a test for [predicting] preterm birth does not mean you can do anything about it. This study takes those tests results and implements a pragmatic treatment bundle to see if you can decrease the issues associated with preterm birth.”

The control arm, masked to test results, received usual care; the intervention arm received test results. Women identified as high risk in the intervention arm were offered daily vaginal progesterone (200 mg daily), low-dose aspirin (81 mg daily) and weekly nursing phone calls; lower-risk women in the intervention arm received usual care.

The primary outcomes included neonatal length of stay and a composite morbidity index. Follow-up continued through delivery and neonatal discharge.

The test classified 23.5% of participants in the intervention arm as being at higher risk for preterm birth.

In the intention-to-treat analysis, researchers observed a 20% reduction in composite morbidity index (adjusted OR = 0.8; 95% CI, 0.66-0.95; P = .015), an 9% reduction in neonatal length of stay (aOR = 0.91; 95% CI, 0.88-0.94; P < .001), an 8% reduction in NICU length of stay (aOR = 0.92; 95% CI, 0.88-0.97; P = .003) and a 22% reduction in NICU admission (aOR = 0.78; 95% CI, 0.65-0.95; P = .006).

“The study results are strong; so much so that the [data safety monitoring board] recommended halting enrollment at the interim review due to efficacy in reaching the coprimary outcomes,” Iriye told Healio. “To prevent one NICU admission one would have to screen 41 patients. To prevent one NICU day, one would have to screen 3.1 patients.”

Iriye said researchers plan to further analyze subpopulations in the PRIME study and assess economic costs.

“It is up to our societies to look at these data after it is peer-reviewed to see if people want to move forward with it as a test, but these data appear strong,” Iriye told Healio. “It could be a great, possible step forward.”

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Brian K. Iriye, MD, can be reached on X (Twitter): @DrBrianIriye