PRIME trial: Biomarker screening cuts NICU admissions in first pregnancies

A biomarker-guided screening strategy significantly reduced neonatal intensive care unit (NICU) admissions and composite neonatal morbidity in nulliparous pregnancies, according to a secondary analysis of the PRIME randomized controlled trial (NCT04301518) published in The Journal of Maternal-Fetal & Neonatal Medicine.¹

Preterm birth (PTB), (delivery before 37 weeks of gestation) is the leading cause of neonatal mortality and a major source of long-term childhood morbidity, with preterm neonates accounting for a disproportionate share of NICU admissions and associated complications, including:

• Respiratory distress syndrome
• Bronchopulmonary dysplasia
• Sepsis
• Intraventricular hemorrhage, according to the study authors.²

Nulliparous pregnancies carry a consistently higher PTB risk than those following a prior full-term birth, yet risk stratification in this population is limited because current approaches rely largely on clinical history and cervical length, tools that together explain fewer than one-third of PTBs.¹

How does the IGFBP4/SHBG biomarker identify PTB risk?

The analysis centered on the IGFBP4/SHBG ratio, a mid-second-trimester maternal blood test measuring the ratio of insulin-like growth factor-binding protein 4 to sex hormone-binding globulin. The biomarker has been validated in large multicenter studies demonstrating 75% sensitivity and 74% specificity for spontaneous PTB (sPTB), with an area under the receiver operating characteristic curve of 0.75.

The PRIME trial was a 19-center randomized controlled trial evaluating screen-guided care using the IGFBP4/SHBG ratio vs. routine care in otherwise low-risk singleton pregnancies. Participants randomized to the screen-guided care arm who screened as higher risk for PTB were offered a bundled intervention of vaginal progesterone, low-dose aspirin, and weekly telephonic nursing support. All others received routine care. Models were adjusted for pre-enrollment aspirin use and COVID-19 status.

Of 5018 PRIME participants, 1783 were nulliparous (G1P0) and were included in this secondary analysis.

What were the key outcomes in nulliparous participants?

Significant reductions in composite neonatal morbidity scores were identified in the screen-guided care arm vs. routine care. The NICU admission rate was 12.8% in the screen-guided care arm compared with 16.4% in the routine care arm (P = .039), equating to a number needed to screen of 28 nulliparous pregnancies to prevent 1 NICU admission. After adjustment for pre-enrollment aspirin use and COVID-19 status, the screen-guided care arm had significantly fewer NICU admissions (OR 0.75; 95% CI, 0.57-0.98; P = .036).

NICU admission reductions were concentrated in spontaneous PTBs among nulliparous pregnancies. The bundled intervention was well-tolerated, with no serious adverse events reported among nulliparous participants in the screen-guided care arm, highlighting the support from study authors regarding the clinical utility of biomarker-guided preventive strategies in first-time pregnancies with no prior obstetric history.

References:

1. Sciscione AC, Gyamfi-Bannerman C, Walker M, Shahbaba B, Godt J, Iriye BK. Biomarker screen-guided care for preterm birth risk in nulliparous pregnancies: a subgroup analysis of the PRIME randomized controlled trial. The Journal of Maternal-Fetal & Neonatal Medicine. Published online July 8, 2026. Accessed July 14, 2026. https://www.tandfonline.com/doi/full/10.1080/14767058.2026.2689850
2. Ohuma EO, Moller AB, Bradley E, et al. National, regional, and global estimates of preterm birth in 2020, with trends from 2010: a systematic analysis. Lancet. 2023;402(10409):1261–1271. doi:10.1016/s0140-6736(23)00878-4.