Biomarker Screening in Second Trimester May Improve Neonatal Outcomes

AURORA, Colo. — Among those at low-risk for preterm birth, a blood-based biomarker screening test during the second trimester identified pregnancies at higher risk for preterm birth, and a treatment plan improved neonatal outcomes, the PRIME randomized control trial found.

Compared to usual care, those who were identified as higher risk and received low-dose aspirin, progesterone, and extra nursing calls had lower scores on the Neonatal Morbidity and Mortality Index (NMI) scale (OR/HR 0.75, 95% CI 0.62-0.91, P=0.003), reported Brian Iriye, MD, of Hera Women’s Health in Las Vegas.

This group also had shorter lengths of neonatal hospital stays (OR/HR 0.82, 95% CI 0.69-0.99, P=0.044), Iriye said in a late-breaking presentation at the Society for Maternal-Fetal Medicine annual meeting.

Additionally, an intention-to-treat analysis found significant reductions in the following outcomes:

• Neonatal medical index (OR/HR/IRR 0.80, P=0.019)
• Neonatal length of stay (OR/HR/IRR 0.92, P<0.001)
• Neonatal intensive care unit (NICU) length of stay (OR/HR/IRR 0.94, P=0.017)
• NICU admission (OR/HR/IRR 0.80, P=0.018)

Based on the findings, Iriye said the number needed to screen in order to prevent one NICU day was 3.1 and to prevent one NICU admission was 41.

Preterm birth stems from etiologies ranging from stress and environmental factors to infections, abnormalities, and disorders. For the past decade, the U.S. has consistently had a preterm birth rate around 10.4%. However, current screening protocols fail to identify more than half of pregnancies who deliver preterm.

“These limitations emphasize the need for broader strategies to identify conditions at risk,” Iriye said.

David Hackney, MD, a maternal-fetal medicine physician at Case Western Reserve University in Cleveland, who was not involved in the study, noted that there are many ways to identify patients at higher risk for preterm delivery, though what to do about it is the tougher question.

“What they importantly did was they both looked at the predictor and then looked at an intervention,” Hackney said, noting that neonatal outcomes were rightly included as the ultimate measure. Though, he noted, it was unclear in this trial which element of the intervention caused the improved outcomes — the aspirin, progesterone, or extra support from weekly nursing calls.

“The question is going to be, what caused the benefit?” Hackney said, noting he’s eager to see the final publication of this study.

The trial took place at 19 U.S. centers from 2020 to 2023 and included 5,018 singleton pregnancies. Patients were at low-risk for preterm birth and between 18 weeks’ and 20 weeks 6 days’ gestation. Prior preterm birth, short cervix, severe maternal conditions, and known genetic or fetal anomalies were exclusion criteria, as were recent COVID infection, certain chronic medical conditions, and maternal drug use.

Researchers measured the ratio of maternal circulating insulin-like growth factor-binding protein 4 to sex hormone-binding globulin, which is a validated predictor for spontaneous preterm birth when drawn in the middle of the second trimester.

Patients were randomized 1:1 to usual care or prevention; those in the control arm were blinded to their test results while those in the prevention arm received theirs. Patients in the prevention arm who were deemed low risk had no change in care but those who were higher risk were offered 81 mg of low-dose aspirin and 200 mg vaginal progesterone daily, and weekly nursing calls. Baseline characteristics between groups were similar; mean maternal age was 30-31 and the population was ethnically diverse.

Co-primary outcomes included neonatal length of stay and a composite neonatal morbidity and mortality index, both of which utilized a modified intention to treat population. Analyses were adjusted for pre-enrollment low-dose aspirin use, parity, and COVID status.

Iriye noted some limitations, including that the co-primary evaluation in the modified intention to treat population may have overestimated the effects and that because the biomarker results were disclosed in the prevention arm it may have affected treatment patterns.

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