Urinary prostaglandin metabolites as biomarkers for human labour: Insights into future predictors

Abstract

Prostaglandins and other related molecules in the eicosanoid family have long been implicated in the process of both term and preterm labour. Although, exactly which eicosanoids are involved and whether they have utility as biomarkers for labour, remains to be shown. The objective of this study was to determine whether urinary prostaglandins and related molecules a) change with labour and/or cervical changes, at term and preterm, and/or b) are associated with timing of delivery in individuals with threatened preterm labour. Pregnant individuals were recruited into the following groups: n = 32 term non-labour, n = 49 term labour, n = 15 preterm non-labour controls, n = 43 threatened preterm labour with preterm delivery, and n = 44 threatened preterm labour with term delivery. Metabolites of prostaglandins PGE2, PGF2α, PGD2, and PGI2 as well as 8-isoprostane were measured by ELISA. In addition, in a small (n = 24) subset of samples, 147 eicosanoids were measured using a mass-spectrometry based targeted lipidomics panel. At term labour prostaglandin PGF2α and PGE2 and PGF2α metabolites were increased compared to term non-labour. There were no changes in any prostaglandin metabolites prior to labour onset. Prostaglandin I2 metabolite was lower in individuals with threatened preterm labour who delivered preterm compared to those who went on to deliver at term. In our discovery cohort, we identified 20 additional eicosanoids as highly expressed in maternal urine, include members of the prostaglandin, hydroxyeicosatetraenoic acid (HETE), epoxyeicosatrienoic acid (EET), dihydroxy-octadecenoic acid (DiHOME), dihydroxy-eicosatrienoic acid (diHETrE), isoprostane, and nitro fatty acid eicosanoid families. In conclusion, we did not identify any prostaglandins that would have utility as predictors for term or preterm labour, however, we have identified diverse eicosanoids that have not been previously explored in the context of pregnancy and labour, highlighting novel areas for biomarker research.