Maternal plasma microRNAs as potential biomarkers for triaging pregnancies of unknown location and ectopic pregnancy diagnosis

Abstract

Background

Pregnancy of unknown location (PUL) is classified if an early pregnancy is not visualised on transvaginal ultrasonography (TVUS). Biomarkers currently used to triage PUL outcomes have varying accuracy. Delayed or missed diagnosis of ectopic pregnancies (EP) continue to cause significant morbidity and mortality. We investigated whether maternal plasma microRNAs (miRNAs) can predict and differentiate high-risk EP from viable (VIUP) or non-viable (NVIUP) intrauterine pregnancies.

Methods

Plasma was collected from women with PUL/EP (n = 120), mostly between four to eight weeks’ gestation, where outcomes of EP (n = 39), VIUP (n = 58) and NVIUP (miscarriage, n = 23) were determined using TVUS. Nanostring nCounter miRNA assay was used to examine the expression of ∼800 miRNAs in 22 women. Differentially expressed miRNAs were validated using RT-qPCR in 98 women.

Results

Nanostring nCounter miRNA assay identified 19 miRNAs which were expressed significantly higher in EP/NVIUP compared with VIUP. Two miRNAs were validated in a second, separate validation cohort using RT-qPCR: hsa-miR-21-5p in EP was 2.8-fold higher than in VIUP (p = 0.03, ROC AUC = 0.64), and hsa-miR-411-5p had 0.2-fold decreased expression (p = 0.02, ROC AUC = 0.66). Combining the divergent miRNAs as a ratio improved discrimination of EP from VIUP (p < 0.001, ROC AUC = 0.74).

Conclusion

Plasma miRNAs are differentially expressed in EP and VIUP and are detectable as early as four gestational weeks. Exploring miRNA targets may further understanding of EP pathophysiology, offering the potential to use miRNA as predictive and diagnostic markers in early pregnancy.