New biomarker offers early detection of preterm birth risk

New biomarker offers early detection of preterm birth risk | Image Credit: © ondrooo - © ondrooo - stock.adobe.com.

Introduction

Risk stratification for spontaneous preterm birth (sPTB) may be performed at various gestational ages using a first trimester circulating microparticle (CMP) biomarker, according to a recent study published in the American Journal of Obstetrics & Gynecology.¹

Preterm birth (PTB) is the leading cause of neonatal morbidity and mortality worldwide, with risks increased by delivery at an earlier gestational age.² Many of these cases are spontaneous, but there are currently no maternal or fetal antecedents to the onset of labor in 2/3 of sPTB cases.¹

“While there is an increasing consensus that sPTB represents a syndrome rather than a single pathologic entity, it has been both ethically and physically difficult to study the pathophysiology of the uteroplacental interface,” wrote investigators.

Study objective and methology

Investigators conducted a study to evaluate the efficacy of a first trimester 7-marker set of CMP-derived proteins for predicting patients’ sPTB risk. Participants from the Nulliparous Pregnancy Outcomes Study: monitoring mothers-to-be study were included in the analysis, having been recruited in the first trimester and performing study visits at 6-, 16-, and 22-weeks’ gestation.

A study visit also occurred during delivery. Participants completed questionnaires and psychosocial instruments during the study visits, alongside collection of biological specimens such as plasma samples. Plasma samples obtained during the first trimester were included in the analysis.

PTB was defined as delivery before 37-weeks’ gestation. Any PTB, including preterm labor and preterm premature ruptured membranes, was considered sPTB.

Laboratory analysis

Size exclusion chromatography was utilized to enrich for CMPs from plasma. There were 440 Plasma-enriched CMP samples processed for use in quantifying biomarkers by liquid chromatography-tandem mass spectrometry. Samples were matched based on race and ethnicity, maternal age, smoking status, gestational age, and study site.

Risk categorization and findings

Clinical groups included gestational age under 32 weeks, 32 to under 37 weeks, and full-term (FT). Cases were patients with sPTB, while the remaining participants were controlled. These patients were matched 2:3.

There were 40 cases of sPTB under 32-weeks’ gestation, 40 between 32 and 34 weeks, and 80 at 35 or 36 weeks included in the analysis. The in vitro diagnostic multivariate index assay model assigned these patients to the low risk (LR), medium risk (MR), or high risk (HR) group.

Significant differences were noted for the 3 risk categories in both the development set and validation set, with many sPTB cases under 28-weeks’ gestation being captured within the HR stratum. The correlation had greater significance when including FT birth samples in the analysis.

The 3 risk categories also had statistically significant differences following adjustment to the actual sPTB incidence rate per final gestation week at delivery, with mean risk proportions of 8.6%, 59.8%, and 31.6% in the HR, MR, and LR groups, respectively. During HR classification, 72% of extremely PTB cases were identified.

Positive predictive values for HR were 7.46% at up to 32-weeks’ gestation, 8.95% at up to 34 weeks, and 13.34% at up to 35 weeks. Negative predictive values for LR were 99.59%, 99.18%, and 98.58%, respectively.

Conclusion

These results indicated efficacy from a CMP-based protein biomarker model toward predicting sPTB risk. Specifically, the model was effective for identifying very early PTB risk.

“Further clinical refinement and validation, coupled with trials of effective preventive therapies for those identified at the highest risk, is necessary,” wrote investigators. “Findings from such studies may provide a novel means to reduce sPTB during early gestation.”

References

1. Rosenblatt KP, Zhang Z, Doss R, et al. A multisite study to develop and validate first trimester, circulating microparticle biomarkers for tiered risk stratification of spontaneous preterm birth in nulliparas. Am J Obstet Gynecol. 2025;232:319.e1-21. doi:10.1016/j.ajog.2024.05.032
2. Katz J, Lee AC, Kozuki N, et al. Mortality risk in preterm and small-for-gestational-age infants in low-income and middle-income countries: a pooled country analysis. Lancet. 2013;382(9890):417-425. doi:10.1016/S0140-6736(13)60993-9