Assessment of current biomarkers and interventions to identify and treat women at risk of preterm birth

Abstract

Preterm birth remains an important global problem, and an important contributor to under-5 mortality. Reducing spontaneous preterm birth rates at the global level will require the early identification of patients at risk of preterm delivery in order to allow the initiation of appropriate prophylactic management strategies. Ideally these strategies target the underlying pathophysiologic causes of preterm labor. Prevention, however, becomes problematic as the causes of preterm birth are multifactorial and vary by gestational age, ethnicity, and social context. Unfortunately, current screening and diagnostic tests are non-specific, with only moderate clinical risk prediction, relying on the detection of downstream markers of the common end-stage pathway rather than identifying upstream pathway-specific pathophysiology that would help the provider initiate targeted interventions. As a result, the available management options (including cervical cerclage and vaginal progesterone) are used empirically with, at best, ambiguous results in clinical trials. Furthermore, the available screening tests have only modest clinical risk prediction, and fail to identify most patients who will have a preterm birth. Clearly defining preterm birth phenotypes and the biologic pathways leading to preterm birth is key to providing targeted, biomolecular pathway-specific interventions, ideally initiated in early pregnancy Pathway specific biomarker discovery, together with management strategies based on early, mid-, and-late trimester specific markers is integral to this process, which must be addressed in a systematic way through rigorously planned biomarker trials.

Keywords: biomarkers; interventions; limitations; preterm birth; screening tools.

Figure 1

The pathways to preterm labor and preterm birth are multifactorial and complex. Multiple molecular mechanisms are influenced by a variety of risk factors, including genetic, epigenetic, biological, behavioral, social, clinical, and environmental influences. Reprinted with permission from Rubens et al. (3); © 2024 American Association for the Advancement of Science.

Figure 2

Potential biomarkers to identify women at risk of preterm birth and targeted interventions. Provided by Rachel M Tribe. fFN, fetal fibronectin; qfFN qualitative fFN; pIGFBP1, phosphorylated insuline-like growth factor binding protein 1, PAMG1, placental alpha microglobulin-1; PreTRM, PreTRM^®.

Figure 3

Suggested screening algorithm and possible treatment strategies for women identified as at-risk for preterm birth (singleton pregnancies). Provided by Marian Kacerovsky and Rachel M Tribe.