Metabolomics and preterm birth: What biomarkers in cervicovaginal secretions are predictive of high-risk pregnant women?

Abstract

Prematurity is the most important cause of perinatal mortality and morbidity and has serious consequences for the health of women and child later in life. Until now, the best predictive test for spontaneous preterm birth is ultrasound measurement of uterine cervical length. However, the physiological mechanism related to preterm births is still unclear. Can we improve the prediction of spontaneous preterm birth? Are there measurable physiological chemical biomarkers in biological fluids that could be more reliable predictors of preterm birth? Our hypothesis is that release mechanisms involving multiple biochemical reactions play a specific role in precipitating the onset of labor. The cascade of these biochemical events leads to perturbations in the metabolome which can be detected with high resolution and sensitive instruments using robust technologies, such as mass spectrometry. The main objective of this project was to perform a pilot mass spectrometry metabolomic study of women who had a spontaneous preterm birth compared to controls using the uterine cervical length as a selective factor. Non-invasive collection of cervicovaginal secretions from 15 women was performed: 5 with a short cervix who had a spontaneous preterm birth compared to a control cohort with a short cervix ( n = 5), and another control cohort with a long cervix ( n = 5). A total of 1908 metabolites were detected in these women. Markers of interest were identified by multivariate analysis. Further studies are planned on larger numbers of women followed by characterization of biomarkers of interest by mass fragmentation, isolation, purification and NMR studies. This metabolomic approach may allow the development of new strategies for the management of women at high-risk for spontaneous preterm birth.